Weight-Adjusted vs Fixed Low Doses of Low Molecular Weight Heparin For Venous Thromboembolism Prevention in COVID-19 (COVI-DOSE)
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|ClinicalTrials.gov Identifier: NCT04373707|
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : November 23, 2020
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||602 participants|
|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)|
|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 :||November 2021|
|Estimated Study Completion Date :||November 2021|
Active Comparator: Low Prophylactic Dose of Low Molecular Weight Heparin
Enoxaparin, Tinzaparin, Nadroparin, Dalteparin
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%.
Experimental: Weight-Adjusted Prophylactic Dose Low Molecular Weight Heparin
Enoxaparin, Tinzaparin, Nadroparin, Dalteparin
For example (Enoxaparin):
- Venous thromboembolism [ Time Frame: 28 days ]Risk of deep vein thrombosis or pulmonary embolism or venous thromboembolism-related death
- Major bleeding [ Time Frame: 28 days ]Risk of major bleeding defined by the ISTH
- 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
- Net Clinical Benefit [ Time Frame: 28 days and 2 months ]Risk of Venous Thromboembolism and Major Bleeding
- 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
- Arterial Thrombosis [ Time Frame: 28 days ]Risk of arterial thrombosis at any sites
- All-Cause Mortality [ Time Frame: 28 days and 2 months ]Risk of all-cause mortality
- 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
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
|Contact: Yohann Bernard, Res Proj Man||+18.104.22.168.52.72||y.bernard@chru-nancy.Fr|
|Contact: Saïda Khaled-Jousselin, Res Proj Man||+22.214.171.124.52.77||s.khaled-jousselin@chru-nancy.Fr|
|Study Director:||El Mehdi Siaghy||Research and Innovation Department, Nancy University Hospital|
|Principal Investigator:||Stéphane Zuily, MD, PhD||Nancy Academic Hospital|