Therapeutic vs. prophylactic bemiparin in hospitalized patients with non-severe COVID-19 (BEMICOP): an open-label, multicenter, randomized trial

Marcos, María; Carmona-Torre, Francisco; Vidal Laso, Rosa; Ruiz-Artacho, Pedro; Filella, David; Carbonell, Cristina; Jimenez-Yuste, Victor; Schwartz, Juana; Llamas, Pilar; Alegre, Félix; Sádaba, Belén; Núñez-Córdoba, Jorge; Yuste, José Ramón; Fernández-García, Javier; Lecumberri, Ramón

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.