Prourokinase vs Standard Care for Patients With Mild Ischemic Stroke
Authors: Xiong Yunyun , Meng Xia , Jin Aoming , Campbell Bruce C. V. , Xu Anding , Dong Qiang , Xu Yun , Pan Yuesong , Jiang Yong , Niu Siying , Li Zhiliang , Zhuang Xianbo , Guo Na , Yuan Zhimei , Kong Zhenyu , Zong Lixia , Duan Chunmiao , Cao Zhixin , Wang Liyuan , Hao Manjun , Wu Shuangzhe , Feng Xueyan , Li Hao , Wu Na , Li Zixiao , Zhao Xingquan , Wang Yongjun ,   PUMICE Investigators, Khatri Pooja , Fan Dongsheng , Peng Bin , Xian Ying , Chang Liguo , Yang Xiafeng , Li Jianhua , Tian Defeng , Xiong Xiaomin , Liu Xuechang , Li Fengqin , Xi Jiming , Wei Zigeng , Jiang Juan , Zhang Ming , Dai Hongguo , Cao Yunsi , Zhao Jinguo , Feng Yefang , Zhang Shuquan , Fan Bosheng , Wang Ruiyi , Ji Xiangjun , Jiang Changhao , Han Xianwen , Chen Zhongfeng , Song Zhiwei , Song Yantao , Qu Minqiang , Liu Xiaodong , Zhang Sheng , Kong Zhenyu , Zhao Yong , Li Xuekong , Yang Chunjie , Kang Zhe , Guo Wenbo , Wang Cunrui , Kong Fanping , Liu Xintong , Xiong Shujuan , Guo Jianmin , Zhu Haibao , Zhao Jiabin , Shi Xiaoqiang , Zhao Yue , He Jinzhao , Wang Hongbao , Shi Fuhua , Liu Zongtao , Gao Feng , Yu Juming , Xing Wenli , Zhang Rongpin , Wang Lijun , Wang Liying , Li Guanglei , Li Xiangqing , Gao Lianbo , Sun Zengqiang , Man Honghao , Zhao Yutie , Dang Zongyan , Wu Wei , Li Haitao , Zhao Xinxia , Xu Lihua , Wang Rui , Shi Jinfeng , Guo Baihai , Zhao Kelin , Zhai Qijin , Liang Zhigang , Chen Guanrong , Zhang Bingqi , Li Zhiliang , Zhang Hong , Bei Yuzhang , Xu Changming , Li Xiaoyan , Zhang Liang , Wang Haitao , Li Huqing , Hao Zhihua , Sun Ping , Li Xiaosong , Zheng Jianghuan , Meng Xisi , Di Weiying , Yang Hongqin , Wang Baojun 
Published: January 2025

Importance

Trials have not demonstrated superiority of alteplase or tenecteplase vs standard care in patients with mild stroke and have raised safety concerns. Prourokinase is an alternative fibrinolytic that may have a favorable safety profile, and the benefit-risk profile of prourokinase in mild stroke is unknown.

Objective

To investigate the efficacy and safety of prourokinase in mild ischemic stroke within 4.5 hours of symptom onset.

Design, Setting, and Participants

This was a multicenter, prospective, open-label, blinded–end point randomized clinical trial conducted from November 2022 through December 2023 with 3 months of follow-up. The trial was conducted at 89 hospitals in China. Patients with a baseline National Institutes of Health Stroke Scale score of 5 or less (scores range from 0-42, with higher scores indicating more severe neurological deficit) within 4.5 hours from the time the patient was last known to be well. Patients with intention to proceed to endovascular treatment were excluded.

Interventions

Eligible patients were randomly assigned in a 1:1 ratio to receive prourokinase, 35 mg (15-mg bolus + 20-mg infusion over 30 minutes) or standard care, including antiplatelet or anticoagulant therapy, at the discretion of local investigators.

Main Outcomes and Measures

The primary outcome was modified Rankin Scale score of 0 or 1 (range, 0-6, with higher scores indicating greater disability) at day 90. Safety outcomes were symptomatic intracranial hemorrhage and death.

Results

Of 3836 patients who underwent screening, 1446 (37.7%) were enrolled in the trial. Median (IQR) age was 65.9 (57.7-72.7) years, and 948 were male (65.5%). A total of 723 patients were assigned to prourokinase and 723 to standard care. The primary outcome occurred in 639 patients (88.5%) in the prourokinase group and 658 (91.0%) in the standard care group (relative risk, 0.97; 95% CI, 0.94-1.01; 2-sided P = .12). Symptomatic intracranial hemorrhage was 0.7% (5 of 723 patients) with prourokinase and 0% with standard care, and mortality at 90 days was 2.3% and 1.4%, respectively.

Conclusions and Relevance

Results of this randomized clinical trial demonstrate that prourokinase was not superior to standard care to improve the functional outcomes for patients with mild ischemic stroke within 4.5 hours after symptom onset but had a similar safety profile.

Trial Registration

ClinicalTrials.gov Identifier: NCT05507645