Yogendrakumar, V.Campbell, B.C.Churilov, L.Garcia-Esperon, C.Choi, P.M.C.Cordato, D.J.Guha, P.Sharma, G.Chen, C.Mcdonald, A.Thijs, V.Mamun, A.Dos Santos, A.Balabanski, A.H.Kleinig, T.J.Butcher, K.S.Devlin, M.J.O'Rourke, F.Donnan, G.A.Davis, S.M.et al.2025-05-092025-05-092024International Journal of Stroke, 2024; 20(3):367-3721747-49301747-4949https://hdl.handle.net/2440/144447Rationale: 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, blindedendpoint, 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.en© 2024 World Stroke Organization. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).Acute stroke therapy; ischemic stroke; treatment; tPA; thrombolysis; TNKHumansTissue Plasminogen ActivatorFibrinolytic AgentsTomography, X-Ray ComputedTreatment OutcomeReperfusionProspective StudiesTime FactorsAgedFemaleMaleTime-to-TreatmentTenecteplaseIschemic StrokeJournal article10.1177/17474930241308660723121Kleinig, T.J. [0000-0003-4430-3276]