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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
1,000
For example (Enoxaparin): * 4000IU twice a day in patients \<50kg * 5000IU twice a day in patients 50-70kg * 6000IU twice a day in patients 70-100kg * 7000IU twice a day in patients above 100kg
For example (Enoxaparin): From 4000IU once a day in patients admitted in medical ward to 4000IU twice a day in patients admitted in the ICU. In patients with severe renal insufficiency (GFR=15-30 mL/min/1.73m²), LMWH doses will be reduced by 50%.
Amiens Academic Hospital
Amiens, France
Besançon Academic Hospital
Besançon, France
Brest Academic Hospital
Brest, France
Civil Hospital
Colmar, France
Dijon Academic Hospital
Dijon, France
Kremlin Bicêtre Academic Hospital
Le Kremlin-Bicêtre, France
Lille Academic Hospital
Lille, France
Groupe Hospitalier Unéos
Metz, France
Metz-Thionville Regional Hospital
Metz, France
Montpellier Academic Hospital
Montpellier, France
...and 7 more locations
Venous thromboembolism
Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death
Time frame: hospitalization stay (up to 28 days)
Major bleeding
Risk of major bleeding defined by the ISTH
Time frame: hospitalization stay (up to 28 days)
Major Bleeding and Clinically Relevant Non-Major Bleeding
Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH
Time frame: hospitalization stay (up to 28 days)
Net Clinical Benefit
Risk of Venous Thromboembolism and Major Bleeding
Time frame: hospitalization stay (up to 28 days) and 60 days
Venous Thromboembolism at other sites
Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb
Time frame: hospitalization stay (up to 28 days)
Arterial Thrombosis
Risk of arterial thrombosis at any sites
Time frame: hospitalization stay (up to 28 days)
All-Cause Mortality
Risk of all-cause mortality
Time frame: hospitalization stay (up to 28 days) and 60 days
Factors associated with the risk of venous thromboembolism
Identification of associations between the risk of venous thromboembolism and clinical (eg. past medical history of thrombosis, cardiovascular risk factors, treatments, severity of COVID-19) and laboratory variables (e.g. D-dimers, fibrinogen, CRP) collected in the eCRF
Time frame: hospitalization stay (up to 28 days)
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