Systematic Immediate Vitamin K Antagonist Reversal with Prothrombin Complex Concentrate in Patients with Recent Mild Traumatic Brain Injury (PREVACT): A Multicenter, Randomized, Controlled Trial

Background: Trauma brain injury (TBI) in patients receiving vitamin K antagonist (VKA) is associated with a high rate of intracranial hemorrhage (ICH) and subsequent functional impairment. Aims: To assess the efficacy of prompt systematic reversal of anticoagulation with 4‐factor prothrombin complex concentrate (PCC) in patients presenting to Emergency Department for recent isolated mild TBI while receiving VKA for atrial fibrillation. Methods: Open‐label with blinded endpoint clinical trial. We planned to randomized 400 patients to systematic immediate VKA reversal with 25 UI/ kg of PCC before any investigation (intervention group) or usual care meaning reversal only in case of intracranial bleeding on the initial cranial CTscan performed as soon as possible (control group) in 21 hospitals. The primary outcome was the rate of ICH on a cranial CT‐scan performed 24 hours after inclusion. Results: The study was prematurely stopped for logistical reasons after the inclusion of 203 patients, 98 were evaluable in the intervention group and 99 in the control group (table). On the H24 cranial CT‐scan, 6/98 patients (6.1%) in the intervention group had intracranial bleeding versus 12/99 patients (12.1%) in the control group (odds ratio: 0.48 [95% confidence interval 0.14–1.44]). As compared to the initial CT‐scan, the rate of ICH onset or extension was 1/98 (1.1%) in the intervention group versus 5/99 (5.1%) in the control group. Three patients (3.1%) in the intervention group had a thromboembolic event within the 30 days following inclusion and none in the control group. Patients’ functional outcomes are mentioned in the figure. Conclusion(s): In patients with recent mild TBI and receiving VKA, prompt and systematic reversal with PCC did not significantly reduce the rate of ICH at 24 hours. However, the study was prematurely stopped and does not exclude a clinically important benefit (ClinicalTrials.gov Identifier: NCT01961804; funded by the French Health Government; approved by the CPP‐Ouest‐2 ethics committee). [Table presented] [Figure presented]