Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial

Parsons, Mark W.; Yogendrakumar, Vignan; Ng, Felix C.; Deepak, Akshay; Choi, Philip M. C.; Kleinig, Timothy J.; Cordato, Dennis J.; Wu, Teddy Y.; Fink, John N.; Ma, Henry; Phan, Thanh G.; Markus, Hugh S.; Churilov, Leonid; Molina, Carlos A.; Tsai, C-H; Lee, J-T; Jeng, J-S; Strbian, D; Meretoja, A; Arenillas, JF; Buck, BH; Devlin, MJ; Brown, H; Garcia-Esperon, Carlos; Butcher, KS; O'Brien, B; Sabet, A; Wijeratne, T; Bivard, A; Grimley, RS; Agarwal, S; Munshi, SK; Donnan, GA; Davis, SM; Campbell, Bruce C. V.; Miteff, Ferdinand; Spratt, Neil J.; Levi, Christopher R.; TASTE investigators,; Russell, Michelle L.; Sharma, Gagan; Chen, Chushuang; Lin, Longting; Chew, Beng Lim

Title: Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial
Creator: Parsons, Mark W.; Yogendrakumar, Vignan; Ng, Felix C.; Deepak, Akshay; Choi, Philip M. C.; Kleinig, Timothy J.; Cordato, Dennis J.; Wu, Teddy Y.; Fink, John N.; Ma, Henry; Phan, Thanh G.; Markus, Hugh S.; Churilov, Leonid; Molina, Carlos A.; Tsai, C-H; Lee, J-T; Jeng, J-S; Strbian, D; Meretoja, A; Arenillas, JF; Buck, BH; Devlin, MJ; Brown, H; Garcia-Esperon, Carlos; Butcher, KS; O'Brien, B; Sabet, A; Wijeratne, T; Bivard, A; Grimley, RS; Agarwal, S; Munshi, SK; Donnan, GA; Davis, SM; Campbell, Bruce C. V.; Miteff, Ferdinand; Spratt, Neil J.; Levi, Christopher R.; TASTE investigators,; Russell, Michelle L.; Sharma, Gagan; Chen, Chushuang; Lin, Longting; Chew, Beng Lim
Relation: NHMRC.GNT1079696 http://purl.org/au-research/grants/nhmrc/1079696
Relation: Lancet Neurology Vol. 23, Issue 8, p. 775-786
Publisher Link: http://dx.doi.org/10.1016/S1474-4422(24)00206-0
Publisher: The Lancet Publishing Group
Resource Type: journal article
Date: 2024
Description: Background: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. Methods: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0–1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of −0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. Findings: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63–82), baseline National Institutes of Health Stroke Scale score of 7 (4–11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI −0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [−0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI −0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI −0·02 to 0·05]). Interpretation: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible.
Subject: patient; perfusion imaging; ischaemic stroke; alteplase; SDG 3; Sustainable Development Goal
Identifier: http://hdl.handle.net/1959.13/1509470
Identifier: uon:56246
Identifier: ISSN:1474-4422
Language: eng
Reviewed

Hits: 1245
Visitors: 1228
Downloads: 0