Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

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; Bruce Campbell; Leanne K Casaubon; Luciana Catanese; Kausik Chatterjee; Philip M C Choi; 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; Fabrico 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; Amy Y X Yu; George Zachariah; Atif Zafar; Charlotte Zerna; Michael D Hill; TEMPO-2 investigators

doi:10.1016/S0140-6736(24)00921-8

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Lancet. 2024 May 16:S0140-6736(24)00921-8. doi: 10.1016/S0140-6736(24)00921-8. Online ahead of print.

Authors

Shelagh B Coutts¹, Sandeep Ankolekar², Ramana Appireddy³, Juan F Arenillas⁴, Zarina Assis⁵, Peter Bailey⁶, Philip A Barber⁷, Rodrigo Bazan⁸, Brian H Buck⁹, Ken S Butcher¹⁰, Marie-Christine Camden¹¹, Bruce Campbell¹², Leanne K Casaubon¹³, Luciana Catanese¹⁴, Kausik Chatterjee¹⁵, Philip M C Choi¹⁶, Brian Clarke¹⁷, Dar Dowlatshahi¹⁸, Julia Ferrari¹⁹, Thalia S Field²⁰, Aravind Ganesh²¹, Darshan Ghia²², Mayank Goyal²³, Stefan Greisenegger²⁴, Omid Halse²⁵, Mackenzie Horn⁷, Gary Hunter²⁶, Oje Imoukhuede²⁷, Peter J Kelly²⁸, James Kennedy²⁹, Carol Kenney⁷, Timothy J Kleinig³⁰, Kailash Krishnan³¹, Fabrico Lima³², Jennifer L Mandzia³³, Martha Marko²⁴, Sheila O Martins³⁴, George Medvedev³⁵, Bijoy K Menon³⁶, Sachin M Mishra⁹, Carlos Molina³⁷, Aimen Moussaddy³⁸, Keith W Muir³⁹, Mark W Parsons⁴⁰, Andrew M W Penn⁴¹, Arthur Pille⁴², Octávio M Pontes-Neto⁴³, Christine Roffe⁴⁴, Joaquin Serena⁴⁵, Robert Simister⁴⁶, Nishita Singh⁴⁷, Neil Spratt⁴⁸, Daniel Strbian⁴⁹, Carol H Tham⁵⁰, M Ivan Wiggam⁵¹, David J Williams⁵², Mark R Willmot⁵³, Teddy Wu⁵⁴, Amy Y X Yu⁵⁵, George Zachariah⁵⁶, Atif Zafar⁵⁷, Charlotte Zerna⁵⁸, Michael D Hill⁵⁹; TEMPO-2 investigators

Collaborators

TEMPO-2 investigators:
Marina Salluzzi, Nicole Blenkin, Ashley Dueck, Craig Doram, Qiao Zhang, Carol Kenney, Karla Ryckborst, Shelly Bohn, Quentin Collier, Frances Taylor, B Cord Lethebe, Anitha Jambula, Kayla Sage, Lana Toussaint, Supryia Save, Jaclyn Lee, N Laham, A A Sultan, A Deepak, A Sitaram, Andrew M Demchuk, A Lockey, A Micielli, A Wadhwa, B Arabambi, B Graham, Chrysi Bogiatzi, Darshan Doshi, D Chakraborty, Diana Kim, D Vasquez, D Singh, Dominic Tse, E Harrison, E E Smith, E Teleg, E Klourfeld, G Klein, I A Sebastian, J Evans, J Hegedus, J Kromm, K Lin, K Ignacio, Kimia Ghavami, M Ismail, M Moores, M A Panzini, M Boyko, M A Almekhlafi, Nancy Newcommon, N Maraj, O Imoukhuede, O Volny, Peter Stys, Phillipe Couillard, P Ojha, P Eswaradass, Raed Joundi, R Singh, R M Asuncion, R T Muir, S Dey, S Mansoor, S Wasyliw, S Nagendra, Sherry Hu, S Althubait, S Chen, S Bal, Stephen Van Gaal, Steven Peters, Sucharita Ray, S Chaturvedi, Suresh Subramaniam, Vivian Fu, K Villaluna, G Maclean, P King-Azote, C Ma, A Plecash, C Murphy, J Gorman, L Wilson, L Zhou, O Benevente, P Teal, S Yip, S Mann, B Dewar, M Demetroff, R Shamloul, R Beardshaw, S Roberts, D Blaquiere, G Stotts, M Shamy, O Bereznyakova, R Fahed, W Alesefir, Suzy Lavoie, A Hache, K Collard, A Mackey, S Gosselin-Lefebvre, S Verreault, B Beauchamp, L Lambourn, A Khaw, L Mai, L Sposato, M Bres Bullrich, R Azarpazhooh, S Fridman, A Kapoor, A Southwell, E Bardi, I Fatakdawala, M Kamra, K Lopes, N Popel, V Norouzi, A Liu, A M Liddy, B Ghoari, C Hawkes, C A Enriquez, D J Gladstone, H A Manosalva Alzate, H Khosravani, J J Hopyan, K Sivakumar, M Son, M I Boulos, M A Hamind, R H Swartz, R Murphy, S Reiter, T Fitzpatrick, V Bhandari, J Good, M Penn, M Naylor, S Frost, A Cayley, F Akthar, J Williams, L Kalman, L Crellin, R Wiegner, R S Singh, T Stewart, W To, S Singh, A Pikula, C Jaigobin, F Carpani, F Silver, H Janssen, J Schaafsma, M Del Campo, M Alskaini, P Rajendram, P Fairall, B Granfield, D Crawford, J Jabs, L White, L Sivakumar, L Piquette, T Nguyen, A Nomani, A Wagner, A Alrohimi, A Butt, A D'Souza, B Gajurel, C Vekhande, H Kamble, H Kalashyan, M Lloret, M Benguzzi, N Arsalan, N Ishaque, R Ashayeriahmadabad, R Samiento, S Hosseini, S Kazi, S Das, T Sugumar, D Selchen, P Kostyrko, A Muccilli, A G Saposnik, C Vandervelde, K Ratnayake, S McMillan, A Katsanos, A Shoamanesh, D J Sahlas, V Naidoo, V Todorov, H Toma, J Brar, J Lee, M Horton, S Chen, E Shand, S Weatherby, A Jin, B Durafourt, S Jalini, A Gardner, C Tyson, E Junk, K Foster, K Bolt, N Sylvain, S Maley, L Urroz, L Peeling, M Kelly, R Whelan, R Cooley, J Teitelbaum, A Boutayeb, A Moore, E Cole, L Waxman, N Ben-Amor, R Sanchez, S Khalil, A Nehme, C Legault, D Tampieri, E Ehrensperger, L Vieira, M Cortes, M Angle, M Hannouche, M Badawy, K Werner, S Wieszmuellner, A Langer, A Gisold, H Zach, P Rommer, S Macher, S Blechinger, W Marik, W Series, M Baumgartinger, S Krebs, J Koski, S Eirola, T Ivanoff, A Erakanto, L Kupari, G Sibolt, J Panula, L Tomppo, M Tiainen, M Ahlstrom, N Martinez Majander, O Suomalainen, S Raty, C Levi, E Kerr, J Allen, L P Kaauwai, L Belevski, M Russell, S Ormond, A Chew, A Loiselle, A Royan, B Hughes, C Garcia Esperon, E Pepper, F Miteff, J He, M Lycett, M Min, N Murray, N Pavey, R Starling de Barros, S Gangadharan, S Dunkerton, S Waller, T Canento Sanchez, T Wellings, G Edmonds, K A Whittaker, M Ewing, P Lee, R Singkang, A McDonald, A Dos Santos, C Shin, D Jackson, J Tsoleridis, L Fisicchia, N Parsons, N Shenoy, S Smith, A Sharobeam, A Balabanski, A Park, C Williams, D Pavlin-Premri, E Rodrigues, F Alemseged, F Ng, H Zhao, J Beharry, J L Ng, J Williamson, J Z W Wong, K Li, M K Kwan, M Valente, N Yassi, R Cooley, V Yogendrakumar, B McNamara, C Buchanan, C McCarthy, G Thomas, K Stephens, M Chung, M F Chung, M Tang, T Busch, T Frost, R Lee, N Stuart, N Pachani, A Menon, B Borojevic, C M Linton, G Garcia, E P Callaly, H Dewey, J Liu, J Chen, J Wong, K Nowak, K To, N S Lizak, O Bhalala, P Park, P Tan, R Martins, R Cody, R Forbes, S K Chen, S Ooi, S Tu, Y L Dang, Z Ling, J Cranefield, R Drew, A Tan, C Kurunawai, J Harvey, J J Mahadevan, L Cagi, L Palanikumar, L N Chia, R Goh, S El-Masri, B Urbi, C Rapier, H Berrill, H McEvoy, R Dunning, S Kuriakose, T Chad, V Sapaen, A Sabet, D Shah, D Yeow, K Lilley, K Ward, M Mozhy Mahizhnan, M Tan, C Lynch, S Coveney, K Tobin, J McCabe, M Marnane, S Murphy, M Large, B Moynihan, K Boyle, E Sanjuan, M Sanchis, S Boned, O Pancorbo, V Sala, L Garcia, A Garcia-Tornel, J Juega, J Pagola, K Santana, M Requena, M Muchada, M Olive, P J Lozano, M Rubiera, M Deck, N Rodriguez, B Gomez, F J Reyes Munoz, A S Gomez, A C Sanz, E C Garcia, G Penacoba, M E Ramos, M de Lera Alfonso, A Feliu, L Pardo, P Ramirez, A Murillo, D Lopez Dominguez, J Rodriguez, M Terceno Izaga, M Reina, S B Viturro, U Bojaryn, V A Vera Monge, Y Silva Blas, R R Siew, S J Agustin, C Seet, T Tianming, A d'Emden, A Murray, A Welch, K Hatherley, N Day, W Smith, E MacRae, E S Mitchell, A Mahmood, J Elliot, S Neilson, V Biswas, C Brown, A Lewis, A Ashton, D Werring, R Perry, R Muhammad, Y C Lee, A Black, A Robinson, A Williams, A Banaras, C Cahoy, G Raingold, M Marinescu, N Atang, N Bason, N Francia, S Obarey, S Feerick, J Joseph, U Schulz, R Irons, J Benjamin, L Quinn, M Jhoots, R Teal, G Ford, G Harston, H Bains, I Gbinigie, P Mathieson, R Irons, C H Sim, E Hayter, K Kennedy, L Binnie, N Priestley, R Williams, R Ghatala, S Stratton, A Blight, L Zhang, A Davies, H Duffy, J Roberts, J Homer, K Roberts, K Dodd, K Cawley, M Martin, S Leason, S Cotgreave, T Taylor, A Nallasivan, S Haider, T Chakraborty, T Webster, A Gil, B Martin, B Joseph, C Cabrera, D Jose, J Man, J Aquino, S Sebastian, M Osterdahl, M Kwan, M Matthew, N Ike, P Bello, P Wilding, R Fuentes, R Shah, S Mashate, T Patel, U Nwanguma, V Dave, A Haber, A Lee, A O'Sullivan, B Drumm, A C Dawson, T Matar, V Biswas, D Roberts, E Taylor, E Rounis, A El-Masry, C O'Hare, D Kalladka, S Jamil, S Auger, O Raha, M Evans, F Vonberg, S Kalam, A Ali Sheikh, I H Jenkins, J George, J Kwan, J Blagojevic, M Saeed, M Haji-Coll, M Tsuda, M Sayed, N Winterkron, N Thanbirajah, O Vittay, R Karim, R C Smail, S Gauhar, S Elmamoun, S Malani, S Pralhad Kelavkar, J Hiden, P Ferdinand, R Sanyal, R Varquez, B Smith, C Okechukwu, E Fox, E Collins, K Courtney, S Tauro, C Patterson, D McShane, E Kerr, G Roberts, J McIImoyle, K McGuire, P Fearon, P Gordon, K Isaacs, K Lucas, L Smith, L Dews, M Bates, S Lawrence, S Heeley, V Patel, Y M Chin, D Sims, E Littleton, J Khaira, K Nadar, A Kieliszkowska, B Sari, C Domingos Belo, E Smith, E Y Manolo, J Aeron-Thomas, M Doheny, M Garcia Pardo, M Recaman, M C Tibajia, M Aissa, Y Mah, T Yu, V Patel, S Meenakshisundaram, S Heller, R Alsukhni, O Williams, M Farag, M Benger, A Engineer, M Aissa, S Bayhonan, S Conway, A Bhalla, D Nouvakis, E Theochari, F Boyle, J Teo, J King-Robson, K Y Law, L Sztriha, M Ismail, A McGovern, D Day, J Mitchell-Douglas, J Francis, A Iqbal, P Punjabivaryani, J Anonuevo Reyes, M Anonuevo Reyes, M Pauls, A Buch, A Hedstrom, C Hutchinson, C Kirkland, J Newham, G Wilkes, L Fleming, N Fleck, A Franca, B Chwal, C Oldoni, G Mantovani, G Noll, L Zanella, M Soma, T Secchi, W Borelli, B P Rimoli, G H da Cunha Silva, L A Machado Galvao Mondin, R Barbosa Cerantola, A K Imthon, A S Esaki, M Camilo, O C Vincenzi, R R Ds Cruz, M B Morillos, G G Riccioppa Rodrigues, K Santos Ferreira, A M Pazini, M A Pena Pereira, A L A de Albuquerque, C E Massote Fontanini, C F Matinez Rubio, D T Dos Santos, F A Dias, F F A Alves, C Milani, B Pegorer Santos, F Winckler, J T De Souza, L A M Bonome, V A Cury Silva, R S Teodoro, G P Modolo, N C Ferreira, D F Barbosa Dos Santos, J C Dos Santos Moreira, A B Cruz Guedes de Morais, J Vieira, G Mendes, J P de Queiroz

Affiliations

¹ 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.
² Department of Neurology, King's College Hospital London, UK.
³ Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada.
⁴ Stroke Program, Department of Neurology, Hospital Clínico Universitario, Valladolid, Spain; Valladolid Health Research Institute, Department of Medicine, University of Valladolid, Valladolid, Spain.
⁵ Department of Imaging, Foothills Medical Centre, Calgary, AB, Canada; Alberta Children's Hospital, Calgary, AB, Canada.
⁶ Griffith University, Gold Coast, QLD, Australia.
⁷ Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁸ Botucatu Medical School, São Paulo State University, San Paulo, Brazil.
⁹ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
¹⁰ School of Clinical Medicine, University of New South Wales, NSW, Australia.
¹¹ CHU de Québec-Hôpital de l'Enfant-Jésus, Quebec City, QC, Canada.
¹² Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
¹³ University Health Network-Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
¹⁴ McMaster University, Population Health Research Institute, Hamilton, ON, Canada.
¹⁵ Countess of Chester Hospital NHS Foundation Trust, Chester, UK.
¹⁶ Department of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, VIC, Australia; Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia.
¹⁷ St George's University Hospitals, London, UK.
¹⁸ Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, ON, Canada.
¹⁹ Department of Neurology, St John's of God Hospital Vienna, Vienna, Austria.
²⁰ Vancouver Stroke Program, Division of Neurology, University of British Columbia, Vancouver, BC, Canada.
²¹ Department of Clinical Neurosciences, 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; the O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
²² Fiona Stanley Hospital, Murdoch, Western Australia, University of Western Australia, Perth, WA, Australia.
²³ 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; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
²⁴ Department of Neurology, Medical University of Vienna, Vienna, Austria.
²⁵ Imperial College Healthcare Trust, London, UK.
²⁶ University of Saskatchewan, Saskatoon, SK, Canada.
²⁷ Red Deer Regional Hospital Centre, Red Deer, AB, Canada.
²⁸ School of Medicine University College Dublin-Mater University Hospital Dublin, Dublin, Ireland.
²⁹ Acute Multidisciplinary Imaging and Interventional Centre, John Radcliffe Hospital, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
³⁰ Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia; Department of Medicine, University of Adelaide, Adelaide, SA, Australia.
³¹ Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
³² Hospital Geral De Fortaleza, Fortaleza, Brazil.
³³ Department of Clinical Neurological Sciences, Western University, London, ON, Canada.
³⁴ Hospital de Clínicas de Porto Alegre, Hospital Moinhos de Vento, Porto Alegre, Brazil.
³⁵ Royal Columbian Hospital, University of British Columbia, Vancouver, BC, Canada.
³⁶ 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.
³⁷ Vall d'Hebron Stroke Center, Hospital Vall d'Hebron, Barcelona, Spain.
³⁸ Montreal Neurological Institute, McGill University Health Centre, Montreal, QC, Canada.
³⁹ School of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
⁴⁰ Department of Neurology, Liverpool Hospital, UNSW South West Sydney, Sydney, NSW, Australia.
⁴¹ Victoria General Hospital, Victoria, BC, Canada.
⁴² Neurology Department, Hospital Moinhos de Vento, Porto Alegre, Brazil.
⁴³ Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil.
⁴⁴ Stroke Research, Keele University, Stoke-on-Trent, UK.
⁴⁵ Stroke Unit, Neurology Department, Hospital Trueta de Girona, Fundació Institut d'Investigació Biomèdica de Girona Dr Josep Trueta, Girona, Spain.
⁴⁶ University College Hospitals London, London, UK.
⁴⁷ Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
⁴⁸ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia; Heart and Stroke Program, Hunter Medical Research Institute, Newcastle, NSW, Australia; Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia.
⁴⁹ Department of Neurology, Helsinki University Hospital and University ofHelsinki, Helsinki, Finland.
⁵⁰ National Neuroscience Institute, Singapore.
⁵¹ Royal Victoria Hospital, Belfast, UK.
⁵² RCSI University of Medicine and Health Sciences and Beaumont Hospital, Dublin, Ireland.
⁵³ University Hospitals Birmingham NHS Trust, Birmingham, UK.
⁵⁴ Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
⁵⁵ Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁵⁶ Cambridge University Hospitals NHS Trust, Cambridge, UK.
⁵⁷ Unity Health Toronto, St Michael's Hospital, Toronto, ON, Canada.
⁵⁸ Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Städtisches Klinikum Dresden, Dresden, Germany.
⁵⁹ 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; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

PMID: 38768626
DOI: 10.1016/S0140-6736(24)00921-8

Abstract

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.

Associated data

ClinicalTrials.gov/NCT02398656