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CLINICAL TRIAL article

Front. Neurol.
Sec. Neurotrauma
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1443982
This article is part of the Research Topic Assessment and Treatment Interventions for Traumatic Brain Injury View all 14 articles

Initial clinical evidence on biperiden as antiepileptogenic after traumatic brain injury. A Randomized Clinical Trial

Provisionally accepted
Maira L. Foresti Maira L. Foresti 1,2Eliana Garzon Eliana Garzon 3,4Mariana T. Moraes Mariana T. Moraes 3Rafael P. Valeriano Rafael P. Valeriano 3João Paulo Santiago João Paulo Santiago 3Gustavo M. Santos Gustavo M. Santos 3Natália M. Longo Natália M. Longo 3Carla Baise Carla Baise 3Joaquina C. Andrade Joaquina C. Andrade 3Maria Alice Susemihl Maria Alice Susemihl 5Claudia C. Leite Claudia C. Leite 3Maria Da Graça Naffah Mazzacoratti Maria Da Graça Naffah Mazzacoratti 6Wellingson S. Paiva Wellingson S. Paiva 3Almir F. De Andrade Almir F. De Andrade 3Manoel J. Teixeira Manoel J. Teixeira 3Luiz E. Mello Luiz E. Mello 7*
  • 1 Federal University of São Paulo, São Paulo, Brazil
  • 2 D'or Institute for Research and Teaching, Rio de Janeiro, Rio de Janeiro, Brazil
  • 3 Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
  • 4 Hospital Sirio Libanes, São Paulo, Brazil
  • 5 Independent researcher, São Paulo, Brazil
  • 6 Paulista School of Medicine, Federal University of São Paulo, São Paulo, São Paulo, Brazil
  • 7 Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

The final, formatted version of the article will be published soon.

    There is currently no efficacious intervention for preventing post-traumatic epilepsy (PTE). Preclinical studies support the potential use of anticholinergics for this condition. The purpose of this study was to evaluate the effects of biperiden as an intervention for preventing PTE. A randomized, double-blinded clinical trial was conducted at HC/FMUSP between 2018-2022. Adults with acute traumatic brain injury (TBI) were randomly assigned to receive biperiden or placebo, for 10 days. The primary outcome was the incidence of PTE while the secondary outcomes included the frequency of seizures, the frequency of any adverse events and mortality after 24 months. The study was powered at a planned enrolment of 132 patients. The trial began in January 2018 and was halted by researchers on March 2020 (and terminated in December 2022) in the face of the global COVID-19 pandemic. Overall, 123 participants were randomized and 112 contributed with data for modified mITT analysis, being that 61 (49.5%) participants completed the 24-month follow-up consult. Data analysis indicated lack of evidence of biperiden for either, the incidence of post-traumatic epilepsy (2.6, 95%CI, 0.65-10.57; P = .170) or the mortality rate (1.57, 95%CI, P=.248). The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912-3.1597; p <0.001). The present study suggests that there was insufficient evidence regarding the effect of biperiden in preventing PTE after TBI, which underpins the need for larger studies.Clinical trial registration: ClinicalTrials.gov Identifier: NCT01048138.

    Keywords: Acute traumatic brain injury, Post traumatic epilepsy, seizure, Epilepsy, Anticholinergic, Biperiden

    Received: 14 Jun 2024; Accepted: 25 Jul 2024.

    Copyright: © 2024 Foresti, Garzon, Moraes, Valeriano, Santiago, Santos, Longo, Baise, Andrade, Susemihl, Leite, Naffah Mazzacoratti, Paiva, De Andrade, Teixeira and Mello. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Luiz E. Mello, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

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