Tenecteplase for Acute Non–Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke

Importance The efficacy and safety of intravenous tenecteplase in non–large vessel occlusion acute ischemic stroke beyond 4.5 hours after symptom onset remain uncertain. Objective To assess the efficacy and safety of intravenous tenecteplase administered 4.5 to 24 hours after stroke onset in patients with non–large vessel occlusion and salvageable brain tissue. Design, Setting, and Participants This randomized, open-label, blinded end-point clinical trial was conducted at 48 centers in China. A total of 566 patients with non–large vessel occlusion stroke and evidence of potentially salvageable tissue determined on perfusion imaging presenting within 4.5 to 24 hours of the time last seen well were recruited between June 2, 2023, and August 4, 2025 (final follow-up, October 28, 2025). Interventions Patients were randomly assigned 1:1 using a minimization algorithm to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg; n = 282) or standard medical treatment (n = 284). Main Outcomes and Measures The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin Scale at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and mortality within 90 days. Results Among the 570 patients randomized, 566 were included in the primary analysis (median age, 68 IQR, 59-75 years; 196 female 34.6%). An excellent functional outcome was observed in 123 of 282 patients (43.6%) in the tenecteplase group and 97 of 284 (34.2%) in the control group (risk ratio, 1.28 95% CI, 1.04-1.57; P = .02). The incidence of symptomatic intracranial hemorrhage at 2.8% was higher with tenecteplase than with standard medical treatment at 0% (risk difference, 2.85% 95% CI, 1.16%-5.54%; P = .004), and the mortality at 90 days was 5.0% and 3.2%, respectively (risk ratio, 1.57 95% CI, 0.69-3.57; P = .28). Conclusions and Relevance Among patients with non–large vessel occlusion acute ischemic stroke and salvageable brain tissue, intravenous tenecteplase administered 4.5 to 24 hours after onset resulted in a greater likelihood of an excellent functional outcome at 90 days than standard care but had an increased risk of symptomatic intracranial hemorrhage. Trial Registration ClinicalTrials.gov Identifier: NCT05752916