Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.
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Author
Coutts, Shelagh BAnkolekar, Sandeep
Appireddy, Ramana
Arenillas, Juan F
Assis, Zarina
Bailey, Peter
Barber, Philip A
Bazan, Rodrigo
Buck, Brian H
Butcher, Ken S
Camden, Marie-Christine
Campbell, Bruce C V
Casaubon, Leanne K
Catanese, Luciana
Chatterjee, Kausik
Choi, Philip M C
Clarke, Brian
Dowlatshahi, Dar
Ferrari, Julia
Field, Thalia S
Ganesh, Aravind
Ghia, Darshan
Goyal, Mayank
Greisenegger, Stefan
Halse, Omid
Horn, Mackenzie
Hunter, Gary
Imoukhuede, Oje
Kelly, Peter J
Kennedy, James
Kenney, Carol
Kleinig, Timothy J
Krishnan, Kailash
Lima, Fabricio
Mandzia, Jennifer L
Marko, Martha
Martins, Sheila O
Medvedev, George
Menon, Bijoy K
Mishra, Sachin M
Molina, Carlos
Moussaddy, Aimen
Muir, Keith W
Parsons, Mark W
Penn, Andrew M W
Pille, Arthur
Pontes-Neto, Octávio M
Roffe, Christine
Serena, Joaquin
Simister, Robert
Singh, Nishita
Spratt, Neil
Strbian, Daniel
Tham, Carol H
Wiggam, M Ivan
Williams, David J
Willmot, Mark R
Wu, Teddy
Yu, Amy Y X
Zachariah, George
Zafar, Atif
Zerna, Charlotte
Hill, Michael D
Publication date
2024-05-17
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Background: Individuals 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. Methods: In 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. Findings: The 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). Interpretation: There 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. Funding: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.Citation
Coutts SB, Ankolekar S, Appireddy R, Arenillas JF, Assis Z, Bailey P, Barber PA, Bazan R, Buck BH, Butcher KS, Camden MC, Campbell BCV, Casaubon LK, Catanese L, Chatterjee K, Choi PMC, Clarke B, Dowlatshahi D, Ferrari J, Field TS, Ganesh A, Ghia D, Goyal M, Greisenegger S, Halse O, Horn M, Hunter G, Imoukhuede O, Kelly PJ, Kennedy J, Kenney C, Kleinig TJ, Krishnan K, Lima F, Mandzia JL, Marko M, Martins SO, Medvedev G, Menon BK, Mishra SM, Molina C, Moussaddy A, Muir KW, Parsons MW, Penn AMW, Pille A, Pontes-Neto OM, Roffe C, Serena J, Simister R, Singh N, Spratt N, Strbian D, Tham CH, Wiggam MI, Williams DJ, Willmot MR, Wu T, Yu AYX, Zachariah G, Zafar A, Zerna C, Hill MD; TEMPO-2 investigators. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial. Lancet. 2024 Jun 15;403(10444):2597-2605. doi: 10.1016/S0140-6736(24)00921-8. Epub 2024 May 17. Erratum in: Lancet. 2024 Jun 15;403(10444):2596. doi: 10.1016/S0140-6736(24)01209-1.Type
ArticleOther
Additional Links
http://www.sciencedirect.com/science/journal/01406736PMID
38768626Journal
The LancetPublisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1016/S0140-6736(24)00921-8