Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial
Authors: 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 , Parsons Mark , Xu Jiali , Xie Suling , Liu Cheng , Han Dan , Levi Christopher R. , Wang David , Holiday Elizabeth , Cao Wenjie , Fang Kun , Dong Yi , Ge Liang , Guo Ying , Wang Deyun , Xiao Caixia , Li Dena , Feng Jinghuai , Luo Zhuangying , Yang Wen , Chen Lian , Cao Li , Zhao Yuwu , Deng Jiangshan , Li Dan , Te Rigele , Jiang Zidian , Ye Guangdong , Zhu Fuhou , Pan Yongmei , Chaoge Amuguleng , Qi Zhanchao , Li Xiangchao , Yu Ling , Tian Xinxin , Kang Lianjing , Wang Jian , Shen Yaoyan , Dai Jiying , Li Xianhuan , Zhang Yuxin , Bai Jie , Li Naichao , Su Ya , Yao Liying , Jia Qingxu , Guo Liyan , Li Yingying , Sang Haifeng , Zhao Lihua , Lu Yujuan , Zhu Chunxue , Hu Liang , Li Youmei , Liu Lingyun , Zhu Xiaoqiong , Xu Shukun , Kong Yuming , Yao Zhiwen , Xu Hui , Zhang Xiaoguang , Xue Jie , Ma Yanting , Chen Shuhua , Wan Zhiwen , Ding Ying , Li Zhizhang , Cui Xiankai , Wang Ping , Jiang Shanshan , Zhang Dong , Sun Hongxian , Feng Xiaoli , Wang Yaqiong , Ma Chunlin , Wang Tiandong , Wang Shaoshuai , Li Zuopeng , Li Jun , Wang Xiafei , Zhao Guangjian , Gong Yanxue , Zhang Shirui , Wang Liquan , Liu Xueyuan , Zhang Quanbin , Zhang Xiang , Sun Jiping , Lu You , Huang He , Gong Li , Zhou Yuchen , Qian Siyu , Li Wenjian , Shen Rui , Xu Yi , Zhao Jingjing , Wu Guang , Liu Bing , Chen Yuedong , Shen Zhan , Yuan Miao , Chen Hongtao , Qiao Lukuang , Sun Jin , Chen Weijie , Liu Wenpeng , Shen Liwei , Yang Xiaoli , Shi Yonghui , Chen Qiang , Tian Jisha , Gong Fan , Zhu Juehua , Zhou Bin , Ding Dongxue , Ji Kangxiang , Wang Jinglei , Gao Junfeng , Yang Xiaoli , Mei Hua , Chen Xiaojin , Wu Weiwei , Xue Jing , Wang Jing , Sun Hongwei , Zhai Yun , Zhang Guang , Sun Yanyan , Li Fang , Sun Hongwei , Wei Ran , Zhang Weina , Wang Xinyao , Zou Xin , Ren You , Cao Feihu , Lin Gaoping , Li Gang , Huang Zhengyu , Qiu Qianqian , Cheng Xuehong , Zhang Xiaoxi , Cai Zhiduo , Xin Ranran , Liu Dandan , Zhao JingJing , Lu Zhenchan , Jiang Xuanfei , Liu Keqin , Zhang Xiong , Mo Lijuan , Zhang Yuqing 
Published: January 2025

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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];
P
=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];
P
=0.002). There were no significant differences in clinical efficacy outcomes or rates of hemorrhagic transformation between the groups.

CONCLUSIONS:

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.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04516993.