Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke
Authors: Wang Anxin , Jia Baixue , Zhang Xuelei , Huo Xiaochuan , Chen Jianhuang , Gui Liqiang , Cai Yefeng , Guo Zaiyu , Han Yuqing , Peng Zhaolong , Jing Ping , Chen Yongjun , Liu Yan , Yang Yong , Wang Fengyun , Sun Zengqiang , Li Tong , Sun Hongxia , Yuan Haicheng , Shao Hongmin , Gao Lianbo , Zhang Peipei , Wang Feng , Cao Xiangyang , Shi Wanchao , Li Changmao , Yang Jianwen , Zhang Hong , Wang Feng , Deng Jianzhong , Liu Yanjie , Deng Weisheng , Song Cunfeng , Chen Huisheng , He Li , Zhao Hongdong , Li Xianfeng , Yang Hong , Zhou Zhiming , Wang Yilong , Miao Zhongrong ,   BAST Investigators, Tang Shuncong , Wang Baojun , Fang Xing , Sun Weiming , Li Di , Liu Shugai , Peng Zhiqiang , Yu Chuanqing , Wang Lizhi , Huang Xiaosong , Li Yongjun , Lv Haidong , Xie Xiangdong , Yang Heyun , Li Chaomao , Chen Zhonglun , Liu Zanhua , Xing Wenli , Lin Delin , Wang Lijun , Zhang Liyan , Ju Weiping , Yu Chunlei , Zhang Jingyu , Zuo Yingting , Zhang Yijun , Zhang Xiaoli , Tian Xue , Mo Dapeng , Li Xiaoqing , Chen Guojuan , Wu Haibo , Qu Duan , Wang David , Ren Zeguang , Li Hao , Xu Anding , Zhang Meng , Xu Qin 
Published: June 2023

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 &amp;lt; .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:NCT03539445