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

• Status: Recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Central Hospital, Nancy, France
• Collaborators: Grand Est Region; Ministry of Health, France; University Hospital of Saint-Etienne
• Treatments: Dalteparin; Enoxaparin; Enoxaparin sodium; Heparin, Low-Molecular-Weight; Nadroparin; Tinzaparin

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