Intra-Arterial Urokinase After Endovascular Reperfusion for Acute Ischemic Stroke
Authors: Chang Liu, Changwei Guo, Fengli Li, Nizhen Yu, Jiacheng Huang, Zhouzhou Peng, Weilin Kong, Jiaxing Song, Xiang Liu, Shitao Fan, Chengsong Yue, Boyu Chen, Chong Zheng, Xingyun Yuan, Jian Sheng, Youlin Wu, Bo Sun, Zengqiang Zhao, Minzhen Zhu, Ling Han, Qiang Shi, Zhongbin Xia, Xianjin Shang, Fengguang Li, Rongzong Li, Feixue Yue, Shunfu Jiang, Dengwen Song, Min Song, Yuanjun Shan, Chawen Ding, Li Yao, Yong Yang, Junbin Chen, Wencheng He, Feibao Pan, Wensheng Zhang, Tieying Cai, Shibo Han, Wei Li, Gongbo Li, Chen Gong, Liping Huang, Cheng Huang, Duolao Wang, Johannes Kaesmacher, Thanh N. Nguyen, Raul G. Nogueira, Jeffrey L. Saver, Wenjie Zi, Yangmei Chen, Qingwu Yang, Tao Qiu, Yihong Huang, Dai Zheng, Zhongyong Peng, Sizhi Tang, Chuang Li, Rongtong Li, Yongtao Guo, Chaoxiong Shen, Xiurong Zhu, Yugang Wang, Lei Zhang, Haitao Guan, Tao Xu, Jie Yang, Linyu Li, Dahong Yang, Jinfu Ma, Xu Xu, Xiaolei Shi, Shihai Yang, Wenzhe Sun, Zhixi Wang, Shuyu Jiang, Zhiyuan Wang
Journal: JAMA (2025)

Importance Persisting or new thrombi in the distal arteries and the microcirculation have been reported to limit the benefits of successful endovascular thrombectomy for patients with acute ischemic stroke. It remains uncertain whether intra-arterial thrombolysis by urokinase following near-complete to complete reperfusion by thrombectomy improves outcomes among patients with ischemic stroke due to large vessel occlusion. Objective To assess the efficacy and adverse events of intra-arterial urokinase after near-complete to complete reperfusion by thrombectomy for acute ischemic stroke due to large vessel occlusion. Design, Setting, and Participants This investigator-initiated, randomized, open-label, blinded–end point trial was implemented at 35 hospitals in China, enrolling 535 patients with proximal intracranial large vessel occlusion presenting within 24 hours of time last known well, who achieved near-complete or complete reperfusion by endovascular thrombectomy and did not receive intravenous thrombolysis prior to the procedure. Recruitment took place between November 15, 2022, and March 29, 2024, with final follow-up on July 4, 2024. Interventions Eligible patients were randomly assigned to the intra-arterial urokinase group (a single dose of intra-arterial 100 000 IU urokinase injected in the initial target territory; n = 267) or control group (without intra-arterial thrombolysis; n = 267). Main Outcomes and Measures The primary efficacy outcome was the percentage of patients achieving survival without disability (modified Rankin Scale score of 0 or 1) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. Results A total of 535 patients were enrolled (median age, 69 years; 223 [41.8%] female) and 532 (99.6%) completed the trial. The percentage of patients with survival without disability at 90 days was 45.1% (120/266) in the intra-arterial urokinase group and 40.2% (107/266) in the control group (adjusted risk ratio, 1.13 [95% CI, 0.94-1.36]; P = .19). Mortality at 90 days (18.4% vs 17.3%, respectively; adjusted hazard ratio, 1.06 [95% CI, 0.71-1.59]; P = .77) and incidence of symptomatic intracranial hemorrhage (4.1% vs 4.1%, respectively; adjusted risk ratio, 1.05 [95% CI, 0.45-2.44]; P = .91) were not significantly different between groups. Conclusions and Relevance Among patients with acute ischemic stroke due to large vessel occlusion, adjunct intra-arterial urokinase after near-complete to complete reperfusion by endovascular thrombectomy did not significantly increase the likelihood of survival without disability at 90 days. Trial Registration ChiCTR.org.cn Identifier: ChiCTR2200065617