Therapeutic vs. prophylactic bemiparin in hospitalized patients with non-severe COVID-19 (BEMICOP): an open-label, multicenter, randomized trial
María Marcos 1 , Francisco Carmona-Torre 2 , Rosa Vidal Laso 3 , Pedro Ruiz-Artacho 4 , David Filella 5 , Cristina Carbonell 6 , Victor Jimenez-Yuste 7 , Juana Schwartz 8 , Pilar Llamas 9 , Félix Alegre 10 , Belén Sádaba 8 , Jorge Núñez-Córdoba 8 , José Ramón Yuste 11 , Javier Fernández-García 8 , Ramón Lecumberri 1
Thrombophylaxis with low molecular weight heparin (LMWH) 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 non-severe COVID-19 pneumonia and elevated D-dimer.
Patients were randomized to therapeutic-dose bemiparin (115 IU/Kg daily) vs. 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 (ISTH 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 (21.9%) in the therapeutic-dose group and 6 patients (18.2%) in the prophylactic-dose (absolute risk difference 3.6% [95% 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 non-severe pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin did not improve clinical outcomes compared to standard prophylactic doses.