Cheng Xin, Hong Lan, Lin Longting, Churilov Leonid, Ling Yifeng, Yang Nan, Fu Jianliang, Lu Guozhi, Yue Yunhua, Zhang Jin, Wang Feng, Wang Ziran, Zhao Yanxin, Zhou Xiaoyu, Peng Zhaolong, Wu Danhong, Zhao Liandong, Zhai Qijin, Yu Xiaofei, Fang Qi, Shao Xiangzhong, Tang Ying, Zhang Diwen, Geng Yu, Zhang Yue, Fan Bosheng, Zhang Bing, Yin Congguo, Chen Yangmei, Zhang Yiran, Liu Xinyu, Li Siyuan, Yang Lumeng, Parsons Mark, Dong Qiang
Department of Neurology, National Center for Neurological Disorders, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China (X.C., L.H., Y.L., Yiran Zhang, X.L., S.L., L.Y., Q.D.).
Department of Neurology, Ingham Institute for Applied Medical Research, University of New South Wales South Western Sydney Clinical School, Australia (L.L., M.P.).
Stroke. 2025 Feb;56(2):344-354. doi: 10.1161/STROKEAHA.124.048375. Epub 2025 Jan 2.
Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.
Patients with ischemic stroke presenting 4.5 to 24 hours from the last known well, with a favorable penumbral profile and an associated large/medium vessel occlusion, were randomized 1:1 to either 0.25 mg/kg tenecteplase or the best medical treatment. A favorable penumbral profile was defined as a hypoperfusion lesion volume to infarct core volume ratio >1.2, with an absolute volume difference >10 mL, and an ischemic core volume <70 mL. The primary outcome was the achievement of major reperfusion without symptomatic intracranial hemorrhage within 24 to 48 hours post-randomization. Major reperfusion was defined as the restoration of blood flow of >50% of the involved ischemic territory. Secondary outcomes included recanalization, infarct growth, major neurological improvements, change in the National Institutes of Health Stroke Scale score, hemorrhagic transformation within 24 to 48 hours, systemic bleeding at discharge, and modified Rankin Scale (score 0-1, score 0-2, score 5-6, and modified Rankin Scale distribution) at 90 days. The comparison of the primary outcome between groups was conducted using modified Poisson regression with a log-link function and robust error variance, adjusted for time from the last known well to randomization, the site of vessel occlusion, and planned endovascular treatment.
Among 224 enrolled patients, 111 were assigned to receive tenecteplase and 113 to receive the best medical treatment (including 23% [n=26] of participants who received intravenous tissue-type plasminogen activator). The mean (SD) age of the tenecteplase group and the best medical treatment group was 64.2 (10.4) and 63.6 (11.0) years old, with 72.1% (n=80) and 70.8% (n=80) male enrolled, respectively. A proportion of 54.9% (n=123) of patients were transferred to the catheter room for preplanned endovascular treatment. The primary outcome occurred in 33.3% (n=37) of the tenecteplase group versus 10.8% (n=12) in the best medical treatment group (adjusted relative risk, 3.0 [95% CI, 1.6-5.7]; =0.001). Tenecteplase significantly increased the recanalization rate compared with the best medical treatment (35.8% [n=39] versus 14.3% [n=16], adjusted relative risk, 2.5 [95% CI, 1.4-4.4]; =0.002). There were no significant differences in clinical efficacy outcomes or rates of hemorrhagic transformation between the groups.
Administered at a dose of 0.25 mg/kg intravenously, tenecteplase increased reperfusion without symptomatic intracranial hemorrhage in patients with ischemic stroke selected by imaging in late-time window treatment but did not change clinical outcomes at 90 days.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04516993.
将静脉溶栓的时间窗延长至最后一次已知健康状态后的24小时是否有效和安全尚不清楚。我们旨在确定替奈普酶在延长时间窗内治疗中国急性缺血性卒中伴大/中血管闭塞患者的疗效和安全性。
最后一次已知健康状态后4.5至24小时出现缺血性卒中、具有良好半暗带特征且伴有大/中血管闭塞的患者，按1:1随机分为接受0.25mg/kg替奈普酶治疗组或最佳药物治疗组。良好半暗带特征定义为低灌注病变体积与梗死核心体积之比>1.2，绝对体积差>10mL，且缺血核心体积<70mL。主要结局是随机分组后24至48小时内实现主要再灌注且无症状性颅内出血。主要再灌注定义为受累缺血区域血流恢复>50%。次要结局包括再通、梗死灶扩大、主要神经功能改善、美国国立卫生研究院卒中量表评分变化、24至48小时内出血转化、出院时全身出血以及90天时改良Rankin量表（0-1分、0-2分、5-6分以及改良Rankin量表分布）。采用具有对数链接函数和稳健误差方差的改良泊松回归对组间主要结局进行比较，并根据从最后一次已知健康状态到随机分组的时间、血管闭塞部位和计划的血管内治疗进行调整。
在224例入组患者中，111例被分配接受替奈普酶治疗，113例接受最佳药物治疗（包括23%[n=26]接受静脉注射组织型纤溶酶原激活剂的参与者）。替奈普酶组和最佳药物治疗组的平均（标准差）年龄分别为64.2（10.4）岁和63.6（11.0）岁，男性入组比例分别为72.1%（n=80）和70.8%（n=80）。54.9%（n=123）的患者被转至导管室进行预先计划的血管内治疗。主要结局在替奈普酶组中发生率为33.3%（n=37），在最佳药物治疗组中为10.8%（n=12）（校正相对风险，3.0[95%CI，1.6-5.7]；P=0.001）。与最佳药物治疗相比，替奈普酶显著提高了再通率（35.8%[n=39]对14.3%[n=16]，校正相对风险，2.5[95%CI，1.4-4.4]；P=0.002）。两组间临床疗效结局或出血转化发生率无显著差异。
静脉注射剂量为0.25mg/kg时，替奈普酶可使晚期时间窗治疗中经影像学筛选的缺血性卒中患者增加再灌注且无症状性颅内出血，但90天时未改变临床结局。
