BIPERIDEN Trial: Early Observations of a Randomized, Double-Blind, Placebo-Controlled Study on the Prevention of Post-Traumatic Epilepsy
Abstract number :
3.447
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2025
Submission ID :
1439
Source :
www.aesnet.org
Presentation date :
12/8/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Maira Licia Foresti, PhD – Instituto D'Or de Pesquisa e Ensino (IDOR) - SP, Brazil
Eliana Garzon, MD, PhD – Sociedade Beneficente de Senhoras Hospital Sírio-Libanês - SP, Brazil
Erika Silva, PhD – Sociedade Beneficente de Senhoras Hospital Sírio-Libanês, SP, Brazil
Carla Pinheiro, PhD – Sociedade Beneficente de Senhoras Hospital Sírio-Libanês, SP, Brazil
Luiz Eugênio Mello, MD, PhD – Instituto D'Or de Pesquisa e Ensino (IDOR) - SP, Brazil
Rationale: Traumatic brain injury (TBI) is a leading cause of acquired epilepsy worldwide, and the development of post-traumatic epilepsy (PTE) remains a major challenge in neurocritical care. Despite its clinical relevance, there are currently no effective strategies to prevent epileptogenesis in this setting. Experimental data suggest that biperiden, an anticholinergic agent, may interfere with mechanisms underlying epileptogenesis, raising the possibility of its use as a disease-modifying therapy. This trial investigates the potential of biperiden to prevent PTE in TBI patients.
Methods: ClinicalTrials.gov: NCT04945213.This prospective multicenter interventional study, in Brazil, started in January 2023 and will include 312 adult patients admitted to emergency care units with a diagnosis of moderate or severe TBI. Following inclusion and exclusion criteria, patients are randomized using block randomization to receive double-blind treatment with placebo or biperiden for 10 days. Follow-up occurs at specific time windows up to 2 years. Primary outcomes are PTE incidence and severe adverse events. Since the trial is ongoing, descriptive data is presented.
Results: Ethical approval: 39005920.8.1001.5461. To date, 212 of the 312 planned patients have been enrolled. Among them, 203 (95%) were randomized, and 44/203 (21.6%) were excluded, mostly due to screening failure (91%) in the acute setting. The cohort is predominantly male (81%), with traffic accidents (71%) and falls from height (23%) being the leading causes of trauma. Glasgow Coma Scale at scene was 6 in 13.2% of patients, while at hospital admission the most frequent score was 3 (33.5%). Importantly, 81% of patients received the first treatment dose within 12 h after TBI, 30% completed all 40 protocol doses, and 37% received at least 30 doses during the 10-day intervention. So far, 63 and 22 participants have already completed the one-year and two-year visits, respectively. Seven patients developed PTE within a mean of 10.4 ± 8.2 months after TBI, and another 7 are under detailed investigation due to seizure-like events. Thirty-one patients died during the study period.
Conclusions: The BIPERIDEN trial is advancing as an important multicenter randomized clinical study designed to evaluate an antiepileptogenic intervention in TBI. Recruitment and longitudinal follow-up have demonstrated feasibility of the protocol, with timely initiation of treatment and satisfactory adherence, despite the challenges of emergency care. Early descriptive data confirms the expected severity profile of enrolled patients and the observed incidence of PTE. These early observations underscore the feasibility and relevance of testing biperiden as a potential disease-modifying therapy, paving the way for definitive results on efficacy and safety.
Funding: FAPESP 18/24561–5; PROADI-SUS 25000.014325/2021-33; 25000.173556/2023-40; National Council for Scientific and Technological Development – CNPq (311619/2019–3).
Anti-seizure Medications