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. 2025 Oct 27:e254152.
doi: 10.1001/jamaneurol.2025.4152. Online ahead of print.

Thrombolysis With Tenecteplase for Minor Disabling Stroke: Secondary Analysis of the TEMPO-2 Randomized Clinical Trial

Yiran Zhang  1   2 , Brian H Buck  1   2 , Philip A Barber  3 , Kausik Chatterjee  4 , Brian Clarke  5 , Philip M C Choi  6   7 , Gary Hunter  8 , Aravind Ganesh  3   9   10   11 , Sachin M Mishra  1 , David Williams  12 , Bruce C V Campbell  13 , Dar Dowlatshahi  14   15 , Ken S Butcher  16 , Kailash Krishnan  17 , M Ivan Wiggam  18 , Timothy J Kleinig  19   20 , Keith W Muir  21 , Charlotte Zerna  3   22 , Thalia S Field  23 , Mayank Goyal  3   10   24 , Amy Y X Yu  25 , Christine Roffe  26 , Andrew M Demchuck  3   9   10   24   27 , Mark W Parsons  28   29 , Rodrigo Bazan  30 , Sandeep Ankolekar  31 , James Kennedy  32 , Bijoy K Menon  3   9   10   24   27 , Jennifer L Mandzia  33 , Arthur Pille  34 , Peter J Kelly  35 , Martha Marko  36 , Nishita Singh  37 , Shabnam Vatanpour  3 , Fabrico O Lima  38 , Luciana Catanese  39 , MacKenzie Horn  3 , Darshan Ghia  40   41 , Julia Ferrari  42 , Stefen Greisenegger  36 , Michael D Hill  3   9   10   24   27 , Shelagh B Coutts  3   9   10   24 ; TEMPO-2 Investigators
Collaborators, Affiliations

Thrombolysis With Tenecteplase for Minor Disabling Stroke: Secondary Analysis of the TEMPO-2 Randomized Clinical Trial

Yiran Zhang et al. JAMA Neurol. .

Abstract

Importance: Outcomes following intravenous thrombolysis for minor ischemic stroke may vary based on the presence of disabling deficits.

Objective: To determine whether intravenous tenecteplase improves outcomes according to US National Institutes of Health Stroke Scale (NIHSS) score-based definitions of pretreatment disabling deficits.

Design, setting, and participants: This is a secondary analysis of the TEMPO-2 (Tenecteplase vs Standard of Care for Minor Ischemic Stroke With Proven Occlusion) randomized clinical trial, conducted between April 27, 2015, and January 19, 2024. Patients were followed up for 90 days. The TEMPO-2 trial was conducted across 48 sites globally among patients with minor ischemic stroke (NIHSS 0-5) and proven intracranial occlusion within 12 hours of onset. Patients were divided into having nondisabling vs disabling syndromes at presentation as per the TREAT Task Force consensus. Other established definitions of disabling stroke from the ARAMIS trial and the National Institute of Neurological Disorders and Stroke trial were explored. Data analysis was completed from July 2024 to September 2024.

Interventions: Intravenous tenecteplase (0.25 mg/kg) vs nonthrombolytic standard of care.

Main outcomes and measures: The primary outcome was a return to baseline modified Rankin scale score at 90 days.

Results: Among 886 enrolled patients, 2 withdrew consent and 884 were included in the secondary analysis. Among 884 patients analyzed (369 women [41.7%]; median [IQR] age, 72 [61-80] years), 100 (11.3%) had disabling and 784 (88.7%) had nondisabling deficits. Patients with disabling deficits had higher median (IQR) baseline NIHSS scores (4 [3-5] vs 2 [1-3]), later presentations (onset to hospital arrival time: 288 [153-412] minutes vs 133 [70-310] minutes), and longer onset to treatment time (411 [307-560] minutes vs 278 [170-462] minutes) than those with nondisabling deficits. In the disabling group, the primary outcome following tenecteplase, compared with standard of care, occurred in 29 patients (54.7%) vs 32 patients (68.1%) (adjusted risk ratio [aRR], 0.81; 95% CI, 0.60-1.10). This neutral treatment effect was consistent in patients without disabling deficits (280 [73.9%] vs 306 [75.6%]; aRR, 0.98; 95% CI, 0.91-1.07; P for interaction = .32).

Conclusions and relevance: In this secondary analysis of the TEMPO-2 randomized clinical trial, current definitions of disabling symptoms based on NIHSS score at baseline did not modify the neutral treatment effect of intravenous tenecteplase in patients with minor stroke and intracranial occlusion. Together with converging evidence comparing intravenous thrombolysis to nonthrombolytic standard of care, this analysis suggests the need to reevaluate thrombolysis in minor disabling stroke.

Trial registration: ClinicalTrials.gov Identifier: NCT02398656.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ganesh reported holding stock options in Let's Get Proof (Collavidence Inc) and SnapDx and personal fees from Alexion, Biogen, Eisai, and Servier Canada outside the submitted work. Dr Wiggam reported personal fees from Boehringer Ingelheim outside the submitted work. Dr Muir reported grants from the British Heart Foundation during the conduct of the study; grants from Boehringer Ingelheim and the UK National Institute for Health and Care Research; personal fees and nonfinancial support from Boehringer Ingelheim; and personal fees from Brainomix, IschemaView, Life Molecular Imaging, and Takeda outside the submitted work. Dr Field reported personal fees from AstraZeneca, Bayer, and for providing expert witness testimony and serving as a board member of DESTINE Health and the Vancouver General Hospital Foundation outside the submitted work. Dr Yu reported grants from Canada Research Chair, the Canadian Institute of Health Research (CIHR), the Heart and Stroke Foundation of Canada, and Physician Services outside the submitted work. Dr Demchuk reported honoraria for continuing medical education lectures and advisory board work from Boehringer Ingelheim and Roche, respectively, outside the submitted work and holding a patent for Circle CVI (stroke imaging software) issued. Dr Mandzia reported grants from CIHR during the conduct of the study. Dr Pille reported personal fees from Boehringer Ingelheim outside the submitted work. Dr Marko reported personal fees from Boehringer Ingelheim and grants from Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien outside the submitted work. Dr Lima reported lecture fees from Boehringer Ingelheim Brazil during the conduct of the study. Dr Hill reported grants to the University of Calgary from Boehringer Ingelheim Canada, the CIHR, and the Heart & Stroke Foundation of Canada; grants to the University of Calgary and University of Glasgow from the British Heart Foundation during the conduct of the study; grants from the CIHR and Medtronic for the ESCAPE-MeVO study outside the submitted work; holding patients for US patent 62/086077 licensed to Circle CVI and US patent 10,916,346 licensed to Circle CVI; and serving as President of the not-for-profit Canadian Neurological Sciences Federation. Dr Coutts reported grants from the British Heart Foundation, CIHR, and the Heart and Stroke Foundation of Canada and financial support for the off-the-shelf study drug (tenecteplase) from Boehringer Ingelheim during the conduct of the study. No other disclosures were reported.

Comment in

  • doi: 10.1001/jamaneurol.2025.4164

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