IMPORTANCE: Whether intravenous tenecteplase prior to endovascular treatment (EVT) for ischemic stroke reduces disability in the late time window is unclear.
OBJECTIVE: To investigate the adverse events and efficacy of tenecteplase prior to EVT in patients 4.5 to 24 hours after ischemic stroke onset due to proximal middle cerebral artery (MCA) occlusion.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase 3, randomized, open-label, blinded end point, superiority trial conducted at 40 centers in China. Adult (=18 years) patients with acute ischemic stroke 4.5 to 24 hours after last known to be well due to MCA-M1 or proximal M2 occlusion with salvageable brain tissue (ischemic core volume <70 mL, mismatch ratio =1.8, and mismatch volume =15 mL) identified on computed tomography-perfusion or magnetic resonance-perfusion-diffusion imaging were enrolled from January 25, 2024, through July 21, 2025, and followed up for 90 days. Final follow-up occurred on October 14, 2025.
INTERVENTIONS: Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg) before EVT (n = 199) or EVT alone (n = 192).
MAIN OUTCOMES AND MEASURES: The primary outcome was functional independence, defined as a score of 0 to 2 on the modified Rankin Scale (range, 0-6, with higher scores indicating greater disability) at 90 days. Adverse events outcomes included symptomatic intracranial hemorrhage and death.
RESULTS: All of the 391 patients enrolled (median age, 68 years [IQR, 59-75]; 155 [39.6%] females) completed the trial. Functional independence at 90 days occurred in 88 patients (44.2%) in the tenecteplase before EVT group and 83 patients (43.2%) in the EVT alone group (adjusted relative rate, 1.01 [95% CI, 0.83-1.24]; P = .89; risk difference, 0.99% [95% CI, -8.84% to 10.83%]). Mortality within 90 days was 12.7% (25/197) in the tenecteplase before EVT group and 14.2% (27/190) in the EVT alone group. Symptomatic intracranial hemorrhage within 36 hours was 5.1% (10/197) and 2.6% (5/190), respectively.
CONCLUSIONS AND RELEVANCE: In patients presenting to EVT-capable centers 4.5 to 24 hours after stroke onset with proximal MCA occlusion, intravenous tenecteplase before EVT did not improve clinical outcomes vs EVT alone.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06221371.
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Neurology |  |
This is a trial of adults with acute ischemic stroke 4.5-24 hours after last known to be well due to MCA-M1 or proximal M2 occlusion with salvageable brain tissue (ischemic core volume <70 mL, mismatch ratio=1.8, and mismatch volume=15 mL). They were randomized to intravenous tenecteplase + endovascular treatment or endovascular treatment alone. Enrolment reached the sample size in the pretrial power calculation. There were no statistically significant between-group differences in any measured outcomes, including functional independence at 90 days, modified Rankin score, symptomatic intracranial hemorrhage, severe disability, and mortality.
This randomized study helps further define which patients with acute stroke are or are not good candidates for IV thrombolysis. While highly selected patients who are not candidates for thrombectomy may benefit within the 4.5-to-24-hour window, this study suggests that thrombolysis is not beneficial for late presenting patients who will get a thrombectomy. This study was small and there were numerically more good outcomes with thrombolysis, so it's possible there is a small net benefit that this study was underpowered to detect. For now, IV thrombolysis is not indicated in late presenting patients undergoing thrombectomy.