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

Pulmonary Embolism Clinical Trial

— COVI-DOSE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04373707
• Other study ID #: 2020-001709-21
• Status: Completed
• Phase: Phase 4
• Start date: May 13, 2020
• Est. completion date: September 14, 2021

Study information

• Verified date: August 2023
• Source: Central Hospital, Nancy, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: September 14, 2021
• Est. primary completion date: April 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID
• Deep Vein Thrombosis
• Embolism
• Pulmonary Embolism
• Thromboembolism
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis

Intervention

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
• 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%.

Locations

Country	Name	City	State
France	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

Sponsors (4)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France	Grand Est Region, Ministry of Health, France, University Hospital of Saint-Etienne

Country where clinical trial is conducted

France, 

References & Publications (1)

Zuily S, Lefevre B, Sanchez O, Empis de Vendin O, de Ciancio G, Arlet JB, Khider L, Terriat B, Greigert H, Robert CS, Louis G, Trinh-Duc A, Rispal P, Accassat S, Thiery G, Montani D, Azarian R, Meneveau N, Soudet S, Le Mao R, Maurier F, Le Moing V, Quere — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous thromboembolism	Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death	hospitalization stay (up to 28 days)
Secondary	Major bleeding	Risk of major bleeding defined by the ISTH	hospitalization stay (up to 28 days)
Secondary	Major Bleeding and Clinically Relevant Non-Major Bleeding	Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH	hospitalization stay (up to 28 days)
Secondary	Net Clinical Benefit	Risk of Venous Thromboembolism and Major Bleeding	hospitalization stay (up to 28 days) and 60 days
Secondary	Venous Thromboembolism at other sites	Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb	hospitalization stay (up to 28 days)
Secondary	Arterial Thrombosis	Risk of arterial thrombosis at any sites	hospitalization stay (up to 28 days)
Secondary	All-Cause Mortality	Risk of all-cause mortality	hospitalization stay (up to 28 days) and 60 days
Secondary	Factors associated with the risk of venous thromboembolism	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	hospitalization stay (up to 28 days)

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