Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial

Vignan Yogendrakumar^{1

2

3}, Bruce C V Campbell^{2

3}, Leonid Churilov³, Carlos Garcia-Esperon^{4

5}, Philip M C Choi⁶, Dennis J Cordato⁷, Niruta Dhimal⁷, Liudmyla Olenko³, Prodipta Guha², Gagan Sharma², Chushuang Chen⁵, Amy McDonald², Vincent Thijs^{8

9}, Abul Mamun¹⁰, Angela Dos Santos^{2

11

10}, Anna H Balabanski^{2

12}, Timothy J Kleinig¹³, Ken S Butcher¹¹, Michael J Devlin¹⁴, Fintan O'Rourke¹⁵, Geoffrey A Donnan², Stephen M Davis², Christopher R Levi^{4

5}, Henry Ma^{1

16}, Mark W Parsons^{3

4

5

7}; ETERNAL-LVO Investigators

Collaborators, Affiliations

Collaborators

ETERNAL-LVO Investigators:
Nawaf Yassi, Bernard Yan, Michael Valente, Henry Zhao, Angelos Sharobeam, Laura Fisicchia, David Jackson, Peter Mitchell, Richard Dowling, Hannah Johns, Birendra Rokaha, Andrew Bivard, Ashley Park, Margaret Ma, Presaad Pillai, James Beharry, Helen Dewey, Tessa Busch, Malcohm Chung, Narelle Stuart, Peter Park, Branko Borojevic, Joseph Wong, Channa Senanayake, Oneil Bhalala, Karen Robinson, Bailey McNamara, Edward Callaly, Tanya Frost, Karen Stephens, Pakeeran Siriratnam, Ross Cody, Tharani Chandran, Casey Linton, Nathaniel Lizak, Shelton Leung, Peter Tan, Dennis Young, Felix Ng, Gayleen Chappell, Thanh Phan, Marie Veronic Hervet, Carol Bendall, Jennifer Cranefield, Roy Drew, Neil Spratt, Beng Lim, Alvin Chew, Michelle Russell, Shu Ren, Julie Hennessy, Leon Edwards, Christopher Blair, Timmy Pham, Jasmeen Khan, Longting Lin, Rumbidzai Teramayi

Affiliations

¹ Division of Neurology, Department of Medicine, The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, ON, Canada (V.Y.).
² Department of Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. (V.Y., B.C.V.C., P.G., G.S., A. McDonald, A.D.S., A.H.B., G.A.D., S.M.D.).
³ Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. (V.Y., B.C.V.C., L.C., L.O., M.W.P.).
⁴ Hunter New England Local Health District, New Lambton Heights, New South Wales, Australia (C.G.-E., C.R.L., M.W.P.).
⁵ Faculty of Medicine, University of Newcastle, New South Wales, Australia (C.G.-E., C.C., C.R.L., M.W.P.).
⁶ Department of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, Victoria, Australia (P.M.C.C.).
⁷ Department of Neurology, Liverpool Hospital, University of New South Wales, Ingham Institute, Australia. (D.J.C., N.D., M.W.P.).
⁸ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. (V.T.).
⁹ Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia (V.T.).
¹⁰ Department of Neurology, Campbelltown Hospital, Campbelltown, New South Wales, Australia (A. Mamun, A.D.S.).
¹¹ School of Clinical Medicine, University of New South Wales, Ingham Institute, Australia. (A.D.S., K.S.B.).
¹² Department of Neuroscience, School of Translational Medicine and Alfred Health, Melbourne, Australia (A.H.B.).
¹³ Department of Neurology, Royal Adelaide Hospital, South Australia, Australia (T.J.K.).
¹⁴ Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia (M.J.D.).
¹⁵ Department of Aged Care, Stroke and Rehabilitation, Bankstown-Lidcombe Hospital, Bankstown (F.O.R.).
¹⁶ Department of Medicine and Neurology, School of Clinical Science at Monash Health, Monash University, Melbourne, Victoria, Australia (H.M.).

PMID: 40927857
DOI: 10.1161/STROKEAHA.125.052511

Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial

Vignan Yogendrakumar et al. Stroke. 2025.

. 2025 Sep 10.

doi: 10.1161/STROKEAHA.125.052511. Online ahead of print.

Authors

Collaborators

ETERNAL-LVO Investigators:
Nawaf Yassi, Bernard Yan, Michael Valente, Henry Zhao, Angelos Sharobeam, Laura Fisicchia, David Jackson, Peter Mitchell, Richard Dowling, Hannah Johns, Birendra Rokaha, Andrew Bivard, Ashley Park, Margaret Ma, Presaad Pillai, James Beharry, Helen Dewey, Tessa Busch, Malcohm Chung, Narelle Stuart, Peter Park, Branko Borojevic, Joseph Wong, Channa Senanayake, Oneil Bhalala, Karen Robinson, Bailey McNamara, Edward Callaly, Tanya Frost, Karen Stephens, Pakeeran Siriratnam, Ross Cody, Tharani Chandran, Casey Linton, Nathaniel Lizak, Shelton Leung, Peter Tan, Dennis Young, Felix Ng, Gayleen Chappell, Thanh Phan, Marie Veronic Hervet, Carol Bendall, Jennifer Cranefield, Roy Drew, Neil Spratt, Beng Lim, Alvin Chew, Michelle Russell, Shu Ren, Julie Hennessy, Leon Edwards, Christopher Blair, Timmy Pham, Jasmeen Khan, Longting Lin, Rumbidzai Teramayi

Affiliations

¹ Division of Neurology, Department of Medicine, The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, ON, Canada (V.Y.).
² Department of Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. (V.Y., B.C.V.C., P.G., G.S., A. McDonald, A.D.S., A.H.B., G.A.D., S.M.D.).
³ Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. (V.Y., B.C.V.C., L.C., L.O., M.W.P.).
⁴ Hunter New England Local Health District, New Lambton Heights, New South Wales, Australia (C.G.-E., C.R.L., M.W.P.).
⁵ Faculty of Medicine, University of Newcastle, New South Wales, Australia (C.G.-E., C.C., C.R.L., M.W.P.).
⁶ Department of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, Victoria, Australia (P.M.C.C.).
⁷ Department of Neurology, Liverpool Hospital, University of New South Wales, Ingham Institute, Australia. (D.J.C., N.D., M.W.P.).
⁸ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. (V.T.).
⁹ Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia (V.T.).
¹⁰ Department of Neurology, Campbelltown Hospital, Campbelltown, New South Wales, Australia (A. Mamun, A.D.S.).
¹¹ School of Clinical Medicine, University of New South Wales, Ingham Institute, Australia. (A.D.S., K.S.B.).
¹² Department of Neuroscience, School of Translational Medicine and Alfred Health, Melbourne, Australia (A.H.B.).
¹³ Department of Neurology, Royal Adelaide Hospital, South Australia, Australia (T.J.K.).
¹⁴ Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia (M.J.D.).
¹⁵ Department of Aged Care, Stroke and Rehabilitation, Bankstown-Lidcombe Hospital, Bankstown (F.O.R.).
¹⁶ Department of Medicine and Neurology, School of Clinical Science at Monash Health, Monash University, Melbourne, Victoria, Australia (H.M.).

PMID: 40927857
DOI: 10.1161/STROKEAHA.125.052511

Abstract

Background: To assess the efficacy and safety of tenecteplase in patients presenting within 24 hours of symptom onset with a large vessel occlusion and target mismatch on perfusion computed tomography.

Methods: ETERNAL-LVO was a prospective, randomized, open-label, blinded end point, phase 3, superiority trial where adult participants with a large vessel occlusion, presenting within 24 hours of onset with salvageable tissue on computed tomography perfusion, were randomized to tenecteplase 0.25 mg/kg or standard care across 11 primary and comprehensive stroke centers in Australia. The primary outcome was the modified Rankin Scale score of 0 to 1 or return to baseline at 90 days via a modified Poisson regression model. Secondary outcomes include the modified Rankin Scale, considered as an ordinal variable, and symptomatic intracerebral hemorrhage.

Results: Following trial initiation, a supply shortage of the investigational product hindered recruitment. When supply resumed, phase 3 evidence had emerged supporting tenecteplase use within 4.5 hours of stroke onset, including large vessel occlusion. ETERNAL-LVO was, therefore, terminated early. Two hundred forty-two participants (median age: 73 years, 43% female, 79% undergoing EVT) were included in the modified intention-to-treat analysis; 120 received tenecteplase and 122 received standard care. No difference in the primary outcome was observed between the tenecteplase (n=44, 37%) and standard care (n=52, 43%; adjusted risk ratio, 0.90 [95% CI, 0.66-1.21]; P=0.48). No significant differences in an ordinal analysis of the modified Rankin Scale were observed between the 2 treatment groups. In a planned per-protocol analysis, the odds of improvement by 1 point in the modified Rankin Scale were doubled in the tenecteplase-treated transfer subgroup compared with standard care transfer patients (odds ratio, 2.61 [95% CI, 1.07-6.40]). Symptomatic intracerebral hemorrhage occurred in 5 (4%) participants assigned to tenecteplase and was present in 1 (1%) participant assigned to standard care.

Conclusions: Treatment with tenecteplase did not increase the likelihood of a favorable functional outcome, but early stoppage of the study prevents definitive conclusions from being drawn.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04454788.

Keywords: cerebral hemorrhage; hematoma; perfusion; tenecteplase; tomography.

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Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial

Collaborators

Affiliations

Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial

Authors

Collaborators

Affiliations

Abstract

Associated data

LinkOut - more resources

Full Text Sources

Medical