Four-Factor Prothrombin Complex Concentrate to Reduce Post-Traumatic Hemorrhage in Patients with Major Trauma, the PROCOAG Trial: Study Protocol for a Randomized Multicenter Double-Blind Superiority Study

Abstract

\n Background: Optimal management of severe trauma patients with active hemorrhage relies on adequate initial resuscitation. Early administration of coagulation factors improves post-traumatic coagulation disorders and four-factor prothrombin complex concentrate (PCC) might be useful in this context. Our main hypothesis is that four-factor PCC in addition to a massive transfusion protocol decrease blood product consumption at day one in severe trauma patients with major bleeding.Methods This is a prospective, randomized, multicenter, double-blind, parallel, controlled superiority trial. Eligible patients are trauma patients with major bleeding admitted to a French level-I trauma centre. Patients randomized in the treatment arm receive 1 mL/kg four-factor PCC within one-hour post-admission while patients randomized in the controlled group receive 1 mL/kg of saline solution 0.9% as a placebo. The primary endpoint is the amount of blood products transfused in the first 24 hours post-admission (including red blood cells, frozen fresh plasma and platelets). The secondary endpoints are the amount of each blood product transfused in the first 24 hours, time to achieve prothrombin time ratio < 1.5, time to hemostasis, number of thrombo-embolic events at 28 days, mortality at 24 hours and 28 days, number of intensive care unit (ICU)-free days, number of ventilator-free days during ICU stay, number of hospital-free days within the first 28 days, hospitalization status at day 28, Glasgow outcome scale extended for patients with brain lesions on initial cerebral imaging, and cost of each strategy at day 8 and 28. Inclusions have started in December 2017 and are expected to be complete by June 2021. Discussion: If PCC reduces total blood consumption at day one after severe trauma, this therapy, in adjunction to a classic massive transfusion protocol, may be used empirically on admission in patients at risk of massive transfusion to enhance coagulation. Moreover, this treatment may decrease blood product related complications and may improve clinical outcome after post-traumatic hemorrhage. Trial registration: This study has been prospectively registered on clinical trial on July 14, 2017 NCT03218722