Intra-Arterial Tenecteplase After Successful Reperfusion in Large Vessel Occlusion Stroke

作者：Xianhua Hou, Jiacheng Huang, Li Wang, Yuxuan He, Jiaxing Song, Changwei Guo, Shihai Yang, Xiaolei Shi, Lin Chen, Qu Liu, Junfeng Su, Lin Zeng, Maojun Jiang, Boyu Chen, Xiangping Cheng, Shengli Chen, Hong‐Hua Pan, Xiaoping Shen, Youlin Wu, Xionglin Tang, Jian Wang, Shibo Han, Tianqiang Pu, Changchuan Wu, Fengguang Li, Lei Qu, Zhongjie Fu, Huan Liu, Li Yu, Bin Mei, Yanbo Cheng, Zicheng Hu, Haochun Zhang, Tao Lv, Min Wu, Rui Xu, Qinglin Ye, Liangbo Kong, Shuai Mi, Junhua Wu, Yu Wang, Zhenxuan Tian, Wenzhe Sun, Jinfu Ma, Xu Xu, Yazhou Wu, Duolao Wang, Raul G. Nogueira, Thanh N. Nguyen, Jeffrey L. Saver, Wenjie Zi, Zhenhua Zhou · 发表于：JAMA Neurology · 年份：2025 · DOI：10.1001/jamaneurol.2025.2036 · 被引用次数：25 · 研究领域：Acute Ischemic Stroke Management、Intracerebral and Subarachnoid Hemorrhage Research、Cerebrovascular and Carotid Artery Diseases

Importance: The optimal dose, safety, and efficacy of intra-arterial tenecteplase after successful reperfusion by endovascular thrombectomy for large vessel occlusion (LVO) is unknown. Objective: To evaluate the dose-dependent adverse events and signals of efficacy of intra-arterial tenecteplase in LVO after successful reperfusion with thrombectomy, defined as an Extended Treatment in Cerebral Infarction score of 2b-3. Design, Setting, and Participants: This open-label, blinded-outcome assessment trial, incorporating a 14 + 8 dose-escalation (phase 1b, nonrandomized) and dose-expansion (phase 2a, randomized) design, was conducted in China between 2023 and 2024, with follow-up continuing through November 2024. This was a multicenter clinical trial including patients with LVO and successful reperfusion within 24 hours of last known well. Interventions: In phase 1b, intra-arterial tenecteplase, 0.0313, 0.0625, 0.1250, 0.1875 mg/kg; in phase 2a, intra-arterial tenecteplase 0.0313 or 0.0625 mg/kg, or control (without intra-arterial thrombolysis). Main Outcomes and Measures: The primary outcome in phase 1b was symptomatic intracranial hemorrhage (sICH) within 24 hours. The primary outcome in phase 2a was 90-day no-disability outcome (modified Rankin Scale score 0-1). Results: A total of 205 patients (phase 1b: 48, phase 2a: 157) were enrolled and analyzed. The median (IQR) age was 71 (60-77) years, and 113 (55.1%) were male. In phase 1b, 1 of 14 and 2 of 22 patients with sICH were ...