• Mark W Parsons, Vignan Yogendrakumar, Leonid Churilov, Carlos Garcia-Esperon, CampbellBruce C VBCVMelbourne Brain Centre, Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia., Michelle L Russell, Gagan Sharma, Chushuang Chen, Longting Lin, Beng Lim Chew, Felix C Ng, Akshay Deepak, ChoiPhilip M CPMCDepartment of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, VIC, Australia., Timothy J Kleinig, Dennis J Cordato, Teddy Y Wu, John N Fink, Henry Ma, Thanh G Phan, Hugh S Markus, Carlos A Molina, Chon-Haw Tsai, Jiunn-Tay Lee, Jiann-Shing Jeng, Daniel Strbian, Atte Meretoja, Juan F Arenillas, Brian H Buck, Michael J Devlin, Helen Brown, Ken S Butcher, Billy O'Brien, Arman Sabet, Tissa Wijeratne, Andrew Bivard, Rohan S Grimley, Smriti Agarwal, Sunil K Munshi, Geoffrey A Donnan, Stephen M Davis, Ferdinand Miteff, Neil J Spratt, Christopher R Levi, and TASTE investigators.
• Department of Neurology, Liverpool Hospital, University of New South Wales, Ingham Institute, Liverpool, NSW, Australia; Melbourne Brain Centre, Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia; Hunter New England Local Health District, New Lambton Heights, NSW, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; Faculty of Medicine, University of Newcastle, Newcastle, NSW, Australia. Electronic address: mark.parsons@unsw.edu.au.
• Lancet Neurol. 2024 Aug 1; 23 (8): 775786775-786.

BackgroundIntravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging.MethodsThis international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed.FindingsRecruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]).InterpretationThe findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible.FundingAustralian National Health Medical Research Council; Boehringer Ingelheim.Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

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