Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

Autor:	Menon BK; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Calgary, Canada. Electronic address: bkmmenon@ucalgary.ca., Buck BH; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Singh N; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Deschaintre Y; Department of Neurosciences, Université de Montréal, Montreal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada., Almekhlafi MA; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Calgary, Canada., Coutts SB; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Calgary, Canada., Thirunavukkarasu S; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Khosravani H; Department of Medicine (Division of Neurology), Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., Appireddy R; Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada., Moreau F; Université de Sherbrooke, Sherbrooke, QC, Canada., Gubitz G; Queen Elizabeth Health Sciences Centre, Halifax, NS, Canada., Tkach A; Kelowna General Hospital, Kelowna, BC, Canada., Catanese L; Hamilton Health Sciences Centre and McMaster University, Hamilton, ON, Canada., Dowlatshahi D; Department of Medicine, University of Ottawa and the Ottawa Heart Research Institute, Ottawa, ON, Canada., Medvedev G; University of British Columbia and the Fraser Health Authority, New Westminster, BC, Canada., Mandzia J; London Health Sciences Centre and Western University, London, ON, Canada., Pikula A; Toronto Western Hospital and the University of Toronto, Toronto, ON, Canada., Shankar J; University of Manitoba, Winnipeg, MB, Canada., Williams H; Queen Elizabeth Hospital, Charlottetown, PE, Canada., Field TS; Vancouver Stroke Program and the Division of Neurology, University of British Columbia, Vancouver, BC, Canada., Manosalva A; Medicine Hat Regional Hospital, Medicine Hat, AB, Canada., Siddiqui M; Grey Nuns Community Hospital, Edmonton, AB, Canada., Zafar A; St Michael's Hospital, Toronto, ON, Canada., Imoukhuede O; Red Deer Regional Hospital, Red Deer, AB, Canada., Hunter G; University of Saskatchewan, Saskatoon, SK, Canada., Demchuk AM; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Calgary, Canada., Mishra S; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Gioia LC; Department of Neurosciences, Université de Montréal, Montreal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada., Jalini S; Division of Neurology, Department of Medicine, Queen's University, Kingston, ON, Canada., Cayer C; Centre de recherche du CHUS, Centre intégré Universitaire de Santé et des Services Sociaux de l'Estrie, Sherbrooke, QC, Canada., Phillips S; Queen Elizabeth Health Sciences Centre, Halifax, NS, Canada., Elamin E; Kelowna General Hospital, Kelowna, BC, Canada., Shoamanesh A; Hamilton Health Sciences Centre and McMaster University, Hamilton, ON, Canada., Subramaniam S; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Kate M; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Jacquin G; Department of Neurosciences, Université de Montréal, Montreal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada., Camden MC; Enfant-Jésus Hospital, Centre Hospitalier Universitaire de Québec, Laval University, Québec City, QC, Canada., Benali F; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Alhabli I; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Bala F; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Horn M; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Stotts G; Department of Medicine, University of Ottawa and the Ottawa Heart Research Institute, Ottawa, ON, Canada., Hill MD; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, Calgary, Canada., Gladstone DJ; Department of Medicine (Division of Neurology), Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., Poppe A; Department of Neurosciences, Université de Montréal, Montreal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada., Sehgal A; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Zhang Q; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Lethebe BC; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada., Doram C; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Ademola A; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada., Shamy M; Department of Medicine, University of Ottawa and the Ottawa Heart Research Institute, Ottawa, ON, Canada., Kenney C; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada., Sajobi TT; Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine and Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada., Swartz RH; Department of Medicine (Division of Neurology), Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Jazyk:	angličtina
Zdroj:	Lancet (London, England) [Lancet] 2022 Jul 16; Vol. 400 (10347), pp. 161-169. Date of Electronic Publication: 2022 Jun 29.
DOI:	10.1016/S0140-6736(22)01054-6
Abstrakt:	Background: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. Methods: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. Findings: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. Funding: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit. Competing Interests: Declaration of interests BKM has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. SBC is principal investigator of the TEMPO-2 trial, for which Boehringer Ingelheim provides the study drug (tenecteplase). LC has received payments by Servier and consulting fees from Ischaemavie RAPID, Circle NV, and Canadian Medical Protective Association. JS has a grant from Medtronic to the University of Manitoba. AMD has received consulting fees from Medtronic and honoraria from Boehringer Ingelheim. LCG is on advisory boards for AstraZeneca and Servier and has stock options in AstraZenca. ASh has received consulting fees from Bayer, Servier Canada, Daiichi Sanyko Compan, AstraZeneca, VarmX, and Takeda; honoraria from Bayer and Daiichi Sankyo; is on an advisory board for Bayer; and has stock options in Ensho. MDH has received consulting fees from Sun Pharma and Brainsgate and has stock options in Circle NVI. DJG has received consulting fees from HSL Therapeutics. APo has received a project research grant from Stryker and honoraria from BMS-Pfizer. TTS has received consulting fees from Circle NVI. RHS has stock options in FollowMD and receives salary support for research from the Heart & Stroke Foundation of Canada, Sandra Black Centre for Brain Resilience & Recovery, and Ontario Brain Institute. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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