• Shelagh B Coutts, Sandeep Ankolekar, Ramana Appireddy, Juan F Arenillas, Zarina Assis, Peter Bailey, Philip A Barber, Rodrigo Bazan, Brian H Buck, Ken S Butcher, Marie-Christine Camden, CampbellBruce C VBCVDepartment of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia., Leanne K Casaubon, Luciana Catanese, Kausik Chatterjee, ChoiPhilip M CPMCDepartment of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, VIC, Australia; Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia., Brian Clarke, Dar Dowlatshahi, Julia Ferrari, Thalia S Field, Aravind Ganesh, Darshan Ghia, Mayank Goyal, Stefan Greisenegger, Omid Halse, Mackenzie Horn, Gary Hunter, Oje Imoukhuede, Peter J Kelly, James Kennedy, Carol Kenney, Timothy J Kleinig, Kailash Krishnan, Fabricio Lima, Jennifer L Mandzia, Martha Marko, Sheila O Martins, George Medvedev, Bijoy K Menon, Sachin M Mishra, Carlos Molina, Aimen Moussaddy, Keith W Muir, Mark W Parsons, Andrew M W Penn, Arthur Pille, Octávio M Pontes-Neto, Christine Roffe, Joaquin Serena, Robert Simister, Nishita Singh, Neil Spratt, Daniel Strbian, Carol H Tham, M Ivan Wiggam, David J Williams, Mark R Willmot, Teddy Wu, YuAmy Y XAYXNeurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., George Zachariah, Atif Zafar, Charlotte Zerna, Michael D Hill, and TEMPO-2 investigators.
• Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: scoutts@ucalgary.ca.
• Lancet. 2024 Jun 15; 403 (10444): 259726052597-2605.

BackgroundIndividuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.MethodsIn this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual.FindingsThe trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059).InterpretationThere was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis.FundingHeart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

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