Official Title
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
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.

Completed
COVID
Thrombosis
Pulmonary Embolism
Deep Vein Thrombosis

Drug: Enoxaparin

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
Other Name: Array

Drug: Enoxaparin

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%.
Other Name: Array

Eligibility Criteria

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

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
France
Locations

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

Emile Muller Hospital
Mulhouse, France

Nancy Academic Hospital
Nancy, France

George Pompidou European Hospital
Paris, France

Lariboisière Academic Hospital
Paris, France

St Etienne Academic Hospital
Saint-Étienne, France

Strasbourg Academic Hospital
Strasbourg, France

Toulouse Academic Hospital
Toulouse, France

Central Hospital, Nancy, France
NCT Number
Keywords
Covid
thrombosis
Venous Thromboembolism
Pulmonary Embolism
Deep Vein Thrombosis
Low Molecular Weight Heparin
MeSH Terms
Pulmonary Embolism
Thrombosis
Embolism
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Enoxaparin
Dalteparin
Tinzaparin
Heparin, Low-Molecular-Weight
Nadroparin
Enoxaparin sodium