Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04373707
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : May 14, 2020
Sponsor:
Collaborators:
Ministry of Health, France
Grand Est Region
University Hospital of Saint-Etienne
Information provided by (Responsible Party):
Central Hospital, Nancy, France

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
COVID Thrombosis Pulmonary Embolism Deep Vein Thrombosis Drug: Enoxaparin Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 602 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)
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
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Venous thromboembolism [ Time Frame: 28 days ]
    Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death


Secondary Outcome Measures :
  1. Major bleeding [ Time Frame: 28 days ]
    Risk of major bleeding defined by the ISTH

  2. Major Bleeding and Clinically Relevant Non-Major Bleeding [ Time Frame: 28 days ]
    Risk of Major Bleeding and Clinically Relevant Non-Major Bleeding Defined by the ISTH

  3. Net Clinical Benefit [ Time Frame: 28 days and 2 months ]
    Risk of Venous Thromboembolism and Major Bleeding

  4. Venous Thromboembolism at other sites [ Time Frame: 28 days ]
    Risk of venous thrombosis at other sites: e.g. superficial vein, catheters, hemodialysis access, ECMO, splanchnic, encephalic, upper limb

  5. Arterial Thrombosis [ Time Frame: 28 days ]
    Risk of arterial thrombosis at any sites

  6. All-Cause Mortality [ Time Frame: 28 days and 2 months ]
    Risk of all-cause mortality

  7. Factors associated with the risk of venous thromboembolism [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04373707


Contacts
Layout table for location contacts
Contact: Yohann Bernard, Res Proj Man +33.3.83.15.52.72 y.bernard@chru-nancy.Fr
Contact: Saïda Khaled-Jousselin, Res Proj Man +33.3.83.15.52.77 s.khaled-jousselin@chru-nancy.Fr

Locations
Layout table for location information
France
Amiens Academic Hospital Not yet recruiting
Amiens, France
Contact: Simon Soudet         
Besançon Academic Hospital Not yet recruiting
Besançon, France
Contact: Nicolas Meneveau         
Contact: Patricia Costa         
Brest Academic Hospital Not yet recruiting
Brest, France
Contact: Francis Couturaud         
Civil Hospital Not yet recruiting
Colmar, France
Contact: Wael Younès         
Dijon Academic Hospital Not yet recruiting
Dijon, France
Contact: Béatrice Terriat         
Marseille Academic Hospital Not yet recruiting
Marseille, France
Contact: Gabrielle Sarlon-Bartoli         
Metz-Thionville Regional Hospital Not yet recruiting
Metz, France
Contact: Julien Bertrand         
Montpellier Academic Hospital Not yet recruiting
Montpellier, France
Contact: Isabelle Quéré         
Emile Muller Hospital Not yet recruiting
Mulhouse, France
Contact: Amer Hamadé         
Nancy Academic Hospital Recruiting
Nancy, France
Contact: Stéphane Zuily         
George Pompidou European Hospital Not yet recruiting
Paris, France
Contact: Olivier Sanchez         
St Etienne Academic Hospital Not yet recruiting
Saint-Étienne, France
Contact: Patrick Mismetti         
Strasbourg Academic Hospital Not yet recruiting
Strasbourg, France
Contact: Dominique Stephan         
Toulouse Academic Hospital Not yet recruiting
Toulouse, France
Contact: Alessandra Bura-Rivière         
Sponsors and Collaborators
Central Hospital, Nancy, France
Ministry of Health, France
Grand Est Region
University Hospital of Saint-Etienne
Investigators
Layout table for investigator information
Study Director: El Mehdi Siaghy Research and Innovation Department, Nancy University Hospital
Principal Investigator: Stéphane Zuily, MD, PhD Nancy Academic Hospital
Layout table for additonal information
Responsible Party: Central Hospital, Nancy, France
ClinicalTrials.gov Identifier: NCT04373707    
Other Study ID Numbers: 2020-001709-21
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: May 14, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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 Central Hospital, Nancy, France:
COVID
Thrombosis
Venous Thromboembolism
Pulmonary Embolism
Deep Vein Thrombosis
Low Molecular Weight Heparin
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Embolism
Thrombosis
Thromboembolism
Embolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Enoxaparin
Dalteparin
Tinzaparin
Heparin, Low-Molecular-Weight
Nadroparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action