A Multicenter, Randomized-Controlled Trial to Evaluate the Efficacy and Safety of Antithrombotic Therapy for Prevention of Arterial and Venous Thrombotic Complications in Critically-Ill COVID-19 Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 390
- 试验地点
- 1
- 主要终点
- Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation
研究概览
简要总结
The researchers wanted to learn how to help sick patients who are in the hospital because of COVID-19. They are trying to find out the best way that is safe to stop blood clots that could be dangerous from forming in patients with COVID-19. This research study happened at 34 hospitals.
All patients in the study took medicines that help prevent blood clots. These medicines are called blood thinners or anticoagulants. Patients got different amounts of blood thinners to see what works better and is safer. Researchers randomly chose some patients to get more and some to get less.
The researchers also wanted to know if another medicine called clopidogrel can safely help stop blood clots from forming. This kind of medicine helps keep parts of the blood, called platelets, from sticking together. In some patients who did not have other reasons to take a platelet-blocker the researchers randomly chose the patient to take clopidogrel or not. This type of medicine is also called an antiplatelet.
详细描述
This is a multicenter, open-label, randomized-controlled trial in critically-ill patients with novel coronavirus disease 2019 (COVID-19) evaluating the efficacy and safety of full-dose vs. standard prophylactic dose anticoagulation and of antiplatelet vs. no antiplatelet therapy (in a nested second randomization) for prevention of venous and arterial thrombotic events. In a subcohort without an ongoing indication for antiplatelet therapy at screening, the second randomization is performed to either antiplatelet or no antiplatelet therapy
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years (male or female)
- •Acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)
- •Currently admitted to an intensive care unit (ICU)
排除标准
- •Ongoing (>48 hours) or planned full-dose (therapeutic) anticoagulation for any indication
- •Ongoing or planned treatment with dual antiplatelet therapy
- •Contraindication to antithrombotic therapy or high risk of bleeding due to conditions including, but not limited to, any of the following:
- •History of intracranial hemorrhage, known central nervous system (CNS) tumor or CNS vascular abnormality
- •Active or recent major bleeding within the past 30 days with untreated source
- •Platelet count <70,000 or known functional platelet disorder
- •Fibrinogen <200 mg/dL
- •International normalized ratio (INR) >1.9
- •History of heparin-induced thrombocytopenia
- •Ischemic stroke within the past 2 weeks
- •Patients who meet the following criterion are excluded from the second randomization (antiplatelet therapy vs. no antiplatelet therapy):
- •Ongoing or planned antiplatelet therapy, including aspirin monotherapy
研究组 & 干预措施
Full-dose anticoagulation (FDAC)
- Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the control as per institutional therapeutic target for treatment of venous thrombotic events (VTE)
- Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours
- With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days
干预措施: Unfractionated Heparin IV (Drug)
Full-dose anticoagulation (FDAC)
- Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the control as per institutional therapeutic target for treatment of venous thrombotic events (VTE)
- Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours
- With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days
干预措施: Enoxaparin 1 mg/kg (Drug)
Full-dose anticoagulation (FDAC)
- Unfractionated heparin (UFH) administered intravenously with a nomogram targeting an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the control as per institutional therapeutic target for treatment of venous thrombotic events (VTE)
- Enoxaparin 1 mg/kg administered subcutaneously (SC) every 12 hours
- With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days
干预措施: Clopidogrel (Drug)
Standard-dose prophylactic anticoagulation (SDPAC)
- Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if creatinine clearance CrCl <30 ml/min)
- Heparin 5,000 units administered subcutaneous three times daily
- With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days
干预措施: Clopidogrel (Drug)
Standard-dose prophylactic anticoagulation (SDPAC)
- Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if creatinine clearance CrCl <30 ml/min)
- Heparin 5,000 units administered subcutaneous three times daily
- With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days
干预措施: Unfractionated heparin SC (Drug)
Standard-dose prophylactic anticoagulation (SDPAC)
- Enoxaparin 40 mg administered subcutaneously (SC) once daily (reduce to 30 mg if creatinine clearance CrCl <30 ml/min)
- Heparin 5,000 units administered subcutaneous three times daily
- With or without anti-platelet therapy: Clopidogrel 300 mg administered once orally on the day of randomization, followed by 75 mg administered once daily on subsequent days
干预措施: Enoxaparin 40 mg SC (Drug)
结局指标
主要结局
Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation
时间窗: 28 days or until hospital discharge, whichever earlier
The efficacy of these interventions was analyzed using an unmatched win ratio. * The number of wins was found by comparing every patient in the FDAC (Full-dose anticoagulation) arm to every patient in the SDPAC (Standard dose prophylactic anticoagulation) arm to determine a 'win' and totaling up the number of wins in each arm. * A 'win' is a point in the favor of the arm it is given to. For each comparison of one patient in full dose arm compared to one patient in the standard dose arm, a 'win' is given to arm with the patient who had a component of the composite endpoint either lower in the hierarchy than the paired patient, or if the patient did not have any component of the composite while the paired patient did experience a component event of the composite. * Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia, or clinically silent DVT.
Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy
时间窗: 28 days or until hospital discharge, whichever earlier
The efficacy of these interventions was analyzed using an unmatched win ratio. * The number of wins was found by comparing every patient in the Anti-platelet group to every patient in the No Anti-platelet group arm to determine a 'win' and totaling up the number of wins in each arm. * A 'win' is a point in the favor of the arm it is given to. For each comparison of one patient in full dose arm compared to one patient in the standard dose arm, a 'win' is given to arm with the patient who had a component of the composite endpoint either lower in the hierarchy than the paired patient, or if the patient did not have any component of the composite while the paired patient did experience a component event of the composite. * Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia, or clinically silent DVT.
次要结局
- Clinically Evident Venous or Arterial Thrombotic Events: Anti-platelet Therapy Versus No Anti-platelet Therapy(28 days or until hospital discharge, whichever earlier)
- Clinically Evident Venous or Arterial Thrombotic Events: Full-dose Anticoagulation Versus Standard-dose Prophylactic Anticoagulation(28 days or until hospital discharge, whichever earlier)