COVID, Deep Vein Thrombosis, Pulmonary Embolism, Thrombosis
Conditions
Keywords
COVID, Thrombosis, Venous Thromboembolism, Pulmonary Embolism, Deep Vein Thrombosis, Low Molecular Weight Heparin
Brief summary
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.
Interventions
DRUGEnoxaparin
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
Sponsors
Ministry of Health, France
Grand Est Region
University Hospital of Saint-Etienne
Central Hospital, Nancy, France
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Multicenter randomized (1:1) controlled open-label trial, stratified on disease severity (admission to ICU or not)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Venous thromboembolism | hospitalization stay (up to 28 days) | Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding and Clinically Relevant Non-Major Bleeding | hospitalization stay (up to 28 days) | Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH |
| Net Clinical Benefit | hospitalization stay (up to 28 days) and 60 days | Risk of Venous Thromboembolism and Major Bleeding |
| Venous Thromboembolism at other sites | hospitalization stay (up to 28 days) | Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb |
| Major bleeding | hospitalization stay (up to 28 days) | Risk of major bleeding defined by the ISTH |
| All-Cause Mortality | hospitalization stay (up to 28 days) and 60 days | Risk of all-cause mortality |
| Factors associated with the risk of venous thromboembolism | hospitalization stay (up to 28 days) | 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 |
| Arterial Thrombosis | hospitalization stay (up to 28 days) | Risk of arterial thrombosis at any sites |
Countries
France
Outcome results
None listed