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

Autor:	Coutts SB; 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., Ankolekar S; Department of Neurology, King's College Hospital London, UK., Appireddy R; Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada., Arenillas JF; Stroke Program, Department of Neurology, Hospital Clínico Universitario, Valladolid, Spain; Valladolid Health Research Institute, Department of Medicine, University of Valladolid, Valladolid, Spain., Assis Z; Department of Imaging, Foothills Medical Centre, Calgary, AB, Canada; Alberta Children's Hospital, Calgary, AB, Canada., Bailey P; Griffith University, Gold Coast, QLD, Australia., Barber PA; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Bazan R; Botucatu Medical School, São Paulo State University, San Paulo, Brazil., Buck BH; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Butcher KS; School of Clinical Medicine, University of New South Wales, NSW, Australia., Camden MC; CHU de Québec-Hôpital de l'Enfant-Jésus, Quebec City, QC, Canada., Campbell BCV; Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia., Casaubon LK; University Health Network-Toronto Western Hospital, University of Toronto, Toronto, ON, Canada., Catanese L; McMaster University, Population Health Research Institute, Hamilton, ON, Canada., Chatterjee K; Countess of Chester Hospital NHS Foundation Trust, Chester, UK., Choi PMC; Department of Neuroscience, Box Hill Hospital, Eastern Health, Melbourne, VIC, Australia; Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia., Clarke B; St George's University Hospitals, London, UK., Dowlatshahi D; Department of Medicine, University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, ON, Canada., Ferrari J; Department of Neurology, St John's of God Hospital Vienna, Vienna, Austria., Field TS; Vancouver Stroke Program, Division of Neurology, University of British Columbia, Vancouver, BC, Canada., Ganesh A; 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., Ghia D; Fiona Stanley Hospital, Murdoch, Western Australia, University of Western Australia, Perth, WA, Australia., Goyal M; 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., Greisenegger S; Department of Neurology, Medical University of Vienna, Vienna, Austria., Halse O; Imperial College Healthcare Trust, London, UK., Horn M; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Hunter G; University of Saskatchewan, Saskatoon, SK, Canada., Imoukhuede O; Red Deer Regional Hospital Centre, Red Deer, AB, Canada., Kelly PJ; School of Medicine University College Dublin-Mater University Hospital Dublin, Dublin, Ireland., Kennedy J; Acute Multidisciplinary Imaging and Interventional Centre, John Radcliffe Hospital, Radcliffe Department of Medicine, University of Oxford, Oxford, UK., Kenney C; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Kleinig TJ; Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia; Department of Medicine, University of Adelaide, Adelaide, SA, Australia., Krishnan K; Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK., Lima F; Hospital Geral De Fortaleza, Fortaleza, Brazil., Mandzia JL; Department of Clinical Neurological Sciences, Western University, London, ON, Canada., Marko M; Department of Neurology, Medical University of Vienna, Vienna, Austria., Martins SO; Hospital de Clínicas de Porto Alegre, Hospital Moinhos de Vento, Porto Alegre, Brazil., Medvedev G; Royal Columbian Hospital, University of British Columbia, Vancouver, BC, Canada., Menon BK; 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., Mishra SM; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Molina C; Vall d'Hebron Stroke Center, Hospital Vall d'Hebron, Barcelona, Spain., Moussaddy A; Montreal Neurological Institute, McGill University Health Centre, Montreal, QC, Canada., Muir KW; School of Neuroscience and Psychology, University of Glasgow, Glasgow, UK., Parsons MW; Department of Neurology, Liverpool Hospital, UNSW South West Sydney, Sydney, NSW, Australia., Penn AMW; Victoria General Hospital, Victoria, BC, Canada., Pille A; Neurology Department, Hospital Moinhos de Vento, Porto Alegre, Brazil., Pontes-Neto OM; Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil., Roffe C; Stroke Research, Keele University, Stoke-on-Trent, UK., Serena J; Stroke Unit, Neurology Department, Hospital Trueta de Girona, Fundació Institut d'Investigació Biomèdica de Girona Dr Josep Trueta, Girona, Spain., Simister R; University College Hospitals London, London, UK., Singh N; Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada., Spratt N; 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., Strbian D; Department of Neurology, Helsinki University Hospital and University ofHelsinki, Helsinki, Finland., Tham CH; National Neuroscience Institute, Singapore., Wiggam MI; Royal Victoria Hospital, Belfast, UK., Williams DJ; RCSI University of Medicine and Health Sciences and Beaumont Hospital, Dublin, Ireland., Willmot MR; University Hospitals Birmingham NHS Trust, Birmingham, UK., Wu T; Department of Neurology, Christchurch Hospital, Christchurch, New Zealand., Yu AYX; Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., Zachariah G; Cambridge University Hospitals NHS Trust, Cambridge, UK., Zafar A; Unity Health Toronto, St Michael's Hospital, Toronto, ON, Canada., Zerna C; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Städtisches Klinikum Dresden, Dresden, Germany., Hill MD; 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.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2024 Jun 15; Vol. 403 (10444), pp. 2597-2605. Date of Electronic Publication: 2024 May 17.
DOI:	10.1016/S0140-6736(24)00921-8
Abstrakt:	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. Competing Interests: Declaration of interests SBC received grant funding from the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada (HSFC), and the British Heart Foundation (BHF) to complete the TEMPO-2 study. Boehringer Ingelheim provided off-the-shelf study drug (tenecteplase) for the study. JFA has received public research grants from the Spanish Ministry of Science, the regional health department, the European Commission, and a private research grant from AstraZeneca. He has received consultant or speaker fees from Pfizer-BMS, Medtronic, and Amgen, and travel support from Daiichi-Sankyo. KSB reports speaker fees from Boehringer Ingelheim and AstraZeneca. LC has received consulting or speakers fees from Roche. JF reports speaker fees from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Pfizer, Sankyo, and Daiichi. AG reports a grant from Microvention; speaker fees from Alexion, Biogen, and Servier Canada; and stock options for SnapDx and Collavidence. DG reports honoraria from Boehringer Ingelheim, Ipsen, and Eisai. MG reports grant funding from Medtronic and Cerenovus and consulting fees from Mentice, CSL Behring, MicroVention, and Medtronic. TSF participated in an advisory board for Roche. FL reports speaker fees and travel support from Boehringer Ingelheim. BKM has been paid honoraria from Boehringer Ingelheim and Roche. MM has received honoraria from Boehringer Ingelheim for participation at an advisory board on the approval of tenecteplase for treatment of acute ischaemic stroke. SOM has received speaker fees from Boehringer, Medtronic, Penumbra, Bayer, Pfizer, Novartis, Novo Nordisk, Servier, and Daiichi Sankyo. KWM reports grant funding from the BHF, and the Stroke Association; consultancy fees from Boehringer Ingelheim, Biogen, IschaemaView; lecture fees from Boehringer Ingelheim, IschaemaView, and Brainomix; and non-financial support (drug supply for ATTEST-2 trial) from Boehringer Ingelheim. MWP is on Boehringer Ingelheim Advisory Board for Metalyse in stroke. AP received speaker fees from Boehringer Ingelheim and travel support from AstraZeneca for attending a meeting. OMP-N has received speaker fees from Boehringer Ingelheim and AstraZeneca. RS is part funded by the UCLH Biomedical Research Centre. DS reports an unrestricted educational grant from Boehringer Ingelheim. MIW reports sponsorship or financial assistance to support attendance at scientific meetings from Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo UK, and Bayer; honoraria for lectures given at education meetings from Boehringer Ingelheim, Bristol Myers Squibb, and AstraZeneca; and payment for participation in advisory panels from Boehringer Ingelheim and Daiichi Sankyo UK. DJW is the Co-principal Investigator for Health Research Board of Ireland, Award–Improving Pathways for Acute Stroke and Rehabilitation. AYXY reports salary support from the HSFC. MDH reports grant funding from CIHR, HSFC, Alberta Innovates, and study drug from Boehringer Ingelheim; grants from NoNo and Medtronic; consulting fees from Sun Pharma Brainsgate; and a DSMB member role on many stroke clinical trials. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu