Late-Window Tenecteplase Improves Functional Outcomes but Increases Bleeding Risk in Non-Large Vessel Ischemic Stroke: JAMA
China: A new study of patients with non–large vessel occlusion acute ischemic stroke who had salvageable brain tissue, intravenous tenecteplase given 4.5 to 24 hours after symptom onset, improved the likelihood of an excellent functional outcome at 90 days compared with standard care. However, it was associated with a higher risk of symptomatic intracranial hemorrhage.
The findings come from the OPTION randomized clinical trial, published in JAMA, led by Gaoting Ma from the Department of Neurology at Xuanwu Hospital, Capital Medical University, Beijing, China, along with colleagues. The study addresses a long-standing clinical question regarding whether thrombolytic therapy can be safely and effectively extended beyond the conventional 4.5-hour window in patients with acute ischemic stroke caused by non–large vessel occlusion who still demonstrate viable brain tissue on imaging.
Current guidelines restrict intravenous thrombolysis to a short window after stroke onset. Advances in perfusion imaging, however, now allow identification of patients with salvageable brain tissue well beyond this period. The OPTION trial evaluated whether tenecteplase could improve outcomes when given in this extended time window.
The multicenter, randomized, open-label trial with blinded outcome assessment was conducted at 48 centers in China. From June 2023 to August 2025, 566 patients presenting 4.5 to 24 hours after last known well with salvageable tissue on imaging were enrolled and randomly assigned in a 1:1 ratio to receive intravenous tenecteplase (0.25 mg/kg; maximum 25 mg) or standard medical care.
The primary outcome was the proportion of patients achieving an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days.
The key findings of the study were as follows:
- A higher proportion of patients achieved excellent functional recovery at 90 days with tenecteplase compared with standard care (43.6% vs 34.2%), reflecting a statistically significant 28% relative increase in the likelihood of good outcomes.
- Symptomatic intracranial hemorrhage within 36 hours was observed in 2.8% of patients receiving tenecteplase, while no such events occurred in the standard care group.
- Mortality at 90 days was numerically higher in the tenecteplase group than in the control group (5.0% vs 3.2%), but this difference did not reach statistical significance.
The authors acknowledged several limitations, including the open-label design, potential variability in perfusion imaging thresholds, and the exclusive enrollment of a Chinese population, which may limit generalizability. Despite these caveats, the overall findings suggest that carefully selected patients with non–large vessel occlusion stroke may benefit from late-window thrombolysis.
In conclusion, the OPTION trial provides evidence that intravenous tenecteplase administered up to 24 hours after stroke onset can improve functional outcomes in patients with salvageable brain tissue, albeit with an increased risk of intracranial bleeding. These results support reconsidering and potentially expanding the thrombolysis time window in this specific patient population.
Reference:
Ma G, Mo R, Zuo Y, et al. Tenecteplase for Acute Non–Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke: The OPTION Randomized Clinical Trial. JAMA. Published online February 05, 2026. doi:10.1001/jama.2026.0210
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