2023 · ECLINICALMEDICINE

Effect of weight-adjusted intermediate-dose versus fixed-dose prophylactic anticoagulation with low-molecular-weight heparin on venous thromboembolism among noncritically and critically ill patients with COVID-19: the COVI-DOSE trial, a multicenter, randomised, open-label, phase 4 trial

Zuily, Stephane, Lefevre, Benjamin, Sanchez, Olivier, de Vendin, Ombeline Empis, de Ciancio, Guillaume, Arlet, Jean-Benoit, Khider, Lina, Terriat, Beatrice, Greigert, Helene, Robert, Celine S., Louis, Guillaume, Trinh-Duc, Albert, Rispal, Patrick, Accassat, Sandrine, Thiery, Guillaume, Montani, David, Azarian, Reza, Meneveau, Nicolas, Soudet, Simon, Le Mao, Raphael, Maurier, Francois, Le Moing, Vincent, Quere, Isabelle, Yelnik, Cecile M., Lefebvre, Nicolas, Martinot, Martin, Delrue, Maxime, Benhamou, Ygal, Parent, Florence, Roy, Pierre-Marie, Presles, Emilie, Goehringer, Francois, Mismetti, Patrick, Bertoletti, Laurent, Rossignol, Patrick, Couturaud, Francis, Wahl, Denis, Thilly, Nathalie, Laporte, Silvy, COVI-DOSE Investigators

Journal: ECLINICALMEDICINE
Année: 2023
Volume: 60
Article: 102031
Mois: JUN
DOI: 10.1016/j.eclinm.2023.102031

Abstract

Background Venous thromboembolism is a major complication of coronavirus disease 2019 (COVID-19). We hypothesized that a weight-adjusted intermediate dose of anticoagulation may decrease the risk of venous thromboembolism COVID-19 patients.Methods In this multicenter, randomised, open-label, phase 4, superiority trial with blinded adjudication of outcomes, we randomly assigned adult patients hospitalised in 20 French centers and presenting with acute respiratory SARS-CoV-2. Eligible patients were randomly assigned (1:1 ratio) to receive an intermediate weight adjusted prophylactic dose or a fixed-dose of subcutaneous low-molecular-weight heparin during the hospital stay. The primary outcome corresponded to symptomatic deep-vein thrombosis (fatal) pulmonary embolism during hospitalization (COVI-DOSE ClinicalTrials.gov number: NCT04373707).Findings Between May 2020, and April 2021, 1000 patients underwent randomisation in medical wards (noncritically ill) (80.1%) and intensive care units (critically ill) (19.9%); 502 patients were assigned to receive a weight-adjusted intermediate dose, and 498 received fixed-dose thromboprophylaxis. Symptomatic venous thromboembolism occurred in 6 of 502 patients (1.2%) in the weight-adjusted dose group and in 10 of 498 patients (2.1%) in the fixed-dose group (subdistribution hazard ratio, 0.59; 95% CI, 0.22-1.63; P = 0.31). There was a twofold increased risk of major or clinically relevant nonmajor bleeding: 5.9% in the weight-adjusted dose group and 3.1% in the fixed-dose group (P = 0.034).Interpretation In the COVI-DOSE trial, the observed rate of thromboembolic events was lower than expected in patients hospitalized for COVID-19 infection, and the study was unable to show a significant difference in the risk of venous thromboembolism between the two low-molecular-weight-heparin regimens.Funding French Ministry of Health, CAPNET, Grand-Est Region, Grand-Nancy Metropole.Copyright & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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