Effectiveness of Weight-adjusted Prophylactic Low Molecular Weight Heparin Doses Compared With Lower Fixed Prophylactic Doses to Prevent Venous Thromboembolism in COVID-2019. The Multicenter Randomized Controlled Open-label Trial COVI-DOSE
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,000
- 试验地点
- 17
- 主要终点
- Venous thromboembolism
研究概览
简要总结
Worldwide observational studies indicate a significant prothrombogenic effect associated with SARS-CoV-2 infection with a high incidence of venous thromboembolism (VTE), notably life-threatening pulmonary embolism.
According to recommendations for acute medical illnesses, all COVID-19 hospitalized patients should be given VTE prophylaxis such as a low molecular weight heparin (LMWH). A standard prophylactic dose (eg. Enoxaparin 4000IU once daily) could be insufficient in obese patients and VTE has been reported in patients treated with a standard prophylactic dose.
In COVID-19 patients, guidelines from several international societies confirm the existence of an hypercoagulability and the importance of thromboprophylaxis but the "optimal dose is unknown" and comparative studies are needed.
In view of these elements, carrying out a trial comparing various therapeutic strategies for the prevention of VTE in hospitalized patients with COVID-19 constitutes a health emergency.
Thus, we hypothesize that an increased prophylactic dose of weight-adjusted LMWH would be greater than a lower prophylactic dose of LMWH to reduce the risk of life-threatening VTE in hospitalized patients. The benefit-risk balance of this increase dose will be carefully evaluated because of bleeding complications favored by possible renal / hepatic dysfunctions, drug interactions or invasive procedures in COVID-19 patients.
This multicenter randomized (1:1) open-label controlled trial will randomize hospitalized adults with COVID-19 infection to weight-adjusted prophylactic dose vs. lower prophylactic dose of LMWH.
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
- Single (Outcomes Assessor)
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
- •Adult patient hospitalized for a probable/confirmed COVID-19 infection (confirmed by serology/polymerase chain reaction or by radiologic signs of COVID-19 pneumonia in the setting of clinical and laboratory abnormalities suggestive of a SARS-CoV-2 infection)
- •Signed informed consent
- •Patient affiliated to the Social Security
排除标准
- •Renal insufficiency with a GFR<15 mL/min/1.73m²
- •Acute kidney injury KDIGO3
- •Prophylactic dose of low molecular weight heparin for more than 3 days
- •Curative dose of low molecular weight heparin for more than 1 day
- •Recurrent catheter/hemodialysis access thromboses
- •ECMO required in the next 24h
- •Contraindication to low molecular weight heparin
- •High bleeding risk (e.g. uncontrolled severe systemic hypertension, recent major bleeding, disseminated intravascular coagulopathy, thrombocytopenia < 75G/L)
- •History of heparin-induced thrombocytopenia
- •Contraindication to blood-derived products
- •Impossibility to perform a doppler ultrasound of the lower limbs (e.g. above the knee amputation, severe burn injuries)
- •Expected death in the next 48h
- •Vulnerable subjects according to articles L. 1121-5, L. 1121-7 et L1121-8 of French Public Health Code
研究组 & 干预措施
Low Prophylactic Dose of Low Molecular Weight Heparin
Enoxaparin, Tinzaparin, Nadroparin, Dalteparin
干预措施: Enoxaparin (Drug)
Weight-Adjusted Prophylactic Dose Low Molecular Weight Heparin
Enoxaparin, Tinzaparin, Nadroparin, Dalteparin
干预措施: Enoxaparin (Drug)
结局指标
主要结局
Venous thromboembolism
时间窗: hospitalization stay (up to 28 days)
Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death
次要结局
- Major Bleeding and Clinically Relevant Non-Major Bleeding(hospitalization stay (up to 28 days))
- Venous Thromboembolism at other sites(hospitalization stay (up to 28 days))
- Arterial Thrombosis(hospitalization stay (up to 28 days))
- Factors associated with the risk of venous thromboembolism(hospitalization stay (up to 28 days))
- Major bleeding(hospitalization stay (up to 28 days))
- Net Clinical Benefit(hospitalization stay (up to 28 days) and 60 days)
- All-Cause Mortality(hospitalization stay (up to 28 days) and 60 days)
研究者
Stéphane Zuily
MD, PhD
Central Hospital, Nancy, France