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

被引：12

作者：

Zuily, Stephane ^{[1
,34
,38
]}

Lefevre, Benjamin ^{[2
]}

Sanchez, Olivier ^{[3
,36
,38
]}

de Vendin, Ombeline Empis ^{[4
]}

de Ciancio, Guillaume ^{[5
]}

Arlet, Jean-Benoit ^{[6
]}

Khider, Lina ^{[7
]}

Terriat, Beatrice ^{[8
]}

Greigert, Helene ^{[8
]}

Robert, Celine S. ^{[9
]}

Louis, Guillaume ^{[10
]}

Trinh-Duc, Albert ^{[11
]}

Rispal, Patrick ^{[11
]}

Accassat, Sandrine ^{[12
]}

Thiery, Guillaume ^{[13
]}

Montani, David ^{[14
]}

Azarian, Reza ^{[15
]}

Meneveau, Nicolas ^{[16
]}

Soudet, Simon ^{[17
]}

Le Mao, Raphael ^{[18
]}

Maurier, Francois ^{[19
]}

Le Moing, Vincent ^{[20
]}

Quere, Isabelle ^{[21
]}

Yelnik, Cecile M. ^{[22
]}

Lefebvre, Nicolas ^{[23
]}

Martinot, Martin ^{[24
]}

Delrue, Maxime ^{[25
]}

Benhamou, Ygal ^{[26
]}

Parent, Florence ^{[14
]}

Roy, Pierre-Marie ^{[27
]}

Presles, Emilie ^{[28
,35
,37
]}

Goehringer, Francois ^{[29
]}

Mismetti, Patrick ^{[28
,38
]}

Bertoletti, Laurent ^{[30
,35
]}

Rossignol, Patrick ^{[31
,39
,40
]}

Couturaud, Francis ^{[32
,38
,41
]}

Wahl, Denis ^{[1
]}

Thilly, Nathalie ^{[33
]}

Laporte, Silvy ^{[28
,35
,37
]}

机构：

[1] Univ Lorraine, Vasc Med Div, Rare Vasc & System Autoimmune Dis Reg Referral Ct, CHRU Nancy, Nancy, France

[2] Univ Lorraine, CHRU Nancy, Dept Infect & Trop Dis, APEMAC, F-54000 Nancy, France

[3] Univ Paris Cite, Hop Europeen Georges Pompidou, AP HP, Dept Resp & Intens Care Med, F-75015 Paris, France

[4] CHRU Nancy, Dept Surg Intens Care Unit, F-54000 Nancy, France

[5] CHRU Nancy, Dept Cardiol, F-54000 Nancy, France

[6] Hop Europeen Georges Pompidou, APHP, Internal Med Dept, F-75015 Paris, France

[7] Univ Paris, Hop Europeen Georges Pompidou, AP HP, Vasc Med Dept, F-75015 Paris, France

[8] Dijon Univ Hosp, Dept Vasc Med & Angiol, F-21000 Dijon, France

[9] CHR Metz Thionville, Dept Infect Dis, F-57000 Metz, France

[10] CHR Metz Thionville, Intens Care Unit, F-57000 Metz, France

[11] CH St Esprit, Internal Med Dept, F-47000 Agen, France

[12] CHU St Etienne, Dept Vasc Med, F-42000 St Etienne, France

[13] CHU St Etienne, Med Intens Care Unit, F-42000 St Etienne, France

[14] Univ Paris Saclay, Hop Bicetre, APHP, Dept Resp & Intens Care Med,Pulm Hypertension Nat, F-94270 Le Kremlin Bicetre, France

[15] CH Versailles, Dept Resp Med, F-78150 Le Chesnay, France

[16] Univ Franche Comte, Dept Cardiol, CHU Jean Minjoz, EA 3929, F-25000 Besancon, France

[17] CHU Amiens Picardie, Dept Vasc Med, F-80000 Amiens, France

[18] CHU Brest, Dept Internal Med, Vasc Med & Pulmonol, F-29200 Brest, France

[19] UNEOS, Department Internal Med, F-57070 Metz Vantoux, France

[20] CHRU Montpellier, Dept Infect & Trop Dis, F-34000 Montpellier, France

[21] CHU Montpellier, Dept Vasc Med, IDESP, F-34000 Montpellier, France

[22] Univ Lille, Dept Internal Med & Clin Immunol, CHU Lille, Inserm UMR 1167,North & North West Syst & Autoimm, F-59000 Lille, France

[23] Hop Univ Strasbourg, Dept Trop & Infect Dis, F-67000 Strasbourg, France

[24] Hop Civils Colmar, Dept Trop & Infect Dis, F-68000 Colmar, France

[25] Lariboisiere Hosp, APHP, Hematol Lab & Thrombosis Unit, Paris, France

[26] Univ Rouen Normandie, Normandie Univ, Dept Internal Med, Inserm UMR 1096, F-76000 Rouen, France

[27] Univ Angers, Dept Emergency Med, CHU Angers, F-49000 Angers, France

[28] Univ Jean Monnet, Inserm U1059, SAINBIOSE, Meyzieu, France

[29] CHRU Nancy, Dept Infect & Trop Dis, F-54000 Nancy, France

[30] Univ Jean Monnet, Serv Med Vasc & Therapeut, Inserm, CHU St Etienne,CIC 1408, St Etienne, France

[31] Univ Lorraine, Inserm, CIC P 1433, CHRU Nancy,UMR 1116,F CRIN INI CRCT, F-54000 Nancy, France

[32] Univ Bretagne Occidentale, Dept Internal Med & Chest Dis, CHU Brest, Nancy, France

[33] Univ Lorraine, CHRU Nancy, Dept Methodol Promot Invest, APEMAC, F-54000 Nancy, France

[34] Inserm, UMR 1116 DCAC, F-54000 Nancy, France

[35] F CRIN INNOVTE Network, F-42000 St Etienne, France

[36] Inserm, Innovat Therapies Haemostasis, Paris, France

[37] CHU St Etienne, Unite Rech Clin Innovat Pharmacol, Paris, France

[38] CHU St Etienne, Serv Med Vasc & Therapeut, Unite Rech Clin Innovat Pharmacol, Paris, France

[39] Princess Grace Hosp, Dept Med Specialties & Nephrol Hemodialys, Quai Jean Charles Rey, Monaco

[40] Ctr Hemodialyse Prive Monaco, Quai Jean Charles Rey, Monaco

[41] Inserm, UMR 1304, GETBO, F-29200 Brest, France

来源：

ECLINICALMEDICINE | 2023年 / 60卷

关键词：

COVID-19; Venous thromboembolism; Heparin; Anticoagulation;

D O I：

10.1016/j.eclinm.2023.102031

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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/).

引用

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