通过有效再灌注大血管闭塞患者的半暗带组织来延长替奈普酶的时间窗：一项多中心、前瞻性、随机、开放标签、盲终点、对照3期试验的原理与设计
Extending the time window for tenecteplase by effective reperfusion of penumbral tissue in patients with large vessel occlusion: Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial.
作者信息
Yogendrakumar Vignan, Campbell Bruce Cv, Churilov Leonid, Garcia-Esperon Carlos, Choi Philip Mc, Cordato Dennis J, Guha Prodipta, Sharma Gagan, Chen Chushuang, McDonald Amy, Thijs Vincent, Mamun Abul, Dos Santos Angela, Balabanski Anna H, Kleinig Timothy J, Butcher Ken S, Devlin Michael J, O'Rourke Fintan, Donnan Geoffrey A, Davis Stephen M, Levi Christopher R, Ma Henry, Parsons Mark W
机构信息
Department of Neurology, Melbourne Brain Centre, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
Department of Medicine, The University of Melbourne, Parkville, VIC, Australia.
出版信息
Int J Stroke. 2025 Mar;20(3):367-372. doi: 10.1177/17474930241308660. Epub 2024 Dec 31.
RATIONALE
The benefit of tenecteplase in the treatment of large vessel occlusion (LVO) patients presenting within 24 h of symptom onset remains unclear.
AIM
This study aimed to assess the effectiveness and safety of tenecteplase, compared to standard of care, in patients presenting within the first 24 h of symptom onset with an LVO and target mismatch on perfusion computed tomography (CT).
METHODS AND DESIGN
The "Extending the time window for Tenecteplase by Effective Reperfusion of peNumbrAL tissue in patients with Large Vessel Occlusion" (ETERNAL-LVO) trial is a prospective, randomized, open-label, blinded-endpoint, phase 3, parallel-group, superiority trial with covariate-adjusted 1:1 randomization, and adaptive sample size re-estimation. Patients with an anterior circulation LVO stroke, who present within 24 h of stroke onset or last known well with a target mismatch on computed tomography perfusion (CTP) or magnetic resonance imaging (MRI), will be randomized to tenecteplase (0.25 mg/kg) or standard of care (alteplase 0.90 mg/kg or conservative management at clinician discretion) prior to undergoing endovascular therapy.
STUDY OUTCOMES
The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) of 0-1 (no disability) or return to baseline mRS at 3 months. Secondary and safety outcomes include the proportion of patients with an mRS of 0-2 at 3 months, an ordinal analysis of the mRS at 3 months, the proportion of patients with symptomatic intracerebral hemorrhage (sICH), the proportion of patients with death due to any cause, and the proportion of patients with mRS 5-6 at 3 months (severe disability or death).
DISCUSSION
The ETERNAL-LVO trial will build on the current evidence for tenecteplase in the > 4.5-h window. Specifically, this trial will evaluate tenecteplase in a patient population who have access to endovascular therapy but may incur delays to endovascular therapy commencement or require transfer from a primary to a comprehensive stroke center.
TRIALS REGISTRATION
ClincialTrials.gov: NCT04454788.
理论依据
替奈普酶治疗症状发作24小时内出现大血管闭塞（LVO）患者的获益尚不清楚。
目的
本研究旨在评估与标准治疗相比，替奈普酶对症状发作24小时内出现LVO且灌注计算机断层扫描（CT）显示存在目标不匹配的患者的有效性和安全性。
方法与设计
“通过有效再灌注大血管闭塞患者的半暗带组织来延长替奈普酶的时间窗”（ETERNAL-LVO）试验是一项前瞻性、随机、开放标签、盲终点、3期、平行组、优效性试验，采用协变量调整的1:1随机化，并进行适应性样本量重新估计。前循环LVO卒中患者，在卒中发作24小时内或最后一次已知健康状态时，计算机断层扫描灌注（CTP）或磁共振成像（MRI）显示存在目标不匹配，将在接受血管内治疗前随机分为替奈普酶组（0.25mg/kg）或标准治疗组（阿替普酶0.90mg/kg或由临床医生酌情进行保守治疗）。
研究结果
主要结局是改良Rankin量表（mRS）评分为0 - 1（无残疾）或3个月时恢复至基线mRS的患者比例。次要结局和安全性结局包括3个月时mRS评分为0 - 2的患者比例、3个月时mRS的序贯分析、症状性脑出血（sICH）患者比例、任何原因导致的死亡患者比例以及3个月时mRS为5 - 6的患者比例（严重残疾或死亡）。
讨论
ETERNAL-LVO试验将基于替奈普酶在>4.5小时时间窗内的现有证据。具体而言，本试验将评估替奈普酶在可接受血管内治疗但可能延迟开始血管内治疗或需要从初级卒中中心转至综合卒中中心的患者群体中的疗效。
试验注册
ClinicalTrials.gov：NCT04454788。
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