OncoTrials - мониторинг клинических исследований

Описание

This study is a prospective, single-arm, interventional, multicenter study to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the Akura Thrombectomy System in subjects with acute pulmonary embolism (PE).

Критерии включения

• * The patient is 18 years of age or older and deemed medically eligible for interventional procedure, per institutional guidelines and clinical judgement
• * Clinical signs, symptoms and presentation consistent with acute PE
• * PE symptom duration ≤ 14 days
• * CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery)
• * CTA evidence of RV/LV ratio of ≥ 0.9 (NOTE: Enrollment qualification assessment is based on the Investigator`s interpretation of RV/LV ratio at baseline)
• * Systolic BP ≥ 90 mmHg (initial SBP may be /< 90 mmHg but ≥ 80 mmHg if the pressure recovers with volume resuscitation)
• * Stable HR /< 130 BPM prior to the procedure

Критерии исключения

• * Prior PE /<180 days from index procedure
• * Thrombolytic use within 30 days prior to baseline CTA
• * Pulmonary hypertension with peak pulmonary arterial pressure (PAP) /> 70 mmHg by right heart catheterization
• * Vasopressor requirement after fluids to keep pressure at ≥ 90 mmHg
• * FiO2 requirement /> 40% or /> 6 LPM (to keep oxygen saturation /> 90%)
• * Hematocrit /< 28% (Note: hematocrit required within 6 hrs. of index procedure)
• * Platelets /< 100,000/μL
• * eGFR /<30 ml/min per 1.73 m2
• * International normalized ratio (INR) /> 3
• * Major trauma injury severity score (ISS) /> 15
• * Presence of intracardiac lead in right ventricle or atrium placed ≤ 6 months of enrollment
• * Cardiovascular or pulmonary surgery within the last 7 days
• * Actively progressing cancer treated by chemotherapeutics
• * Known bleeding diathesis or coagulation disorder
• * Left bundle branch block
• * History of severe or chronic pulmonary arterial hypertension
• * History of chronic left heart disease with left ventricular ejection fraction ≤ 30%
• * History of uncompensated heart failure.
• * History of underlying lung disease that is oxygen dependent
• * History of chest irradiation
• * History of heparin-induced thrombocytopenia (HIT)
• * Contraindication to systemic or therapeutic doses of anticoagulants
• * Known anaphylactic reaction to radiographic contrast agents that cannot be pretreated
• * Known residual iliac deep vein thrombosis (DVT), inferior vena cava (IVC) clot or clot in transit (right atrium and/or right ventricle)
• * CTA imaging or other evidence that suggest, in the opinion of the investigator, the Subject is not appropriate for mechanical thrombectomy intervention (e.g. inability to navigate to target location, predominantly chronic clot or non-clot embolus)
• * Life expectancy /< 90 days, as determined by investigator (e.g., stage 4 cancer, frailty or severe COVID infections)
• * Female who is pregnant or nursing
• * Current participation in another investigational drug or device treatment study

Описание

This study is conducted to evaluate the efficacy and safety of lenvatinib plus transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and hepatic artery infusion chemotherapy (HAIC) with FOLFOX regemen (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for large hepatocellular carcinoma (/> 7cm) with portal vein tumor thrombosis (PVTT).

Критерии включения

• * a confirmed diagnosis of HCC
• * the largest intrahepatic lesion />7 cm
• * presence of PVTT on imaging
• * tumor recurrence after curative treatment (hepatectomy or ablation) is eligible for enrollment
• * Eastern Cooperative Oncology Group performance status ≤1
• * Child-Pugh class A/B
• * adequate hematologic and organ function, with leukocyte count/>3.0×10/^9/L, neutrophil count/>1.5×10/^9/L, platelet count≥75×10/^9/L, hemoglobin 85 g/L, alanine transaminase and aspartate transaminase≤5×upper limit of the normal, creatinine clearance rate≤1.5×upper limit of the normal
• * life expectancy of at least 3 months

Критерии исключения

• * Diffuse HCC
• * accompanied with vena cava tumor thrombus
• * central nervous system involvement
• * previous treatment with TACE, HAIC, TAE, radiotherapy, or systemic therapy
• * organ (heart and kidneys) dysfunction, unable to tolerate TACE or HAIC treatment
• * history of other malignancies
• * uncontrollable infection
• * history of HIV
• * history of organ or cells transplantation
• * prothrombin time prolongation />4 s

Описание

Patients with genitourinary cancers (ex: bladder, testicular, kidney) are at high risk of developing blood clots if they receive systemic therapy (ex: chemotherapy, immunotherapy). Blood clots cause pain, may require hospitalization and invasive testing, and in some cases cause death. In fact, blood clots are one of the leading causes of death in patients with cancer. Furthermore, patients who develop a blood clot require medication to thin the blood for a prolonged (sometimes indefinite) period of time, and this can disrupt other important cancer treatments. Studies have shown that using low dose blood thinners to prevent blood clots during systemic therapy is effective in some patients with cancer. However very few patients in these studies had genitourinary cancers, therefore physicians in Canada are not sure if recommending blood thinners to patients with genitourinary cancers is useful or safe. Safety is a primary concern because blood thinners may cause bleeding, and patients with genitourinary cancers may have higher risk of bleeding than patients with other types of cancer. The investigators hypothesize that blood thinners are effective and safe for reducing blood clots in patients with genitourinary cancers. The objective of this study is to determine if a large clinical trial testing the effectiveness and safety of low dose blood thinners for preventing blood clots in patients with genitourinary cancers receiving systemic therapy is feasible.

Критерии включения

• * Patients who are starting systemic therapy for active GU cancer (bladder, testis, ureter/renal pelvis, kidney, urethral, penile) except for prostate cancer.
• * Age ≥ 18
• * Eligible systemic therapies include chemotherapy, targeted therapies (tyrosine kinase inhibitors and antiangiogenic therapy), and immunotherapies.
• * Patients must be initiating systemic therapy with a minimum planned treatment duration of 8 weeks.

Критерии исключения

• * Anticoagulation (prophylactic or therapeutic dosing) required for another indication for entire duration of study
• * Known allergies to rivaroxaban
• * Concomitant use of dual antiplatelet therapy (two antiplatelet medications oncomitantly)
• * Ongoing refractory bleeding that may be exacerbated by rivaroxaban.
• * Concomitant use of strong inducers or inhibitors of CYP3A4 or glycoprotein-P (known interaction with rivaroxaban).
• * Severe renal insufficiency (Creatinine clearance /<30 mL/min (defined by Cockcroft-Gault))
• * Severe liver disease (e.g. acute clinical hepatitis, chronic active hepatitis, cirrhosis)
• * Thrombocytopenia /< 50 x 109/L
• * Life expectancy under 6 months.
• * Pregnancy (if child bearing age under 50 and sexually active, documentation of use of effective contraception or negative B- HCG is required)
• * Patient is breastfeeding or lactating
• * History of condition at increased bleeding risk including, but not limited to:
• cerebral infarction (hemorrhagic or ischemic), active peptic ulcer disease with recent bleeding, spontaneous or acquired impairment of hemostasis in the previous 4 weeks.
• * Chronic hemorrhagic disorder
• * Inability to adhere to protocol or obtain consent.
• * Patients may be excluded from the study for other reasons, at the investigator`s discretion.

Описание

The goal of this observational study is to evaluate the predictive efficacy of the Modified Caprini Risk Assessment Score and D-Dimer in identifying and managing lower extremity venous thrombosis (LEVT) among cardiothoracic surgery patients in Baghdad. The main questions it aims to answer are:

Does combining the Modified Caprini Score with D-Dimer improve the accuracy of predicting lower extremity venous thrombosis (LEVT) compared to using each tool independently? Can these tools effectively guide clinical decisions for lower extremity venous thrombosis (LEVT) prevention and management in this patient population?

Participants will:

Undergo risk assessment for lower extremity venous thrombosis (LEVT) using the Modified Caprini Score and have their D-Dimer levels measured during their hospital stay.

Be monitored for clinical outcomes, including confirmed lower extremity venous thrombosis (LEVT) incidence, need for anticoagulation therapy, and complications such as pulmonary embolism or recurrent thrombosis.

Критерии включения

• * Inpatients with a hospital stay over 3 days
• * Written informed consent obtained from patients or their legal guardians.
• * Availability for postoperative follow-up to assess outcomes like LEVT development or related complications.

Критерии исключения

• * Preexisting LEVT or Pulmonary Embolism: Diagnosed before the index surgery.
• * Severe Coagulopathy: Patients with inherited or acquired bleeding disorders (e.g., hemophilia, advanced liver disease).
• * receiving any anticoagulation therapy for any reason.
• * patients who did not undergo a postoperative D-dimer test.
• * Incomplete Data: missing essential clinical or laboratory data for Modified Caprini Score calculation or D-Dimer measurement.
• * Pregnancy: pregnant women or those within six weeks postpartum.
• * Noncompliance: Patients unwilling or unable to adhere to study follow-up protocols.

Описание

Sobi.BIVV001-003 is an open-label, 2-period, fixed sequence study for intra-participant comparison of the PK profiles of efanesoctocog alfa and the extended half-life rFVIII products damactocog alfa pegol or turoctocog alfa pegol after a single i.v. injection in previously treated males, 18-65 years of age, with severe haemophilia A.

Participants who are receiving treatment with damoctocog alfa pegol (n/~12) or turoctocog alfa pegol (n/~12) will be enrolled in the study. The study will start with a screening period (up to 28 days), including a wash-out period prior to start of the actual study period.

During the the first visit, a single dose of damactocog alfa pegol or turoctocog alfa pegol (corresponding to the participant`s pre-study treatment) will be administered. A PK sampling period will follow over 7 visits. Following completion of the PK sampling of the original treatment regimen, the patients will be given a single dose of efanesoctocog alfa at visit 8, after which a new PK sampling period will follow (visit 8-15).

The primary objective for the study is to compare the half-life of efanesoctocog alfa with that of the two comparator drugs after a single iv. injections.

Secondary objectives include comparison of area under the curve for efanesoctocog alfa vs. the two comparator drugs, characterization of PK parameters for all three drugs as well as well as to evaluate safety and tolerability of a single iv. injection of efanesoctocog alfa.

Критерии включения

• * Participant must be male, 18 to 65 years of age, inclusive, at the time of signing the informed consent form (ICF).
• * Severe haemophilia A, defined as /<1 IU/dL (/<1%) endogenous FVIII activity, as documented in historical medical records from a clinical laboratory demonstrating /<1% FVIII coagulant activitiy or a documented genotype known to produce severe haemophilia A.
• * Previous treatment for haemophilia A with any marketed recombinant and/or plasma derived FVIII for at least 150 exposure days.
• * Currently receiving treatment with damoctocog alfa pegol or turoctocog alfa pegol at Screening.

Критерии исключения

• * Any history of a positive inhibitor test, defined as />0.6 Bethesda units (BU)/mL in at least two consecutive Bethesda inhibitor assays, or any value greated than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL. Family history of inhibitors will not exclude the participant.
• * Positive FVIII inhibitor result (assessed by central laboratory), defined as ≥0.6 BU/mL at Screening.

Описание

For bridging the available global clinical data of rVIII-SingleChain, with the Chinese population, the aim of this study in China is to investigate the pharmacokinetics (PK) of rVIII-SingleChain after an initial and repeat dose and to assess efficacy and safety during 2 to 3 times weekly prophylaxis treatment with rVIII-SingleChain in male Chinese PTPs with severe hemophilia A (FVIII activity less than /[/</] 1%).

Критерии включения

• * Male Chinese participants /<= 65 years of age.
• * Participants with severe hemophilia A (FVIII activity /< 1%).
• * Participants who have received FVIII products for />= 150 EDs (/>= 6 years of age) or />= 50 EDs (/< 6 years of age).

Критерии исключения

• * Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein.
• * Known congenital or acquired coagulation disorder other than congenital FVIII deficiency.
• * Currently receiving intravenous (IV) immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
• * Receiving any cryoprecipitate, whole blood, or plasma within 30 days before administration of rVIII-SingleChain.
• * Use of traditional or herbal Chinese medicine(s) with an impact on hemophilia, including coagulation, within 28 days before Day 1 and / or refusal to abstain from these during the study until the end of the participant`s participation in the study.

Описание

Central venous (CVC) is essential in modern healthcare but unfortunately associated with complications, including thrombosis. In a recently published study, it was showed that 12 out of 12 deceased patients had subclinical CVK-related thrombosis (Rockholt et al.). To shed light on this problem, the current studies were designed. In sub-study 1, deceased patients with CVC who are referred for clinical autopsy are included. Before the autopsy, the deceased will be examined with a photon-counting computed tomography (CT) scan and the results will be compared.

In sub-study 2, living patients with CVC who are referred for various CT scans without contrast, are included. After informed consent, the patient will be examined with the photon-counting CT, whose reliability has been validated in Part 1 and the incidence of subclinical CVC-related thrombosis will be reported.

Критерии включения

• Substudy 1
• Inclusion Criteria:
• * Diseased patients with an indwelling central venous catheter and a clinical indication for autopsy
• * Informed and signed consent from next of kind

Критерии исключения

• * None
• Substudy 2 Inclusion Criteria
• * Living patients with an indwelling central venous catheter who are referred to a CT scan without iv contrast
• * Informed and signed consent from the patient
• Exclusion Criteria
• - GFR /<15 mL/min/1.73 m2

Описание

Prospective, multicenter, open label, randomized controlled clinical trial to compare the effects of an early catheter-directed treatment plus conventional care with conventional care in patients with high-risk pulmonary embolism

Критерии включения

• 1. Pulmonary embolism as confirmed by CT angiogram with high mortality risk as defined by ESC guidelines:
• a) One of the following: i. Cardiac arrest or ii. obstructive shock (systolic BP /<90 mmHg or vasopressors required to achieve a BP ≥90 mmHg despite an adequate filling status), in combination with end-organ hypoperfusion (cold, clammy skin, oliguria or serum lactate ≥2 mmol/L) and b) Signs of right-ventricular dysfunction on transthoracic echocardiogram or CT scan
• 2. Age ≥18 years

Критерии исключения

• 1. Contraindications for catheter-based treatment
• 2. Contraindications to systemic fibrinolytic treatment or anticoagulation/*
• 1. Active, potentially life-threatening bleeding
• 2. Surgery within 24h before screening
• 3. Cranial or spinal surgery within 14d before screening
• 4. Stroke within 14d before screening
• 5. Intracranial tumor
• 6. Any condition not listed here but estimated as clinically relevant as judged by the treating investigator
• 3. Pregnancy
• * Patients with contraindications to systemic fibrinolysis or anticoagulation can be enrolled in a third study arm (registry) and undergo catheter-directed therapy.

Описание

The aim of this project is to determine the measurement properties (namely reliability and validity) of a set of clinical assessments, measuring different aspects of physical function.

Критерии включения

• * Diagnosed Hemophilia Types A or B
• * Adult people ≥ 18 years
• * Patients on prophylactic factor or non-factor replacement treatment, or on demand factor replacement treatment.
• * Able to walk for 20 meters independently, with or without walking aid
• * Signed informed consent to participate in the study

Критерии исключения

• * Severe health conditions like severe cardiovascular, pulmonary, neurological or musculoskeletal diseases.
• * Unable to perform the assessments due to disability or language problems.

Описание

A Clinical Study on the Safety and Effectiveness of CD7 CAR-T Cell Sequential Allo-HSCT and Kidney Transplantation in the treatment of Schimke immuno-osseous dysplasia

Критерии включения

• * 1. Diagnosed as SIOD and was in stage 5 of chronic kidney disease
• * 2. Having allogeneic HSCT indications, at least suitable donors (relatives) for haploidentical allogeneic transplantation and kidneys from stem cell transplantation donors;
• * 3. serum total bilirubin ≤ 1.5 times the upper limit of normal, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were both ≤ 3 times the upper limit of the normal range.
• * 4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
• * 5. There is no active pulmonary infection, and the oxygen saturation during air inhalation is more than 92%；
• * 6. Estimated survival time ≥ 3 months;
• * 7. ECOG performance status 0 to 1;
• * 8. Pregnant/lactating women, or male or female patients who have fertility and are willing to take effective contraceptive measures at least 6 months after the last cell infusion during the study period;
• * 9. Those who voluntarily participated in this trial and provided informed consent

Критерии исключения

• * 1. Allergic to pretreatment measures
• * 2. received any containing ATG/ALG such IST、alemtuzumab、high-dose cyclophosphamide (≥ 45mg/kg/day) , received CsA treatment within 6 months, or used thrombopoietin receptor (tpo-r) agonists in the past;
• * 3. Patients with the history of epilepsy or other CNS disease;
• * 4. Patients with prolonged QT interval time or severe heart disease;
• * 5. Previous recipients of allogeneic hematopoietic stem cell transplantation or organ transplantation
• * 6. People infected with HIV, active hepatitis B or hepatitis C virus, and patients with active infection who are not cured;
• * 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• * 8. Patients with malignant tumor;
• * 9. People with other genetic diseases；
• * 10. After receiving CD7 car-t treatment, patients who were unable to accept subsequent kidney transplantation due to severe infection or poor amplification of car-t in vivo.
• * 11. Any situation that researchers believe may increase the risk to the subjects or interfere with the trial results.

Описание

Surgical hip replacement (total hip arthroplasty, THA) is associated with a high risk of venous thromboembolism, but the appropriate duration of postoperative medical thromboprophylaxis ("anticoagulation") remains highly controversial. The international randomized controlled trial (RCT) "ENhanced recovery and ABbreviated LEngth of Anticoagulation for Thromboprophylaxis after primary Hip Arthroplasty" (ENABLE-Hip) will enroll patients undergoing elective THA that are eligible for early mobilization after surgery. The trial will compare a regimen of short-duration (10-day) postoperative anticoagulation (experimental group) to standard-duration (35-day) postoperative anticoagulation (control group) using the direct oral anticoagulant Rivaroxaban (brand name: Xarelto) at the recommended dose. Thus, ENABLE-Hip will be the first major RCT to directly test an overall reduction in the duration of post-THA thromboprophylaxis instead of replacing one antithrombotic drug or regimen by another. Follow-up visits after hospital discharge will be on day 35 and on day 90 after surgery. The primary outcome is acute symptomatic proximal deep vein thrombosis, or symptomatic or fatal pulmonary embolism, within 90 days after surgery. If ENABLE-Hip will demonstrate `non-inferiority` of the experimental intervention, its benefits will be obvious, as patients are spared many days of unnecessary (and potentially harmful in terms of bleeding risk) anticoagulation.

Критерии включения

• 1. Written informed consent
• 2. Age between 18 and 85 years
• 3. Scheduled to undergo elective unilateral primary THA and eligible for perioperative management based on the ERAS protocol
• 4. Baseline Timed Up and Go (TUG) test scoring /< 20 seconds, corresponding to a good mobility status before surgery
• 5. Capability to understand and comply with the protocol requirements (e.g., sufficient knowledge of German language to answer the questionnaires, ability to swallow intact capsules).
• 6. Pregnancy and contraception:
• 1. Pregnancy test: Negative serum pregnancy test at screening for women of childbearing potential (WOCBP).
• 2. Contraception: WOCBP and men who are able to father a child, willing to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of drug treatment and allowing for a safe wash out period of at least 5 days for female or for male subjects after the last dose of trial medication. This is a very conservative estimate, considering the `worst case scenario` of a substantially prolonged half-life up to 13 hours (e.g., in older patients and/or those with renal dysfunction) (28), and calculating for at least 8 half-lives to ensure practically non-detectable levels and effects of rivaroxaban.

Критерии исключения

• 1. Previous DVT or PE
• 2. Hip or lower limb fracture in the previous three months
• 3. Major surgical procedure within the previous three months
• 4. Active cancer defined as metastatic cancer, or cancer requiring chemotherapy or radiation therapy
• 5. Active peptic ulcer disease, gastritis, or prior gastrointestinal bleeding
• 6. Obesity with body mass index (BMI) /> 40 kg/m2 body surface area
• 7. Severe renal impairment defined as estimated glomerular filtration rate /< 30ml/min
• 8. Severe hepatic impairment defined as Child Pugh Class B or C
• 9. Uncontrolled intercurrent illness (i.e., active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, interstitial lung disease, serious gastrointestinal conditions /[e.g., diarrhea, malabsorption/], psychiatric illness)
• 10. Active or recent major bleeding at any site, or presence of any major risk factor for bleeding, which, in the judgment of the investigator, may significantly increase the bleeding risk during postoperative anticoagulation treatment
• 11. Any other medical condition representing a contraindication to discharge within 6 days after surgery
• 12. Expected requirement for major surgery within a 90-day period post THA
• 13. Need for long-term anticoagulation (e.g., atrial fibrillation, previous VTE)
• 14. Need for chronic antiplatelet therapy except for acetylsalicylic acid (ASA) at a dose ≤ 100 mg daily or clopidogrel 75 mg daily
• 15. Previous participation in this trial
• 16. Life expectancy /< 6 months
• 17. Participation in another interventional clinical trial within the last 30 days prior to inclusion, unless during the observational follow-up period
• 18. History of hypersensitivity to the investigational medicinal product (IMP) or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the IMP

Описание

The rationale for conducting this open-label phase 4 study is to assess whether once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) improves the disease course of existing synovial hypertrophy and prevents the risk of joint bleeds in patients with moderate or severe haemophilia A. The use of imaging assessments will allow for objective detection and monitoring of synovial hypertrophy, and thus expand on the previous findings demonstrating positive effects of once-weekly prophylaxis with efanesoctocog alfa (50 IU/kg) on joint health.

Критерии включения

• 1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. Parents` or legally designated representatives` consent is required for patients who are /<18 years of age or unable to give consent, or as applicable per local laws. Patients who are /<18 years of age should provide assent in addition to the parents`/legally designated representatives` consent, if appropriate.
• 2. Male or female patients who are ≥12 years of age and diagnosed with moderate or severe haemophilia A (defined as ≤5% of normal FVIII clotting activity) at the time of signing the ICF.
• 3. A female patient is eligible to participate if she is not pregnant at enrolment and does not plan to become pregnant during the study. A woman of child-bearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test at the Screening Visit.
• 4. Must have received prophylactic treatment per local label with any marketed FVIII product or emicizumab for ≥12 months prior to the Baseline Visit.
• 5. Have at least one eligible index joint (ankle, elbow, knee).
• 6. Have 12 months of documented pre-study treatment data on haemophilia prescriptions and on treated bleeding episodes prior to the Baseline Visit.
• 7. Willingness and the ability of the patient or their legally designated representative to complete training in the use of the study patient diary and to complete the diary throughout the study.

Критерии исключения

• 1. Blood clotting disorders other than haemophilia A
• 2. Already on efanesoctocog alfa treatment
• 3. Positive inhibitor result (assessed by local laboratory) from the Screening Visit, defined as ≥0.6 Bethesda units (BU)/mL.
• 4. History of inhibitors without successful immune tolerance induction (ITI)
• * Successful ITI is defined as:
• * Negative inhibitor titer (/<0.6 BU/mL)
• * FVIII recovery /> 66% of expected
• * FVIII half-life ≥ 6 hours
• 5. ITI performed within the last 2 years prior to the Baseline Visit.
• 6. Currently receiving treatment with any of the prohibited concomitant medications, as specified by the protocol.
• 7. Planned major orthopaedic procedure in any eligible index joint during the course of the study.
• 8. Patients are not eligible for participation in the study if they cannot undergo MRI assessments at the Baseline Visit.
• 9. Patients with known hypersensitivity to the active substance or to any of the excipients.
• 10. Patient not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures.
• 11. Enrolment in a concurrent clinical interventional study, or intake of an investigational medicinal product (IMP), within 3 months prior to inclusion in the study.

Описание

Despite being generally benign tumors, meningiomas are associated with an increased risk for thrombembolic complications after surgical resection. The molecular mechanisms underlying this circumstance are still unknown.

In this prospective observational trial, the investigators aim to evaluate the changes in coagulation and platelet function caused by tumor resection.

Blood samples are obtained by patients undergoing meningioma resection before and immediately after resection to detect said changes.

As a control cohort, blood samples are obtained from patients undergoing resection for glioma.

Критерии включения

• * Patients undergoing resection for meningioma or
• * Patients undergoing resection for glioma or
• * Healthy controls
• * written consent for study participation

Критерии исключения

• -

Описание

The objective of this randomized clinical trial is to evaluate the safety and efficiency of different anticoagulation schemes with heparin for venous thromboembolism prevention in patients with hypertensive intracerebral hemorrhage. The main questions it aims to answer are:

* What is the optimal time for the beginning of anticoagulation with heparin to efficiently prevent venous thromboembolism in patients with hypertensive intracerebral hemorrhage? Early beginning (within the first 2 days but not earlier than 12 hours after the admission of a patient) or delayed beginning (on the third day after the admission of a patient)?
* Which of the two timeframes (early or delayed) for anticoagulation beginning is the most safe in terms of bleeding complications including intracerebral hemorrhage expansion?

Researchers will compare the results of early and delayed start of anticoagulation using heparin in patients with hypertensive intracerebral hemorrhage to define the optimal start time for anticoagulation that provides the most favourable efficiency/safety profile.

Participants will:

* Undergo a computed tomography (CT) scan of the brain on hospital admission and then 12-24 hours after the hospital admission and 24 hours after the beginning of venous thromboembolism prophylaxis using heparin;
* Undergo the ultrasound examination of lower extremity deep veins on hospital admission and then once every 7 days;
* Receive prophylactic doses of low molecular weight heparin or unfractionated heparin either beginning within the first 2 days but not earlier than 12 hours after the hospital admission or starting on the 3rd day after the hospital admission.

Критерии включения

• * the presence of hypertensive intracerebral hemorrhage

Критерии исключения

• * Intracerebral hemorrhage expansion detected on the basis of a computed tomography scan of the brain 12-24 hours after a hospital admission (i.e. before the initiation of venous thromboembolism prophylaxis with heparin)
• * Being on an anticoagulant during preadmission period and on day of hospital admission
• * Death within the first 2 days after hospital admission
• * Detection of venous thromboembolism in a patient at the moment of hospital admission
• * Surgical management of hypertensive intracerebral hemorrhage before the beginning of venous thromboembolism prophylaxis using heparin
• * The presence of a malignancy (cancer) in a patient at the moment of hospital admission

Описание

The EMPOWER trial is a pilot multi-center, placebo-controlled (normal saline), double-blind (patient and outcome assessor), crossover, 2-year randomized trial in female outpatients with von Willebrand disease (VWD) and heavy menstrual bleeding to determine trial feasibility and viability, and to explore assay sensitivity of the proposed efficacy clinical outcomes for a definitive randomized controlled trial

Критерии включения

• 1. Patient capable of providing informed consent;
• 2. Female patients with HMB over the age of 18 years, for whom prophylactic treatment with Wilate® is deemed clinically appropriate according to the medical discretion (based on their expert opinion given consideration of the patient`s bleeding history and responsiveness to treatment) of the treating hemostasis-focused physician practicing at a Hemophilia Treatment Center;
• 3. Modified PBAC score /> 100 at screening;
• 4. Patients with a diagnosis of inherited von Willebrand disease (any type);
• 5. Stable treatment for HMB and iron deficiency anemia for 3 cycles before entering the study and anticipated to remain unchanged for the duration of the study;
• 6. Patients willing to have an infusion administered by a nurse over the course of the study period;
• 7. Patients who agree to use only the feminine hygiene products supplied by the sponsor.

Критерии исключения

• 1. Diagnosed with any other known bleeding disorder;
• 2. Pregnancy or plans to become pregnant within the duration of the study;
• 3. Breastfeeding or plans to breastfeed within the duration of the study;
• 4. Known hypersensitivity reactions to human plasma-derived products or any ingredient in the formulation;
• 5. Known antibodies to VWF or FVIII;
• 6. Severe liver disease;
• 7. Anticipated initiation of the following: oral, transdermal, injectable, and vaginal ring hormonal contraceptives; GnRH analogues; or a hormonal intrauterine device (IUD) within the study period;
• 8. Anticipated elective procedure that is expected to require intensive treatment with VWF or FVIII for />10 days during the study period;
• 9. Patients with />2 risk factors for VTE (risk factors are determined at discretion of treating physician) or recent history of thrombosis (i.e. within the last year).
• 10. Patient concurrently receiving desmopressin (desmopressin cannot be taken concurrently with Wilate®, except for in the context of escalation treatment for excessive bleeding).
• 11. Anticipated initiation of any new therapies for the treatment of heavy menstrual bleeding 3 weeks prior to enrollment

Описание

This study will be conducted as a randomized controlled trial with a parallel design to determine the impact of an interactive video developed for the care of surgical patients wearing anti-embolism stockings on nursing students` learning outcomes. The research hypotheses are as follows: H0a: There is no significant difference in knowledge levels related to anti-embolism stocking care between the experimental and control groups. H0b: There is no significant difference in skill levels related to anti-embolism stocking care between the experimental and control groups.

Критерии включения

• * The student`s academic average must be above 2.00.
• * The student must own a smartphone, tablet, or laptop/desktop computer capable of downloading the video.
• * The student must have internet access.
• * The student must be willing to participate in the study voluntarily.

Критерии исключения

• * Graduates of health vocational high schools.
• * Students who have failed the Surgical Diseases Nursing course.
• * Students who have not participated in any of the stages of the study.
• * Students who voluntarily decide to withdraw from the study.

Описание

The objective of this randomized controlled trial is to compare the safety and efficacy of low dose Apixaban (2.5 mg bid) in addition to guideline directed medical therapy vs guideline directed medical therapy alone in the prevention of left ventricular thrombus formation (after 30-days) following primary PCI in patients with acute anterior myocardial infarction with severe LV dysfunction.

Критерии включения

• * Patients aged 18-65 years
• * Presenting with acute anterior STEMI
• * Severe LV dysfunction (EF/<35%) with antero-apical akinesis, dyskinesis, or aneurysm
• * WIHTOUT evidence of LV thrombus.

Критерии исключения

• * Patients with previous anterior myocardial infarction or LAD revascularization procedures
• * Patients with cardiogenic shock
• * Patients with LV thrombus
• * Patients with advanced CKD (Cr /> 2 and those on hemodialysis)
• * Recent ICH or major bleed requiring transfusion, low platelet counts /<100,000
• * History of recent CVA ( within past three months)
• * Patients with atrial fibrillation or other indications for chronic anticoagulation
• * Pregnant patients and those with hematological disorders

Описание

In France, venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT), is the 3rd leading cause of cardiovascular disease, leading to major public health problems. Despite current monitoring and treatment, the recurrence rate and the rate of haemorrhagic complications remain high, at 18.5% and 12% respectively in the year following the thrombotic event.

Patients with PE diagnosed in the emergency department are very often admitted to hospital.

However, according to international recommendations on the treatment of PE, outpatient management with early discharge could be envisaged but is rarely carried out in practice, particularly for non-severe PE (spESI = 0).

Current post-pulmonary embolism follow-up involves an early medical consultation with a specialist after discharge from hospital, with follow-up at 1, 3 and 6 months. The aim is to evaluate anticoagulant treatment (high-risk medication), investigate the causes of PE, monitor the patient and decide whether or not to continue anticoagulant treatment 6 months after diagnosis.

Patients diagnosed with non-severe PE can only be monitored as soon as they are discharged from hospital, thanks to an organised and specific care pathway involving healthcare professionals working in towns and cities as well as in hospitals.

In 2018, the French authorities created a new healthcare profession, the advanced practice nurse (APN). They are said to be one of the /'answers/' to making care pathways, including PE, even more relevant by improving the quality of patient care and strengthening the town-hospital link.

Thanks to their training and expertise, IPAs can carry out the following activities:

* Observation, collection and interpretation of data in the context of patient monitoring in his/her area of expertise;
* Prescribing, renewing prescriptions and carrying out technical procedures as part of patient follow-up in their area of expertise;
* Designing, implementing and evaluating preventive and therapeutic education measures.

Thus, by intervening at specific times throughout the course of a patient/'s diagnosis of a non-severe PE, the involvement of the IPA in the patient/'s follow-up, in addition to current recommendations, would make it possible to reduce the risk of haemorrhagic complications associated with the use of anticoagulants.

Критерии включения

• * Person who has given oral consent
• * Person affiliated to the social security system
• * Over 18 years of age
• * Resident in the 21-52 region
• * Emergency care at Dijon University Hospital or Langres University Hospital less than 24 hours after diagnosis of non-severe pulmonary embolism (spESI = 0)
• Symptomatic PE is confirmed if there is :
• * a high pre-test clinical probability and a high probability ventilation-perfusion (V/Q) lung scan according to the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria
• * a proximal DVT diagnosed by ultrasound in a patient with symptoms of PE;
• * a positive CT pulmonary angiogram (PA) showing a central filling defect highlighted by contrast material or a complete occlusion in a segmental or more proximal pulmonary artery.
• * No contraindication to anticoagulant treatment

Критерии исключения

• * Person not affiliated to or not benefiting from a social security scheme
• * Person subject to a legal protection measure (curatorship, guardianship)
• * Person subject to a legal protection measure
• * Pregnant women, women in labour or breastfeeding mothers
• * An adult who is incapable or unable to give consent
• * Minors
• * Contraindication to anticoagulant treatment

Описание

The main objective of this clinical trial is to evaluate of the safety /& efficacy of the Ceretrieve device within 24 hours post thrombectomy procedure. This means to assess that the use with the Ceretrieve neuro-thrombectomy device that is designed to treat acute ischemic stroke patients raises no safety concerns and that it is found to be effective when it is used according to its intended purpose, which is revascularization of patients with acute ischemic stroke secondary to intracranial large vessel occlusive disease (involving the internal carotid artery, middle cerebral artery- M1 and M2 segments, basilar, and vertebral arteries).

The study researchers will compare the efficacy and safety results of this study to data derived from the literature of FDA approved neuro-thrombectomy devices. The study hypothesis is that The Ceretrieve device would achieve successful reperfusion performance shall be similar to the safety /& performance derived from the literature.

The primary outcomes that will be measures are:

Performance:

Successful reperfusion, defined as core laboratory-adjudicated modified Thrombolysis in Cerebral Ischemia (mTICI) score 2b-3 within three passes of the Ceretrieve system without any rescue.

Safety:

Symptomatic intra-cranial hemorrhage within 24 (18-36) hours of the study procedure.

Patients who will participate in this study will be followed for a time period of 3 months. After discharge from the medical center, they will be asked to arrive to a one visit at the clinic for safety data collection and evaluation.

Критерии включения

• 1. Age ≥18 years of age
• 2. Clinical signs consistent with acute ischemic stroke
• 3. Subject is able to be treated within 24 hours of stroke symptom onset.
• 4. Pre-stroke modified Rankin Score of 0 or 1
• 5. NIHSS /> 6 at the time of screening
• 6. If intravenous thrombolysis (IVT) is indicated, initiation of IVT should be administered as soon as possible and no later than 4.5 hours of onset of stroke symptoms (onset time is defined as the last time when the patient was witnessed to be at baseline neurologic status), with investigator verification that the subject has received/is receiving the correct IVT dose for the estimated weight.
• 7. Intracranial occlusion defined as Modified Thrombolysis in Cerebral Infarction (mTICI) 0-1 flow confirmed by angiography that is accessible to the mechanical thrombectomy device in the following locations:
• 1. Intracranial internal carotid artery 2. M1 and/or M2 segment of the MCA 3. Vertebral artery 4. Basilar artery Note: M1 segment of the MCA is defined as the arterial trunk from its origin at the ICA to the first bifurcation or trifurcation into major branches neglecting the small temporo-polar branch.
• 8. A valid completed informed consent in accordance with the local ethics committee regulations.

Критерии исключения

• 1. Female who is pregnant or lactating or has a positive pregnancy test at time of admission.
• 2. Rapid neurological improvement prior to study enrolment suggesting resolution of signs/symptoms of stroke
• 3. Known serious sensitivity to radiographic contrast agents
• 4. Known sensitivity to nickel, titanium metals, or their alloys
• 5. Subjects already enrolled in other investigational studies that would interfere with study endpoints
• 6. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency. (A subject without history or suspicion of coagulopathy does not require INR or prothrombin time lab results to be available prior to enrolment.)
• 7. Life expectancy of less than 90 days
• 8. Clinical presentation suggests a subarachnoid hemorrhage, even if the initial CT or MRI scan is normal.
• 9. Suspicion of aortic dissection
• 10. Subject with a comorbid disease or condition that would confound the neurological and functional evaluations or compromise survival or ability to complete follow-up assessments.
• 11. Known to currently use or abuses alcohol (defined as regular or daily consumption of more than four alcoholic drinks per day).
• 12. Known arterial condition (e.g., proximal vessel stenosis or pre-existing stent) that would prevent the device from reaching the target vessel and/or preclude safe recovery of the device
• 13. Subject who requires balloon angioplasty or stenting of the carotid artery at the time of the index procedure
• 14. Angiographic evidence of carotid dissection
• 15. Imaging exclusion criteria:
• * CT or MRI evidence of hemorrhage on presentation
• * CT or MRI evidence of mass effect or intra-cranial tumor (except small meningioma)
• * CT or MRI evidence of cerebral vasculitis
• * CT or MRI-DWI showing ASPECTS 0-5 (or pc-ASPECTS 0-6 in the posterior circulation). Alternatively, if automated core volume assessment software is used, MRI-DWI or CTP core /> 70cc.
• * CT/MRI shows evidence of carotid dissection or complete cervical carotid occlusion requiring a stent
• * Any imaging evidence that suggests, in the opinion of the investigator, that the subject is not appropriate for mechanical thrombectomy intervention while utilizing an aspiration approach (e.g. inability to navigate to the target lesion, moderate/large infarct with poor collateral circulation, etc.).
• 16. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation) as confirmed by angiography, or clinical evidence of bilateral strokes or strokes in multiple territories.

Описание

This is a multicenter, prospective, longitudinal, observational cohort study to investigate thrombosis and hemostasis diseases in Chinese patients. This study will collect basic information, diagnostic and treatment information, as well as medical expense information of patients from medical records.The incidence and risk factors of thrombosis and hemostasis diseases, the treatment methods, prognosis and medical expenses of these patients in China will be analyzed. The study will use questionnaire to measure the exposure of patients, and prospectively follow-up to collect the prognosis information.

Критерии включения

• * Patients who were diagnosed as thrombosis and hemostasis diseases.

Критерии исключения

• * Long-term follow-up information for patients is not available for any reason, such as not being available or having a serious concomitant disease.
• * Patients with alcohol and drug addictions or mental illness affect their ability to comply with study requirements.
• * According to the investigator, there are conditions that may endanger the patient`s safety or affect his/her compliance.

Описание

The main aim of the study is to evaluate the effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) in children. This study will enroll those participants who have been previously treated with VWF product or with a plasma-derived VWF (pdVWF) product. In this study, participants will be treated with rVWF for 12 months.

During the study, participants will visit the study clinic 6 times after treatment initiation.

Критерии включения

• 1. The participant has a documented diagnosis of severe VWD (baseline von Willebrand factor ristocetin cofactor activity /[VWF:RCo/] /<20 internal units per deciliter /[IU/dL/]) with a history of substitution therapy with VWF concentrate required to control bleeding and a diagnosis of VWD type 1, type 2 (2A, 2B, 2M, 2N), or type 3. Diagnosis is confirmed, when applicable, by genetic testing and/or by multimer analysis, which may be documented in participant`s history or at screening.
• 2. The participant is /<18 years of age at the time of screening.
• 3. Prescreening treatment requirements:
• 1. The participant has been receiving OD therapy with VWF products for at least 12 months (for participants />=2 years of age) prior to screening, has experienced at least 1 VWF-treated bleeding event during (excluding menorrhagia/heavy menstrual bleeding /[HMB/], as applicable) in the last 12 months, and prophylactic treatment is recommended by the investigator (Prior OD participants); or
• 2. The participant has been receiving prophylactic treatment with pdVWF products for at least 12 months prior to screening (for participants />=2 years of age) and switching to prophylaxis with rVWF is recommended by the investigator (Switch participants).
• 3. For participants /<2 years of age, the required duration for prior OD therapy with VWF products or for prior prophylactic treatment with pdVWF products is at least 6 months. Prior OD participants /<2 years of age should have experienced at least 1 VWF-treated bleeding event during the last 6 months based on medical records and be recommended to receive prophylactic treatment by the investigator.
• 4. For participants />=2 years of age, the participant has available records that reliably evaluate type, frequency, severity, and treatment of BEs for at least 12 months preceding enrollment. For participants /<2 years of age, the participant has available records that reliably evaluate type, frequency, severity and treatment of BEs for at least 6 months preceding enrollment.
• 5. If />=12 years old at the time of screening, the participant has a body mass index (BMI) />=15 but /<40 kilogram per square meter (kg/m/^2). If />=2 to /<12 years old at the time of screening, the participant has a BMI of />=5th and /<95th percentile (per Centers for Disease Control and Prevention /[CDC/] clinical charts). For younger participants who are /<2 years old, the "weight-for-age" clinical charts (5th to 95th percentile) provided by the CDC should be utilized to ensure the participant has a body weight of />=5th and /<95th percentile based on gender (for clinical charts provided by CDC, refer to: https://www.cdc.gov/growthcharts/clinical_charts.htm).
• 6. Female participants of childbearing potential (that is, had onset of menses/reached puberty) must have a negative blood/urine pregnancy test result at screening and agree to employ highly effective birth control measures for the duration of their participation in the study.
• 7. The participant has voluntarily provided assent (if appropriate) and the legally authorized representative(s) has provided informed consent.
• 8. The participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol, which should also be confirmed based on a prescreening evaluation held between the investigator and the sponsor to ensure no eminent risk is present that could challenge the participant`s compliance with the study requirements.

Критерии исключения

• 1. The participant has been diagnosed with pseudo VWD or another hereditary or acquired coagulation disorder other than VWD (example, qualitative and quantitative platelet disorders or elevated prothrombin time/international normalized ratio 1.4).
• 2. The participant has a history or presence of a VWF inhibitor at screening.
• 3. The participant has a history or presence of an factor VIII (FVIII) inhibitor with a titer />=0.4 Bethesda units (BU) (by the Nijmegen-modified Bethesda assay) or />=0.6 BU (by the Bethesda assay).
• 4. The participant has a known hypersensitivity to any of the components of the study drugs, such as mouse or hamster proteins.
• 5. The participant has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies, or animal allergies.
• 6. The participant has a medical history of a thromboembolic event.
• 7. The participant is human immunodeficiency virus (HIV)-positive with an absolute helper T cell (CD4) count /<200 per cubic millimeter or microliter (/mm/^3).
• 8. The participant has been diagnosed with significant liver disease per the investigator`s medical assessment of the participant`s current condition or medical history or as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) greater than 5 times the upper limit of normal (ULN), hypoalbuminemia, portal vein hypertension (example, presence of otherwise unexplained splenomegaly, history of esophageal varices), or liver cirrhosis classified as Child-Pugh class B or C.
• 9. The participant has been diagnosed with renal disease, with a serum creatinine level />=2.5 milligram per deciliter (mg/dL).
• 10. The participant has a platelet count /<100,000 per milliliter (/mL) at screening (because participants with type 2B VWD are considered eligible for this study, for participants with type 2B VWD, platelet count/[s/] at screening will be evaluated in consultation with the sponsor, taking into consideration historical trends in platelet counts and the investigator`s medical assessment of the participants condition).
• 11. The participant has been treated with an immunomodulatory drug, excluding topical treatment (example, ointments, nasal sprays), within 30 days prior to signing the informed consent (or assent, if appropriate).
• 12. The participant is pregnant or lactating at the time of enrollment.
• 13. The participant has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection, dysplasia).
• 14. The participant has participated in another clinical study involving another IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
• 15. The participant has not received OD or prophylactic treatment with a VWF product prior to this study.
• 16. The participant has a progressive fatal disease and/or life expectancy of less than 15 months.
• 17. The participant is already scheduled for a surgical intervention that will have to be performed while the participant is participating in the study.
• 18. The participant is unable to complete screening procedures and/or comply with the requirements of the protocol in the opinion of the investigator, based on the joint prescreening evaluation held between the investigator and the sponsor.
• 19. The participant has a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude.
• 20. The participant is member of the study team or in a dependent relationship with one of the study team members, which includes close relatives (that is, children, partner/spouse, siblings, and parents) as well as employees.

Описание

The aim of this study was to prospectively evaluate vascular catheter-related thrombosis and risk factors using daily bedside ultrasonography after oncologic and non-oncologic major surgery.

Критерии включения

• * Adult patient (18-80 years old)
• * No hematological disease causing hypercoagulability
• * Not receiving anticoagulant/antifibrinolytic medications at the therapy dose
• * The vascular structure can be visualized with US
• * No thrombosis in the US control before catheter placement
• * The catheter is not inserted for renal replacement therapy

Критерии исключения

• * Presence of renal failure
• * Pediatric patients
• * Presence of hematological malignancy
• * Inadequate US imaging

Описание

This is a national, multicenter, retrospective/prospective, observational study in Taiwan designed to assess effectiveness, safety, and usage of efanesoctocog alfa prophylaxis treatment in hemophilia A participants. The data related to efanesoctocog alfa effectiveness, safety and usage will be recorded prospectively during routine visits for up to 5 years following enrollment initiation and the retrospective data will be collected at least 12 months and up to 24 months prior to efanesoctocog alfa initiation. Joint imaging data will be collected in centers performing Joint U/S and/or MRI (≥6 years old). At least 12 months of retrospective data will also be collected from medical records, as available. Prospectively collected data will be recorded at routine clinical visits during a five-year follow-up period. The end of study is defined as the last participant`s last visit. No intervention will be administered, and no study related visits are required.

Критерии включения

• * Participants with all ages and diagnosis of moderate-severe hemophilia A without current and/or at least three years of un-detectable inhibitor (/<0.6 BU)
• * Participants with moderate to severe hemophilia A as defined by FVIII level ≤ 5%
• * Participants starting efanesoctocog alfa prophylaxis treatment as per standard of care no more than three months prior to the enrollment date
• * Participants aged 6 years and older are able to undergo MRI examinations (sedation given, if necessary, and per investigator discretion)
• * Participants are able to undergo joint examinations
• * Physician`s decision to treat the participant with efanesoctocog alfa is made prior to and independently of participation in the study
• * Signed and dated informed consent provided by the participant, or by the participant`s legally acceptable representative for participants under the legal age before any study-related activities are undertaken. Assent should be obtained for pediatric participants according to local regulations

Критерии исключения

• * Participants with coagulation disorders other than hemophilia A
• * Participants diagnosed with other known bleeding disorder
• * Participants currently receive factor therapy and have signs of decreased response to FVIII therapy
• * Participants with a baseline PS score of greater than 6 in both ankles for each joint
• * Enrollment in another concurrent clinical interventional study, or intake of an Investigational Medicinal Product within 3 months prior to inclusion in this study
• * Pregnant female participants
• The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Описание

The goal of this clinical trial is to find out the clinical and cost effectiveness of Thromboprophylaxis in participants who have been placed in a plaster cast or splint after injury.

The main questions it aims to answer are:

* whether giving tablets to people at high risks of clots after a leg injury is as good as injections (standard care)
* whether giving any medication after a leg injury is better than standard care (advice only) for people at low risk of clots.

Participants will be assessed to be high risk (TiLLI High) or low risk (TiLLI Low). People who are at high risk of clots will have either tablets or injections to reduce their risk. People at low risk will receive tablets, injections or no medication.

Drug treatments will be provided for the duration of immobilisation or up to 42 days (whichever is earlier), in accordance with current NICE guidelines. The participants will be followed up for 90 days following randomisation.

Критерии включения

• * Age />/= 16 years
• * Placed in temporary lower limb immobilisation (rigid cast or brace) as a result an injury that occurred within the last 7 calendar days

Критерии исключения

• * Hospital admission is required direct from the emergency department, minor injuries unit, or fracture clinic setting with an expected length of stay />2 calendar days.
• * Absolute contraindication or known hypersensitivity to anticoagulants, including history of end stage renal failure (eGFR /<20ml/min/1.73m2), hepatic failure or use of concomitant systemic treatment with azole-antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole), HIV protease inhibitors (e.g. ritonavir) or active substances strongly inhibiting elimination pathways such as CYP3A4 or P-gp (such as clarithromycin, erythromycin or dronaderone) or a history of heparin induced thrombocytopenia.
• * Pregnancy, actively seeking conception, or active breastfeeding.
• * Preceding use of anticoagulant treatment for />3 calendar days at prophylactic or therapeutic dose.
• * Prior enrolment in the TiLLI study.
• * Non-rigid immobilisation (crepe bandage, tubigrip support, strapping).
• * Time since prescription of rigid immobilisation />3 calendar days
• * Co-enrolment onto a CTIMP where an anticoagulant is administered
• * People lacking the capacity to consent
• * Inability or refusal to use acceptable contraception up until after the last administration of IMP. Only applicable for women of childbearing potential who have been randomised to receive apixaban or rivaroxaban

Описание

Pregnancy is associated with major changes affecting all satges of hemostasis. Certain procoagulant factors are increased, such as factors VII, VIII, IX, X, XII, fibrinogen and Von Willebrand factor. Anticoagulant molecules are also affected by pregnancy, notably the protein C - protein S (PC - PS) system. overall, PC activity is little affected by pregnancy, increasing in the 2nd trimester and decreasing in the 3rd, but remaining within normal values. PS decreases from the first trimester of pregnancy, then progressively with gestational age. Antithrombin is stable during pregnancy.

The increased in most coagulation factors, combined with the decrease in concentrations of anticoagulant molecules, creates a state of relative hypercoagulability that protects women from bleeding during homostatic challenge of childbirth, but predisposes them to venous thromboembolic events.

The risk of venous thromboembolism (VTE) during pregnancy is increased compared to non-pregnant women of the same age. The post-partum period is also considered a thrombotic risk state for up to 12 weeks after delivery. Data on the incidence of VTE as a function of gestational age are contradictory: depending on the study, incidence may be stable or increase with advancing pregnancy.

Low-molecular-weight heparin (LMWH) is the anticoagulant treatment of choice for prophylactic or curative treatment of VTE during pregnancy.

Physiological changes during pregnancy may alter the pharmacokinetic properties of LMWH. The increased volume of distribution and higher glomerular filtration rate may result in a reduced anticoagulant effect. On the other hand, the state of hypercoagulability probably counteracts the anticoagulant effect of LMWH. Nevertheless, the need to adjust doses during pregnancy remains controversial, and monitoring of anti-Xa activity is not clearly recommended. The optimal dose of LMWH in pregnant women, for both preventive and curative treatment, remains poorly understood. Initiation of treatment with LMWH therefore requires discussion of the dosage to be administered.

Assessment of anticoagulation using more precise tools than those currently available on a routine basis could be useful in this context.

Thrombinography enables the amount of thrombin generated in the presence of coagulation activators to be assessed over time. This tool can be used to assess the impact of in vitro addition of different doses of LMWH in pregnant versus non-pregnant women and in the postpartum period.

In this pilot study, the investigators propose to evaluate thrombin generation, before and after in vitro addition of LMWH, in pregnant women longitudinally, during the 3 trimesters of pregnancy, postpartum and post-pregnancy.

Критерии включения

• * Normal 1st trimester pregnancy
• * Age /> 18

Критерии исключения

• * Coagulation disease (Von Willebrand disease, known coagulation factor deficiency before pregnancy)
• * VTE history
• * First-degree family history of idiopathic VTE
• * Known biological risk factor for thrombosis Inherited deficiencies in coagulation inhibitors (antithrombin, protein C, protein S) Factor V Leiden polymorphism Prothrombin gene 20210G/>A polymorphism Anti-phospholipid antibodies
• * Current anticoagulant use (VKA, heparins, etc.)
• * Gestational diabetes detected in the 1st trimester
• * Pre-existing type 1 and type 2 diabetes
• * History of pathological pregnancy Premature delivery Postpartum hemorrhage Preeclampsia
• * Hepatopathy
• * Obesity (BMI ≥ 30)
• * Infections (HIV, HBV, HCV...)
• * Autoimmune diseases
• * Pregnancy resulting from in vitro fertilization protocol
• * Multiple pregnancy
• * Patient under guardianship, curatorship or safeguard of justice
• * Patient not covered by a social security scheme
• * Patient deprived of liberty

Описание

Rationale: A novel point-of-care device capable of measuring factor VIII (FVIII) activity and thrombin generation (TG) is currently under development. Utilization of this device in a home situation could potentially transform hemophilia care and improve patients` autonomy.

Objective: To explore the potential consequences of home monitoring of hemostatic parameters in patients with hemophilia A

Study design: Cross-sectional observational study consisting of semi-structured interviews and focus groups

Study population: Approximately 10 patients treated with vitamin K antagonists engaging in self-monitoring of coagulation at home and approximately 20 patients with hemophilia A.

Main study parameters/endpoints: The main outcome of this study is to assess series of interrelated themes related to the unmet needs of hemophilia patients and the envisioned potential consequences of home monitoring on these unmet needs.

Secondary outcomes include: identifying key features of a home monitoring platform to be used in hemophilia care, describing the experienced consequences of implementing home self-monitoring in anticoagulation treatment, assessing the current experiences of patients with self-monitoring, and providing an overview of the burdens and unmet needs experienced by patients with hemophilia with current hemophilia care.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk associated with participation in this study is negligible. Minor patients will be included in this study only if informed consent is given by both the patient and his/her caregiver (in patients between 12-16 years old). Gathering the insights of caregivers of minor patients on the current care for hemophilia and potential consequences of home self-monitoring is vital, as their experiences and needs might differ significantly from older patients. Participating in this study does not entail direct benefits. However, patients who participate can contribute to the development of future monitoring systems, which have the potential to alleviate the current burden of their disease and treatment.

Критерии включения

• Patients treated with vitamin K antagonists Inclusion criteria
• * Aged /> 16 years
• * Patient using vitamin K antagonist for any indication
• * Registered at the "Trombosezorg dichterbij"
• * Self-testing INR at home for /> 3 months
• * A history of monitoring INR at a care facility (not self-testing)
• * Signed informed consent form
• * Able to speak and understand Dutch or English without a translator

Критерии исключения

• • Unwilling to consent with the study or with audio recording
• Hemophilia A patients Inclusion criteria
• * Diagnosis of congenital hemophilia A, with or without inhibitors
• * Receiving prophylactic treatment
• * Patients aged ≥ 12 years or caregivers of patients aged /< 12 years old
• * Signed informed consent form
• * Able to speak and understand Dutch or English without a translator Exclusion criteria
• * No diagnosis of congenital hemophilia A
• * Unwilling to consent with the study or with audio recording
• Hemophilia healthcare professionals Inclusion criteria
• * Hematologist, hemophilia nurse, pharmacist or healthcare provider currently involved in the care for patients with hemophilia
• * At least /> 3 years clinical experience in hemophilia care
• * Signed informed consent form
• * Able to speak and understand Dutch or English without a translator

Описание

After hip or knee replacement all patients receive a standardized treatment with blood thinners, this medication is called thrombosis prophylaxis. However, despite this standard treatment some individuals still develop venous thrombosis (VTE), while others experience bleeding. This indicates that not all patients have the same VTE risk following surgery. Individualizing the amount of thrombosis prophylaxis following surgery might lead to less thrombotic and bleeding events. In this study the investigators individualize the treatment with thrombosis prophylaxis based on the medical history of a patient.

The main questions this study aims to answer are:

Can thrombosis prophylaxis be shortened in patients with a low VTE risk to decrease the risk of bleeding without increasing the risk of VTE? Does an increase in the dose and duration of thrombosis prophylaxis in patients with a high VTE risk reduce the risk of VTE without inducing an unacceptable risk of bleeds?

Researchers will compare both the shortened treatment in low VTE risk patients and the intensified and extended treatment in high VTE risk patients with the standard treatment to assess the risk of VTE and bleeding in comparison to the standard treatment.

Participants will receive 4 questionnaires to evaluate whether they have experienced a VTE or bleed. For this study no additional hospital visits are necessary.

Критерии включения

• * Scheduled to undergo an elective total hip arthroplasty or total knee arthroplasty
• * Aged 18 years or older

Критерии исключения

• * Primary arthroplasty for fractures
• * Revision surgery
• * Hemiarthroplasty
• * Pregnancy
• * Current use of therapeutic anticoagulant therapy of any type (e.g., LMWH, DOAC, vitamin K antagonist)
• * A contraindication for either study drug
• * Insufficient knowledge of the Dutch language
• * Insufficient mental or physical ability to fulfil trial requirements
• * Active malignancy (i.e. cancer diagnosis within six months before surgery (excluding basal-cell or squamous-cell carcinoma of the skin), recently recurrent or progressive cancer or any cancer that required anti-cancer treatment within six months before surgery)
• * Patients using thrombocyte aggregation inhibitors that cannot be temporarily discontinued at the discretion of their treating physician

Описание

RCT of High-Risk Pulmonary Embolism Comparing FlowTriever System vs. Standard of Care

Критерии включения

• 1. Age at enrollment ≥18 years
• 2. Objective evidence of a proximal filling defect in at least one main or lobar pulmonary artery
• 3. High-risk class of acute PE
• 4. RV dysfunction, as defined RV/LV ratio ≥1.0
• 5. Ability to begin randomized Index Treatment within 4 hours
• 6. Willing and able to provide informed consent, or if unable, through a Legal Authorized Representative, with permitting research without prior consent as a third option (for Europe and UK sites only), provided compliance with IRB/EC approvals and adherence to regulatory, ethical and national standards

Критерии исключения

• 1. Prolonged cardiac arrest with loss of consciousness and/or neurological deficit.
• 2. Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the patient is not appropriate for catheter-based intervention
• 3. Known pre-existing CTEPH, or CT signs of chronic PE that may point to pre-existing CTEPH
• 4. Recent stroke (/<14 days)
• 5. Recent cranial or spinal surgery (/<14 days)
• 6. Life-threatening active bleeding or hemorrhage into a critical area
• 7. Known intracranial tumor
• 8. End-stage medical condition with life expectancy /<3 months (irrespective of the severity of acute PE), as determined by the Investigator
• 9. Known sensitivity to radiographic contrast agents that, in the Investigator`s opinion, cannot be adequately pre-treated
• 10. Inability to anticoagulate the patient, or known to have heparin-induced thrombocytopenia (HIT)
• 11. Current participation in another drug or device study that may interfere with the conduct of this trial
• 12. Ventricular arrhythmias refractory to treatment at the time of enrollment
• 13. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being or that could prevent, limit, or confound the protocol-specified assessments), including a contraindication to use of FlowTriever System per local approved labeling
• 14. Subject is part of a vulnerable population (e.g., currently pregnant, breastfeeding or incarcerated) per local definitions
• 15. Subject has previously completed or withdrawn from this study
• 16. Subject has received prior thrombolytic (systemic or catheter-directed) or thrombectomy (surgical or catheter-based) therapy for index PE, within 30 days prior to randomization

Описание

The purpose of this research is to measure changes in venous blood flow with an air-filled bladder under an intermittent pneumatic compression device cuff (used to prevent deep venous thrombosis) or venous diagnostic device cuff (used to detect deep venous thrombosis). The devices being used in the study are investigational and not FDA-cleared.

Критерии включения

• * Venous ultrasound study to evaluate for lower extremity DVT unilateral and/or bilateral within previous 72 hours.

Критерии исключения

• * Patients with inaccessible target limb (ultrasound limb) due to bandages (wound, burn, lesion, etc) or cast.
• * Patients with leg trauma, fracture, above or below knee amputation, or other condition in which compressing on the calf is medically inappropriate or not possible.
• * Patients unable to provide informed written consent.

Описание

Background:

Diseases related to the immune system, blood clots, and blood vessels can affect every part of the body. These diseases are now known to be interrelated: People who have strokes, blood clots in their legs, or autoimmune disease, for example, are at greater risk of complications in the heart, brain, and other organs. Researchers want to learn more about how these diseases start, how they change over time, and how they affect different organs.

Objective:

To learn more about how inflammation and diseases of the blood vessels start and how they change over time.

Eligibility:

People aged 5 years and older with a disease related to blood clots, the immune system, or blood vessels. Healthy relatives of people with these diseases and unrelated healthy volunteers are also needed.

Design:

Participants will have a baseline visit: They will provide a medical history, physical exam and blood test. All other tests and procedures are optional; these may be spread over more than 1 day:

Tests of heart and lung function.

Fill in a family tree form.

Imaging scans

Treadmill or bike stress tests and a 6-minute walk test.

Tests of blood pressure and the flow of blood through vessels.

Photos of the face and body.

Eye exams, with photos taken of the retina.

Saliva and urine samples.

Biopsies (tissues samples) of the skin and fat.

Tests of thinking and mental function.

Evaluations by other medical specialists.

Participants may opt to return for repeat testing for up to 90 months (7.5 years).

Some visits may be done by telehealth.

Критерии включения

• * INCLUSION CRITERIA:
• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• * Age />= 5 years at the time of consent
• * Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document
• In addition, the following cohort-specific inclusion criteria apply:
• Affected Subjects:
• -Known or possible thrombotic, immune, or vascular disorder after review of the subject s medical records and/or discussion of medical history
• Relatives of Affected Subjects:
• -Being a relative of an affected subject
• Unrelated Healthy Controls:
• -In good general health as evidenced by medical history

Критерии исключения

• An individual who meets any of the following criteria will be excluded from participation in this study:
• -Any condition that in the opinion of the Investigator would warrant exclusion
• Unrelated Healthy Controls:
• * Unrelated healthy volunteers who decline to have blood drawn and/or tissue studies or who do not consent to have samples stored for future research
• * Cognitively impaired individuals

Описание

Rivaroxaban versus enoxaparin for prophylaxis of venous thromboembolism in morbidly obese patients undergoing bariatric surgery: An open_label randomized controlled trial

Критерии включения

• * Age: 20-60 years, both sexes.
• * ASA physical status class I to III.
• * BMI 35-50 kg/m²

Критерии исключения

• * Severe cardiac disorder
• * chronic renal failure
• * liver cirrhosis
• * major psychological disorder

Описание

Cell-free fetal DNA (cffDNA) is present in the maternal blood from the early first trimester of gestation and makes up 5%-20% of the total circulating cell-free DNA (cfDNA) in maternal plasma. Its presence in maternal plasma has allowed development of noninvasive prenatal diagnosis for single-gene disorders (SGD-NIPD). This can be performed from 9 weeks of amenorrhea and offers an early, safe and accurate definitive diagnosis without the miscarriage risk associated with invasive procedures. One of the major difficulties is distinguishing fetal genotype in the high background of maternal cfDNA, which leads to several technical and analytical challenges. Besides, unlike noninvasive prenatal testing for aneuploidy, NIPD for monogenic diseases represent a smaller market opportunity, and many cases must be provided on a bespoke, patient- or disease-specific basis. As a result, implementation of SGD-NIPD remained sparse, with most testing being delivered in a research setting.

The present project aims to take advantage of the unique French collaborative network to make SGD-NIPD possible for theoretically any monogenic disorder and any family.

Критерии включения

• * pregnant woman with 9 weeks of amenorrhea or more
• * singleton pregnancy
• * undergoing invasive PND in a context of family history of SGD involving the following genes : HBB, CFTR, FMR1, SMN1, DMPK, DMD, NF1, HTT, F8, F9, GCK, L1CAM, PKHD1, ATP7A or undergoing prenatal counselling in a context of maternal history of diabetes MODY-GCK
• * germinal pathogenic paternal and/or maternal mutations previously identified
• * age 18 years old or over
• * signing an informed consent

Критерии исключения

• * at risk of another SGD
• * at risk of SGD involving a de novo pathogenic mutation in a previous child
• * woman under legal protection

Описание

EYE-TIE-201 is a 2-part study to investigate the safety and effectiveness of a new drug being developed called EYE201.

All participants in the study will receive a total of 3 injections of EYE201 into the study eye, spaced at 4 weeks apart.

In the first part, termed the multiple ascending dose (MAD) portion of study, the safety of EYE201 will be assessed at increasing doses in branch retinal vein occlusion (BRVO) participants. Approximately 12 participants will be entered in this part of the study.

In the second part of the study, called the dose finding part, 2 doses of EYE201 will be selected and their effectiveness will be compared. This portion of the study assesses the safety and preliminary efficacy of EYE201 in patients with diabetic macular edema (DME) or neovascular macular degeneration (NVAMD). Approximately 80 participants will be entered in this part of the study.

Критерии включения

• General Key Inclusion Criteria
• * Written informed consent before the first study-related activity
• * Be male or female ≥ 18 years of age
• * If female, have a negative serum pregnancy test at Screening and further negative urine tests immediately before each dose of study medication if the participant is a female of childbearing potential.
• General

Критерии исключения

• * Be pregnant or breastfeeding
• * Have a history of cataract surgery and/or minimally invasive glaucoma surgery in the study eye within 90 days of Screening
• * Have uncontrolled blood pressure, defined as systolic ≥180 mmHg and/or diastolic ≥100 mmHg while a participant is at rest.
• * Have had Yttrium-Aluminum Garnet laser capsulotomy in the study eye within 90 days of Screening
• * Have had Pan-retinal Photocoagulation or focal thermal laser photocoagulation in the study eye
• * Have tractional retinal detachment in the study eye
• * Have uncontrolled glaucoma (defined as IOP ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye
• BRVO-specific Inclusion Criteria
• Participants must:
• * Be diagnosed with BRVO in the study eye
• * Have a ETDRS BCVA letter score between ≤ 70 and ≥ 35 (20/40 to 20/200 Snellen equivalent) in the study eye
• * Have a CST of ≥ 325 μm in the study eye on SDOCT as determined by the IRC at Screening
• * Have a decrease in vision in the study eye determined by the Investigator to be primarily the result of BRVO BRVO-specific Exclusion Criteria
• Participants must not:
• * Have macular edema in the study eye considered to be secondary to a cause other than BRVO (e.g., DME, Irvine-Gass syndrome)
• * Have active iris or angle neovascularization or neovascular glaucoma in the study eye
• * Have proliferative retinopathy, central retinal vein occlusion, or hemiretinal vein occlusion
• DME-specific Inclusion Criteria
• Participants must:
• * Have Type 1 or Type 2 diabetes mellitus and a glycated hemoglobin A1c (HbA1c) of ≤ 12%
• * Have a ETDRS BCVA letter score between ≤ 70 and ≥ 35 (20/40 to 20/200 Snellen equivalent) in the study eye
• * Have a CST of ≥ 325 μm in the study eye on SDOCT as determined by the IRC at Screening
• * Have a decrease in vision in the study eye determined by the Investigator to be primarily the result of DME
• DME-specific Exclusion Criteria
• Participants must not:
• * Have macular edema in the study eye considered to be secondary to a cause other than DME (eg, retinal vein occlusion, Irvine-Gass syndrome)
• * Have active iris or angle neovascularization or neovascular glaucoma in the study eye
• * Have high-risk proliferative diabetic retinopathy characteristics in the study eye
• NVAMD-specific Inclusion Criteria
• Participants must:
• * Be ≥ 50 years of age
• * Have a ETDRS BVCA letter score between ≤ 70 and ≥ 35 (20/40 to 20/200 Snellen equivalent) in the study eye
• * Subfoveal CNV secondary to AMD, with a total lesion size (including blood, scar/atrophy /& neovascularization) of ≤ 9-disc areas, of which at least 50% must be active CNV in the study eye
• * Have a CST of ≥ 325 μm in the study eye on SDOCT as determined by the IRC at Screening
• * Be treatment naïve with vision loss in the study eye secondary to NVAMD diagnosed within 21 days prior to the Day 1 study treatment NVAMD-specific Exclusion Criteria
• Participants must not:
• * Have had previous thermal subfoveal laser therapy in the study eye
• * Have any subfoveal atrophy or scarring, blood over the fovea, or subfoveal fibrosis in the study eye. Additionally, no more than 25% of the total lesion size may be made up of scarring or atrophy
• * Have had previous photodynamic therapy with Visudyne in the study eye
• * Have diabetic retinopathy in the study eye

Описание

Adult patients on extracoporeal membrane oxygenation (ECMO) frequently experience bleeding, which is in part caused by acquired von Willebrand syndrome (vWS). Prior in vitro studies have shown that the addition of recombinant von Willebrand Factor (vWF) to ECMO patient blood samples, normalizes platelet adhesion and thrombus formation. This study is a phase I study, where adult ECMO patients with refractory bleeding will be treated with recombinant vWF a single time. The primary objectives are to evaluate the safety, tolerability, and pharmacokinetics of recombinant vWF in adult ECMO patients.

Критерии включения

• 1. Adult patients (18 years or greater)
• 2. On extracorporeal membrane oxygenation
• 3. Major bleeding defined by CTCAE class 3 or greater
• 4. Off systemic anticoagulation for at least 4 hours

Критерии исключения

• 1. Platelet count less than 40 x 109/L
• 2. International normalized ratio/> 2.0
• 3. Fibrinogen less than 150 mg/dL
• 4. Current participation in another clinical trial (interventional)
• 5. Heparin induced thrombocytopenia (active)
• 6. Acute liver failure, as indicated by bilirubin />20 mg/dL or new onset hepatic encephalopathy
• 7. Patient or legally authorized representative unable to give informed consent
• 8. Allergy to recombinant von Willebrand Factor or any component of the product based on prior exposure
• 9. Of childbearing age and positive pregnancy test during the same hospital admission, a pregnancy test will be mandatory for all women of child-bearing age
• 10. Known congenital or acquired thrombophilia
• 11. History of deep venous thrombosis, pulmonary embolism, circuit thrombosis, disseminated intravascular coagulation (DIC), ischemic stroke, ST elevation myocardial infarction (STEMI), or arterial thrombosis in the last 3 months.
• 12. History of hypersensitivity to vWF concentrate
• 13. Known history of vWF antibodies

Описание

The purpose of this screening study is to accumulate information regarding bleeding events, quality of life, and the social and clinical impact of bleeds in participants with Von Willebrand Disease (VWD). Data from this study will be used to establish baseline bleeding and treatment rates in a population of participants with VWD and act as comparator data for future clinical study outcomes.

Критерии включения

• 1. Has the ability to provide informed consent to participate in the study, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (R2) (2016) and applicable national and international regulations, before any protocol directed interventions are carried out.
• 2. Has an understanding, ability, and willingness to comply with Study procedures and restrictions.
• 3. Is 16 years or older at the time of screening.
• 4. First approximately 50 participants: congenital Type 1 VWD with a residual VWF antigen and/or activity less than 40 IU/dL (40%)
• Next approximately 50 participants: Type 1 VWD with residual VWF antigen and activity less than 50 IU/dL (50%)
• After the first approximately 100 participants: congenital Type 1, Type 2A, Type 2M, Type 2N, or Type 3 VWD
• Note: Participants may be enrolled if they have documented laboratory results for VWF antigen and activity within their medical records confirming their diagnosis (consistent with International Society on Thrombosis and Hemostasis /[ISTH/]/American Society of Hematology /[ASH/] diagnostic guidelines or British Society for Haematology /[BSH/]/ United Kingdom Haemophilia Centre Doctors; Organisation /[UKHCDO/] diagnostic guidelines). For Type 1 VWD in the first part of the study, participants also need to have a documented laboratory result within the last 2 years showing a VWF antigen and/or activity level less than 40 IU/dL. Participants meeting eligibility criteria based on documented results will proceed with having samples collected at Screening to further characterize their antigen and activity levels. These may be repeated up to 2 further times if the results are not consistent with their documented diagnosis and levels are greater than 40 IU/dL.
• If participants do not have confirmed results in their medical records as described above, the screening assessment may be repeated up to 2 further times to establish baseline levels for inclusion.
• 5. Has symptomatic disease as defined by a history of bruising or bleeding events, and typically experiencing bleeding symptoms every month.

Критерии исключения

• 1. Has a personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial vein thrombosis events.
• 2. Has a significant family history of unprovoked thromboembolic events in first degree relatives.
• 3. Has a congenital or acquired bleeding disorder other than VWD.
• 4. Has planned major surgery within the next 6 months.
• 5. Is pregnant or plans to become pregnant within the next 6 months.
• 6. Has any concurrent disease, treatment (including ongoing anticoagulation, antiplatelet, or non-steroidal anti-inflammatory drugs), condition, medication, or abnormality in clinical laboratory tests which may impact on the participant`s bleeding symptoms or affect their ability to complete the study, in the Investigator`s opinion.
• 7. Has received any investigational product within 30 days prior to screening.

Описание

The goal of this study is to determine whether the Platelet Clot Stiffness (PCS) measured by QUANTRA® is predictive of an abnormality in primary haemostasis intraoperatively in cardiac surgery performed under extracorporeal circulation.

The aim is to compare the assessment of platelet function by QUANTRA® (data called PCS, obtained in around ten minutes) with laboratory tests which are validated, but which cannot be used in current practice (response time too long, in particular). We are therefore seeking to determine whether QUANTRA is reliable in the search for a primary hemostasis anomaly, defined by significant thrombocytopenia (platelet count below 100G/L), and/or a prolongation of platelet occlusion time measured by PFA-200® (normal or increased).

This clinical research project will last 12 months. It will take place in the cardiac surgery operating room at CHU Félix Guyon, and will involve 100 patients.

Patients who have consented to participate in this research project will be managed in the operating room in the usual way, with no change to their usual care (in terms of treatments received). At the end of the surgery, we will add 3 blood samples (maximum 8.1ml) for analysis to assess platelet function and compare with QUANTRA data.

This blood sample will be the only procedure performed. Medical management remains standard and will not be disrupted by this test.

Критерии включения

• Patients
• * Hospitalized for scheduled cardiac surgery performed under extracorporeal circulation, including coronary bypass, valve replacement, aortic arch and combined surgeries.

Критерии исключения

• Patients:
• * with preoperative hematocrit /< 35% and preoperative platelet count /< 80,000 G/L (validity of PFA-200® Test)
• * With known congenital or acquired Willebrand`s disease, or known platelet dysfunction.
• * On double antiaggregation, not discontinued at the time of surgery
• * Vulnerable patients: minors or protected adults, pregnant women, patients not affiliated to the social security system.
• * Emergency situation

Описание

The goal of this single-arm, prospective clinical trial is to evaluate the safety and efficacy of neoadjuvant therapy combining sintilimab with stereotactic body radiation therapy (SBRT) in patients with resectable hepatocellular carcinoma (HCC) with branch portal vein tumor thrombus. The main questions it aims to answer are:

1. Is the combination of sintilimab and SBRT safe as neoadjuvant therapy?
2. How effective is this combination in treating resectable HCC with branch PVTT? Participants will be given a combination treatment of sintilimab and SBRT. Researchers will monitor their health conditions to assess the safety and effectiveness of this treatment protocol.

Критерии включения

• * Age greater than 18 years, regardless of gender.
• * Voluntary participation, as evidenced by signed informed consent, with the willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• * Diagnosis of hepatocellular carcinoma confirmed either histologically, cytologically, or based on characteristic imaging features (ultrasound, CT, MRI) and laboratory tests.
• * Presence of measurable disease lesions per modified RECIST (mRECIST) criteria.
• * Visible branch portal vein tumor thrombus (Japanese classification Vp1-Vp3 or Cheng`s classification I-II) on imaging, deemed resectable after multidisciplinary consultation.
• * No history of other malignancies.
• * No prior treatments including targeted therapy, systemic chemotherapy, interventional treatments, surgical interventions, or radiotherapy before enrollment.
• * Expected survival of at least 3 months.
• * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• * Liver function classified as Child-Pugh A (score ≤6).
• * Adequate organ and bone marrow function indicated by: serum creatinine ≤1.5 times the upper limit of normal, estimated glomerular filtration rate ≥50 mL/min/1.73m/^2; total bilirubin ≤2 times the upper limit of normal; AST and ALT ≤2.5 times the upper limit of normal; AST/ALT ratio ≤3 times the upper limit of normal; platelet count ≥70×10/^9/L, white blood cells count ≥3000/mm/^3, and absolute neutrophil count ≥1500/mm/^3 without transfusion to meet entry criteria.
• * Female participants of childbearing potential must have a negative serum pregnancy test within 3 days prior to the commencement of the study medication, agree to use a highly effective method of contraception (e.g., intrauterine device, contraceptives, or condoms) during the study period and for 3 months after the last dose of study medication. Male participants with partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study period and for 3 months after the last dose of study medication.

Критерии исключения

• * Previous treatments including interventional, immunotherapy, chemotherapy, or targeted therapy.
• * Presence of confirmed distant metastasis on imaging or portal vein tumor thrombus involving the main portal vein (Vp4).
• * Presence of refractory ascites or hepatic encephalopathy.
• * Concurrent malignancy in other organs.
• * Impaired organ function (hematologic, hepatic, renal) that precludes tolerance of treatment.
• * Significant cardiac arrhythmias, myocardial ischemia, severe atrioventricular block, heart failure, or severe valvular heart disease.
• * Severe bone marrow failure.
• * Diagnosis of active autoimmune disease requiring any form of systemic treatment.
• * Participation in another oncology clinical trial within the last 3 months.
• * History of active tuberculosis or persistent, uncontrollable infections.
• * Pregnant or breastfeeding participants.
• * History of infection with the Human Immunodeficiency Virus (HIV).
• * Any condition that, in the opinion of the investigator, would make participation in the study inappropriate.

Описание

Newborns with congenital heart disease (CHD) are at increased risk of developing postpartum and postoperative blood clots after cardiac surgery. The molecular mechanisms that are responsible for the clotting profile predisposing children to blood clots in the early stages of life are currently not well described.

The goal of this proposal is to prospectively collect plasma samples from ten (10) neonates with antenatal diagnosis of severe congenital heart disease (CHD) to better understand mechanisms responsible for abnormal clotting in the perioperative period.

Критерии включения

• * All neonates with a diagnosis of severe Congenital Heart Disease undergoing surgery at Boston Children`s Hospital in the first week of life

Критерии исключения

• * None

Описание

The BeCoMe-9 Study (BE-101-01) is a Phase 1/2, first in human, multi-center, open-label, dose-escalation study to evaluate the safety and clinical activity of a single intravenous (IV) dose of BE-101 in adults with moderately severe or severe Hemophilia B. Once infused, BE-101 is designed to engraft and continuously secrete FIX into the circulation to restore clinically meaningful levels of active FIX. BE-101 is an autologous (person`s own cells) B Cell Medicine (BCM) which uses CRISPR/Cas9 gene editing to precisely insert human FIX gene into those cells.

Критерии включения

• * Adult Males (≥18) with moderately severe to severe Hemophilia B (FIX deficiency)
• * Received ≥50 exposure days to Factor IX products preceding enrollment.
• * Currently receiving prophylaxis treatment
• * Adequate organ function and clinical labs
• * Able to tolerate study procedures including leukapheresis.

Критерии исключения

• * Pre-existing or history of specific diseases
• * B-Cell malignancy, EBV lymphoproliferative disease
• * Primary immunodeficiency disease or disorder (PIDD) or systemic immuno-suppression
• * Arterial and/or venous thromboembolic events within 2 years prior to dosing
• * History of anaphylaxis or nephrotic syndrome
• * Active infection (HIV, Hep B or C)
• * History of inhibitor to FIX or inhibitor
• * History of an allergic reaction or anaphylaxis to FIX products
• * Within 6 months from BE-101 administration:
• * Planned surgical procedure
• * Previously dosed with gene therapy or participated in an interventional clinical study
• * Planned participation in clinical trial within one year after BE-101
• * Administration of a vaccine within 28 days of dosing
• Other protocol-defined inclusion/exclusion criteria may apply.

Описание

This study will test how different doses of study medicine (Inno8) work in the healthy men. The purpose of this study is to prove safety of Inno8 in healthy men, which will support further development of Inno8 in people with Haemophilia A. The study is divided into two parts, called the single ascending dose (SAD) part and multiple ascending dose (MAD) part, and each part will have more than one cohort (like sub-parts). No matter which part the participants will be enrolled in, they will either get the study medicine (Inno8) or a dummy medicine that looks like the study medicine but has no effect on the body (placebo). Which treatment participants get is decided by chance. The study medicine is a new medicine that cannot yet be prescribed by doctors. In the SAD part participants will receive a single injection of study medicine or placebo, and the study will last for up to 9 weeks. In the MAD part, participants will receive 1-2 tablets of study medicine or placebo daily for 10 days, and the study will last for up to 11 weeks.

Критерии включения

• * Male
• * Age 18-45 years (both inclusive) at the time of signing informed consent
• * Body mass index between 18.5 and 29.9 Kilogram Per Square Meter (kg/m/^2) (both inclusive)
• * Body weight between 60.0 and 100.0 Kilogram (kg) (both inclusive)
• * Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator

Критерии исключения

• * Factor VIII activity greater than or equal to (≥) 150% at screening
• * Increased risk of thrombosis, e.g. known history of personal or first-degree relative(s) with unprovoked deep vein thrombosis
• * Any clinical signs or established diagnosis of venous or arterial thromboembolic disease
• * Any of the thrombophilia markers listed below:
• * Protein C, protein S or antithrombin below the lower normal laboratory range
• * Factor II activity, activated protein C resistance, lupus anticoagulant, anti-cardiolipin antibody (IgG and IgM) or anti-β2 glycoprotein I antibody (IgG and IgM) outside the normal laboratory range at screening

Описание

This study is a prospective, single-arm, multicenter study to evaluate the safety and effectiveness of the Vertex Pulmonary Embolectomy System in participants presenting with clinical signs and symptoms of acute pulmonary embolism.

Критерии включения

• 1. Age ≥ 18 years /< 80 years
• 2. Acute onset of symptoms ≤ 14 days consistent with the presence of pulmonary embolism.
• 3. CTA evidence (site determined) of proximal PE (filling defect in at least one main or interlobar pulmonary artery)
• 4. RV/LV ratio of /> 0.9 on CTA as assessed by investigator (site determined).
• 5. Systolic blood pressure ≥ 90 mmHg (initial SBP may be ≥ 80 mmHg if the pressure recovers to ≥ 90 mmHg with fluids)
• 6. Subject or subject`s legally authorized representative (LAR) is willing and able to provide written informed consent prior to receiving any non-standard of care Protocol-specific procedures
• 7. Subject is willing and able to comply with all Protocol-required follow-up visits

Критерии исключения

• 1. Thrombolytic use within 30 days of baseline CTA
• 2. Pulmonary hypertension with peak pulmonary artery pressure /> 70 mmHg by right heart catheterization (site determined)
• 3. Vasopressor requirement after fluids to keep pressure ≥ 90 mmHg
• 4. Unstable heart rate /> 130 beats per minute prior to procedure
• 5. FiO2 requirement /> 40% or /> 6 LPM to keep oxygen saturation /> 90%
• 6. Hematocrit /< 28%
• 7. Platelets /< 100,000/μL
• 8. Serum baseline creatinine /> 1.8 mg/dL
• 9. International normalized ratio (INR) /> 3
• 10. Major trauma injury severity score (ISS) /> 15 within the past 14 days
• 11. Presence of intracardiac lead in the right ventricle or right atrium placed /<180 days prior to the index procedure
• 12. Cardiovascular or pulmonary surgery within last 30 days
• 13. Actively progressing cancer requiring chemotherapy
• 14. Known bleeding diathesis or coagulation disorder
• 15. Left bundle branch block
• 16. History of severe or chronic pulmonary arterial hypertension
• 17. History of chronic left heart disease with left ventricular ejection fraction ≤ 30%
• 18. History of decompensated heart failure
• 19. Patients on extracorporeal membrane oxygenation (ECMO)
• 20. History of underlying lung disease that is oxygen dependent
• 21. History of chest irradiation
• 22. History of heparin-induced thrombocytopenia (HIT)
• 23. Contraindication to systemic or therapeutic doses of heparin or anticoagulants
• 24. Known anaphylactic reaction to radiographic contrast agents that cannot be pretreated
• 25. Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the Subject is not appropriate for mechanical thrombectomy intervention
• 26. Life expectancy of /< 365 days, as determined by Investigator
• 27. Female who is pregnant or nursing
• 28. Current participation in another investigational drug or device treatment study
• 29. Inability to lay flat for procedure
• 30. Known presence of right-to-left cardiac shunt
• 31. History of Hemorrhagic or Ischemic Stroke, including Transient Ischemic Attack, within last 90 days
• 32. Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis

Описание

The purpose of this study is to evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) plus half-dose donafenib (a kind of anti-angiogenesis agents) in advanced hepatocellular carcinoma (BCLC-C Stage) accompanied by tumor thrombosis-associated portal hypertension.

Критерии включения

• 1. The patient voluntarily joined the study and signed an informed consent form;
• 2. ≥18 and ≤ 75 years old, both male and female;
• 3. Pathologically confirmed hepatocellular carcinoma, at least one measurable focus without local treatment (according to mRECIST or RECIST 1.1 requirements;
• 4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
• 5. BCLC-C stage accompanied by tumor thrombosis-associated portal hypertension;
• 6. Newly diagnosed patients who have not received local or systemic therapy in the past;
• 7. Expected survival period ≥ 3 months;
• 8. The functions of vital organs meet the following requirements (no blood components, cell growth factors and other corrective treatment drugs are allowed within 14 days before the first administration): the absolute count of neutrophils≥1.5×10/^9/L; Platelet ≥50×10/^9/L; Hemoglobin ≥60 g/L; Serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH)≤1×ULN (if abnormal, the levels of FT3 and FT4 should be examined at the same time, if the levels of FT3 and FT4 are normal, they can be included in the group); Bilirubin≤2×ULN (within 7 days before the first administration); ALT and AST ≤5×ULN (within 7 days before the first dose); Serum creatinine≤1.5×ULN;
• 9. Child-Pugh score ≤ 13 points;
• 10. Diagnosed with portal hypertension-related complications: Gastrointestinal bleeding; refractory or recurrent ascites; hepatic pleural effusion; portal vein tumor thrombus exceeds 50% of lumen area.
• 11. Non-surgical sterilization or female patients of childbearing age need to use a medically approved contraceptive method (such as an intrauterine device, contraceptive, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo surgical sterilization must be negative in serum or urine HCG within 72 hours before enrollment in the study; and must be non-lactating; for male patients whose partners are women of childbearing age, at the last time use effective methods for contraception within 3 months.

Критерии исключения

• 1. The patient has any active autoimmune disease or a history of autoimmune disease;
• 2. The patient is using immunosuppressive agents or systemic hormone therapy to achieve the purpose of immunosuppression (dose/>10mg/day prednisone or other curative hormones), and continues to use it within 2 weeks before enrollment;
• 3. Severe allergic reaction to any compositions of donafenib tablets or contrast media containing iodine ;
• 4. Central nervous system metastasis;
• 5. Patients who have received liver transplantation in the past;
• 6. Tumor thrombus beyond the portal vein range, such as hepatic vein, inferior vena cava, right atrium, splenic vein, superior mesenteric vein;
• 7. Suffer from high blood pressure and cannot be well controlled by anti-hypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• 8. Uncontrolled cardiac clinical symptoms or diseases, such as: NYHA level 2 or higher heart failure, unstable angina pectoris, myocardial infarction occurred within 1 year, clinically significant supraventricular or ventricular arrhythmia requires treatment or intervention , QTc/>450ms (male); QTc/>470ms (female); Abnormal coagulation function (INR/>2.0, PT/>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow the preventive use of low-dose aspirin and low molecular heparin;
• 9. Child-Pugh score />13 points;
• 10. Arterial/venous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• 11. Known genetic or acquired bleeding and thrombotic tendency (such as hemophilia patients, coagulation dysfunction, thrombocytopenia, etc.);
• 12. Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content/> 1.0 g;
• 13. The patient has active infection, fever of unknown origin within 7 days before medication ≥38.5℃, or baseline white blood cell count />15×109/L;
• 14. Patients with congenital or acquired immune deficiencies (such as HIV-infected persons);
• 15. Moderate to severe pulmonary hypertension, pulmonary artery pressure was assessed by ultrasound />40mmHg；
• 16. The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
• 17. The patient has previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or has previously received apatinib therapy;
• 18. According to the judgment of the investigator, the patient has other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, and other abnormalities which may affect the efficacy and/or safety of patients.

Описание

This is a multicenter, Single-arm, Real-world Study to evaluate the efficacy and safety of Transcatheter arterial chemoembolization (TACE), Lenvatinib combined with Tislelizumab (Triple Therapy) for patients with Hepatocellular Carcinoma (HCC) with bile duct tumor thrombus (BDTT).

Критерии включения

• 1. Age between 18 and 75 years old;
• 2. Patients with clinical diagnosis of Hepatocellular Carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) (refer to the diagnostic criteria of the Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of HCC with BDTT (2020 Edition)), BCLC Stage B or Stage C, and unresectable HCC (decided after multidisciplinary discussion);
• 3. Patients who had not received any tumor-related targeted, immunotherapy, radiotherapy and chemotherapy before enrollment;
• 4. Patients with at least one measurable lesion according to the mRECIST criteria (measurable lesion with a CT/MRI scan length diameter ≥ 10 mm and measurable lesion has not received localized treatment such as TACE, radiofrequency, cryotherapy, etc.);
• 5. ECOG score: 0-1;
• 6. liver function Child-Pugh class A or B; if combined with obstructive jaundice, total bilirubin ≤50umol/L is required. If higher than 50umol/L, biliary drainage is recommended;
• 7. Blood routine: absolute neutrophil count ≥1.5×10/^9/L, Hb≥8.5g/L, PLT≥75×10/^9/L;
• 8. No history of severe cardiac arrhythmia or heart failure; no history of severe ventilatory dysfunction or severe pulmonary infection; no acute or chronic renal failure with creatinine clearance />40mL/min;
• 9. Expected survival time greater than 3 months.

Критерии исключения

• 1. The tumor with extrahepatic metastasis or invaded adjacent organs;
• 2. Patients received other anti-tumor treatments;
• 3. Existence of contraindications to TACE;
• 4. History of allergy to the components or excipients of Lenvatinib or Tislelizumab;
• 5. The patient has any active autoimmune disease or has an autoimmune disease with expected relapse. Patients are on immunosuppressive or systemic hormone therapy for immunosuppression;
• 6. Patients with proteinuria suggestive of ≥ 1 + in routine urine will undergo a 24-hour urine protein test for patients with ≥ 1 g of 24-hour urine protein;
• 7. Patients with co-morbidities of other malignant tumors;
• 8. Patients with co-morbid psychiatric disorders;
• 9. Patients with pregnant or lactating women;
• 10. Patients with organ transplant patients;
• 11. Patients with hypothyroidism or hyperthyroidism.

Описание

The present study aims to evaluate the modification of functional capacity induced by an adapted physical activity program in subjects with haemophilia.

The exercise program used aims to improve joint mobility, muscle strength, static and dynamic balance, motor coordination.

The program is structured in 1 hour sessions of 2 days/week and lasts 6 months.

The primary endpoint is the change in functional capacity calculated as the difference between the baseline assessment and the 3 and 6 month assessment of the 6 Minutes Walking Test measured with the G-Walk (BTS Bioengineering S.p.A).

Критерии включения

• * Diagnosis of hemophilia A or B;
• * Signature of informed consent;
• * Availability of a medical certificate for non-competitive activities

Критерии исключения

• * Active bleeding
• * Severe joint deformities that prevent exercise
• * Insufficiency of communicative and/or sensory functions so severe that it is impossible to understand or carry out the trainer`s instructions (dementia, aphasia, blindness, deafness)
• * Heart failure (NYHA class /> 2)
• * Unstable angina
• * Lung disease requiring oxygen therapy
• * Symptomatic peripheral arterial disease
• * Myocardial infarction or hospitalization within the previous 6 months
• * Symptomatic orthostatic hypotension
• * Hypertension in poor pharmacological control (diastolic/> 95 mmHg, systolic/> 160 mmHg)
• * Significant neurological conditions that impair motor or cognitive function

Описание

The purpose of this study is to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) in combination with PD-1 inhibitors and Lenvatinib in patients with high tumor burden advanced-stage hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Критерии включения

• 1. Age 18 to 80 years old;
• 2. Diagnosis of HCC was confirmed by histologic or cytologic analysis or clinical features according to the American Association for the Study of Liver Diseases (AASLD) guideline;
• 3. At least one measurable intrahepatic lesion as per the RECIST 1.1 criteria;
• 4. HCC staging of the patients are consistent with both the BCLC stage C and the CNLC stage IIIa.
• 5. Presence of PVTT;
• 6. Patients received a first-line lenvatinib+PD-1 (L+P) inhibitors combination or that of HAIC+lenvatinib+PD-1 inhibitors (H+L+P). More specifically, the administration of lenvatinib was concomitant with PD-1 inhibitors, and HAIC was performed either concurrently with, or up to 2 months before or after the L+P inhibitors combination therapy. Patients in the H+L+P group should undergo at least 2 cycles of HAIC, receive at least 2 cycles of PD-1 inhibiors and take at least 2 months of lenvatinib. Patients in the L+P group should receive at least 2 cycles of PD-1 inhibiors, and take at least 2 months of lenvatinib.
• 7. Child-Pugh class A or B7;
• 8. Tumor burden meets up to 7 out criteria.

Критерии исключения

• 1. Patients who took anti-tumor treatments before the combination therapy;
• 2. With other malignant tumors;
• 3. incomplete data.

Описание

Hepatocellular carcinoma (HCC) with main trunk portal vein tumor thrombus (PVTT) has poor prognosis. The main lethiferous factor is the upper gastrointestinal hemorrhage by PVTT-related portal hypertension, then the second is the tumor-caused death. It is vital to prevent the portal hypertension by PVTT.

Критерии включения

• 1. diagnosis of primary HCC, confirmed histologically or clinically according to the criteria of the American Association for the Study of Liver Diseases;
• 2. presence of PVTT with III-IV grade by Cheng`s criteria;
• 3. having PVTT induced portal hypertension;
• 4. with or without PVTT induced acute variceal bleeding;
• 5. metastases with limited five sites and no more two organs involved;
• 6. Number of Intrahepatic tumors were no more than five;
• 7. receipt of Lenvatinib and PD-1 inhibitor as the first-line systemic therapy;
• 8. classified as Child-Pugh class A or B and having an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2;
• 9. no history of other malignancies;
• 10. agreed to participated in this clinical trial;
• 11. Hemameba ≥3.0 x109/L, neutrophil ≥1.5x109/L, hemoglobin≥10.0 g/L, platelet≥100x 109/L, ALT; AST; bilirubin ≤1.5-fold normal, GFR≥60ml/min.

Критерии исключения

• 1. recurrent HCC;
• 2. PVTT at I-II grade by Cheng`s criteria;
• 3. age /< 18 years or /> 75 years;
• 4. advanced HCC with more than five metastases;
• 5. Number of Intrahepatic tumors were more than five;
• 6. no response to Lenvatinib;
• 7. life expectancy less than 3 months.

Описание

Recombinant factor VIII for the prevention of bleeding in women/girls with haemophilia A undergoing major surgery

Критерии включения

• 1. Women/girls with haemophilia A (FVIII:C ≥1-/<40%) according to medical history
• 2. At least 12 years of age
• 3. Scheduled to undergo major elective surgery requiring FVIII treatment
• 4. Freely given written informed consent of the patient, or parent/legal representative where applicable, obtained in accordance with local regulations

Критерии исключения

• 1. Coagulation disorder other than haemophilia A
• 2. Present or past FVIII inhibitor (≥0.6 Bethesda units /[BU/]/mL)
• 3. Severe liver or kidney disease (alanine aminotransferase /[ALT/] and/or aspartate aminotransferase /[AST/] levels />5 times the upper limit of normal; or creatinine />120 μmol/L)
• 4. Known hypersensitivity to Nuwiq`s active substance or its excipients (sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate, poloxamer 188)
• 5. Pregnancy
• 6. Already had surgery in this study
• 7. Current participation in another interventional clinical trial
• 8. Treatment with any investigational medicinal product (IMP) within 30 days prior to screening visit

Описание

To evaluate the safety and efficacy of the Cleaner™ Pro Thrombectomy System for aspiration thrombectomy in patients with acute pulmonary embolism (PE).

Критерии включения

• * At least 18 years of age at the time of consent
• * Clinical signs, symptoms, and presentation consistent with acute PE
• * Onset of PE symptoms occurred within 14 days of presentation
• * Filling defect in at least one main or lobar pulmonary artery evidenced by CTA
• * RV dysfunction on CTA or echocardiography defined as RV/LV ratio />0.9

Критерии исключения

• * tPA use within 14 days prior to baseline CTA
• * Systolic BP /<90 mmHg for 15 min or the requirement of inotropic support to maintain systolic BP ≥90 mmHg
• * Diagnosis of pulmonary hypertension or suspected undiagnosed pulmonary hypertension with peak PA />70 mmHg by right heart catheterization or elevated main pulmonary artery to aorta ratio (MPA:A)
• * History of severe or chronic pulmonary hypertension
• * FiO2 requirement />40% or />6 LPM to keep oxygen saturations />90%
• * Hematocrit /<28%
• * Platelets /<100,000/µL
• * Serum creatinine />1.8 mg/dL
• * INR />3
• * aPTT (or PTT) />50 seconds on no anticoagulation
• * History of heparin-induced thrombocytopenia (HIT)
• * Recent (within six months) history of stroke, transient ischemic attack (TIA), or intracranial bleeding
• * Recent (within one month) history of active bleeding from a major organ
• * Absolute contraindication to anticoagulation
• * Major trauma such as head trauma, or other active intracranial, or intraspinal disease within 14 days
• * Morbidly obese (BMI />45 kg/m2) patient who by the judgement of the investigator is high risk for bleeding
• * Presence of intracardiac lead in the right ventricle or right atrium placed within 6 months
• * Cardiovascular or pulmonary surgery within last 7 days
• * Cancer which requires active chemotherapy
• * Known serious, uncontrolled sensitivity to radiographic agents
• * Life expectancy /<90 days, as determined by investigator
• * Female who is pregnant
• * Intracardiac thrombus
• * Patients who present with cardiac arrest and/or are on extracorporeal membrane oxygenation (ECMO) or ECMO required to perform interventional procedure
• * Simultaneous participation in another investigational study
• * Patients with known coagulation disorders such as antiphospholipid, Protein C, and Protein S
• * Presentation of PE with paradoxical emboli which may be diagnosed by concurrent stroke or concurrent arterialization

Описание

This study is researching 2 different experimental drugs called REGN9933 and REGN7508 (called "study drugs"). The study is focused on adults undergoing a placement of a catheter in the vein, also called a `PICC line`.

The aim of the study is to see how effective the study drug is at preventing venous thromboembolism (VTE) and other related disease after catheter placement.

The study is looking at several other research questions, including:

* What side effects may happen from taking the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)

Критерии включения

• 1. PICC is anticipated to remain in place for at least 14 days
• 2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2 or equivalent functional status as described in the protocol
• 3. Body weight ≥50 kg and ≤130 kg during the screening period
• 4. International normalized ratio (INR) and aPTT values at or below the upper limit of normal as defined by the local lab during the screening period
• 5. Platelet count ≥100 x 10/^9/L during the screening period as described in the protocol

Критерии исключения

• 1. Unsuccessful PICC placement or any other complication associated with this procedure that in the opinion of the study investigator may present any safety concerns to the participant
• 2. History of prior venous thrombosis in the arm in which the PICC is to be placed
• 3. Peripheral catheter(s) in the same arm in which the PICC is to be placed or expected need for peripheral catheter(s) placement in the same arm the PICC is to be placed as described in the protocol
• 4. History of known thromboembolic disease or thrombophilia
• 5. Participants requiring therapeutic or prophylactic anticoagulation and/or antiplatelet therapy as described in the protocol
• 6. Expected to receive cancer therapy or other medication associated with a prior episode of Grade 4 thrombocytopenia as described in the protocol
• 7. Any history of intracranial or intraocular bleeding, excessive operative or post-operative bleeding, traumatic spinal or epidural anesthesia, or history of bleeding diathesis (such as but not limited to Hemophilia A or B, von Willebrand`s disease, fibrinogen deficiency, and other inherited or acquired bleeding disorders)
• Note: Other protocol defined inclusion/exclusion criteria apply

Описание

In 2017, the World Health Organization placed snakebites at the top of its list of neglected tropical diseases in an effort to facilitate funding for prevention programs, improve access to anti-venom, and stimulate new research in this area. Between 5 and 25 cases per 100 000 inhabitants are reported per year in French Guiana and Martinique. Before the era of anti-venom immunotherapy, envenomations by Bothrops snake bites in French Guiana and Martinique could quickly become life-threatening with a mortality rate close to 30%. Today, the administration of fragments of Fab or (Fab`)2 immunoglobulins gives anti-venoms an excellent capacity to neutralise venom toxins, which has reduced mortality to less than 1% in the case of early hospital treatment In French Guiana, envenomation by Bothrops bites is characterized by local signs such as intense pain, rapidly expanding oedema, haemorrhagic phlyctenes and sometimes muscle necrosis. The local inflammatory and haemorrhagic damage is related to the enzymatic activities of the toxins contained in the venom (metallo-proteinases, disintegrins, and phospholipases A2, in particular). At the systemic level, venom serine proteases and metalloproteinases activate the coagulation cascade by multiple mechanisms (activation of coagulation factors X and V and of protrombin, thrombin-like and fibrinogenolytic enzymatic properties) and are responsible for the collapse of coagulation factors making the blood incoagulable. The metalloproteinases "hemorrhagins" destroy the vessel wall and are the cause of locoregional and systemic hemorrhage.

Envenomations by bites of Bothrops lanceolatus in Martinique have particular characteristics. Despite the genetic similarity with their congeners in French Guiana, envenomation by bites of Bothrops lanceolatus is characterized by the development of very intense local inflammatory signs (little haemorrhage) and the occurrence of thrombotic complications such as cerebral, pulmonary or myocardial infarction. The mechanisms behind this thrombotic presentation are not known. The large amount of metalloproteinases in the composition of Bothrops lanceolatus venom is believed to be responsible for destruction of vascular endothelium and pro-thrombotic state. Bothrops lanceolatus bite envenomations have been reported to be frequently complicated by generalized infections, disseminated intravascular coagulation and the occurrence of multi-visceral failure syndrome. This observation suggests abnormalities in endothelial function in which changes in Willebrand factor expression have been implicated.

The investigators hypothesize that plasma Willebrand factor (VW) activity and the intensity of endothelial activation are different depending on the Bothrops snake species involved in the bites in Guyana and Martinique. Due to the specific properties of the venoms of each Bothrops species, the activity of the Willebrand factor (VW) and the consequences in terms of endothelial activation would be different and responsible for the clinico-biological characteristics according to the geographical origin of the snakes.

The investigators will demonstrate that the accumulation of Willebrand factor (VW) and the increase in its activity are responsible for the endothelial activation and micro-thrombosis observed during envenomations by Bothrops lanceolatus bites, whereas the decrease in its activity induced by the venoms of endemic Bothrops from Guyana is responsible for haemorrhagic phenomena.

This study will highlight the importance of changes in Willebrand factor activity on endothelial activation and the initiation of micro-thrombosis in the case of Bothrops lanceolatus envenomations and on primary haemostasis and bleeding disorders in the case of endemic Bothrops in Guyana. This new knowledge is important insofar as individualised therapeutic management can be proposed. Indeed, several studies have shown that adjuvant treatment of thrombotic microangiopathies, such as thrombotic thrombocytopenic purpura, with blood products (fresh frozen plasma) or plasma exchange, improves endothelial dysfunction and the prognosis of patients.

Критерии включения

• * Men or Women, at least 18 years old
• * Be admitted to the Emergency Department of the Martinique University Hospital or the Cayenne University Hospital
• * Be the victim of a confirmed Bothrops snake bite in Martinique or French Guyana. The formal identification of the snake by the patient or his entourage is imperative.
• * Have a confirmed diagnosis of stage III envenomation (regional oedema of the limb and/or moderate general symptoms such as moderate hypotension, malaise, vomiting, abdominal pain, diarrhoea) and stage IV (extensive oedema reaching the trunk and/or severe general symptoms such as prolonged hypotension, shock, anaphylactoid reaction, visceral damage)
• * Be able to receive and understand information related to the research
• * Be able to freely give verbal consent to participate in the proposed research
• * Be able to freely give written informed consent to participate in the plasmathèque
• * Be affiliated to the general social security system

Критерии исключения

• * Pregnant or breastfeeding woman
• * People who have been treated for snakebite with Bothrops anti-venom Bothrofav® or Antivipmyn-tri®.
• * Known disorders of haemostasis such as haemophilia A (factor VIII deficiency), haemophilia B (factor IX deficiency), vitamin K deficiency, hepato-cellular insufficiency, presence of circulating anticoagulant factors
• * Disseminated intravascular coagulation (DIC)
• * Constitutional and acquired Von Willebrand disease
• * Constitutional and acquired thrombopathies
• * Idiopathic thrombocytopenic purpura
• * Person under legal protection (guardianship, curatorship, safeguard of justice), and person deprived of liberty.

Описание

With the development of medical technology and materials and instruments, flow diverter (FD) has gradually become the most important treatment method for the treatment of intracranial aneurysms (IA). At present, FD has been used in more than 250,000 cases worldwide, and the overall 1-year complete occlusion rate of aneurysms can reach 75%-85.5%. However, although the current imaging prognosis of FD is encouraging, the perioperative complications of FD are as high as 12.9%, including ischemic complications, SAH, and parenchymal hemorrhage in 7.3%, 2.0%, and 2.0%, respectively. In addition, an in-stent stenosis of more than 50% within one year has been reported in 10.2 to 15.0% of patients. However, in addition to conventional dual antiplatelet therapy, there is no relevant guideline recommendation or clinical evidence on how to prevent complications after FD implantation in IA patients. Atorvastatin is widely used in the primary and secondary prevention of cardiovascular and cerebrovascular diseases. Its main effect is to improve the incidence of cardiovascular and cerebrovascular events by reducing blood lipids. However, there is no high-quality clinical evidence for the use of atorvastatin in intracranial aneurysm stent implantation. Previous retrospective studies have shown that atorvastatin is the only protective factor for in-stent restenosis after flow diverter implantation in intracranial aneurysms. Therefore, this study planned to conduct a randomized controlled clinical trial to confirm the efficacy and safety of oral atorvastatin in the prevention of cerebrovascular adverse events after stent implantation in patients with unruptured intracranial aneurysms, and to provide objective evidence for the treatment decision of patients with unruptured intracranial aneurysms to prevent cerebrovascular adverse events after flow diverter implantation.

Критерии включения

• 1. male or non-pregnant women aged 18-75 years;
• 2. IA confirmed by CTA, MRA or DSA;
• 3. IA size ranged from 3 mm to 25mm;
• 4. Patients and/or their authorized persons can understand the purpose of the study, voluntarily participate in and sign informed consent;
• 5. patients who were considered by the investigators to be suitable for stent treatment;
• 6. patients who were willing to be followed up and evaluated according to the clinical research protocol.

Критерии исключения

• 1. Patients with contraindications to atorvastatin treatment or patients sensitive to atorvastatin; "Female patients who are preparing for pregnancy, pregnant, or lactating."
• 2. patients with intracranial aneurysm (excluding other cardiovascular and cerebrovascular diseases).
• 3. patients with indications for atorvastatin treatment (according to the Chinese Guidelines for Lipid Management (2023)).
• 4. patients with ruptured aneurysms.
• 5. taking transport protein inhibitors, cyclosporine, protease inhibitors, other lipid-lowering products (fibrates, ezetimibe, evolocumab), antacids, erythromycin, cytochrome P450 enzymes, colchicine and other concomitant drugs that interact with atorvastatin metabolism.
• 6. patients who did not understand or were unwilling to follow up and evaluate according to the clinical research protocol.
• 7. life expectancy /<3 years.

Описание

Participants in this study have a genetic mutation, specifically in the coagulation (blood clotting) Factor 9 gene that causes severe or moderately severe hemophilia B. This study is researching an experimental gene insertion therapy (the adding of a gene into your DNA) called REGV131-LNP1265, also called the "study drug". Gene insertion therapy aims to teach the body how to produce clotting factor long-term, without the need for factor replacement therapy.

The main aim of this study is to find a safe and well-tolerated dose of the study drug by checking the side effects that may happen from taking it.

The study is looking at several other research questions including:

* How much study drug is in the blood at different times
* Whether the body makes antibodies against parts of the study drug, which could make the drug less effective or could lead to side effects. Antibodies are proteins produced by the body`s immune system in response to a foreign substance
* Whether the body makes antibodies against the clotting factor replacement therapy
* How quality of life is affected by hemophilia B and if it changes after taking study drug
* How joint health is affected by hemophilia B and if it changes after taking study drug
* How often visits are required for the emergency room, urgent care center, physician`s office, hospital, telephone or online are required as a result of bleeding events, and if the frequency changes after taking study drug
* How often factor replacement therapy is needed, both on a regular basis for prevention of bleeding, and as needed to treat bleeding events (and it if changes after taking study drug)
* Whether there is a difference in 2 different methods for measuring Factor 9 activity in the blood

Критерии включения

• 1. Confirmed diagnosis of severe or moderately severe hemophilia B with medical history of FIX functional activity (≤2% or /<0.02 IU/mL) or documented genotype known to produce severe hemophilia B
• 2. Currently taking FIX prophylaxis and previous experience with FIX therapy, as defined in the protocol
• 3. Participation in the lead-in period of this interventional study OR a separate lead-in study (R0000-HEMB-2187 /[NCT05568459/]) for at least 6 months for ABR data while taking FIX prophylaxis, as defined in the protocol

Критерии исключения

• 1. History of FIX inhibitor (clinical or laboratory-based assessment) on 2 or more occasions
• 2. Bethesda inhibitor titer greater than the upper limit of normal (ULN) at screening
• 3. Detectable pre-existing antibodies to the adeno-associated virus serotype 8 (AAV8) capsid; as measured by enzyme-linked immunosorbent assay (ELISA) at prescreening (or final lead-in visit, if applicable).
• 4. Any significant underlying liver disease such as: cholestatic liver disease, liver cirrhosis, portal hypertension, splenomegaly, hepatic encephalopathy
• 5. Evidence of advanced liver fibrosis, as defined in the protocol
• 6. Evidence of cirrhosis and/or portal hypertension as assessed by abdominal ultrasound at screening or measured within 6 months prior to the screening visit
• 7. History of arterial or venous thrombo-embolic events, as defined in the protocol
• 8. History of hypersensitivity to corticosteroids or known medical condition that requires chronic administration of corticosteroids
• 9. Previously received any AAV gene-based therapy or intends to receive approved or investigational AAV-based gene therapy other than REGV131-LNP1265 during the study period
• NOTE: Other Inclusion/Exclusion Protocol Defined Criteria Apply

Описание

The purpose of this research is to collect information about how the RevCore Thrombectomy Catheter works to treat stent blockages.

Критерии включения

• 1. Age ≥ 18 years
• 2. Patients with stent age /> 6 weeks
• 3. Location of thrombosed stents in proximal lower extremity deep vein segments including at least common femoral, external iliac, or common iliac vein
• 4. RevCore Thrombectomy Catheter must enter vasculature
• 5. Willing and able to provide informed consent

Критерии исключения

• 1. Exposed stents with broken struts, significantly deformed struts, struts protruding into the vessel
• 2. Stents not wall apposed
• 3. Stents compressed to /<10mm
• 4. Bilateral in-stent thrombosis
• 5. Congenital anatomic anomalies of the iliac veins
• 6. Allergy, hypersensitivity, or thrombocytopenia from heparin or iodinated contrast agents, except for mild to moderate contrast allergies for which pretreatment can be used
• 7. Any contraindication to anticoagulants or antiplatelets that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• 8. Chronic non-ambulatory status
• 9. Known hypercoagulable states (e.g. antiphospholipid syndrome) that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• 10. Inability to secure venous access
• 11. Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject
• 12. Current participation in another investigational drug or device treatment study

Описание

Intimate violence against individuals, which is particularly marked among women, is one of the most widespread human rights violations in the world.

The Women Abuse Screening Tool (WAST) self-questionnaire is a screening tool validated in French.

Our preliminary data describing the association between intimate violence against women and the first attack of unexplained venous thromboembolic disease, show a significant frequency of positive responses to the WAST among women attending a biological hematology consultation at the CHU de Nîmes, for reasons of hemostasis disorders (8% out of the first 200 cases).

The study authors wish to establish the prevalence of this situation among patients presenting to the CHU de Nîmes for hematological exploration and management. They hypothesize that the prevalence of violence against individuals seen in Hematology consultations is higher among individuals with hemostasis pathologies (hemorrhagic and thrombotic pathologies) than those with cellular pathologies, and higher among women than men.

Критерии включения

• * Currently in a relationship or has been in one in the last 12 months, regardless of the length of the relationship
• * Willing to complete the anonymous WAST self-questionnaire
• * able to read and understand French
• * Outpatient consultant at Nîmes University Hospital in one of the following departments:
• * Biological hematology consultation
• * Clinical hematology consultation
• * Vascular medicine consultation

Критерии исключения

• * Individuals under court protection, guardianship or curatorship
• * Individuals unable to read and understand French
• * Individuals who have already completed the WAST questionnaire during the study period
• * Individuals unable to get away from their partner during the consultation to complete the questionnaire in isolation

Описание

Sepsis remains a global scourge. Before the SARS-CoV-2 pandemic, the World Health Organization estimated approximately 49 million cases annually, resulting in 11 million deaths. Defined by dysregulated host response to infection, sepsis leads to vital organ failure. Renal dysfunction affects about half of ICU patients, necessitating extracorporeal renal replacement therapy in approximately 10% of cases, alongside coagulation system involvement typified by thrombocytopenia. Immunothrombotic phenomena are pivotal in sepsis pathophysiology, activating coagulation and disrupting immune responses. Microcirculatory impairment, mediated by neutrophils, monocytes, and platelets, worsens vital organ perfusion. Excessive production of Neutrophil Extracellular Traps (NETs) is implicated in microcirculatory compromise during sepsis.

Критерии включения

• * Patients aged 18 years and older
• * Admitted to the intensive care unit with septic shock, defined as an increase in the Sequential Organ Failure Assessment (SOFA) score of at least 2 points due to infection, requiring vasopressor drugs to maintain a mean arterial pressure (MAP) ≥ 65 mmHg, and a lactate level /> 2 mmol/L (18 mg/dL) despite adequate fluid resuscitation
• * Requiring renal replacement therapy according to consensus indications:
• * KDIGO stage 3 acute kidney injury with oliguria or anuria persisting for more than 72 hours
• * Urea /> 40 mmol/L
• * Plasma potassium /> 5.5 mmol/L despite medical treatment
• * pH /< 7.15 (pure metabolic acidosis with PaCO2 /< 30 mmHg or mixed acidosis with PaCO2 /> 50 mmHg without the possibility of improving alveolar ventilation)
• * Acute pulmonary edema secondary to hydrosaline overload resulting in severe hypoxemia (oxygen flow /> 5 L/min or FiO2 /> 50% during mechanical ventilation to maintain SaO2 /> 95%) despite diuretic therapy
• * Receiving continuous renal replacement therapy with a high-adsorption membrane (oXiris membrane) or a conventional membrane (HF1400 membrane)

Критерии исключения

• * Known history of constitutional thrombopathy (Bernard Soulier disease, Glanzmann thrombasthenia, Gray`s syndrome or dense granule disease)
• * Myelodysplastic or myeloproliferative syndrome
• * Autoimmune thrombocytopenic purpura
• * Acute leukemia
• * Hemorrhagic shock
• * Platelet transfusion within 7 days prior to inclusion
• * Antiplatelet therapy with clopidogrel or ticagrelor within 5 days prior to inclusion, prasugrel or dipyridamole within 7 days prior to inclusion
• * Active HIV infection or hepatitis B or C
• * Pregnant woman
• * Not affiliated to a social security system or not benefiting from such a system

Описание

The objective of this study is to evaluate the safety and effectiveness of the GPX® Embolic Device when used as indicated for embolization requiring distal vessel penetration in 114 subjects in up to 25 investigational sites in the USA, New Zealand, and Canada.

Критерии включения

• 1. Age ≥18 years on the date of consent
• 2. Expected post-procedural lifespan of at least 30 days, in the opinion of the investigator, to allow for participation in all follow-up visits
• 3. Presents with need for peripheral embolization where there is a desire for distal vessel bed penetration including:
• * Vascular tumors (e.g., renal angiomyolipoma, renal cell carcinoma, bone tumors, bleeding tumors, and other vascular tumors)
• * Renal embolization
• * Portal vein branches
• 4. Informed consent granted by the patient or legally authorized representative
• 5. Willing and able to comply with the protocol-specified procedures and assessments

Критерии исключения

• 1. Requires embolization for any of the following applications: a) Neurovasculature b) Coronary vasculature c) Hemorrhage due to trauma d) Non-tumoral focal/active bleeding sites (e.g., gastrointestinal tract, urinary tract, lung) e) Veins other than portal vein f) Aneurysms g) Endoleaks h) Vascular malformations i) Vessels for flow redistribution
• 2. Has undergone an embolization procedure within 30 days prior to consent
• 3. Presents with need for embolization where the risk of clinically significant infarction outweighs the benefit of distal penetration (e.g., gastrointestinal, uterine)
• 4. Embolization target is only intended for temporary occlusion (e.g., bioresorbable biologic embolic agents)
• 5. Known allergy or hypersensitivity to contrast media that cannot be adequately medicated
• 6. Pregnant, planning to become pregnant during the study period, or breastfeeding
• 7. Unresolved systemic infection or localized infection in the targeted region
• 8. Pre-operative laboratory tests and/or physical examination indicate abnormal results, which, in the opinion of the investigator, would clinically confound the study primary endpoints
• 9. Existing medical condition which, in the opinion of the investigator, may cause the subject to be intolerant of an occlusion procedure or non-compliant with the protocol or may confound the data interpretation
• 10. Subject is participating in another device, drug, or procedure clinical investigation and has not completed the study treatment or the other investigation clinically interferes with the endpoints of this study (post-approval registries are allowed as long as the investigator determines there is no clinical interference with study endpoints)
• 11. Vulnerable subject populations (e.g., incarcerated or cognitively challenged adults) 12. Patients with drug or alcohol dependency (within 6 months prior to study entry) that, in the opinion of the investigator, would interfere with safe delivery of the study treatment or with the interpretation of study results
• Intra-procedural exclusion criteria:
• 13. Presence of persistent, flow-limiting vasospasm that is not responsive to chemical or mechanical interventions 14. Presence of collateral pathways potentially endangering normal territories during embolization 15. Blood flow precludes safe delivery of embolic material (e.g., arteriovenous shunting or high, unpredictable flow exists) 16. Anatomy that precludes advancement of the delivery device to target vessel embolization site or delivery of embolic material 17. Dissection in the target vessel 18. The delivery device has already been used with an ionic contrast agent (e.g., Conray® (iothalamate meglumine injection USP 60%), Guerbet)

Описание

Along with the current clinical trial, the efficacy and safety of a 150 mg Bid dabigatran administered within 24 hours of randomization after having first-ever cerebral venous thrombosis compared to 20 mg rivaroxaban were assessed through rate of recurrent VTE, mRS, rate of venous recanalization, HIT score, MoCA test, and central and peripheral hemorrhagic complications

Критерии включения

• * 1-Patients aged 18 and above 2-New diagnosis of symptomatic cerebral venous thrombosis as confirmed on CT/CT venogram or MRI/MR venogram 3-Ability to randomize within 14 days of neuroimaging-confirmed diagnosis 4-The treating clinician thinks that the patient is appropriate for oral anticoagulation as per the standard of care 5-The patient or legally authorized representative can give written informed consent

Критерии исключения

• 1. The patient has known antiphospholipid antibody syndrome with a previous history of venous or arterial thrombosis
• 2. The patient is anticipated to require invasive procedures (e.g., lumbar puncture, thrombectomy, hemicraniectomy) prior to initiation of oral anticoagulation
• 3. Patient is unable to swallow due to depressed level of consciousness
• 4. Impaired renal function (i.e., CrCl /< 30 mL/min using CockroftGault equation)
• 5. Pregnancy; if a woman is of childbearing potential a urine or serum beta human chorionic gonadotropin (β-hCG) test is positive
• 6. Breastfeeding at the time of randomization
• 7. Bleeding diathesis or other contraindication to anticoagulation
• 8. Any concurrent medical condition requiring mandatory antiplatelet or anticoagulant use
• 9. Concomitant use of strong CYP3A4 inducers (e.g., ongoing use of dilantin, carbamazepine, HIV protease inhibitors) or CYP3A4 inhibitors (e.g., diltiazem, ketoconazole)
• 10. Patient has a severe or fatal comorbid illness that will prevent improvement

Описание

To Evaluate the Safety and Efficacy of the Super-Bore 8/7F Thrombosis Aspiration Catheter in the Treatment of Acute Intracranial Large Vessel Occlusion.

Критерии включения

• 1. Aged 18 years or older;
• 2. Clinical presentation consistent with acute ischemic stroke (AIS);
• 3. Able to receive mechanical thrombectomy within 24 hours of onset;
• 4. Pre-morbid mRS score of 0 or 1;
• 5. Baseline NIHSS score of 6 or greater;
• 6. Complete or near-complete occlusion (eTICI 0-1) of the intracranial segment of the internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or the basilar artery (with or without involvement of the intracranial vertebral artery) confirmed by angiography who can undergo intravascular thrombectomy;
• 7. Vessel diameter ≥2.2 mm at the occlusion site;
• 8. ASPECTS or PC-ASPECTS score of 6-10 on NCCT, CTA-source imaging, or DWI-MRI;
• 9. Written informed consent obtained from the patient or the patient`s qualified representative.

Критерии исключения

• 1. Pregnant or lactating women;
• 2. Severe allergic reactions to contrast agents;
• 3. Current participation in other clinical studies;
• 4. Known hereditary or acquired bleeding disorders, platelet count /<50,000/µL, or coagulation factor deficiencies;
• 5. Renal failure with serum creatinine ≥3 mg/dL or Glomerular Filtration Rate (GFR) /<30 mL/min;
• 6. Expected survival /< 6 months or known cancer with metastases;
• 7. Clinical manifestations suggesting subarachnoid hemorrhage, despite normal CT or MRI findings;
• 8. Suspected aortic dissection;
• 9. Known arterial condition in a proximal vessel that requires treatment or prevents access to the site of occlusion or safe recovery of the investigational device (for example, severe stenosis, complete occlusion in the cervical ICA, tandem occlusion);
• 10. High degree of suspicion of intracranial arterial disease (ICAD), such as evidence of multifocal ICAD on CTA, MRA, or DSA, or any other finding that is highly suggestive of ICAD as the underlying etiology of the occlusion;
• 11. Evidence of dissection in the extracranial or intracranial cerebral arteries;
• 12. Intracranial hemorrhage on CT or MRI;
• 13. Evidence of intracranial mass effect or tumor (except small meningiomas defined as ≤ 3cm and asymptomatic)) on CT or MRI;
• 14. Suspicious of cerebral vasculitis or infectious endocarditis;
• 15. Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluation, e.g., dementia with prescribed anti-cholinesterase inhibitor;
• 16. Clinical history, past imaging or clinical judgement suggest that the intracranial occlusion is chronic;
• 17. Excessive vascular access tortuosity or target vessel size that will likely prevent endovascular access with the Super-Bore Aspiration Catheters;
• 18. Intracranial stent implanted in the same vascular territory that would preclude the safe deployment/removal of the thrombectomy devices;
• 19. Occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior circulation/vertebrobasilar system) as confirmed on CTA/MRA, or clinical evidence of bilateral strokes or strokes in multiple territories as determined by the treating physician;
• 20. Known aneurysm at or near the target treatment segment;
• 21. Known glucose level/< 50 mg/dl (2.78 mmol/L) or /> 400 mg/dl (22.20 mmol/L)；
• 22. Patients who, in the opinion of the investigator, are unsuitable for mechanical thrombectomy as evidenced by imaging findings.

Описание

Researchers are looking for a better way to treat people who have acute venous and arterial thrombotic and thromboembolic events. These are severe medical problems due to blood clots forming in and blocking blood vessels.

The study treatment BAY3018250 is under development to treat acute venous and arterial thrombotic and thromboembolic events. It aims to work by dissolving blood clots in the blood vessels.

In this study, participants will be healthy and will not benefit from receiving BAY3018250. However, the study will provide information on how to test BAY3018250 in future studies in people with acute venous and arterial thrombotic and thromboembolic events.

During the study, researchers will use two different methods of giving BAY3018250 to participants. This may help in developing a faster method of giving this treatment in case of emergencies.

The main purpose of this study is to check how safe BAY3018250 is and if it is well tolerated by participants. For this, researchers will study the number and severity of medical problems in:

* healthy Japanese men after receiving different doses of BAY3018250 as an infusion into a vein.
* healthy adult participants after receiving a certain dose of BAY3018250 by an injection.

These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they might be related to the study treatment.

This study will have two parts: Part A and Part B:

- Only healthy Japanese men can join Part A of the study, which will have two groups. In the first group, participants will receive a low dose of BAY3018250. If researchers consider this dose to be safe, the next group will receive a higher dose.

In each group, participants will be randomly assigned to receive BAY3018250 or placebo as an infusion into a vein once during the study. A placebo looks like a study drug but does not have any medicine in it.

- Healthy men and women can join Part B of the study. Participants will be randomly assigned to receive a certain dose of BAY3018250 or placebo by an injection once during the study.

Each participant will be in the study for around 14 weeks, which includes:

* a visit to the hospital within 3 weeks of taking any treatment to confirm if the participant can take part in the study
* a hospital stay of 1 week, during which participants will receive their assigned treatment, have blood and urine tests and complete health check-ups
* six follow-up visits to the hospital until about 11 weeks after receiving the study treatments During the study, the doctors and their study team will check participants` health by performing tests such as blood and urine tests, and checking heart health using an electrocardiogram (ECG) As this study is conducted in healthy participants who will not benefit from the treatment, access to the treatment after the study is not planned.

Критерии включения

• Inclusion:
• Part A:
• * Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and electrocardiogram (ECG).
• * Japanese who was born in Japan and whose parents and grandparents must have been Japanese and who has not lived outside of Japan for more than 10 years and has not significantly modified their diets since leaving Japan.
• * Male
• Part B:
• * Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• * Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, safety laboratory tests, vital signs, and ECG.
• * Male or female (postmenopausal or hysterectomized only)

Критерии исключения

• * Medical disorder, condition (e.g., after surgical procedure), or history of such that would impair the participant`s ability to take part in or complete this study in the opinion of the investigator. This includes family history indicating hereditary predisposition of relevant diseases and history of non- persisting diseases with possible impact on study participation.
• * Increased bleeding risk: known coagulation disorders (e.g., von Willebrand´s disease, hemophilia), periodontitis, symptomatic hemorrhoids, acute gastritis, peptic ulcer, or similar diseases with tendency to lead to bleedings, known sensitivity to common causes of bleeding (e.g., nasal, etc.), or history of hemorrhage and gastrointestinal ulceration within 6 months prior to the screening visit.
• * Family history of hereditary or not explainable bleeding disorders.
• * History of thrombosis or family history of hereditary or not explainable diseases with increased risk for thrombosis or thromboembolic events.
• * Tendency of easy bruising.
• * Platelets out of reference range.
• * Activated partial thromboplastin time (aPTT) or prothrombin time (PT) out of reference range.

Описание

This study study is a prospective, single-arm, multicenter study to evaluate the safety and effectiveness of the Vertex Pulmonary Embolectomy System in participants presenting with clinical signs and symptoms of pulmonary embolism.

Критерии включения

• 1. Age ≥ 18 years /< 80 years
• 2. Acute onset of symptoms ≤ 14 days consistent with the presence of pulmonary embolism.
• 3. CTA evidence (site determined) of proximal PE (filling defect in at least one main or interlobar pulmonary artery)
• 4. RV/LV ratio of /> 0.9 on CTA as assessed by investigator (site determined).
• 5. Systolic blood pressure ≥ 90 mmHg (initial SBP may be ≥ 80 mmHg if the pressure recovers to ≥ 90 mmHg with fluids)
• 6. Subject is willing and able to provide written informed consent prior to receiving any non-standard of care clinical investigation plan specific procedures
• 7. Subject is willing and able to comply with all clinical investigation plan required follow-up visits

Критерии исключения

• 1. Thrombolytic use within 30 days of baseline CTA
• 2. Pulmonary hypertension with peak pulmonary artery pressure /> 70 mmHg by right heart catheterization (site determined)
• 3. Vasopressor requirement after fluids to keep pressure ≥ 90 mmHg
• 4. Unstable heart rate /> 130 beats per minute prior to procedure
• 5. FiO2 requirement /> 40% or /> 6 LPM to keep oxygen saturation /> 90%
• 6. Hematocrit /< 28%
• 7. Platelets /< 100,000/µL
• 8. Serum baseline creatinine /> 1.8 mg/dL
• 9. International normalized ratio (INR) /> 3
• 10. Major trauma injury severity score (ISS) /> 15 within the past 14 days
• 11. Presence of intracardiac lead in the right ventricle or right atrium placed /<180 days prior to the index procedure
• 12. Cardiovascular or pulmonary surgery within last 30 days
• 13. Actively progressing cancer requiring chemotherapy
• 14. Known bleeding diathesis or coagulation disorder
• 15. Left bundle branch block
• 16. History of severe or chronic pulmonary arterial hypertension
• 17. History of chronic left heart disease with left ventricular ejection fraction ≤ 30%
• 18. History of decompensated heart failure
• 19. Patients on extracorporeal membrane oxygenation (ECMO)
• 20. History of underlying lung disease that is oxygen dependent
• 21. History of chest irradiation
• 22. History of heparin-induced thrombocytopenia (HIT)
• 23. Contraindication to systemic or therapeutic doses of heparin or anticoagulants
• 24. Known anaphylactic reaction to radiographic contrast agents that cannot be pretreated
• 25. Imaging evidence or other evidence that suggests, in the opinion of the Investigator, the Subject is not appropriate for mechanical thrombectomy intervention
• 26. Life expectancy of /< 365 days, as determined by Investigator
• 27. Female who is pregnant or nursing
• 28. Current participation in another investigational drug or device treatment study
• 29. Inability to lay flat for procedure
• 30. Known presence of right-to-left cardiac shunt
• 31. History of Hemorrhagic or Ischemic Stroke, including Transient Ischemic Attack, within last 90 days
• 32. Current or history of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic thromboembolic disease (CTED) diagnosis

Описание

Background: It has not been extensively studied in differing populations that endovascular treatment (EVT) for acute and subacute CVST with multimodal imaging selection improves the functional outcome better than standard medical care based on the guidelines. Published experience with endovascular treatment is promising. However, its efficacy has not been confirmed and early selection criteria for EVT are unknown.

Objective:The main objective of the Endovascular treatment or Standard medical Care for Cerebral Venous Sinus Thrombosis (ESCORT) trial is to determine if EVT improves the functional outcome of acute and subacute CVST patients with multimodal imaging selection.

Study Design:The ESCORT trial is a multicenter, prospective, randomized, open-label, blinded endpoint trial.

Study population: Patients are eligible if they have a radiologically criteria proven acute and subacute CVST, obvious symptoms of intracranial hypertension(lumbar puncture pressure≥250mmH2O).

Intervention: Patients will be randomized to receive either EVT or standard medical care (therapeutic doses of heparin). EVT consists of local application of alteplase or urokinase within the thrombosed sinuses, balloon angioplasty, and/or mechanical thrombectomy. Glasgow coma score, NIH stroke scale, ophthalmologic examination, Headache Impact Test-6(HIT-6), EuroQol-5 dimension-5 level(EQ-5D-5L) scale score, multimodal imaging and relevant laboratory parameters will be assessed at baseline.

Endpoints: The primary endpoint is the proportion with good prognosis at 3 months (definition: a. mRS≤1; b. headache score (/<50, HIT-6); c. Frisén=0 grade for papilledema; d. defect of field vision PMD/>-2dB). Secondary outcomes are three-months mRS, HIT-6,Frisén grade for papilledema, situation of EQ-5D-5L, mortality and recanalization rate. Major intracranial and extracranial hemorrhagic complications within one-week after the intervention are the principal safety outcomes. Results will be analyzed according to the`intention-to-treat` principle. Blinded assessors not involved in the treatment of the patient will assess endpoints with standardized questionnaires.

Study size: To detect a 20% relative increase of good prognosis (from 65 to 85%), 224 patients (112 in each treatment arm) have to be included (two-sided alpha, 80% power).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Included patients may benefit directly from EVT. Complications of EVT, most notably intracranial hemorrhages, constitute the most important risk of the study.

Критерии включения

• General inclusion criteria
• 1. age between 18 years and 60 years
• 2. Cerebral venous sinus thrombosis (CVST), confirmed by computed tomographic and magnetic resonance imaging (T1, T2, SWI, DWI, FLAIR), magnetic resonance venography, computed tomographic venography or digital subtraction angiography.
• 3. Patients with CVST who meet the following conditions (1) Within 3 weeks of acute onset (2) There are one of the obvious clinical symptoms: A. symptoms of intracranial hypertension: headache, papilledema, visual acuity and visual field damage; B. Neurological impairment symptoms; C. Seizure; D. Disturbance of consciousness (GCS score≥9)
• 4. Lumbar puncture pressure≥250mmH2O
• 5. Patients or their relatives can sign written informed consent
• Image inclusion criteria
• 1.CT and MRI (T1, T2, MRV, SWI, DWI) are used to screen CVST as acute phase (T1 low signal, T2 equal signal or slightly high signal; CT showed that the corresponding area is high signal) or subacute phase (T1 and T2 high signal) 2.3D-TOF or CE-MRA or CTV are used to screen the types of venous sinus thrombosis occlusion of main drainage which is prone to intracranial hypertension due to venous sinus thrombosis as follows: A.Superior sagittal sinus occlusion: thrombus obliterates the posterior 1/2 segment of superior sagittal sinus
• B.Transverse sinus occlusive type:
• 1. complete thrombosis of the bilateral transverse sinus with or without the corresponding sigmoid sinus involvement
• 2. complete thrombosis of the superior transverse sinus with or without the corresponding sigmoid sinus involvement C.complete thrombosis of the superior sagittal sinus and unilateral transverse sinus with or without the corresponding sigmoid sinus involvement D.complete thrombosis of the superior sagittal sinus and bilateral transverse sinus with the corresponding sigmoid sinus is occluded

Критерии исключения

• 1. Received any thrombolytic therapy within 7 days
• 2. Patients who cannot cooperate or accept MRI examination
• 3. Patients with dementia or mental illness are known to be unable to complete neurological function assessment and follow-up
• 4. Patients with high myopia and eye diseases affecting fundus examination and visual field examination
• 5. The patient has a clear history of primary headache such as migraine, tension headache and cluster headache, and a clear history of secondary headache
• 6. Patients who receive major surgery (excluding lumbar puncture) or a history of severe brain injury within 2 weeks
• 7. Known history of severe allergy to contrast media (excluding rash)
• 8. Gastrointestinal bleeding occurred within 3 months (excluding bleeding from recto anal hemorrhoids)
• 9. Serious liver function or renal dysfunction with written records and affecting normal coagulation function
• 10. Hemorrhagic disease (hemorrhagic disease history) with written records
• 11. Excepting for CVST, patients with any life expectancy less than 1 year (such as advanced cancer)
• 12. Pregnant women (puerperal women can be enrolled)
• 13. Patients with contraindications to anticoagulation or thrombolysis
• 14. Intracranial infectious or malignant tumor secondary to cerebrospinal fluid
• 15. CVST secondary to autoimmune diseases and hematological diseases (such as primary thrombocytosis, myelodysplastic syndrome, leukemia, etc.) and genetic factors
• 16. Concurrent thrombocytopenia (/<100×109/L)
• 17. MRI features showed that the occluded vessels of venous sinus were in chronic phase (T1 and T2 images showed equal signal)
• 18. Severe brain tissue injury symptoms such as obvious space occupying effect due to massive cerebral edema, cerebral infarction or cerebral hemorrhage
• 19. Patients with CVST accompanied by ventricular compression and hydrocephalus requiring surgery
• 20. Participating in clinical trials of any other drugs or medical devices, or may participate in clinical trials of any other drugs or medical devices within 6 months after being enrolled in this clinical trial
• 21. The researchers judge that there are other situations that are not suitable for enrollment

Описание

Rationale:

Cardiac CT acquired during the acute stroke imaging protocol (acute cardiac CT) has recently been shown to have a superior diagnostic yield than transthoracic echocardiography, which is currently the most commonly used method to screen for structural sources of cardioembolism in patients with acute ischemic stroke. The most common finding on acute cardiac CT are cardiac thrombi located in the left atrium (LA) and specifically the left atrial appendage (LAA). The higher diagnostic yield of acute cardiac CT compared to TTE is partially explained because CT allows for better visualization of the LAA, but also because cardiac thrombi may dissolve in the first days after stroke. Whether acute cardiac CT is the optimal diagnostic modality for LA thrombi in stroke patients is unknown, since data comparing it to transoesophageal echocardiography (TEE), which is the reference standard to detect LA thrombi, are lacking. The general hypothesis of this study is that acute cardiac CT is the optimal method to detect LA thrombi in ischemic stroke patients, since TEE can miss LA thrombi that dissolve in the first days after stroke.

Objectives:

1. Determine whether acute cardiac CT has a higher diagnostic probability of detecting LA thrombi compared to TEE or repeated cardiac CT in the subacute phase of ischemic stroke by assessing the rate at which LA thrombi dissolve in the first days after ischemic stroke occurrence.
2. Determine the positive predictive value of acute cardiac CT compared to TEE for the detection of LA thrombi. Study design: Prospective, single-centre, observational cohort Study population: 39 patients of 18 years or older with acute ischemic stroke and a LA thrombus detected on cardiac CT acquired during the acute stroke imaging.

Main study parameters/endpoints:

1. Rate at which LA thrombi visualized on acute cardiac CT dissolve in the first days after ischemic stroke.
2. False-positive rate for detection of left atrial thrombi on acute cardiac CT compared to TEE. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Clinical and imaging patient data which are obtained as part of standard care will be prospectively collected after written informed consent. Patient with a LA thrombus on acute cardiac CT will undergo TEE for research purposes after obtaining written informed consent. TEE is semi-invasive and associated with a small risk of major complications (/<0.2%). Patients will also be exposed to additional radiation (1.4 mSV) due to sequential cardiac CT after TEE. The Radiation Dose Committee deemed this to be an intermediate risk. In a small minority of patients (/<10%), another cardiac CT will be acquired 2 minutes after this sequential cardiac CT to ensure a clear, final assessment of the presence of an atrial appendage thrombus. This will result in a total additional radiation of 3 mSV for the two additional cardiac CT`s. The Radiation Dose Committee deemed this to be an intermediate risk. As part of standard care, patients will be contacted for follow-up evaluation by a trained stroke nurse at 90 days. As a result of ischemic stroke, some patients become incapacitated to an extent they are unable to give informed consent. In these cases, the legal representative will be asked for informed consent. Decreased leveI of consciousness or aphasia are typical clinical characteristics of cardioembolic stroke. Therefore, it is pivotal to also include incapacitated acute ischemic stroke patients. Excluding these patients from the study would render the study non-representative of the study`s target population (acute ischemic stroke patients with cardioembolic stroke due to LA thrombus).

Критерии включения

• * Age 18 years or older
• * Clinical diagnosis of acute ischemic stroke
• * Written informed consent from patient or representative
• * Radiological diagnosis of cardiac thrombus in the LA, including the LAA, on cardiac CT acquired during the initial stroke imaging protocol.

Критерии исключения

• * Patients with a diagnosis other than acute ischemic stroke, such as: transient ischemic attack, intracerebral haemorrhage, subarachnoid haemorrhage, epilepsy, tumor.
• * Absolute contraindication for TEE:
• * Perforated viscus
• * Esophageal stricture
• * Esophageal tumor
• * Esophageal perforation, laceration
• * Esophageal diverticulum
• * Active upper GI bleed
• * Absolute contraindication for repeat cardiac CT
• * Documented previous severe reaction to iodinated contrast media, including anaphylaxis, angioedema and bronchospasm.
• * Severely impaired kidney function defined as estimated glomerular filtration rate of 30 mL/min/1.73 m2.

Описание

Hepatocellular carcinoma (HCC) with main trunk portal vein tumor thrombus (PVTT) has poor prognosis. The main lethiferous factor is the upper gastrointestinal hemorrhage by PVTT-related portal hypertension. Studies have proven that early transjugular intrahepatic portosystemic shunt (TIPS) with 72 hours after acute variceal bleeding is effective.

Критерии включения

• 1. diagnosis of primary HCC, confirmed histologically or clinically according to the criteria of the American Association for the Study of Liver Diseases;
• 2. presence of PVTT with III-IV grade by Cheng`s criteria;
• 3. having PVTT induced portal hypertension;
• 4. TIPS was performed within 72 hours after the endoscopic hemostasis;
• 5. metastases with limited five sites and no more two organs involved;
• 6. number of Intrahepatic tumors were no more than five;
• 7. receipt of Lenvatinib and PD-1 inhibitor as the first-line systemic therapy;
• 8. classified as Child-Pugh class A or B and having an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2;
• 9. no history of other malignancies;
• 10. agreed to participated in this clinical trial;
• 11. Hemameba ≥3.0 x109/L, neutrophil ≥1.5x109/L, hemoglobin≥10.0 g/L, platelet≥100x 109/L, ALT; AST; bilirubin ≤1.5-fold normal, GFR≥60ml/min.

Критерии исключения

• 1. recurrent HCC;
• 2. PVTT at I-II grade by Cheng`s criteria;
• 3. age /< 18 years or /> 75 years;
• 4. advanced HCC with more than five metastases;
• 5. Number of Intrahepatic tumors were more than five;
• 6. no response to Lenvatinib;
• 7. life expectancy less than 3 months.

Описание

A three-arm randomized controlled non-inferiority pilot study comparing anticoagulation strategies using unfractionated heparin, argatroban and enoxaparin for extracorporeal membrane oxygenation support conducted as an investigator-initiated, prospective, parallel group, open-label, active comparator controlled, single center, phase IV study to evaluate the non-inferiority of enoxaparin or argatroban for anticoagulation during ECMO therapy in comparison to the current standard, unfractionated heparin, as measured by the incidence of thromboembolic events during the duration of ECMO therapy

Критерии включения

• * either
• * require ECMO support or
• * have been started on ECMO therapy within the last 12 hours

Критерии исключения

• * Patients exhibiting contraindications to anticoagulation in general or any of the three investigated substances
• * Patients who are pregnant
• * Patients suffering from a clinically relevant pre-existing coagulopathy
• * Patients, for whom screening, randomization and implementation of study protocol cannot be initiated within 12 hours after cannulation
• * Patients receiving ongoing therapeutic systemic anticoagulation prior to ECMO implantation, or exhibiting an indication for therapeutic anticoagulation (e.g., pulmonary embolism)
• * Patients whose total duration of ECMO support lasts less than 24 hours
• * Patients with start of ECMO support during CPR (eCPR)
• * Patients with passive decarboxylation, without an active pumping system
• * Patients, who have been weaned off ECMO support within the last 30 days
• * Patients with central ECMO cannulation and/or after cardiopulmonary bypass

Описание

The JETi Hong Kong PMS is a single-arm, multicenter study to collect real-world data on the safety, performance, and clinical benefits of the JETi System for the treatment of acute and subacute thrombosis in the peripheral vasculature. This is a post-market study that will register approximately 20 subjects at approximately 5 centers in Hong Kong. Subjects participating in this study will be followed for up to 30 days (in cases of prospective consent) after Day 0. Day 0 is defined as the day when the JETi catheter is introduced into the intended vasculature of the subject.

Критерии включения

• 1. Subject was treated or is expected to be treated for acute/subacute thrombosis, as determined by investigator, in the peripheral vasculature with the JETi Hydrodynamic Thrombectomy System.
• 2. Subject or legally authorized representative must provide written informed consent
• 3. Subject must be ≥ 18 years of age and of Asian race.

Критерии исключения

• 1. Subject has previously been registered in the JETi Hong Kong PMS in the last 12 months unless treated in the contralateral limb/different anatomy; patients treated in the contralateral limb/different anatomy within the last 12 months may re-enroll in the study.
• 2. Subject is currently participating in another drug or device clinical investigation.
• 3. Subject has active symptoms and/or a positive test result of COVID-19 or other rapidly spreading infectious agent within the past 20 days.

Описание

We have developed a questionnaire to elucidate the dosing, frequency and indication for the use of emicizumab in patients with Hemophilia A (mild, moderate or severe) ages 0-3 years. We are also collecting data on any pre-, peri and post surgical practices while on emicizumab. More importantly, we are asking if pediatricians are planning to introduce factor 8 to children who are already on emicizumab for primary prophylaxis as well as how and when they are planning to do so. We hope that this data will help inform understanding of current use of emicizumab in infants and young children as a form of primary prophylaxis, especially when venous access has historically been a limiting factor.

Критерии включения

• Patients must meet the following criteria for study entry:
• * Patients who have been prescribed Emicizumab
• * Patients who are 0-36 months of age at the time of starting treatment with Emicizumab
• * Diagnosis of congenital mild, moderate or severe hemophilia with or without an inhibitor

Критерии исключения

• * Patients with acquired Hemophilia A
• * Patients with Hemophilia A and another congenital or acquired bleeding disorder.

Описание

The purpose of the aPCC-emicizumab safety study is to prospectively investigate the safety and hemostatic efficacy of a personalized dose of aPCC in children and adults with hemophilia A and inhibitors on emicizumab prophylaxis during acute bleeding events or prior to procedures.

Критерии включения

• * Moderately severe hemophilia A, defined as FVIII level /<0.02 IU/mL in the central laboratory prior to development of an inhibitor
• * Age ≥6 years of age at time of informed consent
• * Documented on 2 occasions a high titer inhibitor (/>5 BU/mL) with a 72-hour washout within 2 years of enrollment
• * Parent/guardian (caregiver henceforth) or patient has provided written informed consent
• * Adequate hematologic function (Hgb />8 g/dL and platelet count />100,000 µL)
• * Adequate hepatic function (total bilirubin ≤1.5 x ULN and both AST/ALT ≤3x ULN at screening (excluding known Gilbert`s)
• * Adequate renal function (≤2.5 x ULN and CrCl ≥30 mL/min)

Критерии исключения

• * Inherited or acquired bleeding disorder other than hemophilia A excluding low VWF (/>30% VWF:RCo or VWF:GP1bm)
• * Previous or current treatment for thromboembolic disease or signs of thromboembolic disease (excluding previous resolved line associated thrombosis)
• * Conditions that may increase risk of bleeding or thrombosis
• * History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• * Known HIV infection with CD4 count /<200 cells/µL within 24 weeks prior to screening. Testing not required if /<35 years of age.
• * Use of systemic immunomodulators at enrollment or planned use during the study
• * Participants who are at high risk for TMA (for example, have a previous medical/family history of TMA), in the investigator`s judgment
• * Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose additional risk, or would, in the opinion of the investigator, preclude the participant`s safe participation in and completion of the study
• * Every effort will be made to include participants that are considering minor and major procedures over the next 2 years to capture this important data with the goal of 10 procedures.