Coagulopathy of COVID-19: A Pragmatic Randomized Controlled Trial of Therapeutic Anticoagulation Versus Standard Care as a Rapid Response to the COVID-19 Pandemic (RAPID COVID COAG)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 465
- 试验地点
- 1
- 主要终点
- Composite Outcome of ICU Admission, Non-invasive Positive Pressure Ventilation, Invasive Mechanical Ventilation, or All-cause Death up to 28 Days.
研究概览
简要总结
Coagulopathy of COVID-19 afflicts approximately 20% of patients with severe COVID-19 and is associated with need for critical care and death. COVID-19 coagulopathy is characterized by elevated D-dimer, an indicator of fibrin formation and clot lysis, and a mildly prolonged prothrombin time, suggestive of coagulation consumption. To date, it seems that COVID-19 coagulopathy manifests with thromboembolism, thus anticoagulation may be of benefit. We propose to conduct a parallel pragmatic multi-centre open-label randomized controlled trial to determine the effect of therapeutic anticoagulation compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer.
详细描述
2-arm, parallel, pragmatic, multi-centre, open-label randomized controlled trial to determine the effect of therapeutic anticoagulation, with low molecular weight heparin or unfractionated heparin (high dose nomogram), compared to standard care in hospitalized patients with COVID-19 and an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Eligible participants will be randomized to one of two treatment regimens, receiving either therapeutic anticoagulation or standard care until discharged from hospital, death or day 28.
The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation, or all-cause death up to 28 days.
Key secondary outcomes between study arms up to day 28 include:
- All-cause death
- Composite outcome of ICU admission or all-cause death
- Composite outcome of mechanical ventilation or all-cause death
- Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation
- Number of participants who received red blood cell transfusion (≥1 unit)
- Number of participants with transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate
- Renal replacement therapy;
- Number of hospital-free days alive
- Number of ICU-free days alive
- Number of ventilator-free days alive
- Number of organ support-free days alive
- Number of participants with venous thromboembolism
- Number of participants with arterial thromboembolism
- Number of participants with heparin induced thrombocytopenia
- Changes in D-dimer up to day 3
The treatment arm is therapeutic anticoagulation with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram). The choice of LMWH versus UFH will be at the clinician's discretion. LMWH options include: Tinzaparin, Enoxaparin, or Dalteparin. UFH will be administered using a weight-based nomogram with titration according to the center-specific protocol. Therapeutic anticoagulation will be administered until discharged from hospital, 28 days or death. If the patient is admitted to the ICU or requiring ventilatory support, we recommend continuation of the allocated treatment as long as the treating physician is in agreement. The standard care arm is the administration of LMWH, UFH or fondaparinux at thromboprophylactic doses in the absence of contraindication.
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
盲法说明
Blinding of participants, clinical research staff, and clinicians is not possible due to the nature of the intervention. However, the biostatisticians will be blinded at the data analysis phase.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Therapeutic Anticoagulation
Therapeutic anticoagulation with LMWH or UFH (high dose nomogram). The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Therapeutic anticoagulation will be administered until discharged from hospital, 28 days or death. If the patient is admitted to the ICU or requiring ventilatory support, we recommend continuation of the allocated treatment as long as the treating physician is in agreement.
干预措施: Therapeutic Anticoagulation (Drug)
结局指标
主要结局
Composite Outcome of ICU Admission, Non-invasive Positive Pressure Ventilation, Invasive Mechanical Ventilation, or All-cause Death up to 28 Days.
时间窗: Up to 28 days
Composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation, or all-cause death up to 28 days.
次要结局
- All-cause Death(Up to 28 days)
- Composite Outcome of ICU Admission or All-cause Death(Up to 28 days)
- Composite Outcome of Mechanical Ventilation or All-cause Death(Up to 28 days)
- Major Bleeding(Up to 28 days)
- Red Blood Cell Transfusion(Up to 28 days)
- Transfusion of Platelets, Frozen Plasma, Prothrombin Complex Concentrate, Cryoprecipiate and/or Fibrinogen Concentrate(Up to 28 days)
- ICU-free Days Alive up to Day 28(Up to 28 days)
- Renal Replacement Therapy(Up to 28 days)
- Hospital-free Days Alive up to Day 28(Up to 28 days)
- Ventilator-free Days Alive up to Day 28(Up to 28 days)
- Organ Support-free Days Alive up to Day 28(Up to 28 days)
- Venous Thromboembolism(Up to 28 days)
- Arterial Thromboembolism(Up to 28 days)
- Heparin Induced Thrombocytopenia(Up to 28 days)
- Changes in D-dimer(Up to day 3)