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

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dc.contributor.authorYogendrakumar, V.
dc.contributor.authorCampbell, B.C.
dc.contributor.authorChurilov, L.
dc.contributor.authorGarcia-Esperon, C.
dc.contributor.authorChoi, P.M.C.
dc.contributor.authorCordato, D.J.
dc.contributor.authorGuha, P.
dc.contributor.authorSharma, G.
dc.contributor.authorChen, C.
dc.contributor.authorMcdonald, A.
dc.contributor.authorThijs, V.
dc.contributor.authorMamun, A.
dc.contributor.authorDos Santos, A.
dc.contributor.authorBalabanski, A.H.
dc.contributor.authorKleinig, T.J.
dc.contributor.authorButcher, K.S.
dc.contributor.authorDevlin, M.J.
dc.contributor.authorO'Rourke, F.
dc.contributor.authorDonnan, G.A.
dc.contributor.authorDavis, S.M.
dc.contributor.authoret al.
dc.date.issued2024
dc.description.abstractRationale: 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.
dc.description.statementofresponsibilityVignan Yogendrakumarhttp, Bruce CV Campbell, Leonid Churilov, Carlos Garcia-Esperon, Philip MC Choi, Dennis J Cordato, Prodipta Guha, Gagan Sharma, Chushuang Chenhttps, Amy McDonald, Vincent Thijs, Abul Mamun, Angela Dos Santos, Anna H Balabanski, Timothy J Kleinig, Ken S Butcher, Michael J Devlin, Fintan O'Rourke, Geoffrey A Donnan, Stephen M Davis, Christopher R Levi, Henry Ma, and Mark W Parsons, on Behalf of the ETERNAL-LVO Investigators
dc.identifier.citationInternational Journal of Stroke, 2024; 20(3):367-372
dc.identifier.doi10.1177/17474930241308660
dc.identifier.issn1747-4930
dc.identifier.issn1747-4949
dc.identifier.orcidKleinig, T.J. [0000-0003-4430-3276]
dc.identifier.urihttps://hdl.handle.net/2440/144447
dc.language.isoen
dc.publisherSAGE Publications
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1182533
dc.rights© 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).
dc.source.urihttps://doi.org/10.1177/17474930241308660
dc.subjectAcute stroke therapy; ischemic stroke; treatment; tPA; thrombolysis; TNK
dc.subject.meshHumans
dc.subject.meshTissue Plasminogen Activator
dc.subject.meshFibrinolytic Agents
dc.subject.meshTomography, X-Ray Computed
dc.subject.meshTreatment Outcome
dc.subject.meshReperfusion
dc.subject.meshProspective Studies
dc.subject.meshTime Factors
dc.subject.meshAged
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshTime-to-Treatment
dc.subject.meshTenecteplase
dc.subject.meshIschemic Stroke
dc.titleExtending 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
dc.typeJournal article
pubs.publication-statusPublished

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