Zuily S, Lefèvre 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, Quéré I, Yelnik CM, Lefebvre N, Martinot M, Delrue M, Benhamou Y, Parent F, Roy PM, Presles E, Goehringer F, Mismetti P, Bertoletti L, Rossignol P, Couturaud F, Wahl D, Thilly N, and Laporte S
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 Métropole., Competing Interests: Dr. Zuily reports grants from French Ministry of Health, grants from The Grand Est Regional Council, grants from The Grand Nancy Métropole, grants from The Comité ad hoc de pilotage national des essais thérapeutiques et autres recherches sur le COVID-19 (CAPNET, label Priorité Nationale de Recherche–National Research Priority), during the conduct of the study; personal fees from Leo Pharma, personal fees from Bristol Myers Squibb, personal fees from Pfizer, personal fees from Novartis, personal fees from GlaxoSmithKline, personal fees from Amgen, personal fees from Viatris, personal fees from Sanofi, grants from Boehringer Ingelheim, grants from Bayer, outside the submitted work; Dr. Lefevre reports grants from Gilead, grants from ViiV, outside the submitted work; Dr. Sanchez reports grants and personal fees from Bristol Myers Squibb, grants and personal fees from Pfizer, grants and personal fees from Bayer, grants and personal fees from MSD, grants and personal fees from Boehringer Ingelheim, personal fees from Inari, personal fees from Boston Scientific, personal fees from Sanofi, personal fees from Leo Pharma, personal fees from Chiesi, grants from Oxyvie, outside the submitted work; Dr. Empis De Vendin has nothing to disclose; Dr. De Ciancio has nothing to disclose; Dr. Arlet reports grants from Addmedical, grants and other from Novartis, outside the submitted work; Dr. Khider has nothing to disclose; Dr. Terriat has nothing to disclose; Dr. Greigert has nothing to disclose; Dr. Robert has nothing to disclose; Dr. Louis has nothing to disclose; Dr. Trinh-Duc has nothing to disclose; Dr. Rispal has nothing to disclose; Dr. Accassat reports other from Leo Pharma, other from Janssen, other from MSD, outside the submitted work; Dr. Thiery has nothing to disclose; Dr. Montani reports grants and personal fees from Acceleron, grants and personal fees from Janssen, grants and personal fees from Merck, personal fees from Bayer, outside the submitted work; Dr. Azarian has nothing to disclose; Dr. Meneveau reports grants, personal fees and other from Bayer, grants, personal fees and other from Bristol Myers Squibb, grants, personal fees and other from Pfizer, grants from Medtronic, grants and personal fees from Boston Scientific, grants, personal fees and other from Abbott, personal fees from Inari, personal fees from Terumo, outside the submitted work; Dr. Soudet reports grants and personal fees from Leo Pharma, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Pfizer, outside the submitted work; Dr. Le Mao has nothing to disclose; Dr. Maurier has nothing to disclose; Dr. Le Moing has nothing to disclose; Dr. Quéré reports other from Leo Pharma, outside the submitted work; Dr. Yelnik has nothing to disclose; Dr. Lefebvre reports personal fees and other from Pfizer, other from Eumedica, outside the submitted work; Dr. Martinot reports other from Menarini, other from Overcome, outside the submitted work; Dr. Delrue has nothing to disclose; Dr. Benhamou has nothing to disclose; Dr. Parent reports grants from Oxyvie, personal fees from MSD, outside the submitted work; Dr. Roy reports personal fees and other from Bayer, personal fees and other from Boehringer Ingelheim, personal fees and other from Bristol Myers Squibb, personal fees and other from Pfizer, personal fees and other from Aspen, personal fees and other from Sanofi, outside the submitted work; Ms. Presles has nothing to disclose; Dr. Goehringer has nothing to disclose; Dr. Mismetti reports personal fees from Bayer Healthcare, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, personal fees from Sanofi, personal fees from Leo Pharma, personal fees from Aspen, personal fees from Pfizer, outside the submitted work; Dr. Bertoletti reports grants from Bayer, grants and personal fees from MSD, personal fees and other from Leo Pharma, personal fees and other from Bristol Myers Squibb, personal fees and other from Pfizer, outside the submitted work; Dr. Rossignol reports personal fees from AstraZeneca, personal fees from Bayer, personal fees from Boehringer-Ingelheim, personal fees from Cincor, personal fees from KBP, personal fees from Novartis, personal fees from NovoNordisk, personal fees from Roche, personal fees from Vifor/Relypsa, personal fees from Fresenius, personal fees and other from CardioRenal, personal fees from Idorsia, personal fees from Sequana, personal fees from Vifor, non-financial support from G3P, outside the submitted work; Dr. Couturaud reports grants and personal fees (board memberships, symposia or travel) from Bayer, grants and personal fees (board memberships, symposia or travel) from Bristol-Myers Squibb/Pfizer, personal fees (board memberships, symposia or travel) from Merck Sharp and Dohme, personal fees (board memberships, symposia or travel) from Astra Zeneca, personal fees (board memberships or symposia) from Sanofi, personal fees (board memberships or symposia) from Janssen, personal fees (board memberships, symposia or travel) from Leo Pharma, outside the submitted work; Dr. Wahl has nothing to disclose; Dr. Thilly has nothing to disclose; Dr. Laporte reports personal fees from Lilly/Boehringer Ingelheim, personal fees from Bristol Myers Squibb/Pfizer, personal fees from Merck, personal fees from Leo-Pharma, outside the submitted work., (© 2023 The Authors.)