Thromb Haemost 2022; 122(02): 295-299
DOI: 10.1055/a-1667-7534
Letter to the Editor

Therapeutic versus Prophylactic Bemiparin in Hospitalized Patients with Nonsevere COVID-19 Pneumonia (BEMICOP Study): An Open-Label, Multicenter, Randomized, Controlled Trial

María Marcos-Jubilar
1   Hematology Service, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
,
Francisco Carmona-Torre
2   Divison of Infectious Diseases, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
,
Rosa Vidal
3   Hematology Service, Hospital Universitario Fundación Jiménez-Díaz, Madrid, Spain
,
4   Internal Medicine Department, Clínica Universidad de Navarra, Madrid, Spain
5   CIBER Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
,
David Filella
6   Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Cristina Carbonell
7   Internal Medicine Department, Hospital Universitario de Salamanca-IBSAL, Universidad de Salamanca, Salamanca, Spain
,
Víctor Jiménez-Yuste
8   Hematology Service, Hospital Universitario La Paz, Madrid, Spain
,
Juana Schwartz
9   Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain
,
Pilar Llamas
3   Hematology Service, Hospital Universitario Fundación Jiménez-Díaz, Madrid, Spain
,
Félix Alegre
10   Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
,
Belén Sádaba
9   Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain
,
Jorge Núñez-Córdoba
9   Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain
,
José R. Yuste
2   Divison of Infectious Diseases, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
,
Javier Fernández-García
9   Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain
,
Ramón Lecumberri
1   Hematology Service, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
11   CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
,
for the BEMICOP Investigators › Author Affiliations

Abstract

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], –16% –24%]; odds ratio 1.26 [95% CI, 0.37–4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.

Author Contributions

R.L., J.S., M.B.S., and J.J.F.G. designed and drafted the study protocol, which was reviewed by all other authors. M.M.J., F.C., R.V., P.R.A., D.F., C.C., V.J.Y., P.L., F.A., J.R.Y., and R.L. enrolled and/or followed-up patients. R.L. and J.J.F.G. analyzed the data. R.L. drafted the manuscript, which was critically reviewed by all the authors, who approved the final version.


Data Sharing

Anonymized participant data can be made available upon request directed to the corresponding author. Proposals will be reviewed by the sponsor. Once approved, a signed data access agreement will be required.


* A full list of the BEMICOP investigators is included in the [Supplementary Appendix].


Supplementary Material



Publication History

Received: 21 August 2021

Accepted: 10 October 2021

Accepted Manuscript online:
12 October 2021

Article published online:
29 December 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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