Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial
Authors: Ni Jun , Chen Huisheng , Chen Guofang , Ji Yong , Yi Fei , Zhang Zhuobo , Yang Yi , Wu Jin , Cai Xueli , Shao Bei , Wang Jianfeng , Liu Yafang , Geng Deqin , Qu Xinhui , Li Xiaohong , Wei Yan , Ding Jianping , Lü Hua , Huang Yining , Huang Yonghua , Xiao Bo , Gong Tao , Cui Liying ,   on behalf of the study collaboration group, Wang Dong , Han Shugen , Gao Xiaoping , Zhuang Xiaorong , Tan Guojun , Zhu Runxiu , Bi Hongye , Yang Hong , Deng Youqing , Zhou Jinghua , Zheng Shengzhe , Wang Zhiyong , Lu Xiaodong , Li Juntao , Huang Lina , Hu Weimin , Zang Dawei , Yao Xiaoxi , Li Li , Zhao Liandong , Li Luoqing , Wang Shifang , Ke Kaifu , Lu Tianming , Ma Qilin , Zhang Qing , Wang Baojun , Zhao Liang , Dong Hongliang , Gao Wei , Liu Ying , Tang Yamei , Gao Junfeng , Yu Xiaofei , Guo Libin , Lin Haiyan , Wei Xiue , Tian Chenglin , Zhang Tong , Li Yaguo , Wen Guoqiang , Zhou Chengfang , Fang Qi 
Published: July 2020

Abstract
Background
Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke.

Methods
Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram.

Results
In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups.

Conclusions
The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported.

Trial registration
Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827. Retrospectively registered June 13, 2019.