Foresti Maira Licia, Garzon Eliana, de Moraes Mariana Teichner, Valeriano Rafael P S, Santiago João Paulo, Dos Santos Gustavo Mercenas, Longo Natália Mata, Baise Carla, Andrade Joaquina C Q F, Susemihl Maria Alice, Leite Claudia da Costa, Naffah Mazzacoratti Maria da Graça, Paiva Wellingson Silva, de Andrade Almir Ferreira, Teixeira Manuel Jacobsen, Mello Luiz E
Neurology Neuroscience Postgraduation Program, Physiology Department, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Instituto D'Or de Pesquisa e Ensino, São Paulo, Brazil.
Front Neurol. 2024 Aug 7;15:1443982. doi: 10.3389/fneur.2024.1443982. eCollection 2024.
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; = 0.170) or the mortality rate (1.57, 95%CI, 0.73-3.38; = 0.248). The frequency of late post-traumatic seizures was higher for biperiden group (2.03, 95%CI = 0.912-3.1597; <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. ClinicalTrials.gov, identifier: NCT01048138.
目前尚无有效的干预措施来预防创伤后癫痫（PTE）。临床前研究支持抗胆碱能药物在这种情况下的潜在用途。本研究的目的是评估比哌立登作为预防PTE的干预措施的效果。2018年至2022年期间在HC/FMUSP进行了一项随机双盲临床试验。患有急性创伤性脑损伤（TBI）的成年人被随机分配接受比哌立登或安慰剂治疗，为期10天。主要结局是PTE的发生率，次要结局包括癫痫发作频率、任何不良事件的频率以及24个月后的死亡率。该研究计划招募132名患者。该试验于2018年1月开始，2020年3月因全球COVID-19大流行被研究人员叫停（并于2022年12月终止）。总体而言，123名参与者被随机分组，112名参与者提供了数据用于改良意向性分析，其中61名（49.5%）参与者完成了24个月的随访咨询。数据分析表明，没有证据表明比哌立登对创伤后癫痫的发生率（2.6，95%CI，0.65 - 10.57；P = 0.170）或死亡率（1.57，95%CI，0.73 - 3.38；P = 0.248）有影响。比哌立登组创伤后晚期癫痫发作频率更高（2.03，95%CI = 0.912 - 3.1597；P <0.001）。本研究表明，关于比哌立登预防TBI后PTE的效果，证据不足，这突出了进行更大规模研究的必要性。ClinicalTrials.gov标识符：NCT-01048138。
