• CampbellBruce C VBCVDepartment of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Park, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Richard J Dowling, Bernard Yan, Steven J Bush, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Henry Zhao, Fana Alemseged, Felix Ng, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen M Dewey, ChoiPhilip M CPMCEastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia., Helen Brown, Kendal Redmond, David Leggett, John N Fink, Wayne Collecutt, Thomas Kraemer, Martin Krause, Dennis Cordato, Deborah Field, Henry Ma, Bill O'Brien, Benjamin Clissold, Ferdinand Miteff, Anna Clissold, Geoffrey C Cloud, Leslie E Bolitho, Luke Bonavia, Arup Bhattacharya, Alistair Wright, Abul Mamun, Fintan O'Rourke, John Worthington, Andrew A Wong, Christopher R Levi, Christopher F Bladin, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis, and EXTEND-IA TNK Part 2 investigators.
• Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
• JAMA. 2020 Apr 7; 323 (13): 1257-1265.

ImportanceIntravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase.ObjectiveTo determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke.Design, Setting, And ParticipantsRandomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria.InterventionsOpen-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy.Main Outcomes And MeasuresThe primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death.ResultsAll 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]).Conclusions And RelevanceAmong patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned.Trial RegistrationClinicalTrials.gov Identifier: NCT03340493.

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