A multicenter, international, randomized, single-blind, placebo-controlled study of the efficacy and safety of inosine-nicotinamide-riboflavin-succinic acid in the acute period of traumatic brain injury in adults

Background: The combination of inosine, nicotinamide, riboflavin, and succinic acid (INRSA) has previously demonstrated neuroprotective effect. We aimed to study the efficacy and safety of treatment with INRSA in traumatic brain injury (TBI). Materials and methods: In our multicenter, randomized, placebo-controlled, single-blind clinical trial, we studied TBI patients aged 18-60, diagnosed with cerebral contusion without compression, admission Glasgow Coma Scale (GCS) score of 13-14, and posttraumatic amnesia. The INRSA/placebo was administered intravenously twice daily for 10 days. The primary endpoints were the Galveston Orientation and Amnesia Test (performed on days 2-14), and Glasgow Outcome Scale-Extended (GOS-E; assessed on day 90 via telephone interview). Results: Between November 2020 and May 2024, 166 patients were enrolled, median age 43 (IQR 33-51), 113 (68.5%) males, all with admission GCS 13-14, 123 (74.5%) had closed-type TBI. In the interim analysis, complete recovery (GOS-E category 8) was achieved in 24 (30%) patients in the placebo group and 55 (73%) in the INRSA group. The difference in proportions was 44% (95% CI 0.26; 0.62); experimental treatment increased the odds of complete recovery by 6.53 (95% CI 3.30-13.41) compared to placebo. Based on the pre-specified criteria, the independent data monitoring committee recommended termination of the study due to early demonstration of efficacy by one of the two primary endpoints. Conclusion: Treatment with INRSA was associated with improvement in mild TBI outcome, which represents a new potential option for the pharmacological treatment of non-fatal head injury. Further studies might be of research interest and clinical demand. Clinical trial registration: ClinicalTrials.gov, identifier: NCT04631484; unique protocol ID: CTF-III-CCT-2019.