Tenecteplase for Acute Non–Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke
Gaoting Ma, Ran Mo, Yingting Zuo, Qingfeng Ma, Guangjian Zhao, Xiaoxi Yao, J. Liang, Li Zhou, Yong He, Faqing Long, Zhengzhou Yuan, Lei Liu, Guosheng Han, Yan Tan, Zhibing Ai, C.S. Cai, Juan Liu, Liyong Zhang, Haihua Yang, Tingyu Yi, Li Li, Yao Fu, Yanxing Zhang, Xiangzhong Shao, Zhipeng Yu, Saizhen Wu, Yanqiu Du, Lingqun Mao, Hongling Guo, Xufeng Chen, Y Chen, Qiong Zhao, Liyi Chi, Yi Liu, H. Zhang, Guangzong Li, Shujuan Meng, Yue Wu, Jieying Wu, Ziying Jiang, Shaoyuan Lei, Daiquan Gao, Lianmei Zhong, Jens Fiehler, Duolao Wang, Thanh N. Nguyen, Jeffrey L. Saver, Junwei Hao, OPTION Investigators, Guixia Fu, Ming Hu, Qiang Meng, Yujie Jia, GUANGQIN PAN, Ling Liu, Linghua Kong, Qiujiang Xi, L L Liu, Pengfei Wang, Wenjun Qian, Xuying He, Xiaoli Wang, Shifeng Guo, Yutong Ma, Wei Liu, Yangtai Guan, Wei Li, Y J Yang, Dong Wei, Xiaoying Yao, Zhangning Zhao, Li Meng, Xiang Luo, Haiting Li
Abstract
Importance: The efficacy and safety of intravenous tenecteplase in non-large vessel occlusion acute ischemic stroke beyond 4.5 hours after symptom onset remain uncertain. Objective: To assess the efficacy and safety of intravenous tenecteplase administered 4.5 to 24 hours after stroke onset in patients with non-large vessel occlusion and salvageable brain tissue. Design, Setting, and Participants: This randomized, open-label, blinded end-point clinical trial was conducted at 48 centers in China. A total of 566 patients with non-large vessel occlusion stroke and evidence of potentially salvageable tissue determined on perfusion imaging presenting within 4.5 to 24 hours of the time last seen well were recruited between June 2, 2023, and August 4, 2025 (final follow-up, October 28, 2025). Interventions: Patients were randomly assigned 1:1 using a minimization algorithm to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg; n = 282) or standard medical treatment (n = 284). Main Outcomes and Measures: The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and mortality within 90 days. Results: Among the 570 patients randomized, 566 were included in the primary analysis (median age, 68 [IQR, 59-75] years; 196 female [34.6%]). An excellent functional outcome was observed in 123 of 282 patients (43.6%) in the tenecteplase group and 97 of 284 (34.2%) in the control group (risk ratio, 1.28 [95% CI, 1.04-1.57]; P = .02). The incidence of symptomatic intracranial hemorrhage at 2.8% was higher with tenecteplase than with standard medical treatment at 0% (risk difference, 2.85% [95% CI, 1.16%-5.54%]; P = .004), and the mortality at 90 days was 5.0% and 3.2%, respectively (risk ratio, 1.57 [95% CI, 0.69-3.57]; P = .28). Conclusions and Relevance: Among patients with non-large vessel occlusion acute ischemic stroke and salvageable brain tissue, intravenous tenecteplase administered 4.5 to 24 hours after onset resulted in a greater likelihood of an excellent functional outcome at 90 days than standard care but had an increased risk of symptomatic intracranial hemorrhage. Trial Registration: ClinicalTrials.gov Identifier: NCT05752916.