Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke
Anxin Wang, Baixue Jia, Xuelei Zhang, Xiaochuan Huo, Jianhuang Chen, Liqiang Gui, Yefeng Cai, Zaiyu Guo, Yuqing Han, Zhaolong Peng, Ping Jing, Yongjun Chen, Yan Liu, Yong Yang, Fengyun Wang, Zengqiang Sun, Tong Li, Hongxia Sun, Haicheng Yuan, Hongmin Shao, Lianbo Gao, Peipei Zhang, Feng Wang, Xiangyang Cao, Wanchao Shi, Changmao Li, Jianwen Yang, Hong Zhang, Feng Wang, Jianzhong Deng, Yanjie Liu, Weisheng Deng, Cunfeng Song, Huisheng Chen, Li He, Hongdong Zhao, Xianfeng Li, Hong Yang, Zhiming Zhou, Yilong Wang, Zhongrong Miao, Shuncong Tang, Baojun Wang, Xing Fang, Weiming Sun, Di Li, Shugai Liu, Zhiqiang Peng, Chuanqing Yu, Lizhi Wang, Xiaosong Huang, Yongjun Li, Haidong Lv, Xiangdong Xie, Heyun Yang, Chaomao Li, Zhonglun Chen, Zanhua Liu, Wenli Xing, Delin Lin, Lijun Wang, Liyan Zhang, Weiping Ju, Chunlei Yu, Jingyu Zhang, Yingting Zuo, Yijun Zhang, Xiaoli Zhang, Xue Tian, Dapeng Mo, Xiaoqing Li, Guojuan Chen, Haibo Wu, Duan Qu, David Wang, Zeguang Ren, Hao Li, Anding Xu, Meng Zhang, Qin Xu,- Neurology (clinical)
Importance
DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown.
Objective
To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment.
Design, Setting, and Participants
This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022.
Interventions
Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio.
Main Outcomes and Measures
The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity.
Results
Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group.
Conclusions and Relevance
Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo.
Trial Registration
ClinicalTrials.gov Identifier: