Extending the Time Window for Tenecteplase by Effective Reperfusion of Penumbral Tissue in Patients with Large Vessel Occlusion (ETERNAL-LVO): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial

Vignan Yogendrakumar; Bruce Campbell; Leonid Churilov; Carlos Garcia-Esperon; Philip Choi; Dennis Cordato; Prodipta Guha; Gagan Sharma; Chushuang Chen; Amy McDonald; Vincent Thijs; Abul Mamun; Angela Dos Santos; Anna H Balabanski; Timothy Kleinig; Kenneth Butcher; Michael Devlin; Fintan O'Rourke; Geoffrey Donnan; Stephen M Davis; Christopher Levi; Henry Ma; Mark Parsons

doi:10.1177/17474930241308660

Extending the Time Window for Tenecteplase by Effective Reperfusion of Penumbral Tissue in Patients with Large Vessel Occlusion (ETERNAL-LVO): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial

Int J Stroke. 2024 Dec 9:17474930241308660. doi: 10.1177/17474930241308660. Online ahead of print.

Authors

Vignan Yogendrakumar^{1

2

3}, Bruce Campbell^{1

2}, Leonid Churilov¹, Carlos Garcia-Esperon^{4

5}, Philip Choi⁶, Dennis Cordato⁷, Prodipta Guha¹, Gagan Sharma¹, Chushuang Chen⁵, Amy McDonald¹, Vincent Thijs^{8

9}, Abul Mamun¹⁰, Angela Dos Santos^{1

10

11}, Anna H Balabanski^{1

12}, Timothy Kleinig¹³, Kenneth Butcher¹¹, Michael Devlin¹⁴, Fintan O'Rourke¹⁵, Geoffrey Donnan¹, Stephen M Davis¹, Christopher Levi^{4

5}, Henry Ma¹⁶, Mark Parsons^{2

4

5

7}

Affiliations

¹ Melbourne Brain Centre, Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
² Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
³ Division of Neurology, Department of Medicine, The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada.
⁴ Hunter New England Local Health District, New Lambton Heights, New South Wales, Australia.
⁵ Faculty of Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
⁶ Department of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, Victoria, Australia.
⁷ Department of Neurology, Liverpool Hospital, University of New South Wales, Ingham Institute, Liverpool, New South Wales, Australia.
⁸ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
⁹ Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia.
¹⁰ Department of Neurology, Campbelltown Hospital, Campbelltown, New South Wales, Australia.
¹¹ School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
¹² Department of Neuroscience, School of Translational Medicine and Alfred Health, Melbourne, Australia.
¹³ Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹⁴ Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
¹⁵ Department of Aged Care, Stroke and Rehabilitation, Bankstown-Lidcombe Hospital, Bankstown, University of New South Wales, New South Wales, Australia.
¹⁶ School of Clinical Science at Monash Health, Department of Medicine and Neurology, Monash University, Melbourne, Victoria, Australia.

PMID: 39654273
DOI: 10.1177/17474930241308660

Abstract

Rationale: The benefit of tenecteplase in the treatment of large vessel occlusion (LVO) patients presenting within 24 hours of symptom onset remains unclear.

Aim: To assess the effectiveness and safety of tenecteplase, compared to standard of care, in patients presenting within the first 24 hours of symptom onset with a LVO and target mismatch on perfusion 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 hours of stroke onset or last known well with a target mismatch on CTP or 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 a mRS of 0-2 at 3 months, an ordinal analysis of the mRS at 3 months, the proportion of patients with symptomatic intracerebral haemorrhage (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 upon the current evidence for tenecteplase in the >4.5-hour 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.

Keywords: Acute stroke therapy; Ischaemic stroke; TNK; Thrombolysis; Treatment; tPA.

Associated data

ClinicalTrials.gov/NCT04454788