Weight-Adjusted vs Fixed Low Doses of Low Molecular Weight Heparin For Venous Thromboembolism Prevention in COVID-19 (COVI-DOSE)

Central Hospital, Nancy, France

Status and phase

Completed

Phase 4

Conditions

Pulmonary Embolism

Thrombosis

COVID

Deep Vein Thrombosis

Treatments

Drug: Enoxaparin

Study type

Interventional

Funder types

Other

Identifiers

NCT04373707

2020-001709-21

Details and patient eligibility

About

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.

Enrollment

1,000 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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