InterMediate ProphylACtic Versus Therapeutic Dose Anticoagulation in Critically Ill Patients With COVID-19: A Prospective Randomized Study (The IMPACT Trial)
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- 30-day Mortality
研究概览
简要总结
The purpose of this study is to determine if therapeutic dose anticoagulation (experimental group) improves 30-day mortality in participants with COVID-19 compared to those patients receiving the intermediate dose prophylaxis (control group). Following screening, subjects will be randomized 1:1 to intermediate dose prophylaxis or therapeutic dose anticoagulation treatment arms.Treatment will continue for 28 days, followed by a 6 month follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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 old
- •COVID-19 positive on (RT-PCR) nasopharyngeal swab, or suspected COVID-19 infection with detectable SARS-CoV-2 IgG or IgM.
- •Intensive care unit (ICU) patient or non-ICU patient on invasive mechanical ventilation, BiPAP, 100% non-rebreather mask, or high flow oxygen or supplemental oxygen of at least 4 liters per minute nasal cannula.
- •D dimer level greater than 700 ng/mL (3 times the upper limit of normal).
排除标准
- •Objectively documented deep vein thrombosis or pulmonary embolism
- •Patients in whom there is very high suspicion for pulmonary embolism and are on full-dose anticoagulation as per the treating physician
- •Platelets <30,000 not due to disseminated intravascular coagulation (DIC), based on the International Society of Thrombosis and Haemostasis (ISTH) criteria and American Society of Hematology (ASH) Frequently Asked Questions
- •Active bleeding that poses a contraindication to therapeutic anticoagulation in the opinion of the investigator.
- •History of bleeding diathesis (e.g., hemophilia, severe von Willebrand disease, severe thrombocytopathy)
- •History of intracranial hemorrhage in the last 90 days
- •History of ischemic stroke in the past 2 weeks
- •Major neurosurgical procedure in the past 30 days
- •Cardiothoracic surgery in the past 30 days
- •Intra-abdominal surgery in the past 30 days
- •Intracranial malignancy
- •Patients who require therapeutic anticoagulation for other reasons like atrial fibrillation, deep venous thrombosis, pulmonary embolism, or antiphospholipid syndrome.
研究组 & 干预措施
Intermediate Dose Prophylaxis
Subjects will receive one of the following interventions, at their physician's discretion:
- Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min
- Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min
- If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours.
- Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously
干预措施: Enoxaparin sodium (Drug)
Intermediate Dose Prophylaxis
Subjects will receive one of the following interventions, at their physician's discretion:
- Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min
- Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min
- If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours.
- Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously
干预措施: Unfractionated heparin (Drug)
Intermediate Dose Prophylaxis
Subjects will receive one of the following interventions, at their physician's discretion:
- Enoxaparin 0.5 mg/kg subcutaneously every 12 hours if creatinine clearance greater than or equal to 30 ml/min
- Enoxaparin 0.5 mg/kg subcutaneously every 24 hours if creatinine clearance less than 30 mL/min
- If patient develops acute kidney injury: unfractionated heparin 7,500 units subcutaneously every 8 hours.
- Fondaparinux (if history of heparin-inducted thrombocytopenia [HIT]) 2.5 mg daily subcutaneously
干预措施: Fondapariniux (Drug)
Therapeutic Dose Anticoagulation
Subjects will receive one of the following interventions, at their physician's discretion:
-
Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol).
-
Enoxaparin 1 mg/kg subcutaneously every 12 hours
-
Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol.
-
Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight:
-
≥100 kg: 10 mg daily
-
<100 kg but ≥50 kg: 7.5 mg daily
-
<50 kg: 5 mg daily
干预措施: Enoxaparin sodium (Drug)
Therapeutic Dose Anticoagulation
Subjects will receive one of the following interventions, at their physician's discretion:
-
Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol).
-
Enoxaparin 1 mg/kg subcutaneously every 12 hours
-
Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol.
-
Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight:
-
≥100 kg: 10 mg daily
-
<100 kg but ≥50 kg: 7.5 mg daily
-
<50 kg: 5 mg daily
干预措施: Unfractionated heparin (Drug)
Therapeutic Dose Anticoagulation
Subjects will receive one of the following interventions, at their physician's discretion:
-
Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol).
-
Enoxaparin 1 mg/kg subcutaneously every 12 hours
-
Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol.
-
Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight:
-
≥100 kg: 10 mg daily
-
<100 kg but ≥50 kg: 7.5 mg daily
-
<50 kg: 5 mg daily
干预措施: Fondapariniux (Drug)
Therapeutic Dose Anticoagulation
Subjects will receive one of the following interventions, at their physician's discretion:
-
Unfractionated heparin (UFH) to target anti-Xa level 0.3 -0.7 IU/mL or activated partial thromboplastin time (aPTT) (according to institutional protocol).
-
Enoxaparin 1 mg/kg subcutaneously every 12 hours
-
Argatroban (if heparin-induced thrombocytopenia [HIT]), dosed according to institutional protocol.
-
Fondaparinux (if HIT and creatinine clearance greater than or equal to 50 ml/min) dosed by weight:
-
≥100 kg: 10 mg daily
-
<100 kg but ≥50 kg: 7.5 mg daily
-
<50 kg: 5 mg daily
干预措施: Argatroban (Drug)
结局指标
主要结局
30-day Mortality
时间窗: 30 days
Comparison of number of COVID-19 positive patients who have died within 30 days of starting treatment on each treatment arm
次要结局
- Number of Documented Venous Thromboembolism (VTE), Arterial Thrombosis (Stroke, Myocardial Infarction, Other) and Microthrombosis Events(6 months)
- Number of Major and Clinically Relevant Non-major Bleeding Events(6 months)
- Length of Intensive Care Unit (ICU) Stay in Days(6 months)