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EClinicalMedicine
. 2023 Jun;60:102031.
doi: 10.1016/j.eclinm.2023.102031. Epub 2023 Jun 9. 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
Stéphane Zuily 1 2 3 , Benjamin Lefèvre 4 , Olivier Sanchez 5 3 6 , Ombeline Empis de Vendin 7 , Guillaume de Ciancio 8 , Jean-Benoît Arlet 9 , Lina Khider 10 , Béatrice Terriat 11 , Hélène Greigert 11 , Céline S Robert 12 , Guillaume Louis 13 , Albert Trinh-Duc 14 , Patrick Rispal 14 , Sandrine Accassat 15 , Guillaume Thiery 16 , David Montani 17 , Réza Azarian 18 , Nicolas Meneveau 19 , Simon Soudet 20 , Raphaël Le Mao 21 , François Maurier 22 , Vincent Le Moing 23 , Isabelle Quéré 24 , Cécile M Yelnik 25 , Nicolas Lefebvre 26 , Martin Martinot 27 , Maxime Delrue 28 , Ygal Benhamou 29 , Florence Parent 17 , Pierre-Marie Roy 30 , Emilie Presles 31 3 32 , François Goehringer 33 , Patrick Mismetti 31 3 34 , Laurent Bertoletti 35 3 , Patrick Rossignol 36 37 , Francis Couturaud 38 3 39 , Denis Wahl 1 , Nathalie Thilly 40 , Silvy Laporte 31 3 32 ; COVI-DOSE investigators
Collaborators, Affiliations
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.
Keywords: Anticoagulation; COVID-19; Heparin; Venous thromboembolism.
. 2023 Jun;60:102031.
doi: 10.1016/j.eclinm.2023.102031. Epub 2023 Jun 9. 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
Stéphane Zuily 1 2 3 , Benjamin Lefèvre 4 , Olivier Sanchez 5 3 6 , Ombeline Empis de Vendin 7 , Guillaume de Ciancio 8 , Jean-Benoît Arlet 9 , Lina Khider 10 , Béatrice Terriat 11 , Hélène Greigert 11 , Céline S Robert 12 , Guillaume Louis 13 , Albert Trinh-Duc 14 , Patrick Rispal 14 , Sandrine Accassat 15 , Guillaume Thiery 16 , David Montani 17 , Réza Azarian 18 , Nicolas Meneveau 19 , Simon Soudet 20 , Raphaël Le Mao 21 , François Maurier 22 , Vincent Le Moing 23 , Isabelle Quéré 24 , Cécile M Yelnik 25 , Nicolas Lefebvre 26 , Martin Martinot 27 , Maxime Delrue 28 , Ygal Benhamou 29 , Florence Parent 17 , Pierre-Marie Roy 30 , Emilie Presles 31 3 32 , François Goehringer 33 , Patrick Mismetti 31 3 34 , Laurent Bertoletti 35 3 , Patrick Rossignol 36 37 , Francis Couturaud 38 3 39 , Denis Wahl 1 , Nathalie Thilly 40 , Silvy Laporte 31 3 32 ; COVI-DOSE investigators
Collaborators, Affiliations
- PMID: 37350990
- PMCID: PMC10250778
- DOI: 10.1016/j.eclinm.2023.102031
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.
Keywords: Anticoagulation; COVID-19; Heparin; Venous thromboembolism.