OncoTrials - мониторинг клинических исследований

Описание

This is a physician-initiated, observational, monocentric, retrospective and prospective Study. The study is intended to assess the feasibility of mechanical thrombectomy of caval and iliofemoral veins according to normal clinical practice in adult patients with symptomatic acute or subacute ileofemoral or caval deep vein thrombosis objectively diagnosed with CT scan imaging.

Критерии включения

• All patients admitted in the Unit of Vascular Surgery with proximal DVT (inferior vena cava, and/or iliac vein, and/or common femoral vein, and/or deep femoral vein, and/or femoral vein), according to ESVS guidelines (2022).

Критерии исключения

• * Patient treated with thrombolysis drugs within 48 hours prior to the index procedure
• * Active bleeding, recent (/<3 months) gastrointestinal (GI) bleeding, active peptic ulcer, severe liver dysfunction, and bleeding diathesis
• * Impossibility or refusal to give informed consent

Описание

This study is conducted to evaluate the efficacy and safety of lenvatinib plus sintilimab, transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and hepatic artery infusion chemotherapy (HAIC) with FOLFOX regemen (LEN+SIN+DEB-TACE+HAIC) versus lenvatinib plus sintilimab and DEB-TACE (LEN+SIN+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; prothrombin time prolongation ≤4 seconds
• * life expectancy of at least 3 months

Критерии исключения

• * 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

Описание

The goal of this observational study is to learn the safety and efficacy of edoxaban and rivaroxaban in Chinese population with the age range from 18 to 80 years who take edoxaban or rivaroxaban to treat their cerebral venous thrombosis (CVT). The main question it aims to answer are:

* Do cerebral veins or venous sinuses recanalize during the treatment period of edoxaban and rivaroxaban?
* Do the bleeding events occur during the treatment period of edoxaban and rivaroxaban?

The main tasks participants will be asked to do:

* Participants will comply fully with the prescribed regimen and take the edoxaban or rivaroxaban as directed at the specified dosage.
* Participants will return to hospital for scheduled follow-up assessments at months 3, 6, 9, and 12 post-enrollment to undergo face-to-face visits with investigators.

Критерии включения

• 1. Patient aged from 18 to 80 years and no gender preference;
• 2. Diagnosis of CVT as confirmed on MRBTI/MRV or CT/CTV or DSA;
• 3. Acute or subacute CVT from onset to door within 4 weeks;
• 4. The treating clinician irrelevant to the study is of the opinion that the patient is appropriate for edoxaban or rivaroxaban;
• 5. Patient or legally authorized representative is able to give written informed consent.

Критерии исключения

• 1. Patient refuse to take edoxaban or rivaroxaban to treat CVT;
• 2. Pregnancy or breastfeeding women at the time of enrollment, or women who plan to get pregnant during study;
• 3. Patient is anticipated to require invasive procedure (e.g. thrombectomy, hemicraniectomy) prior to initiation of oral anticoagulation;
• 4. CVT secondary to central nervous system infection or severe head trauma;
• 5. It is in the proliferative stage of malignant tumors currently or within 6 months of diagnosis;
• 6. Bleeding diathesis or other contraindication to anticoagulation;
• 7. Any concurrent medical condition requiring mandatory antiplatelet or anticoagulant use;
• 8. Concomitant use of strong CYP3A4 or P-gp inhibitors;
• 9. Impaired renal function (CrCl/<30 mL/min using Cockcroft-Gault equation) or investigator anticipate the CrCl lower than 30 mL/min during study;
• 10. Impaired liver function (ALT or AST exceeds twice the normal upper limit) or diagnosed as acute hepatitis currently;
• 11. Patient is unable to swallow due to depressed level of consciousness or other reasons;
• 12. Patient has a severe or fatal comorbid illness with life expectancy less than 6 months;
• 13. Patient with severe hypertension (SBP≥180mmHg and/or DBP≥110mmHg);
• 14. Patient is known to be allergic to edoxaban or rivaroxaban.

Описание

The registry is to evaluate the safety and feasibility of catheter-directed aspiration for patients with high-risk and intermediate-high-risk pulmonary embolism using Acostream.

Критерии включения

• * 18≤Age≤85
• * Clinical symptoms and presentation consistent with pulmonary embolism (PE).
• * PE symptoms duration ≤ 14 days.
• * High risk PE patients with absolute contraindications to systemic thrombolysis or its failure (refractory circulatory collapse) not eligible for surgical embolectomy.
• * Intermediate-high risk PE patients with right ventricle dysfunction (right ventricle/ left ventricle />0.9) confirmed by computed tomography pulmonary angiography or transthoracic echocardiography.

Критерии исключения

• * Pregnancy.
• * Refusal to sign the informed consent form.
• * Presence of intracardiac thrombus.
• * Presence of chronic left heart failure with an ejection fraction lower than 30% Diagnosed thrombophilia.
• * History of severe or chronic pulmonary hypertension.
• * Serum creatinine level higher than 1.8 mg/dl.
• * Known serious and uncontrolled sensitivity to radiographic agents.

Описание

The goal of this prospective pragmatic randomized clinical trial is to determine if preoperative administration of tranexamic acid (TXA) reduces bleeding during and after major colorectal surgery. The primary questions are:

* Does TXA reduce bleeding during and after surgery (change in hemoglobin from before surgery to lowest value after surgery within 30 days)
* Does TXA reduce bleeding complications within 30 days of surgery (blood transfusion, return to the operating room or procedural intervention for bleeding, death due to bleeding)
* Does TXA increase the risk of thromboembolic complications within 30 days of surgery (cerebrovascular accident, myocardial infarction, deep venous thrombosis, pulmonary embolism)

Researchers will compare preoperative TXA to no TXA to answer the above questions.

Participants who receive TXA will receive 1 g TXA IV at the beginning and end of surgery in the operating room.

Критерии включения

• 1. Adults 18 years or older
• 2. Undergoing elective or non-elective inpatient abdominal and pelvic colorectal surgery

Критерии исключения

• 1. Creatinine clearance less than 30 mL/minute
• 2. Long-term dialysis
• 3. Known defective color vision (color blind)
• 4. Pregnancy
• 5. History of venous or arterial thromboembolism, or active thromboembolic disease
• 6. Disseminated intravascular coagulation (DIC) - clinically suspected and/or confirmed by platelet count on CBC, fibrinogen, INR and PTT.

Описание

This study is a single-arm, open-label, multicenter study evaluating the efficacy and safety of GS1191-0445 injection as a single dose in Chinese subjects with hemophilia A.

GS1191-0445 is an AAV8-based gene therapy vector designed to express B-domain deleted human factor VIII (FVIII) under the regulation of a human liver-specific promoter. Following a single intravenous administration, AAV8 targets hepatocytes and facilitates the specific expression and secretion of FVIII into the bloodstream.

Критерии включения

• 1. Understand the purpose and risks of the study and provide informed consent in accordance with national and local privacy laws:
• 2. Subject must be male, aged />18 years old at the time of signing informed consent, and ≤65 years old:
• 3. Participants with confirmed hemophilia A in their pre-admission history and based on clinical laboratory examination ;
• 4. Subjects had used FVII products for at least 150 exposure days (ED) before enrollment;
• 5. Subject has no prior history of FVIII inhibitors;
• 6. Subjects agree to use a reliable barrier contraceptive method from the date of signing the informed consent
• 7. Subject is willing and able to follow planned visits, treatment plans, and other study procedures.

Критерии исключения

• 1. The subject has any hemorrhagic disorder not related to hemophilia A,
• 2. Abnormal liver function test results of subjects during screening.
• 3. Abnormal laboratory examination of subjects during screening
• 4. The subject has acute or chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection; Or are receiving antiviral treatment for hepatitis B and C;
• 5. Active systemic immune disease.

Описание

The purpose of this study is to develop a unique structure and delivery of home-based exercise through multidisciplinary expertise of cardiovascular medicine specialists and cardiac physiologists using an Interactive Care Plan.

Критерии включения

• Acute intermediate-risk PE, defined as:
• * Intraluminal filling defect in segmental or larger vessels on computed tomography pulmonary angiography or high-probability ventilation/perfusion scan AND
• * Evidence of right ventricular enlargement by computed tomography (RV to LV ratio />1) or echocardiography; and/or right ventricular dysfunction by transthoracic echocardiography. These imaging characteristics must be in the setting of acute PE rather than explained by a prior chronic condition.
• Acute high-risk PE, defined as:
• * Intraluminal filling defect in segmental or larger vessels on computed tomography pulmonary angiography or high-probability ventilation/perfusion scan AND
• * Evidence of right ventricular enlargement by computed tomography (RV to LV ratio />1) or echocardiography; and/or right ventricular dysfunction by transthoracic echocardiography. These imaging characteristics must be in the setting of acute PE rather than explained by a prior chronic condition; AND
• * Hypotension (systolic blood pressure /< 90 mm Hg sustained for more than 15 minutes; or requiring vasopressors) or cardiogenic shock due to acute pulmonary embolism.

Критерии исключения

• * Inability to ambulate independently, which is necessary to perform 6MWD (may be self-reported or as deemed by physical therapy during inpatient evaluation).
• * If patient requires supplemental oxygen during ambulation, this does not exclude patient from participation and will be noted during eCRF.
• * Prior history of pulmonary embolism
• * History of CTEPH or pulmonary arterial hypertension
• * Unable to read a questionnaire in English
• * Unable to return for baseline, 3- or 6-month follow-up visit
• * Pregnancy-associated pulmonary embolism
• * Life expectancy /<1 year based on comorbidities
• * Unable/unwilling to provide informed written consent

Описание

Peripheral intravenous catheters (PIVCs; commonly known as "cannulas") are very small tubes made out of rubber-like materials which are inserted into patients` arms using a needle to allow easy access to veins. They are the most commonly-used medical devices in the world, with almost 10 million placed each year in Australia alone. Approximately 40% (almost 4 million) of these devices stop working (i.e. fail) prior to completion of therapy.

The main goal of this study is to learn if softer, more flexible PIVC tip materials reduce the angle of the catheter tip on the vein surface compared to less flexible materials. Reducing the angle of the tip is believed to reduce rubbing on the inner vein surface and causing irritation, extending the life of the catheter. Other goals of this study are to learn if softer materials affect: volume of oedema (i.e. fluid leakage around the vein); time until catheter failure; clot volume in the vein; changes in vein size in response to catheter insertion; adverse event rates (i.e. changes in rates of specific, reportable symptoms); and determining if certain catheters are better for some people than others. This study is recruiting participants of all genders aged 18 - 75 years old who:

* Are not pregnant
* Have a Body Mass Index (BMI) between 18.5 - 35 kg/m2
* Have a current Australian Medicare card
* Do not have a history of chronic/infectious disease or clotting disorders
* Do not have a history of recreational drug use or alcohol abuse within the past 2 years

Participants will:

* Spend two hours in the clinic for screening blood collection, medical questionnaire and ultrasound imaging of veins
* Have one more flexible catheter and one less flexible catheter placed in opposite arms (i.e. participants will have a total of two catheters placed) which will remain in place either (i) until they fail or (ii) for 72 hours, whichever is earlier
* Spend eight hours per day in the clinic on the day the catheters are placed and the two days following for observation and ultrasound imaging
* Spend four hours in the clinic on the third day following placement of the catheters for observation, ultrasound imaging and catheter removal
* Spend one hour in the clinic 24-96 hours after catheter removal for a follow-up assessment and questionnaire

Критерии включения

• * Adult aged 18-75 years.
• * Not pregnant at time of recruitment and within 48 hrs of Day 1 procedures (self-reported)
• * Normal haematology results as per reference range determined by the laboratory.
• * Normal coagulation results as per reference range determined by the laboratory.
• * Target cephalic veins readily cannulatable (i.e., /> 2 mm)
• * Able and willing to provide verbal and written consent
• * Must be an Australian citizen with current Medicare card

Критерии исключения

• * History of pro coagulative state / condition (e.g., previous deep vein thrombosis)
• * Currently on any anti-coagulant or platelet inhibitor medication. Use of NSAIDs and aspirin will be documented however are not exclusionary.
• * Haemophilia or any current or history of bleeding disorder or tendency
• * Presence or report of current blood borne disease/infection (e.g., hepatitis, HIV, leukemia, lymphoma)
• * History of difficult vascular access
• * Allergy or sensitivity to chlorhexidine gluconate, isopropyl alcohol, latex, or skin adhesives
• * BMI /< 18.5 kg/m2 or ≥ 35 kg/m2
• * Positive results for the urine drug screen at screening or check-in (including opiates, methadone, cocaine, amphetamines)
• * History or presence of alcoholism (self-reported) or drug abuse within the past 2 years
• * A current or previous medical, physical, mental / cognitive disorder or anatomical conditions that, in the opinion of the chief or sub-investigator, would place the patient at risk, would make them unable to perform study procedures or has the potential to confound interpretation of the study results. (e.g., musculo-skeletal injury, chronic back pain)
• * Employed by Terumo, Becton Dickinson, Teleflex Medical, ICUMedical or BBraun (conflict of interest)

Описание

This study will assess the efficacy of multiple-dose of STSP-0601 for the treatment of bleeding episodes in hemophilia A or B patients with inhibitor

Критерии включения

• 1. 12 ≤age≤70 years of age.
• 2. Hemophilia A or B patients.
• 3. Peak historical inhibitor titer ≥ 5 BU and a positive inhibitor test when enrolled.
• 4. Establish proper venous access.
• 5. There were at least 3 bleeding events that required treatment occurred in the past 6 months before screening.
• 6. Agree to use adequate contraception to avoid pregnancy.
• 7. Provide signed informed consent.

Критерии исключения

• 1. Have any coagulation disorder other than hemophilia.
• 2. Plan to receive prophylactic treatment of coagulation factor during the trail.
• 3. Patients plan to receive Emicizumab during the trial.
• 4. Patients received anticoagulant or antifibrinolytic therapy 7 days before the first administration or plan to receive these drugs during the trial.
• 5. Have a history of arterial and/or venous thrombotic events.
• 6. Platelet /<100×109/L.
• 7. Hemoglobin/<90g/L.
• 8. Severe liver or kidney disease.
• 9. Severe bleeding event occurred within 4 weeks before the first administration.
• 10. Accepted major operation or blood transfusion within 4 weeks before the first administration.
• 11. Have a known allergy to STSP-0601.
• 12. Pregnant, lactating, or blood pregnancy test positive female subjects
• 13. Participate in other clinical research within 4 weeks before enrollment (except for participating in prothrombin complex, FVII, FVIIa, FVIII, FIX trails).
• 14. Within 1 day before the first administration, FVII, FVIIa, tranexamic acid, and aminocaproic acid were used. Within 3 days before the first administration, prothrombin complex, FVIII, and FIX were used. Within 4 weeks, treatment with Emicizumab was received.
• 15. Patients not suitable for the trail according to the judgment of the investigators.

Описание

This is a multinational, prospective, open-label, roll-over study in patients with severe haemophilia A, ≥6 years of age, who have completed participation in any of the parental studies with efanesoctocog alfa; XTEND-ed study (LTS16294), FREEDOM study (Sobi.BIVV001-001), or PK comparison study (Sobi.BIVV001-003). The aim of the study is to provide patients with continuous benefit from efanesoctocog alfa treatment and to further continue clinical monitoring for safety and efficacy until efanesoctocog alfa is commercially available in each patient`s respective country (or until March 2027, whichever comes first).

The study starts with the Baseline Visit, which will be done in connection to the End of Study visit (or equivalent) in the respective parent study. Subsequent study visits (on site or phone call) will be done approximately every 13 weeks until End of Treatment. An End of Study safety phone call will be done 14 (+7) days after the End of Treatment Visit.

Критерии включения

• * Capable of giving signed informed consent. Parents or legally designated representatives` consent is required for patients who are below 18 years of age or unable to give consent. Patients who are below 18 years of age may provide assent in addition to the parents`/legally designated representatives` consent, if appropriate.
• * Must have completed one of the required parent studies: Sobi.BIVV001-001, Sobi.BIVV001-003, or LTS16294, and be receiving a clinical benefit from the efanesoctocog alfa treatment, as judged by the Investigator.
• * Willingness and ability of patient or their parent or legally designated representative to complete training in the use of the study patient diary and to complete the diary throughout the study.

Критерии исключения

• * Positive inhibitor result (assessed by central laboratory), defined as ≥0.6 Bethesda units (BU)/mL, at Baseline Visit.
• * Ongoing or planned participation in any interventional clinical study at Baseline Visit.
• * 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.

Описание

Current management of intermediate- and high-risk pulmonary embolism is primarily based on curative subcutaneous or intravenous anticoagulation, with or without systemic fibrinolytic therapy or thrombectomy (8). Initial treatment with low-molecular-weight heparin (LMWH) or fondaparinux is preferred over unfractionated heparin (UFH) due to their lower risk of serious bleeding and heparin-induced thrombocytopenia (HIT) (9). UFH treatment is reserved for patients at risk of hemodynamic instability, renal failure with a GFR /< 30 ml/min, or obesity (8). Biological monitoring of anticoagulation efficacy can be performed by measuring the activated partial thromboplastin time (aPTT), as recommended by the European Society of Cardiology (ESC), or by measuring the antiXa activity of heparin, which has been shown to be beneficial in numerous studies (10,11,12). It is generally accepted that this anticoagulation should be initiated at a curative dose as early as possible (8), as this reduces in-hospital mortality and 30-day mortality (13). However, few studies have examined the impact of the time to achieve effective anticoagulation, and those that have done so have only done so in patients with high-risk pulmonary embolism (14) or have based their anticoagulation monitoring on aPTT and not on antiXa activity (13).

The proposed study aims to evaluate the time to obtain effective anticoagulation and its impact on mortality, thromboembolic recurrence and the occurrence of serious bleeding in patients with clinically significant pulmonary embolism, hospitalized in an intensive care unit as well as the factors that may influence this time. It will also allow to compare the practices of the studied center in terms of initial anticoagulation dose delivered, the initiation or not of a bolus and methods of monitoring anticoagulation with the literature in order to allow an improvement in patient care.

Критерии включения

• * Adult patient (≥18 years old)
• * Hospitalized in the intensive care unit of Hautepierre Hospital (Strasbourg University Hospitals UF 6250) between January 1, 2014, and December 31, 2023
• * With a diagnosis of pulmonary embolism confirmed by a thoracic CT angiogram, a thoracoabdominopelvic CT scan, or a lung scan
• * Having received anticoagulation with curative-dose unfractionated heparin

Критерии исключения

• * Subjects who have expressed objection to the reuse of their data for scientific research purposes. - Patients diagnosed with pulmonary embolism prior to admission to the intensive care unit and for whom we cannot precisely determine the start date of anticoagulation (precision estimated to the nearest hour).
• * Pulmonary embolism not confirmed by contrast imaging (CT angiography)
• * Patients who have not received curative anticoagulation (contraindication)
• * Patients already receiving curative anticoagulation with UFH at the time of diagnosis
• * Patients with low-risk pulmonary embolism defined by an sPESI score of 0
• * Subject under court protection, guardianship, or curatorship

Описание

The purpose of the study is to evaluate the efficacy and safety of SHR-2004 in preventing venous thromboembolism after elective unilateral total knee arthroplasty.

Критерии включения

• 1. Understand the research procedures and methods, volunteer to participate in this trial, and sign the informed consent form in writing;
• 2. Planned elective schedule total knee arthroplasty (TKA) patients;
• 3. Men or women who are ≥ 18 years old and /< 80 years old on the day of signing the informed consent form.

Критерии исключения

• 1. Unable to receive CT angiography of both lower limbs;
• 2. Malignant tumor within one year of the screening;
• 3. Myocardial infarction, transient ischemic attack or ischemic stroke occurred within 6 months of the screening;
• 4. Any medical history that may increase the risk of bleeding or any conditions that the investigator considers to increase the risk of bleeding;
• 5. History of drug abuse;
• 6. Pregnant or lactating women.

Описание

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is a frequent disease and the third most common cause of cardiovascular death in the world after myocardial infarction and stroke. Anticoagulant therapy drastically reduces the risk of early VTE recurrence and death, but it exposes patients to a substantial risk of bleeding. Hence, determining the optimal duration of anticoagulant treatment for VTE is a major public health issue.

When major transient risk factors for VTE are identified (major surgery, immobilization...), patients generally do not need to extend anticoagulation beyond 3 months, whereas for VTE diagnosed in the context of cancer, therapeutic anticoagulation is required for as long as the cancer is considered "active".

However, in more than 50% of cases, venous thromboembolic disease occurs spontaneously, i.e. without any significant clinically detectable circumstance (known as unprovoked venous thromboembolic disease). In such patients, the risk of recurrence is high (35% recurrence rate at 5 years, with a 10% risk of death per recurrence). Scientific societies therefore recommend continuing anticoagulant treatment "indefinitely" (i.e. without programming a stop date or long-term treatment). However, this practice exposes these patients to an ongoing, non-negligible increase in the risk of bleeding, which could ultimately exceed the risk of recurrence of venous thrombo-embolic disease.

Optimizing anticoagulant therapy beyond the first three to six months of treatment is therefore a crucial and challenging issue, which could improve the long-term prognosis of patients with unprovoked thromboembolic venous disease.

Based on the quantitative and qualitative approaches implemented in MORPHEUS project granted by European Commission (HORIZON-HLTH-2022-TOOL-11-01 call), the investigators have combined predictive personalized medicine, through the use of risk biomarkers, with a patient-centered model of medicine, which, while based on an understanding of the patient`s experience, leading to develop Time-Dependent Multicomponent risk prediction scores and socIo-anthropological scales (TDMI) integrated in a shared decision-making process regarding anticoagulant treatment duration in patients with a first episode of unprovoked VTE.

The aim of this study is to demonstrate that this strategy, based on a medical decision-making process shared between patients and physicians and including TDMI, reduces the risk of recurrence of thromboembolic venous disease (fatal or non-fatal), the risk of bleeding and all-cause mortality, and is associated with greater patient satisfaction after a first episode of unprovoked thromboembolic venous disease.

Критерии включения

• * Patient /> or = 18 years,
• * Patient with a first episode of symptomatic unprovoked pulmonary embolism (PE) and/or proximal deep vein thrombosis (DVT) treated for 3 to 6 uninterrupted months with full dose anticoagulant therapy,
• * Signed informed consent.

Критерии исключения

• * Unable or refusal to give informed consent,
• * Isolated distal DVT,
• * Isolated sub-segmental PE
• * Previous unprovoked VTE
• * Known CTEPH
• * Indication for anticoagulation other than DVT or PE (e.g.; atrial fibrillation, mechanic valves...),
• * Interruption of anticoagulation for 14 days or more before the inclusion,
• * Active cancer of less than 24 months,
• * Current pregnancy,
• * Life expectancy /<18 months (e.g.; patients with an end-stage chronic disease)
• * Not affiliated to national insurance, social security (only for France)

Описание

Background:

Long COVID, characterized by persistent symptoms following acute COVID-19 infection, has emerged as a significant public health concern. Symptoms range from fatigue, cognitive impairments, to respiratory difficulties, affecting patients/' quality of life. Dietary interventions, particularly fasting, have historically been used to modulate immune responses and improve health outcomes in various conditions. The Buchinger-Wilhelmi method represents a structured and medically supervised fasting approach. Given the inflammatory nature of long COVID, fasting may offer therapeutic benefits by modulating the immune response, enhancing cellular repair mechanisms, and resetting metabolic processes.

Objectives:

This clinical trial aims to assess the feasibility of a 7-day ambulatory fasting intervention using the Buchinger-Wilhelmi method on long COVID patients as primary objective. As secondary objectives, the study will investigate the potential beneficial impact of fasting on clinical, biological, and psychological parameters over a period of 4 weeks, offering insights into potential therapeutic avenues for long COVID management.

Study timeline:

The research will span a period of 4 weeks

Study population:

This study aims to recruit around 20 participants, who will all receive a fasting intervention using the Buchinger-Wilhelmi method.

Biological sample and data collection:

Participants will undergo various data and sample collection procedures, including blood draws of up to 90 42 ml per visit, collection of peripheral mononuclear cells, stool samples, and completion of questionnaires in a smartphone-based Application (MyCap).

Sample analysis:

The collected samples will be subjected to a range of analyses, including the assessment of serological markers for routine blood chemistry, evaluation of inflammation markers, and examination of stool samples.

Критерии включения

• * Age 18-64
• * Diagnosis Long Covid Syndrome (post-acute COVID-19 symptoms persisting ≥12 weeks)
• * Normal body Mass Index (18.5 to 25 kg/m2)
• * Marginal Iron status ( PF/< 25 ng/ml)
• * Able to communicate in and comprehend English and/or German and/or French language
• * Present written / signed declaration of consent
• * Ability to understand the patient information and willingness to sign the consent form
• * Consent to specimen collection and specimen use

Критерии исключения

• * Current underweight condition (body mass index less than 18.5 kg/m2) or weight loss exceeding 3 kg within the last month or 5 kg within the last three months.
• * Existing / current eating disorder within the past five years (e.g., anorexia, bulimia).
• * Psychiatric condition that limits understanding of the examination protocol (unable to consent)
• * Severe internal disease (e.g. kidney deficiency with creatinine /> 2mg/dl), chronic inflammatory illness other than LCS
• * Participation in another intervention study.
• * Existing vegan diet or fasting during the last six months
• * Pregnancy or breastfeeding status.
• * Presence or suspicion of pre-existing ME/CFS or early autonomous dysfunction
• * Diagnosis of chronic inflammatory bowel diseases, celiac disease or colorectal cancer according to the guidelines of the German Society of Gastroenterology
• * Use of anti-psychotic drugs
• * Antibiotic use during the previous 12 months
• * Start of novel drug therapy
• * Contraindication for additional blood draws (e.g. hemoglobin /<10)

Описание

The objective of this study is to prospectively develop a risk assessment model (RAM) that accurately identifies anticoagulated cancer-associated thrombosis (CAT) patients at low- and high-risk of recurrent venous thromboembolism (VTE) and clinically relevant bleeding within 6 months following the CAT diagnosis and to create a biobank of plasma and whole blood samples for further translational research in cancer genetics and hemostasis.

Критерии включения

• * Objectively documented distal and/or proximal DVT of the limb (upper or lower extremity) and/or PE, splanchnic vein thrombosis and/or cerebral sinus vein thrombosis in presence of active cancer of all types
• * Intended treatment of CAT for at least 6 months with parenteral or oral anticoagulants at therapeutic dosing.
• * Estimated life expectancy /> 6 months
• * Willingness to give an informed consent
• * Age ≥ 18 years

Критерии исключения

• * Unusual site CAT (gonadal vein thrombosis, ovarian vein thrombosis, retinal vein thrombosis)
• * Superficial vein thrombosis
• * Refusal of informed consent /> 72 hrs of anticoagulants
• * Age /< 18 years old

Описание

This study is being done to determine the feasibility and safety of using a novel dose adjusted apixaban for the management of participants with cancer-associated venous thromboembolism (blood clot) or and thrombocytopenia (low number of platelets in the blood). Investigators are also looking to see if participants on this treatment have fewer bleeding episodes.

The name of the study drug involved in this study is:

-Apixiban (a type of anticoagulant)

Критерии включения

• * Active malignancy defined as histologically confirmed diagnosis within last 6 months or received any cancer directed therapy within the last 6 months.
• * Radiologically confirmed newly diagnosed symptomatic deep vein thrombosis or pulmonary embolism within 28 days of enrollment. Includes proximal lower-limb DVT or symptomatic PE. Upper extremity or catheter-associated thrombosis will be included, as will distal lower extremity DVTs.
• * Platelet count /< 75,000/ml (prior to platelet transfusion) within 28 days of VTE diagnosis.
• * Platelet count responsive to transfusion if previously administered (defined as an average platelet increase of at least 10,000/ml over the last 3 transfusions.
• * No evidence of active hemorrhage.
• * No recent history of major hemorrhage (requiring transfusion, hospitalization or intervention) within the last 12 months.
• * No known brain metastases.
• * Age ≥18 years. Because no dosing or adverse event data are currently available on the use of apixaban in participants /<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• * ECOG performance status ≤2
• * Participants must have adequate organ and marrow function as defined below:
• * Total bilirubin ≤ institutional upper limit of normal (ULN)
• * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
• * Glomerular filtration rate (GFR) ≥25 mL/min/1.73/m2
• * Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• * The effects of apixaban on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of apixaban administration.
• * Ability to understand and the willingness to sign a written informed consent document.

Критерии исключения

• * Participants who are receiving any other investigational agents.
• * Participants who have had a thrombectomy, insertion of a caval filter, or require a fibrinolytic agent.
• * Participants that have index events with severe clot burden defined as bilateral proximal lower extremity deep vein thrombosis and saddle embolism or pulmonary embolism with hemodynamic compromise.
• * Participants with acute myeloid leukemia or myelodysplastic syndrome or who are undergoing or have undergone allogeneic stem cell transplant.
• * Participants with luminal gastrointestinal malignancy or genitourinary cancer.
• * Presence of known or prior brain metastasis, given the increased risk of life-threatening intracranial hemorrhage with anticoagulant use. While screening for brain metastases is not standard of care in this population, investigators may obtain brain imaging if clinically indicated prior to initiation of anticoagulation. Imaging is not mandated in order to participate in this study.
• * History of allergic reactions attributed to compounds of similar chemical or biologic composition to apixaban.
• * Participants receiving any medications or substances that are inhibitors or inducers of CYP3A/P-gp are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• * Participants on aspirin (/>100 mg/day), dual antiplatelet therapy, or receiving chronic treatment with NSAIDS
• * Participants with uncontrolled intercurrent illness.
• * Participants at high risk of bleeding such as:
• * Unresected luminal/mucosal GI and GU cancers
• * Active gastric or duodenal cancer
• * History of major bleeding (based on ISTH criteria) in the past 12 months
• * Any prior history of Intracranial hemorrhage (microhemorrhage is not included)
• * Clinical or laboratory concern for ongoing DIC (prolonged PT/APTT or low fibrinogen)
• * Severe renal disease (CKD Stage IV or higher) or liver disease (Child Pugh B/C)
• * Participants with pre-planned major surgery within the study period
• * Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• * Pregnant women are excluded from this study because apixaban has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with apixaban, breastfeeding should be discontinued if the mother is treated with apixaban.
• * Participant must be able to swallow pills.

Описание

This registry is a global prospective, non-randomized, multicenter, observational, active post-market data collection of Inari Medical devices and products.

Критерии включения

• 1. Willing and able to provide informed consent per institution and geographical requirements
• 2. Has received treatment with an eligible Inari Medical device. NOTE: If patients are consented prior to their procedure and the procedure does not take place, the patient will be considered a screen failure.
• 3. Currently within enrollment window relative to their procedure
• 4. Age ≥ 18 years

Критерии исключения

• 1. Is or will be inaccessible for registry follow-up
• 2. Meets exclusion criteria required by local requirements
• 3. Current or planned participation in another drug or device study that, in the investigator`s opinion, would interfere with participation in this registry
• 4. Is pregnant or breastfeeding at the time of enrollment

Описание

The availability of Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) has dramatically altered the management of heart failure (HF) patients, independently of their ejection fraction and glycemic status. A meta-analysis of 57 studies comparing SGLT2-I monotherapy vs. placebo or active comparator showed reductions in major cardiovascular events, but no impact on atherothrombotic events. In fact, a non-significant increase in the risk for non-fatal stroke was observed. Similar trend observed in multiple trials indicate a SGLT2-i class effect. Sotagliflozin is the first dual SGLT1/2 receptor inhibitor, that was shown to significantly reduce atherothrombotic events compared with placebo in diabetic HF patients, suggesting that dual SGLT1/2 inhibitor may have additional properties vs. SGLT2-i. The hypothesis of this study is that dual SGLT1/2 inhibition by sotagliflozin improves thrombogenic profile (i.e. reduces thrombus formation), which could make it a safer and more effective treatment option for cardiovascular (CV) patients than SGLT2-i. To test the hypothesis, the researchers will compare the antithrombotic activity of sotagliflozin vs. empagliflozin in healthy volunteers using a randomized, cross-over study design, where each participant will receive both study treatments (sotagliflozin and empagliflozin) separated by a washout period. Treatment effects will be assessed by measuring ex vivo thrombus formation using the Badimon Perfusion chamber, platelet aggregation using Multiplate Analyzer, and Thromboelastometry using RoTEM Gamma. Study assessments will be performed before initiating (baseline/pre-treatment) and after completion of each treatment.

Критерии включения

• Subjects are eligible if they meet all of the following criteria:
• * Male or female volunteers older than 18 years old.
• * Disease-free as assessed by medical history and physical examination.
• * Ability to provide signed informed consent.

Критерии исключения

• Subjects will be excluded if they meet any of the following criteria:
• * Pregnant or lactating women
• * History of clinically relevant cardiovascular, pulmonary, hepatic, gastrointestinal, renal, metabolic, hematologic, neurologic, respiratory or psychiatric disease, bleeding, acute infectious disease or signs of acute illness.
• * Use of medication within one month prior to study drug administration or within six times the elimination half-life (whichever is longer), except for oral contraceptives or occasional use of acetaminophen or an antihistamine.
• * History of drug abuse or alcohol consumption />20 g/day /[125 ml (30ml=1oz) glass of 10% wine = 12.5 g, 40 mL aperitif of 40% = 17 g, 250 mL glass of 6% beer = 15g/]
• * Loss of />400 mL blood or blood donation within 3 months.
• * Conditions associated with hemorrhagic risk, e.g., frequent epistaxis, gastrointestinal ulcer, hemorrhagic vascular lesions, recent surgery.

Описание

The mini-crush technique is one of the leading 2-stent techniques frequently applied by interventional cardiologists to treat complex bifurcation lesions. In the last 20 years, many technical innovations and iterations of mini-crush technique have been developed, and it maintains its popularity among invasive cardiologists. Moreover, mini-crush and double kissing-crush techniques have been compared in terms of clinical results in both left main and non-left main coronary bifurcation patient populations and no significant difference was found. However, the most important challenges of the mini-crush technique are the rewiring and advancement of a 1:1 non-compliant side-branch balloon after the main branch stent has been implanted. These challenges usually necessitate the use of a low profile balloon or additional support maneuvers (such as anchor balloon). Recently, a novel modified mini-crush-crush technique (controlled balloon-crush) has been introduced to the literature and is one of the most up-to-date crush techniques. The main advantage of this technique over the contemporary mini-crush technique is that the side branch can be easily rewired and the 1:1 size non-compliant balloon can easily pass through the crushed stent structure in the ostial part of the side branch. The basic rationale of this is that the crushing of the side branch stent is done in a more controlled manner (by slowly deflation of the side branch stent balloon) and this causes less disruption of the stent cells. This prospective observational study aims to assess the procedural and 1-year clinical outcomes of the contemporary mini-crush and controlled balloon-crush (modified mini-crush) double stenting techniques in patients with true coronary bifurcation lesions.

Критерии включения

• * Aged />18
• * PCI with mini-crush or controlled balloon-crush
• * Complex coronary bifurcation lesion (Medina 0.1.1 and Medina 1.1.1)

Критерии исключения

• * Non-complex bifurcation anatomy
• * Bail-out 2-stent (reverse mini-crush or reverse controlled balloon-crush)
• * ST-elevation myocardial infarction
• * Cardiogenic shock status
• * In-stent restenosis
• * A history of coronary artery bypass grafting
• * Implantation of bare-metal stent
• * End-stage hepatic or renal disease
• * /<1-year life expectancy

Описание

This study aims to assess physiotherapists` knowledge levels, awareness, perceived roles, adequacy of education received, learning preferences, and external barriers regarding exercise and physical activity in individuals with hemophilia. The findings will help identify physiotherapists` educational needs and contribute to the development of strategies to enhance their effectiveness in hemophilia management.

Критерии включения

• * Profession Group: Participants must be physiotherapists.

Критерии исключения

• * Non-Physiotherapists: Individuals who are not licensed physiotherapists will be excluded from the study.

Описание

The goal of this observational study is to learn about antithrombotic regimens in Multiple myeloma patients. The main question it aims to answer is the efficacy of different types of thromboprophylaxis (antiplatelet agents, heparins, oral anticoagulants) in preventing venous thromboembolism (VTE).

Критерии включения

• 1. Age equal to or greater than 18 years of age.
• 2. New diagnosis of symptomatic MM according to the CRAB or the SLIM criteria of the International Myeloma Working Group
• 3. First active treatment for MM started after recruitment in the study
• 4. Signed informed consent

Критерии исключения

• 1. Patients having had thrombosis within 6 months before diagnosis of MM
• 2. Patients with need of combined antithrombotic regimens (i.e. VKA or DOAC or LMWK and one or two antiplatelet drugs)
• 3. Ongoing first active treatment for MM initiated before the starting of the study.

Описание

We now have very sensitive blood tests that can pick up damage to the heart and find patients who have had a heart attack. However, whilst this is welcome, it does not identify what causes the heart attack and can sometimes pick up other conditions that cause a strain on the heart.

The classic cause of a heart attack is when a blood clot forms on fatty deposits within the heart arteries. This leads to treating patients with blood thinning medication, and this is very effective and saves lives. However, many apparent heart attacks are not caused by blood clots and some may be caused by blood clots but pass unrecognised.

In this proposal, we will test an exciting new imaging test that can `see` from outside the body whether there is a blood clot in the heart arteries. This could provide a major new way of assessing patients to ensure they get the right diagnosis and the right treatment. This could ultimately improve the outcomes of or patients with heart attacks.

We will recruit 80 patients in total who have recently been diagnosed with a heart attack from the cardiology department at the Royal Infirmary of Edinburgh. The research team will review patient`s medical records to determine eligibility for the study.

The research study involves participants undertaking the following research procedures and assessments:

1. A combined Positron Emission Tomography and Computed Tomography (PET-CT) scan of the heart
2. Ultrasound scan of the heart (Echocardiogram)
3. MRI scan of the heart
4. A blood test - a total of up to four tablespoons (60 mL) of blood will be taken for immediate testing and the remaining blood will be stored for future ethically approved studies
5. A follow up questionnaire 6 -12 months following the heart attack

Критерии включения

• * Males and females ≥ 18 years of age
• * Clinical presentation of chest pain, ST-segment deviation within a coronary artery territory on the electrocardiogram, raised cardiac troponin and non-obstructive coronary arteries on invasive coronary angiography as per international societal diagnostic criteria

Критерии исключения

• * /<18 years of age
• * Takatsubo cardiomyopathy
• * Myocarditis
• * Renal failure (estimated glomerular filtration rate /<30 mL/min/1.73 m2)
• * Woman of child-bearing potential who are pregnant or breastfeeding
• * Known allergy or contraindication to iodinated contrast or radiotracer
• * Patients unable to tolerate the supine position
• * Patients unable to provide informed consent

Описание

The Protrieve PROTECTOR Study is a prospective, single-arm, multicenter study of the Protrieve Sheath.

Критерии включения

• 1. Age ≥ 18 years
• 2. Planned intervention for DVT presenting with one or more of the following characteristics indicative of elevated risk for PE:
• 1. Bilateral iliofemoral DVT
• 2. Clot extending into or located in the IVC
• 3. In-stent thrombosis
• 4. Presence of thrombosed IVC filter
• 5. Other features that the investigator deems put the subject at elevated risk for thromboembolism
• 3. Willing and able to provide informed consent

Критерии исключения

• 1. Current symptomatic PE
• 2. Known anatomic inability to place Protrieve device via jugular vein access site
• 3. Presence of clot extending to the IVC-Right Atrial junction or in the SVC
• 4. Subject is pregnant
• 5. Severe allergy to iodinated contrast agents that cannot be mitigated
• 6. INR /> 1.7 if not currently on anticoagulation therapy, platelets /< 50,000/μl which cannot be corrected prior to enrollment, or Hemoglobin /< 8.0 g/dL
• 7. Severe renal impairment in patients who are not yet on dialysis that in the Investigator`s discretion would pose risk to the patient with the use of marketed contrast agents
• 8. Subject is participating in another study that may interfere with this study
• 9. Subject has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject
• 10. Subject has previously completed or withdrawn from this study
• 11. Limb-threatening circulatory compromise (e.g., phlegmasia)
• 12. Uncontrolled severe hypertension on repeated readings (systolic /> 180mmHg or diastolic /> 105mmHg)
• 13. Severe allergy, hypersensitivity to, or thrombocytopenia from heparin
• 14. Inability to provide therapeutic anticoagulation per Investigator discretion
• 15. Known hypercoagulable states that, in the opinion of the Investigator, cannot be medically managed throughout the study period
• 16. Inability to be a candidate for intervention due to medical or technical reasons based on physician judgement

Описание

Hemophilia A is a blood coagulation disorder caused by deficient or dysfunctional clotting factor VIII (FVIII) leading to incomplete haemostasis. Patients with severe Hemophilia A are predisposed to recurrent bleeding episodes (BEs) in joints and soft tissues that culminate in debiltating arthropathy and long-term morbidity. Prophylaxis with plasma-derived or recombinant FVIII concentrates effectively restores FVIII levels in patients with Hemophilia A, and significantly reduces the risk of bleeding. A critical concern for patients receiving FVIII replacement therapy is the development of neutralising antibodies (inhibitors) against the treatment. Inhibitors develop in up to 40% of patients with severe Hemophilia A when first exposed to FVIII treatment, typically within the first 20-30 exposure days (EDs) although a residual risk remains until after 75 EDs. Inhibitors preclude the use of FVIII replacement therapy for prevention and treatment of bleeding.

Eradication of inhibitors therefore remains an important objective for Hemophilia A patients with inhibitors. Immune tolerance induction (ITI) therapy is the only clinically proven strategy for inhibitor eradication, and at least one attempt should be offered to patients with inhibitors. However, while ITI is well-studied and has a 60- 80% success rate, treatment regimens can be expensive and burdensome to patients.

There are limited data on the use of different dose regimen of FVIII ITI in China. The INITIATE Study was designed to observe treatment strategies in patients with hemophilia A with inhibitors, with a focus on evaluating the safety and effectiveness of different dose regimens of ITI. The INITIATE Study includes multiple groups to explore factors that may affect ITI outcomes, and to explore the effects of different treatment methods on patient ITI biomarkers (genomics, transcriptomics, proteins (antibodies).

Критерии включения

• * Severe hemophilia A (FⅧ:C /<2%);
• * Positive for FVIII inhibitors;
• * No allergic reactions to FVIII concentrates.

Критерии исключения

• * Presence of other coagulation-related diseases,
• * Hematological disorders,
• * autoimmune diseases
• * malignancies

Описание

The investigators will use state-of-the-art imaging to look at heart disease in people with haemophilia. Haemophilia is an inherited disorder in which blood does not clot properly because of lack of a key `glue` blood component (chemicals known as factor VIII or IX). People with haemophilia are 40% less likely to die of heart disease, but it is not known exactly why this is. Understanding heart disease in people with haemophilia is important because better treatments for haemophilia mean that these patients are now living longer, but doctors still don`t know if the risk for heart disease in these patients as they age is the same as that for the general population. If these processes are better understand (perhaps less blood clotting is actually protecting the heart from blockage-causing clots), scientists might be able to reduce the risk of heart attacks for everybody.

The UK`s first photon-counting detector cardiac CT scanner generates detailed images of the heart and its blood vessels by counting individual X-ray photons. Together with artificial intelligence tools, it is possible to extract a lot of information from these images. As people age, fat is deposited in the vessels which supply blood to the heart which forms plaques. Plaques cause narrowing of the vessels, reducing blood flow to the heart, and can also burst (rupture), leading to a blood clot and heart attack. The new CT scan will show the type and amount of plaques, and quantify the risk of plaque rupture, in people with haemophilia; and the investigators will compare this to people without haemophilia.

Understanding the role of factor VIII/IX in heart attacks will improve management of heart disease in people with haemophilia, and may also lead to new prevention and treatment strategies that benefit heart health for everyone.

Критерии включения

• * Be willing and able to give informed consent for participation in the study.
• * Male, aged 45 years or above (no upper age limit).
• * Haemophilia A or B with Factor VIII/IX less than 40% (0.40 IU/ml).

Критерии исключения

• * Participants unable or unwilling to give informed consent.
• * Participants unable to understand the English language.
• * Participants unable or unwilling to attend for the necessary scans and investigations.
• * Patients with absolute contra-indications to CT imaging will be excluded from the study. This includes:
• * Any known contraindications to CT iodinated Contrast.
• * Significant renal impairment (eGFR /<30 ml/min).
• * Any other medical conditions which would influence the reliability of the study results determined by the investigators.

Описание

This is a first-in-human (FIH), Phase 1/2, open-label, dose escalation, safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and efficacy study of HMB-002 in participants with VWD. Part A of the study involves a single ascending dose (SAD) design to establish safety, tolerability, PK, and PD effect. In Part B of the study, the safety and tolerability of repeat dosing will be established prior to cohort expansion to explore efficacy.

Критерии включения

• 1. Has the ability to provide informed consent to participate in the study, in accordance with applicable regulations.
• 2. Has an understanding, ability, and willingness to comply with study procedures and restrictions.
• 3. ≥18 and /<65 years.
• 4. Weight 60 to 110 kg, inclusive.
• 5. Congenital Type 1 VWD diagnosis as documented by laboratory results for VWF antigen and activity.
• 6. Vital signs are within the following ranges at Screening:
• 1. Resting pulse rate ≤105 bpm
• 2. Blood pressure (BP):
• * Systolic blood pressure: 90 - 140 mmHg
• * Diastolic blood pressure: 40 - 90 mmHg
• 7. Participants assigned female at birth and of child-bearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of HMB-002.
• 8. Women of childbearing potential (CBP) and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study.
• 9. Participants must meet the following baseline organ function, indicated by laboratory criteria as Screening:
• 1. Renal: Estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73m/^2.
• 2. Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin ≤1.5 upper limit of normal (ULN) range at Screening. For participants with a history of Gilbert`s Syndrome, total bilirubin ≤2 × ULN.
• 3. Hematology: Hemoglobin />85 g/L and platelet count />120 x 10/^9/L.
• 10. PART B ONLY- Participants must be symptomatic as defined by a history of bleeding events. They must have participated in the observational study HMB-002-101_SCR and have recorded bleeding events within this observational study.

Критерии исключения

• 1. History of clinically significant hypersensitivity associated with monoclonal antibody therapies.
• 2. Personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial venous thrombosis.
• 3. High risk thrombophilia: Homozygous Factor V Leiden (FVL), compound heterozygous FVL/Prothrombin gene mutation, Antithrombin /<50%. Congenital Protein C and Protein S deficiency with levels /<50%.
• 4. Requires ongoing bleed prophylaxis with IV factor concentrates.
• 5. Has a positive test for Hepatitis B surface antigen (HbsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening with RNA level above the lower limit of detection.
• 6. Has received any live vaccine within 28 days prior to signing of informed consent and/or is planning to have a live vaccine during the study period.
• 7. Planned major surgery during the course of the study.
• 8. Body mass index (BMI) />35 kg/m/^2 (obese, adjusted for ethnicity).
• 9. Other conditions that substantially increase risk of thrombosis by the discretion of the Investigator.
• 10. Participants who are pregnant or breastfeeding.
• 11. Clinically significant cardiovascular disease.
• 12. Other conditions that substantially increase the risk of cardiovascular events by the discretion of the Investigator.
• 13. Congenital or acquired bleeding disorders other than Type 1 VWD.
• 14. Concurrent disease, treatment, medication, or abnormality in clinical laboratory tests may pose additional risk in the opinion of the investigator.
• 15. Hypersensitivity to study drug or any of the excipients.
• 16. Received investigational medication in another clinical study within 5 half-lives before administration of HMB-002.
• 17. PART A only: Type 1C VWD.

Описание

The purpose of the ERAsE-PE study is to determine whether two different healthy living strategies (along with anticoagulation) might aid in recovery after a patient is hospitalized for pulmonary embolism. Specifically, Investigators will compare changes in Cardiac Effort (#heart beats used during the 6-minute walk test/walk distance) measured after an 8-week program.

Критерии включения

• 1. English speaking (/>18 years old). Daily messages will be sent in English.
• 2. Acute PE with at least one of the following:
• 1. any right ventricular enlargement or dysfunction on echocardiogram;
• 2. CT Angiogram reporting any right ventricular enlargement; or
• 3. elevated cardiac biomarker (NT-pro BNP or troponin above baseline). Criteria for enrollment will be included on source document.
• 3. Rate controlled atrial arrythmias (resting heart rate /<110 beats/m) are eligible for enrollment. This includes atrial fibrillations. This is standard of care management for atrial fibrillation.
• 4. Subjects do need to take prescribed anticoagulation.

Критерии исключения

• 1. Pregnancy.
• 2. Cardiac Effort />3.5 beats/m during 6MWT.
• 3. Resting tachycardia />110 beats/m at hospital discharge.
• 4. Chronic Thromboembolic Pulmonary Hypertension
• 5. Systolic blood pressure />180 mmHg at hospital discharge.
• 6. Inability to walk.
• 7. Estimated prognosis /<12 months at the time of discharge due to underlying co-morbidities (e.g., cancer).
• 8. Advanced neurologic disease and would not be able to comply with the messages.
• 9. Lack of access to email or text messaging 10. Inability or unwillingness to follow daily instructions.

Описание

This trial seeks to evaluate a management strategy after the initial 3 months of standard therapeutic anticoagulation for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT).

Критерии включения

• 1. Adult patients (≥ 18 years old) with active cancer, defined as cancer (other than localized non-melanoma skin cancer) diagnosed or treated within 6 months, or the presence of metastatic, recurrent, or progressive malignancy, ongoing anticancer therapy, or hematological malignancy not in complete remission.
• 2. Objectively confirmed catheter-related upper extremity DVT and treated with any standard therapeutic anticoagulation for at least 3 months.
• 3. Able and willing to provide informed consent.

Критерии исключения

• 1. Active bleeding or other reasons for which anticoagulation is contraindicated.
• 2. Other indications requiring a therapeutic dose of anticoagulation beyond 3 months (such as atrial fibrillation, mechanical heart valve, etc.).
• 3. Not on therapeutic anticoagulation at the time of enrollment (patients whose anticoagulation has been stopped or dose reduced prior to enrollment for any reasons are excluded).
• 4. Known contraindication for apixaban, such as allergy, hypersensitivity, or pregnancy.
• 5. Concomitant use of strong inhibitors or inducers of both cytochrome P450 3A4 (enzyme) and P-glycoprotein.

Описание

Mechanical circulatory support (MCS) with the Impella microaxial pump in the setting of cardiogenic shock/cardiac arrest (CS/CA) is accompanied by substantial risk of life-threatening complications, including hemolysis, thrombotic and bleeding events.

Previous studies in patients on durable MCS suggest that device-induced platelet dysfunction plays a major contributory role in the development of such events and that selected markers of platelet function have the potential to stratify patients according to an elevated risk of adverse events. To date, the potential clinical utility of markers of altered platelet function in patients supported with an Impella pump is unexplored.

The proposed study will analyze changes in platelet function in the setting of Impella support (primary aim) and possibly identify a platelet function "profile" indicative of patients at high-risk to develop adverse events (secondary aim).

The study is a prospective observational study. Changes in the expression levels of markers of both platelet activation and aggregation in patients supported with an Impella pump will be measured. Data will be longitudinally measured: pre-implant (before Impella implantation) and then after 24, 48 and 72h of Impella support. Markers that will be analyzed include surface platelet receptors and platelet microRNAs. Experimental data will be correlated with clinical outcomes, including the occurrence of adverse events.

This study will provide mechanistic insights into the effect of Impella support on the protein and miRNA expression of platelets. The intention is to get a better understanding of distinct pathways of platelet function related to Impella support and their relationship to adverse events. Our data might open the perspective for the future clinical use of markers of platelet function to enhance the early recognition of patients at high risk of developing an adverse event and the definition of novel, personalized therapeutic strategies targeted to platelet biology to prevent their occurrence.

Критерии включения

• * Patients />18yrs-old and /<75yrs-old
• * Cardiogenic shock SCAI class C-D-E
• * primary tMCS with an Impella device (all Impella pumps)
• * Informed consent

Критерии исключения

• * Patients /<18yrs-old or />75yrs-old
• * Refusal to participate to the study

Описание

The goal of this clinical trial is to compare the use of a machine learning-based algorithm and point-of-care D-dimer to laboratory D-dimer and compression ultrasound to exclude deep vein thrombosis in the under extremities in patients referred to a medical department suspected of having deep vein thrombosis. The main aim is to answer are if a machine learning algorithm and point of care D-dimer can exclude deep vein thrombosis in more patients than clinical assessment and D-dimer alone.

Критерии включения

• * Patients referred to the ED due to suspicion of DVT
• * Age ≥ 18 years
• * Able to give informed consent

Критерии исключения

• * Ongoing use of anticoagulation for more than 72 hours
• * Previous participation in the study
• * Life expectancy of less than three months.

Описание

This study is a prospective, single-arm, non-randomized, interventional, multicenter feasibility 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

• 1. Patient is /> 18 and /< 90 years old
• 2. Clinical signs and symptoms consistent with acute PE
• 3. PE symptom duration ≤ 14 days
• 4. CTA evidence of proximal PE (filling defect in at least one main or lobar pulmonary artery as determined by the investigator)
• 5. CTA evidence of RV/LV ratio /> 0.9 note: based on Investigator`s interpretation of RV/LV ratio at baseline;
• 6. Systolic BP ≥ 90 mmHg note: initial SBP may be /< 90 mmHg but ≥ 80 mmHg if the pressure recovers with volume resuscitation
• 7. Stable heart rate (HR) /< 130 BPM prior to procedure
• 8. Patient is deemed medically eligible for interventional procedure(s), per investigator guidelines and clinical judgment.
• 9. Subject or legally authorized representative (LAR) is willing and able to provide written informed consent prior to receiving any non-standard of care protocol specific procedures

Критерии исключения

• 1. Prior PE /< 180 days from index procedure
• 2. Thrombolytic use /< 48 hours prior to baseline CTA
• 3. Pulmonary hypertension with peak pulmonary artery systolic pressure (PASP) />70 mmHg by right heart catheterization
• 4. Vasopressor requirement after fluids to keep pressure at ≥90 mmHg
• 5. FiO2 requirement />40% or />6 LPM to keep oxygen saturation />90%
• 6. Hematocrit /<28% (Note: hematocrit required within 6 hrs. of index procedure)
• 7. Platelets count /<100,000/µL
• 8. eGFR /<30 ml/min per 1.73 m2
• 9. International normalized ratio (INR) />3
• 10. Major trauma injury severity score (ISS) /> 15
• 11. Presence of intracardiac lead in right ventricle or atrium placed within 6 months prior to screening assessment
• 12. Cardiovascular or pulmonary surgery within 7 days of index procedure
• 13. Actively progressing cancer treated by chemotherapeutics
• 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. History of underlying lung disease that is oxygen dependent
• 20. History of chest irradiation
• 21. History of heparin-induced thrombocytopenia (HIT)
• 22. Contraindication to systemic or therapeutic doses of anticoagulants
• 23. Known anaphylactic reaction to radiographic contrast agents that cannot be pretreated
• 24. Known residual iliac deep vein thrombosis (DVT), inferior vena cava (IVC) clot or clot in transit (right atrium and/or right ventricle).
• 25. CTA imaging or other evidence that suggest, in the opinion of the investigator, the Subject is not appropriate for aspiration thrombectomy intervention (e.g., inability to navigate to target location, predominantly chronic clot or non-clot embolus)
• 26. Life expectancy /<90 days, as determined by investigator
• 27. Female who is pregnant or nursing
• 28. Current participation in another investigational drug or device treatment study Note: observational or registry studies may be permitted with Sponsor approval

Описание

The aim of the study is to demonstrate non-inferiority of ANB-002 compared with preventive use of coagulation factor IX (FIX) in adult subjects with hemophilia B with FIX activity ≤2% and without FIX inhibitor. The study will have an open-label single-arm design.

Критерии включения

• * Men diagnosed with hemophilia B aged 18 or older
• * FIX activity ≤2%
• * Absense of FIX inhibitor
• * ≥150 previous exposure days of treatment with FIX concentrates

Критерии исключения

• * Any diseases of blood and hematopoietic organs other than hemophilia B
• * A history of any gene therapy, including ANB-002
• * Diagnosed HIV-infection, not controlled with anti-viral therapy
• * Active HBV or HCV infection
• * Anti-AAV5 antibodies
• * Any active systemic infections or recurrent infections requiring systemic therapy
• * Any other disorders associated with severe immunodeficiency
• * Relevant hepatic disorders or conditions that can be a symptom of existing liver disorder
• * Malignancies with less than 5 years of remission

Описание

TORPEDO-NL will be an investigator-initiated, academically sponsored, multicentre, open-label, randomized controlled trial (RCT).

Patients with high-risk pulmonary embolism (PE) require immediate reperfusion therapy on top of anticoagulation. The standard reperfusion treatment in these patients is full-dose systemic thrombolysis. This carries a significant risk of major bleeding (10-25%) and intracranial haemorrhage (ICH, 3%). Catheter-directed thrombectomy (CDT) is a promising alternative to systemic thrombolysis with a more direct effect on reducing pulmonary artery clot burden and very likely a better safety profile. Randomized trials evaluating the safety and efficacy of CDT in high-risk patients are currently unavailable. The investigators hypothesize that in high-risk PE patients, CDT is superior to the current standard of systemic thrombolysis in terms of mortality and adverse events, i.e., is associated with a lower composite incidence of all-cause mortality, treatment failure, major bleeding and all-cause stroke. The investigators also hypothesize that CDT will lead to a shorter length of stay (LOS) at the intensive care unit (ICU) and in-hospital, faster recovery, and better long-term quality of life (QoL).

Objective: To determine whether CDT in high-risk PE relative to systemic thrombolysis is:

* more effective and safer in terms of a reduction of the composite endpoint on all-cause mortality and adverse events defined as treatment failure, major bleeding and all-cause stroke at day 30 (primary outcome)
* leads to a better Desirability of Outcome Ranking (DOOR) at day 7
* associated with a lower level of oxygen supplementation at 48 hours
* associated with shorter length of stay (LOS) at the intensive care unit (ICU) and in the hospital
* associated with better functional recovery as well as better patient-reported outcomes such as QoL at one year
* cost-effective after a time horizon of one year

Критерии включения

• 1. Adult patients with confirmed acute PE, i.e. contrast filling defect in a lobar or more proximal pulmonary artery on computed tomography pulmonary angiography (CTPA), and/or obstructive shock with echocardiographic confirmed dilatation of the right ventricle and a congested vena cava inferior, both with/without echocardiographic signs of clot in transit or deep vein thrombosis of the leg.
• 2. High risk for mortality, i.e.
• 1. post cardiac arrest (after temporary need for cardiopulmonary resuscitation), OR
• 2. obstructive shock (systolic blood pressure /<90 mmHg and signs of end-organ hypoperfusion (e.g. elevated lactate levels />2 mmol/l) or the need for vasopressors (adrenalin or noradrenalin) to maintain an adequate blood pressure), OR
• 3. persistent hypotension (systolic blood pressure /<90 mmHg or systolic blood pressure drop ≥40 mmHg for at least 15 minutes) not caused by new onset arrhythmia, hypovolemia, or sepsis, OR
• 4. abnormal RV function on transthoracic echocardiography or CTPA AND elevated cardiac troponin levels AND respiratory failure defined as hypoxemia (SaO2 /<90%) refractory to O2 supplementation by nasal cannula or Venturi mask, requiring full face mask O2 supplementation (100% FiO2), high-flow nasal O2, or (non-)invasive mechanical ventilation.
• 3. CDT available and technically feasible so as to allow for a randomization-to-needle time of 60 minutes or less.

Критерии исключения

• 1. "Catastrophic PE", i.e. ongoing cardiac arrest and/or need for extracorporeal cardiopulmonary resuscitation (ECPR) and/or immediate indication for venoarterial extracorporeal membrane oxygenation (VA-ECMO) as judged by the responsible physician(s)
• 2. Glascow Coma Scale /<8 following resuscitation for cardiac arrest
• 3. Alternative diagnosis than acute PE contributing largely to the acute hemodynamic and/or respiratory failure, e.g. sepsis, COPD GOLD 3 or 4, or known heart failure with NYHA Functional Classification of 4, as judged by the treating physician.
• 4. A known "do not admit to the ICU" or "do not resuscitate" directive
• 5. An absolute contraindication to systemic thrombolysis, i.e.
• * History of hemorrhagic stroke
• * Ischemic stroke in past 6 months
• * Central nervous system neoplasm
• * Major trauma, major surgery or major head injury in past 3 weeks (note: mild external laceration of the head after, e.g. syncope, does not count as major head injury, especially when a CT scan of the head shows no hematoma)
• * Active bleeding, life-threatening or into a critically organ/area; OR known severe bleeding diathesis with previous bleeding fulfilling these criteria
• 6. Reperfusion therapy (systemic thrombolysis, surgical thrombectomy or CDT/other catheter directed therapy), or placement of a non-retrieved inferior vena cava filter for acute pulmonary embolism in the past 3 months
• 7. Thrombus in transit through a patent foramen ovale.
• 8. Known chronic thromboembolic pulmonary hypertension (CTEPH), or strong suspicion of CTEPH based on pre-existing clinical findings and combinations of signs of PE chronicity on echocardiography and/or CTPA.
• 9. Known hypersensitivity to systemic thrombolysis, heparin, or to any of the excipients
• 10. If, in the Investigator`s opinion, or after consultation with the local PERT-team or EC-members, the patient is not appropriate for thrombectomy
• 11. Chronic use of full-dose oral or parenteral anticoagulation before presentation.
• 12. Pregnancy
• 13. Current participation in another study that would interfere with participation in this study
• 14. Previous enrolment in this study
• 15. Refusal of deferred consent by the next of kin or by the patient himself to use the data. Deferred consent will not be asked to relatives of patients who die in scene, but are included in the study.

Описание

Two groups of patients will be compared: One group of patients with a history of venous thromboembolic disease and one group without. Both groups will be subjected to a walking test and with electrocardiogram measurements and blood tests.

Критерии включения

• * Inclusion criteria common to both groups :
• * Patients who have given written informed consent.
• * Patients who are affiliated to or beneficiaries of a social security scheme.
• Inclusion criteria specific to the Patient Group:
• * Patients with a personal history of provoked venous thromboembolism, venous thrombosis and/or pulmonary embolism, with the last attack dating back to more than 6 months, and whose clinical phenotype did not justify long-term antithrombotic drug prophylaxis.
• Definition of provoked venous thromboembolism : The clinical criteria used to classify venous thromboembolism as provoked are :
• * First year of combined oestrogen-progestogen oral contraception, or contraception using an oestrogen-impregnated vaginal ring or transcutaneous synthetic oestrogen patch.
• * Hormonal stimulation for oocyte retrieval
• * Pregnancy and 6 weeks post-partum
• * Surgery
• * Trauma
• * Immobilisation in plaster or splint
• * Outbreak of acute infectious disease
• * Acute flare-up of inflammatory disease
• * Prolonged air travel lasting at least 4 hours
• * Prolonged strict bed rest lasting at least 3 consecutive days.
• Inclusion criteria specific to the Control Group:
• * Subjects with no personal history of venous thromboembolism
• * Subjects with no family history of venous thromboembolism in first-degree relatives
• * Subjects of the same sex and age with a tolerance of +/- 5 years in relation to the matched case.

Критерии исключения

• * Patients who are physically unable to perform the 60-minute walking test, for any reason, in particular cardiovascular contraindications to exercise (recent acute coronary syndrome unstable angina, rhythm disorders, tight aortic stenosis, cardiac heart failure, acute myocarditis, pericarditis or endocarditis endocarditis, poorly controlled hypertension, pre-stress blood pressure /> 200/110 mmHg, recent stroke or transient ischemic attack).
• * Patients on anticoagulant or antithrombotic treatment, ongoing or discontinued within the last month.
• * Patients treated for pulmonary embolism who remain dyspneic after anticoagulant treatment and requiring a work-up for pulmonary hypertension.
• * Last surgery dating back to less than 3 months.
• * Known chronic morbidities: diabetes mellitus, chronic inflammatory or infectious disease, heart failure, renal insufficiency, hepatic insufficiency or arterial thrombosis dating back to less than 3 months.
• * For women: treatment containing synthetic or natural estrogen, in progress or discontinued for less than a month
• * Pregnancy within the last year.
• * Difficult venous access.
• * Regular practice of an intensive sporting/physical activity, such as running, tennis, cycling etc. of more than 3 hours per week.

Описание

Introduction: Haemophilic ankle arthropathy manifests as functional (deficit in muscle strength, mobility and proprioception), intra-articular degenerative alterations and chronic pain. Manual therapy techniques are characterised by treating the soft tissues with the aim of modifying their density, relieving pain, reducing tissue sensitivity and improving the ranges of mobility. The objective is to evaluate the safety and effectiveness of a manual therapy protocol in patients with haemophilic ankle arthropathy.

Methods: Randomised crossover clinical trial. 13 patients with haemophilic ankle arthropathy from different regions of Spain will be recruited and randomised into two study groups (experimental and control). Each session of the experimental group will last 50 minutes, with 1 physiotherapy session per week for a period of 3 weeks. Patients will be evaluated at the beginning of the study, after the intervention and after a follow-up period of 4 weeks. The treatment programme includes 10 techniques that must be administered bilaterally. The study variables are the frequency of ankle haemarthrosis, range of movement, pressure pain threshold, pain intensity, joint status, biomechanical analysis of gait and balance, functionality and kinesiophobia.

Expected results: To evaluate the safety of manual therapy in patients with haemophilia. To observe changes in pain, mobility, joint condition, stability and functionality of the ankle, and kinesiophobia.

Критерии включения

• * Patients diagnosed with haemophilia A and B
• * With severe haemophilia phenotype (/<1% FVIII/FIX)
• * Over 18 years of age
• * With a medical diagnosis of ankle arthropathy and with clinical assessment using the Hemophilia Joint Health Score
• * On prophylactic or on-demand treatment with coagulation factor VIII/FIX concentrates

Критерии исключения

• * Patients with neurological or cognitive disorders that prevent them from understanding the questionnaires and physical tests
• * Failure to sign the informed consent document

Описание

The purpose of this study it to test the efficacy of a wearable device to improve symptom management and maximize qualify of life in systemic Sclerosis (SSc) patients in a randomized trial. Specifically, we will evaluate if the Apollo Neuro device may improve the two specific symptoms highest ranked by patients as affecting qualify of life (fatigue, Raynaud phenomenon) as co-primary outcomes.

Критерии включения

• 1. Age ≥ 18 years
• 2. Ability to provide written informed consent,
• 3. Diagnosis of SSc, as defined by the 2013 ACR/EULAR classification of SSc64 with a positive ANA
• 4. Baseline score ≥55 on the FACIT-Fatigue scale,
• 5. Presence of Raynaud phenomenon with ASRAP-SF severity of T-score ≥40,
• 6. Steady daily doses and any immunosuppressive medication, vasodilators or other medications used to treat pulmonary hypertension, antidepressants and anxiolytic use for 4 weeks prior to baseline
• 7. Currently owns and operates an iOS or Android smart phone regularly
• 8. Ability to comply with the clinical visits schedule and the study-related procedures.

Критерии исключения

• 1. History of sympathectomy or stellate ganglion block
• 2. History of Botox injections to the digits within the last 3 months
• 3. Diabetes mellitus
• 4. Major surgery within 8 weeks
• 5. Hospitalization for any reason within four weeks of the study baseline visit
• 6. Active malignancy
• 7. Pregnant or breastfeeding women,
• 8. End-stage renal disease (estimated glomerular filtration rate /< 15 mL/min/1.73m2) or on dialysis,
• 9. Hepatic insufficiency as defined by function worse than Child-Pugh Class B
• 10. Medication exclusions:
• 1. actively prescribed standing doses of beta-blockers,
• 2. actively prescribed standing doses of sedatives, hypnotics, opioids, benzodiazepines or anti-psychotic medications.

Описание

This is a Phase 4, multi-center, observational study conducted in patients aged 12 to 50 years with moderate or severe hemophilia A who are newly starting prophylaxis with efa in the US and Japan.

This study aims to enroll 35 patients.

Критерии включения

• * At enrollment, newly starting prophylaxis therapy with efanesoctocog alfa according to usual clinical practice, with efanesoctocog alfa initiated within 6 months after the enrollment visit
• * Diagnosis of moderate (endogenous FVIII activity between 1% to 5% of normal) or severe (endogenous FVIII activity /<1% of normal) hemophilia A
• * Aged 12 to 50 years at time of enrollment, inclusive
• * Access to a smartphone device (Android version 12.0 or higher; or iOS 13 or higher) with Bluetooth 4.0 (minimum) or 5.0 (recommended) capabilities for compatibility with physical activity tracker
• * Availability of home-based access to internet for electronic patient-reported outcome (ePRO)/diary assessments
• * Willingness to utilize the activity tracking device

Критерии исключения

• * Current diagnosis of a FVIII inhibitor, defined as inhibitor titer ≥ 0.60 BU/mL
• * Use of efanesoctocog alfa for prophylaxis in the 6 months prior to enrollment
• NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Описание

The study has descriptive purposes, with aim of assessing how turoctocog alfa is used in the everyday practice and to provide a baseline for the management of haemophilia A and does not involve any change in the clinical management of participants. Data will be extrapolated from the existing paper based medical records and uploaded to an electronic database specifically created for the study. Baseline information/history will be recorded at time of switching from previous FVIII replacement therapy to turoctocog alfa from the enrolled participants and outcomes will be collected according to participants visit format.

Критерии включения

• * Paediatric and adult male patients
• * On-demand and prophylactic patients with haemophilia A (any severity)
• * Only previously treated patients (previous FVIII replacement therapy) will be included in the study

Критерии исключения

• * Patients diagnosed with coagulation disorders other than haemophilia A such as Von Willebrand disease
• * Patients with documented presence of any FVIII inhibitor

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

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

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

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

The main aim of the study is to evaluate the effectiveness of prophylaxis with vonicog alfa (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 vonicog alfa (rVWF) for 12 months.

During the study, participants will visit the study clinic 5 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 international units per deciliter /[IU/dL/]) with a history of replacement 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, as 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 vonicog alfa (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 />=0.6 Bethesda units per milliliter (/mL).
• 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/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 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.
• 18. 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.
• 19. 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

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. 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 associated with 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 was previously enrolled in this study
• 16. Subject has received prior thrombolytic (systemic or catheter-directed) therapy for any reason 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

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

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

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

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

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

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

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

The purpose of the aPCC-emicizumab safety study is to investigate the hemostatic efficacy as measured by thrombin generation, of a low personalized dose of aPCC (FEIBA) in children and adults with hemophilia A and inhibitors on emicizumab prophylaxis.

Критерии включения

• * Moderately severe hemophilia A, defined as FVIII level /<0.05 IU/mL before 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 (Legally Authorized Representative) or the 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)
• * Had an active bleed requiring factor therapy at screening
• * Previous or current treatment for thromboembolic disease or signs of thromboembolic disease (excluding previously resolved line-associated thrombosis)
• * Had a surgical procedure 14 days before screening
• * Conditions that may increase the risk of bleeding or thrombosis
• * If the patient is treated with rFVIIa or aPCC seven days before screening
• * History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• * Had current use of any medication other than emicizumab that could affect the coagulation system.
• * Known HIV infection with CD4 count /<200 cells/µL within 24 weeks before screening. Testing is 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 an additional risk, or would, in the opinion of the investigator, preclude the participant`s safe participation in and completion of the study

Описание

The human immune system is designed to protect individuals from external sources of infection and internal cell mutation. It works effectively and efficiently until inflammation disturbs its functioning. Once compromised by inflammation, the immune system loses its capacity to recognize antigens and dependably defend the body against disease and illness.

When COVID-19 invades humans, it causes an immune-storm (cytokine-storm) that can directly damage the organ(s), leading to death. The virus is an antigen - a trigger - but it is not the actual reason that causes organ failure and death; instead, it is the body`s over immune reaction that is the cause. In attempting to protect the body, the immune system overreacts to the antigen, which includes the infected cells, which causes a cytokine-storm, and the subsequent and rapid shut down of the infected individual`s organ(s)` structure, leaving the body without sufficient strength or time to fight back. When the medical herbs join the body, it can slow down the immune reaction. Medical herbs benefit the physical body; they protect the cells and organism structure and mediate the immune response, allowing the T cells to kill the virus (mutated or not) internally. Such success has been achieved by the All Natural Medicine Clinic during pre-clinical trials.

This clinical study`s goal is to demonstrate that the immune system can be rebuilt and retrained, using natural medicine (i.e., medical herbs), to kill the virus without causing the immune storm, and to explore the mechanism by which these medical herbs, which have been used for thousands of years for healing, achieve results.

Критерии включения

• A subject will be eligible for inclusion in this study if any of the following criteria apply:
• * Individuals diagnosed with COVID-19 virus infection in the past 1-20 days must submit the proved metrics of COVID-19 virus marks positive during the registration;
• * The age of participants is between 10-70 years old;
• * The participants are received or not received conventional medication treatment, and continuing the treatment patients, could be enrolled in this clinical study;
• * This clinical study is not restricted to gender, age, sex, race, and nationality;
• * The participants must have reports of CBC, C3, C4, IgM, IgG, CD4/CD8, and lungs` images ready before the clinical study;
• * The Participants must repeat the evaluation experiment during and at the end of the clinical study.

Критерии исключения

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:
• * Individuals with a prior COVID-19 virus infection that no longer shows up from COVID-19 testing;
• * Children who are younger than 10-year-old, cannot control themselves to take the medical herbs on time;
• * Elders whose age beyond 70-year-old, with severe underline illness;
• * COVID-19 virus-infected patients who do not feel willing to take medical herbs;
• * Patients diagnosed with COVID-19 virus infection cannot consistently finish the treatment courses for a specific reason;
• * Patients diagnosed with COVID-19 virus infection but do not willing to share their information with the public;
• * Current or past participation within a specified timeframe in another clinical trial, as warranted by this intervention`s administration;
• * Severe patients, when there have insufficient normal cells, can be adjusted, with pre-list diseases life-threatening.