tetano
Editor, Senior Moderator
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[SUP] 1 2 3 [/SUP], Benjamin Lefèvre[SUP] 4 [/SUP], Olivier Sanchez[SUP] 5 3 6 [/SUP], Ombeline Empis de Vendin[SUP] 7 [/SUP], Guillaume de Ciancio[SUP] 8 [/SUP], Jean-Benoît Arlet[SUP] 9 [/SUP], Lina Khider[SUP] 10 [/SUP], Béatrice Terriat[SUP] 11 [/SUP], Hélène Greigert[SUP] 11 [/SUP], Céline S Robert[SUP] 12 [/SUP], Guillaume Louis[SUP] 13 [/SUP], Albert Trinh-Duc[SUP] 14 [/SUP], Patrick Rispal[SUP] 14 [/SUP], Sandrine Accassat[SUP] 15 [/SUP], Guillaume Thiery[SUP] 16 [/SUP], David Montani[SUP] 17 [/SUP], Réza Azarian[SUP] 18 [/SUP], Nicolas Meneveau[SUP] 19 [/SUP], Simon Soudet[SUP] 20 [/SUP], Raphaël Le Mao[SUP] 21 [/SUP], François Maurier[SUP] 22 [/SUP], Vincent Le Moing[SUP] 23 [/SUP], Isabelle Quéré[SUP] 24 [/SUP], Cécile M Yelnik[SUP] 25 [/SUP], Nicolas Lefebvre[SUP] 26 [/SUP], Martin Martinot[SUP] 27 [/SUP], Maxime Delrue[SUP] 28 [/SUP], Ygal Benhamou[SUP] 29 [/SUP], Florence Parent[SUP] 17 [/SUP], Pierre-Marie Roy[SUP] 30 [/SUP], Emilie Presles[SUP] 31 3 32 [/SUP], François Goehringer[SUP] 33 [/SUP], Patrick Mismetti[SUP] 31 3 34 [/SUP], Laurent Bertoletti[SUP] 35 3 [/SUP], Patrick Rossignol[SUP] 36 37 [/SUP], Francis Couturaud[SUP] 38 3 39 [/SUP], Denis Wahl[SUP] 1 [/SUP], Nathalie Thilly[SUP] 40 [/SUP], Silvy Laporte[SUP] 31 3 32 [/SUP]; 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[SUP] 1 2 3 [/SUP], Benjamin Lefèvre[SUP] 4 [/SUP], Olivier Sanchez[SUP] 5 3 6 [/SUP], Ombeline Empis de Vendin[SUP] 7 [/SUP], Guillaume de Ciancio[SUP] 8 [/SUP], Jean-Benoît Arlet[SUP] 9 [/SUP], Lina Khider[SUP] 10 [/SUP], Béatrice Terriat[SUP] 11 [/SUP], Hélène Greigert[SUP] 11 [/SUP], Céline S Robert[SUP] 12 [/SUP], Guillaume Louis[SUP] 13 [/SUP], Albert Trinh-Duc[SUP] 14 [/SUP], Patrick Rispal[SUP] 14 [/SUP], Sandrine Accassat[SUP] 15 [/SUP], Guillaume Thiery[SUP] 16 [/SUP], David Montani[SUP] 17 [/SUP], Réza Azarian[SUP] 18 [/SUP], Nicolas Meneveau[SUP] 19 [/SUP], Simon Soudet[SUP] 20 [/SUP], Raphaël Le Mao[SUP] 21 [/SUP], François Maurier[SUP] 22 [/SUP], Vincent Le Moing[SUP] 23 [/SUP], Isabelle Quéré[SUP] 24 [/SUP], Cécile M Yelnik[SUP] 25 [/SUP], Nicolas Lefebvre[SUP] 26 [/SUP], Martin Martinot[SUP] 27 [/SUP], Maxime Delrue[SUP] 28 [/SUP], Ygal Benhamou[SUP] 29 [/SUP], Florence Parent[SUP] 17 [/SUP], Pierre-Marie Roy[SUP] 30 [/SUP], Emilie Presles[SUP] 31 3 32 [/SUP], François Goehringer[SUP] 33 [/SUP], Patrick Mismetti[SUP] 31 3 34 [/SUP], Laurent Bertoletti[SUP] 35 3 [/SUP], Patrick Rossignol[SUP] 36 37 [/SUP], Francis Couturaud[SUP] 38 3 39 [/SUP], Denis Wahl[SUP] 1 [/SUP], Nathalie Thilly[SUP] 40 [/SUP], Silvy Laporte[SUP] 31 3 32 [/SUP]; 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.