静脉注射替奈普酶治疗发病4.5至6小时的急性缺血性卒中（EXIT - BT2）：原理与设计
Intravenous tenecteplase for acute ischemic stroke between 4.5 and 6 h of onset (EXIT-BT2): Rationale and Design.
作者信息
Wang Yi-Han, Guo Zhen-Ni, Chen Ming-Rui, Yao Zhi-Guo, Nguyen Thanh N, Saver Jeffrey L, Yang Yi, Chen Hui-Sheng
机构信息
Department of Neurology, General Hospital of Northern Theater Command, Shenyang, China.
Department of Neurology, The First Hospital of Jilin University, Changchun, China.
出版信息
Eur Stroke J. 2025 Jun;10(2):624-630. doi: 10.1177/23969873241258058. Epub 2024 Jun 10.
RATIONALE
To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal.
AIM
To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment.Sample size estimates:A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment.
DESIGN
EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5-10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines.
OUTCOME
The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0-1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (-6/+12) h after randomization.
CONCLUSIONS
The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.
理论依据
迄今为止，对于未经过高级神经影像学筛选的急性缺血性卒中（AIS）患者，静脉溶栓的获益仅限于发病4.5小时内。我们的II期EXIT-BT（丁苯酞将溶栓时间窗延长至发病后6小时）试验表明，静脉注射替奈普酶（TNK）在AIS发病4.5至6小时之间具有安全性、可行性及潜在获益。EXIT-BT2试验是一项旨在证实或反驳这一信号的关键研究。
目的
探讨TNK在发病4.5至6小时的AIS患者中，无论有无血管内治疗时的疗效和安全性。样本量估计：根据双侧0.05的显著性水平，以80%的检验效能检验优效性假设，最多需要1440例患者，按年龄、性别、糖尿病史、血管闭塞部位、基线美国国立卫生研究院卒中量表评分、卒中病因及血管内治疗计划进行分层。
设计
EXIT-BT2是一项前瞻性、随机、开放标签、终点盲法评估（PROBE）的多中心研究。发病4.5至6小时的符合条件的AIS患者按1:1随机分配至TNK组或对照组。TNK组将接受TNK（0.25mg/kg，5至10秒内单次推注，最大25mg）。对照组将按照急性缺血性卒中的国家指南接受标准医疗护理。两组将根据国家指南从随机分组至卒中发病后90天接受标准的卒中护理。
结局
主要疗效终点为良好的功能结局，定义为随机分组后90天改良Rankin量表评分为0至1分，而主要安全终点为症状性脑出血，定义为随机分组后24（-6/+12）小时内由颅内出血导致的美国国立卫生研究院卒中量表评分增加≥4分。
结论
EXIT-BT2的结果可能会确定静脉注射TNK在发病4.5至6小时的AIS患者中是否具有良好的风险/获益特征。
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