Clincosm LogoSign in Get a demo

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

Sponsor
Central Hospital, Nancy, France (Other)
Overall Status
Completed
CT.gov ID
NCT04373707
Collaborator
Ministry of Health, France (Other), Grand Est Region (Other), University Hospital of Saint-Etienne (Other)
1,000
Enrollment
17
Locations
2
Arms
16.1
Actual Duration (Months)
58.8
Patients Per Site
3.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
1000 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Multicenter randomized (1:1) controlled open-label trial, stratified on disease severity (admission to ICU or not)Multicenter randomized (1:1) controlled open-label trial, stratified on disease severity (admission to ICU or not)
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Prevention
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
Actual Study Start Date :
May 13, 2020
Actual Primary Completion Date :
Apr 29, 2021
Actual Study Completion Date :
Sep 14, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Low Prophylactic Dose of Low Molecular Weight Heparin

Enoxaparin, Tinzaparin, Nadroparin, Dalteparin

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 Names:
  • Tinzaparin
  • Nadroparin
  • Dalteparin

    		•
    Experimental: Weight-Adjusted Prophylactic Dose Low Molecular Weight Heparin

    Enoxaparin, Tinzaparin, Nadroparin, Dalteparin

    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 Names:
  • Tinzaparin
  • Nadroparin
  • Dalteparin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Venous thromboembolism [28 days]

      Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death

    Secondary Outcome Measures

    1. Major bleeding [28 days]

      Risk of major bleeding defined by the ISTH

    2. Major Bleeding and Clinically Relevant Non-Major Bleeding [28 days]

      Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH

    3. Net Clinical Benefit [28 days and 2 months]

      Risk of Venous Thromboembolism and Major Bleeding

    4. Venous Thromboembolism at other sites [28 days]

      Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb

    5. Arterial Thrombosis [28 days]

      Risk of arterial thrombosis at any sites

    6. All-Cause Mortality [28 days and 2 months]

      Risk of all-cause mortality

    7. Factors associated with the risk of venous thromboembolism [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Amiens Academic Hospital Amiens France
    2 Besançon Academic Hospital Besançon France
    3 Brest Academic Hospital Brest France
    4 Civil Hospital Colmar France
    5 Dijon Academic Hospital Dijon France
    6 Kremlin Bicêtre Academic Hospital Le Kremlin-Bicêtre France
    7 Lille Academic Hospital Lille France
    8 Groupe Hospitalier Unéos Metz France
    9 Metz-Thionville Regional Hospital Metz France
    10 Montpellier Academic Hospital Montpellier France
    11 Emile Muller Hospital Mulhouse France
    12 Nancy Academic Hospital Nancy France
    13 George Pompidou European Hospital Paris France
    14 Lariboisière Academic Hospital Paris France
    15 St Etienne Academic Hospital Saint-Étienne France
    16 Strasbourg Academic Hospital Strasbourg France
    17 Toulouse Academic Hospital Toulouse France

    Sponsors and Collaborators

    • Central Hospital, Nancy, France
    • Ministry of Health, France
    • Grand Est Region
    • University Hospital of Saint-Etienne

    Investigators

    • Study Director: El Mehdi Siaghy, Research and Innovation Department, Nancy University Hospital
    • Principal Investigator: Stéphane Zuily, MD, PhD, Nancy Academic Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Stéphane Zuily, MD, PhD, Central Hospital, Nancy, France
    ClinicalTrials.gov Identifier:
    NCT04373707
    Other Study ID Numbers:
    • 2020-001709-21
    First Posted:
    May 4, 2020
    Last Update Posted:
    Dec 20, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Stéphane Zuily, MD, PhD, Central Hospital, Nancy, France
    COVID
    Thrombosis
    Venous Thromboembolism
    Pulmonary Embolism
    Deep Vein Thrombosis
    Low Molecular Weight Heparin
    Additional relevant MeSH terms:
    Pulmonary Embolism
    Thrombosis
    Embolism
    Thromboembolism
    Venous Thromboembolism
    Venous Thrombosis
    Enoxaparin
    Dalteparin
    Tinzaparin
    Heparin, Low-Molecular-Weight
    Nadroparin
    Enoxaparin sodium

    Study Results

    No Results Posted as of Dec 20, 2021