Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial

作者：Kaibin Huang, Xiaolin Zhao, Yunxiao Zhao, Guoshuai Yang, Saijun Zhou, Zhi Yang, Wenguo Huang, Guohu Weng, Pingyan Chen, Chongyang Duan, Zhenzhou Lin, Shengnan Wang, Xiangmin Liu, Yunqiang Huang, Jiangshan Zhang, Xu Zhang, Hao Li, Songsheng Ye, Yong Gu, Minzhen Zhu, Weiying Chen, Weiwei Quan, Na Liu, Quanfeng Chen, Yuan Chang, Jinzhao He, Zhong Ji, Yongming Wu, Suyue Pan · 发表于：EClinicalMedicine · 年份：2023 · DOI：10.1016/j.eclinm.2023.102305 · 被引用次数：12 · 研究领域：Acute Ischemic Stroke Management、Neurological Disorders and Treatments、S100 Proteins and Annexins

Background: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Methods: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants. Findings: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were includ...