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