Preventing COVID-19 Complications With Low- and High-dose Anticoagulation

Study Overview
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Brief Summary
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The ongoing COVID-19 pandemic affects millions of humans worldwide and has led to thousands of acute medical hospitalizations. There is evidence that hospitalized cases often suffer from an important infection-related coagulopathy and from elevated risks of thrombosis. Anticoagulants may have positive effects here, to reduce the burden of thrombotic disease and the hyperactivity of coagulation, and may also hold beneficial anti-inflammatory effects against sepsis and the development of ARDS. The investigators hypothesize that high-dose anticoagulants, compared with low-dose anticoagulants, lower the risk of venous and arterial thrombosis, disseminated intravascular coagulation (DIC) and mortality. This open-label controlled trial will randomize hospitalized adults with severe COVID-19 infection to therapeutic anticoagulation vs. thromboprophylaxis during the hospital stay.

Official Title
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Preventing COVID-19-associated Thrombosis, Coagulopathy and Mortality With Low- and High-dose Anticoagulation: a Multicentric Randomized, Open-label Clinical Trial

Conditions
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COVID, Sars-CoV2

Intervention / Treatment
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* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patient with COVID-19 infections, admitted to: an acute non-critical medical ward with admission D-dimer levels >1,000ng/mL, or an acute critical ward (ICU, intermediate care unit) Exclusion Criteria: ongoing or planned therapeutic anticoagulation for any other indication contra-indication to therapeutic anticoagulation hypersensitivity to heparin personal history of heparin-induced thrombocytopenia suspected or confirmed bacterial endocarditis bleeding events or tendency due to a suspected or confirmed hemostatic bleeding disorder organic lesion prone to bleeding platelet count <50G/L, Hb level <80g/L ongoing or recent (<30 days) major bleeding, ischemic stroke, trauma, surgery use of dual antiplatelet therapy pregnancy bodyweight <40kg or >150kg. end of life care setting unwillingness to consent ongoing participation in a COVID-19 randomized clinical trial testing another therapeutic intervention

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic anticoagulation<br>Participants will be treated with therapeutic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or intravenous unfractionated heparin, from admission until the end of hospital stay or clinical recovery. | Drug: Enoxaparin<br>* Two different doses of anticoagulation<br>* Other names: Unfractionated heparin;|
| Active Comparator: Prophylactic anticoagulation<br>Participants will be treated with prophylactic doses of subcutaneous low-molecular-weight heparin (enoxaparin) or unfractionated heparin, from admission until the end of hospital stay or clinical recovery. If hospitalized in the intensive care unit, they will receive an augmented thromboprophylaxis regimen as standard of care. | Drug: Enoxaparin<br>* Two different doses of anticoagulation<br>* Other names: Unfractionated heparin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality | Risk of arterial or venous thrombosis, disseminated intravascular coagulation and all-cause mortality | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial thrombosis | Risk of ischemic stroke, myocardial infarction and/or limb ischemia | 30 days | 
| Venous thromboembolism | Risk of symptomatic venous thromboembolism or asymptomatic proximal leg deep vein thrombosis | 30 days | 
| Disseminated intravascular coagulation | Risk of DIC | 30 days | 
| All-cause mortality | Risk of all-cause mortality | 30 days | 
| Sepsis-induced coagulopathy | Risk of SIC | 30 days | 
| Acute respiratory distress syndrome | Risk of ARDS | 30 days | 
| Durations of hospital stay, ICU stay, ventilation | Number of days with these care processes | 30 days | 
| Sequential organ failure assessment score | Highest score per participant | 30 days | 
| Clinical deterioration | Risk of clinical deterioration | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulation, heparin, thrombosis