Weight-Adjusted vs Fixed Low Doses of Low Molecular Weight Heparin For Venous Thromboembolism Prevention in COVID-19
- Conditions
- COVIDPulmonary EmbolismThrombosisDeep Vein Thrombosis
- Interventions
- Registration Number
- NCT04373707
- Lead Sponsor
- Central Hospital, Nancy, France
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1000
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low Prophylactic Dose of Low Molecular Weight Heparin Enoxaparin Enoxaparin, Tinzaparin, Nadroparin, Dalteparin Weight-Adjusted Prophylactic Dose Low Molecular Weight Heparin Enoxaparin Enoxaparin, Tinzaparin, Nadroparin, Dalteparin
- Primary Outcome Measures
Name Time Method Venous thromboembolism hospitalization stay (up to 28 days) Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death
- Secondary Outcome Measures
Name Time Method Arterial Thrombosis hospitalization stay (up to 28 days) Risk of arterial thrombosis at any sites
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
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
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
Major bleeding hospitalization stay (up to 28 days) Risk of 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
All-Cause Mortality hospitalization stay (up to 28 days) and 60 days Risk of all-cause mortality
Trial Locations
- Locations (17)
Nancy Academic Hospital
🇫🇷Nancy, France
Dijon Academic Hospital
🇫🇷Dijon, France
Besançon Academic Hospital
🇫🇷Besançon, France
Lariboisière Academic Hospital
🇫🇷Paris, France
Civil Hospital
🇫🇷Colmar, France
Brest Academic Hospital
🇫🇷Brest, France
Metz-Thionville Regional Hospital
🇫🇷Metz, France
Montpellier Academic Hospital
🇫🇷Montpellier, France
Strasbourg Academic Hospital
🇫🇷Strasbourg, France
Toulouse Academic Hospital
🇫🇷Toulouse, France
George Pompidou European Hospital
🇫🇷Paris, France
Lille Academic Hospital
🇫🇷Lille, France
Emile Muller Hospital
🇫🇷Mulhouse, France
Amiens Academic Hospital
🇫🇷Amiens, France
Kremlin Bicêtre Academic Hospital
🇫🇷Le Kremlin-Bicêtre, France
Groupe Hospitalier Unéos
🇫🇷Metz, France
St Etienne Academic Hospital
🇫🇷Saint-Étienne, France