Tongxinluo and Functional Outcomes Among Patients With Acute Ischemic Stroke
Authors: Dong Yi , Jiang Kaifu , Li Zhenguang , Zhou Yanhua , Ju Bo , Min Lianqiu , He Qiu , Fan Ping , Hu Wenli , Qu Hongdang , Wu Haiqin , Pan Chunlian , Cao Yibing , Lou Xiaoliang , Zhang Guiru , Zhang Jiewen , Hu Fengyun , Dong Qiang ,   TISS Trial Investigators, Zhao Xingquan , Xu Renxian , Guo Li , Zhuang Xiaorong , Zhu Yuhong , Shao Rusheng , Chen Shengli , She Junhong , Lu Changjun , Yan Chuanzhu , Wei Qing , Hong Wenke , Yang Yi , Cui Songbiao , Huang Lina , Feng Juan , Wu Danhong , An Junqi , Sun Ping , Chen Xiaohong , Xiao Bo , Tan Liming , Xiao Jingsong , Liu Huimin , Xie Kang , Liu Ming , Ren Jun , Lu Xuesheng , Cai Min , Chen Xiaofei , Fan Wenhui , Zhang Qing , Hu Fengyun , Liu Bin , Liu Jieyi , Zhan Liping , Wang Yidong , Zhao Yanwen , Geng Deqin , Xu Yun , Qiu Xiaoying , Sun Xuwen , Kong Deqiang , Tang Hongyu , Bi Xiaoying , Wang Yanyong , Dong Xueshuang , Wang Tao , Qu Xiang , Xie Xuemei , He Yun , Shi Jingjing , Yang Xiaomei , Shen Guixi , Xu Jie , Jin Quanwei , Hu Derong , Yang Xiai , Wang Jinglei , Chen Tao , Wang Jianwei , Wang Yingfeng , Dai Yangyang , Wu Jixia , Zhang Haiyan , Gao Feng , Wang Zhaoping , Zhang Aidi , Chen Yishui , Xu Yuanyuan , Zhu Fangfang , Li Youzhong , Zhao Hong , Meng Ying , Shou Guangli , Li Qiang , Xu Wenfang , Li Qianqian , Ye Ming , Shi Peng , Liu Yang , Sun Wenping , Li Dong , Sun Wei , Feng Wei , Li Ji , Song Tianqi , Li Dawei , Guo Jidong , Wang Yan , Gu Juxian , Liu Xiqi , An Zexin , Cui Ningning , Yan Qiuyue , Zhao Ting , Bai Xue , Zheng Wenxin , Bao Zhonglei , Lu Dan , Fang Kun , Zhang Yan , Wang Linwen , Yuan Yating , Peng Xin , Yan Helian , Mei Li , Yuan Hongli , Wu Yujuan , Zhou Yuni , Hou Xianfeng , Liu Yuanliang , Song Xueqin , Shen Ruile , Cao Chunyan , Zhang Jianqiang , Zhang Canfei , Zhang Weixiong , Zhang Zhen , Liu Baoru , Cao Xiaoshuai , Chen Wenna , Du Xiaowei , Bai Yongjie , He Shuang , Shi Xiaohong , Yang Lei , Jiang Shan , Yuan Lipin , Li Gang , Huang Yue , Bai Yingying , Chen Yanan , Liu Jianfeng , He Yonggui , Zhang Rui , Zhang Jinxia , Cao Jinying , Zhang Wenyan , Liu Xing , Mao Wenjing , Deng Chunying , Shi Mingchao , Chu Fengna , Li Yanping , Zhang Lijuan , Dong Xiaolin , Li Jiamin , Jia Wenji , Li Chunyan , Wu Xintian , Yan Yong , Ren Zhanxiu , Peng Rihong , Deng Shan , Xun Weiquan , Lin Baoquan , Lu Tao , Chen Shijian , Li Jian , Lu Xianfu , Qin Haitao , Mo Jinzu , Wei Xiao , He Cong , Wu Peihua , Huang Yan , Gao Wen , Fu Lin , Huang Guangsu , Zhou Ying , Lu Junlei , Huang Yongjun , Huang Chunying , Wu Yufen , Guo Dongli , Wang Jieqiong , Wei Yanli , Chang Hongen , Ren Aiguo , Zhou Zhengcheng , Tan Jianping , Xi Qiujiang , Xiao Lihua , Yang Hongwu , Wang Bo , Zhu Min , Zhou Yiyi , Shi Yan , Wen Qun , Luo Zhiqiang , Cheng Fuxiang , Yang Yang , Pan Linna , Tao Ran , Wu Shuguang , Qian Lai , Fan Weinv , Yu Hu , Yang Yanwen , Yang Juan , Wang Dongqing , Zhao Ying , Li Chongfeng , Li Zhuo , Liu Jiajun , Qian Na , Zhang Yingli , Gong Liying , Zhang Lei , Zhang Xia , Zhai Mingming , Zhang Chengxiang , Liu Lei , Qi Chunbo , Kui Junjie , Shi Shengsheng , Wang Rong , Lai Tianbao , Miao Jiayin , Liu Ying , Li Li , Han Bin , Zhang Xiaolei , Wang Jing , Wang Chao , Zhang Yi , Zhang Qinqin , Chen Wenjun , Sun Yaxuan , Chen Hua , Zhang Chenhong , Lv Rilang , Wang Wan , Zhang Fan , Li Hua , Gong Xiping , Wang Zhan , Ma Yuetao , Wei Na , Wu Di , Wu Jianwei , Fang Ruile , Wang Wenjuan , Hao Zilong , Wu Yakun , Tian Yueming , Shi Nan , Chen Lili , Yuan Min , Li Pei , Liu Jinghua , Wang Sujie , Zhang Jinbiao , Zhong Weibin , Wang Pengfei , Li Yan , Geng Na , Li Mengfan , Tan Ming , Zhang Haixia , Dong Liquan , Gao Ben , Yu Wenwen , Cong Yannan , Zhao Junwu , Li Huagang , Hu Qian , Li Yanling , Sun Hong , Bu Ning , Du Yun , Wang Huqing , Fan Qingyu , Zhai Yuefen , Yao Li , Xu Gang , Zhou Yanlong , Tong Qing , Wang Xiaopeng , Dong Liguo , Wang Yuqiao , Liu Sha , Duan Yinghui , Liu Youwei , Xiao Qing , Ma Xiaolin , Cao Weiwei , Yu Xiangming , Dai Xiaoxiao , Zheng Shengzhe , Xu Yinhua , Liu Chao , Duan Xiaoning , Tang Ning , Yang Xudong , Liu Junmei , Li Jiazhen , Chen Qi , Sun Zhongwen , Tian Long , Ding Na , Ren Mengyang , Wang Fang , Wu Xiaomei , Yin Jun , Yan Yin , Cao Wenying , Li Qin , Deng Jing , Dong Chongya , Huang Jihan , Huang Ruxun , Song Haiqing 
Published: September 2024

Importance

Previous studies revealed limited effectiveness of neuroprotective agents in treating acute ischemic stroke (AIS). Tongxinluo, developed from traditional Chinese medicines, has been recognized as a novel neuroprotective agent with anti-inflammatory properties that stabilize vulnerable plaques in animal models and patients with myocardial infarction.

Objective

To assess the efficacy and safety of Tongxinluo in patients with acute ischemic stroke (AIS).

Design, Setting, and Participants

This multicenter, open-label, double-blind, randomized clinical trial included 2007 patients with AIS and a National Institutes of Health Stroke Scale score between 4 and 22 at admission. The trial was conducted at 50 hospitals in China from March 1, 2014, to October 31, 2016. Data were analyzed from November 14, 2016, to November 16, 2017.

Interventions

Eligible patients were randomized within 72 hours of symptom onset to the Tongxinluo group or the control group. Participants received 4 oral capsules of Tongxinluo or placebo, 3 times a day for 90 days. Other treatment was administrated according to guidelines.

Main Outcomes and Measure

The primary outcome was a favorable functional outcome at day 90 after randomization, defined as a modified Rankin Scale (mRS) score of 0 to 1 (on a scale of 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]). All statistical analyses were performed in a modified intention-to-treat population, defined as all patients who underwent randomization, were given any treatment, and underwent any posttreatment assessment.

Results

Among 2007 patients with AIS who were randomized, 1946 (96.5%) were included in the modified intention-to-treat analysis (973 in the Tongxinluo group and 973 in the control group, with mean [SD] age of 60.5 [9.2] years and 1342 [69.0%] male). Patients in the Tongxinluo group had a significantly higher proportion of favorable functional outcomes at day 90 compared with those in the control group (mRS score of 0-1, 640 [65.8%] vs 575 [59.1%]; odds ratio, 1.33 [95% CI, 1.11-1.60]; P = .002). The prespecified subgroup analyses indicated that, among all subgroups, additional Tongxinluo treatment had similar outcomes.

Conclusions and Relevance

Among patients with ischemic stroke within 72 hours after symptom onset, those additionally receiving Tongxinluo were more likely to have a favorable functional outcome, compared with a placebo group. Further research in patients with thrombolysis and endovascular treatment are needed to explore these outcomes.

Trial registration

ClinicalTrials.gov Identifier: NCT01919671