Vignan Yogendrakumar, Bruce C V Campbell, Leonid Churilov, Carlos Garcia-Esperon, Philip M C Choi, Dennis J Cordato, Niruta Dhimal, Liudmyla Olenko, Prodipta Guha, Gagan Sharma, Chushuang Chen, 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, Mark W Parsons
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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.</p><p><strong>Results: </strong>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]; <i>P</i>=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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04454788.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial.\",\"authors\":\"Vignan Yogendrakumar, Bruce C V Campbell, Leonid Churilov, Carlos Garcia-Esperon, Philip M C Choi, Dennis J Cordato, Niruta Dhimal, Liudmyla Olenko, Prodipta Guha, Gagan Sharma, Chushuang Chen, 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, Mark W Parsons\",\"doi\":\"10.1161/STROKEAHA.125.052511\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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]; <i>P</i>=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]). 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Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial.
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.
期刊介绍：
Stroke is a monthly publication that collates reports of clinical and basic investigation of any aspect of the cerebral circulation and its diseases. The publication covers a wide range of disciplines including anesthesiology, critical care medicine, epidemiology, internal medicine, neurology, neuro-ophthalmology, neuropathology, neuropsychology, neurosurgery, nuclear medicine, nursing, radiology, rehabilitation, speech pathology, vascular physiology, and vascular surgery.
The audience of Stroke includes neurologists, basic scientists, cardiologists, vascular surgeons, internists, interventionalists, neurosurgeons, nurses, and physiatrists.
Stroke is indexed in Biological Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts, CINAHL, Current Contents, Embase, MEDLINE, and Science Citation Index Expanded.
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