Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial

作者：Tao Liu, Jiao Wang, Zhihao Zhao, Weiwei Jiang, Minzhi Zhang, Yunhu Yu, Yang Liu, Mingqi Liu, Linan Chen, Hengzhu Zhang, Yingbiao Hong, Bohe Li, Rutong Yu, Hongming Ji, Liang Mi, Biao Zhao, Chuanxiang Lv, Chenglong Liu, Jianning Zhang, Rongcai Jiang, for the LOCATE Trial Investigators, Tao Liu, Jiao Wang, Zhihao Zhao, Weiwei Jiang, Minzhi Zhang, Yunhu Yu, Yang Liu, Mingqi Liu, Linan Chen, Hengzhu Zhang, Yingbiao Hong, Bohe Li, Rutong Yu, Hongming Ji, Liang Mi, Biao Zhao, Chuanxiang Lv, Chenglong Liu, Jianning Zhang, Rongcai Jiang, Taikun Tang, Sheng Zhu, Hangang Jiang, Zengqiang Liu, Xingchang Li, Jianbo Wei, Tao Jiang, Feng Wei, Lianshu Ding, Weilong Li, Shutian Wei, Li Li, Aiming Li, Xingen Zhu, Ya Peng, Hui Li, Ruijian Zhang, Ruisheng Lin, Ying Xia, Chaoyong Wen, Jian Wu, Qiuhua Jiang, J. Li, Shaochun Yang, Gang Li, Zhimin Wang, Jian Chen, Zejun Chen, Tao Mei, Jianrong Liang, Bin Li, Xiang Gao, Bo Fan, Yezhong Wang, Gang Zhu, Lin Lou, Meihua Li, Jian Ge · 发表于：Signal Transduction and Targeted Therapy · 年份：2025 · DOI：10.1038/s41392-025-02492-5 · 被引用次数：1 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Traumatic Brain Injury Research、Epilepsy research and treatment

To assess the efficacy and safety of L-oxiracetam, a novel nootropic agent, in improving cognition in patients with TBI, we performed a multicentre, double-blind, randomized controlled trial in China. Participants aged 18 to 75 years with TBI (Glasgow Coma Scale score of 10 to 15) were recruited from 51 hospitals from 2019 to 2024. Patients were randomly assigned to L-oxiracetam, 4 g/day, oxiracetam 6 g/day, or placebo in 2:2:1. The primary outcome was the change in the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score from baseline to 90 days post treatment. Secondary outcomes included changes in additional cognitive evaluations, neurological function, activities of daily living (ADL), and adverse events (AEs). The trial was approved by the China National Medical Products Administration (2016L03521), and registered at Clinicaltrials.gov (NCT04205565) and Chinadrugtrials.org.cn (CTR20192539). Five hundred and ninety patients were included (mean age (SD), 50.9 (14.5); 421 males). The least squares (LS) mean of LOTCA change from baseline to 90 days post treatment was 20.45 (95% confidence interval [CI] 17.23, 23.66) in the L-oxiracetam group, 15.90 (95% CI 12.71, 19.10) in the oxiracetam group, and 11.47 (95% CI 7.75, 15.20) in the placebo group (P value < 0.05 for all groups). The LS mean difference of the L-oxiracetam was significantly higher than the placebo group (8.97, 95% CI 5.69,12.26; P < 0.001; Cohen's d = 0.48 [95% CI: 0.26,0.69]) and the oxiracetam ...