Tenecteplase Outperforms Low-Dose Alteplase Before Stroke Thrombectomy: JAMA
Japan: The T-FLAVOR trial showed that standard-dose tenecteplase was superior to low-dose alteplase as bridging thrombolytic therapy before endovascular thrombectomy (EVT) in patients with acute ischemic stroke. Conducted in a Japanese population—considered to have a higher risk of bleeding and where low-dose alteplase remains the standard treatment—the study demonstrated favorable outcomes with tenecteplase without major safety concerns.f
However, researchers noted that additional studies are needed to address concerns that tenecteplase could influence clot migration or cause distal embolization during EVT procedures.
The findings are from a randomized clinical trial published in JAMA Neurology by Manabu Inoue and colleagues. The study was designed to determine whether standard-dose tenecteplase (0.25 mg/kg) could achieve better vessel reopening before thrombectomy than low-dose alteplase (0.6 mg/kg), which continues to be widely used in Japan and several other Asian countries. Researchers emphasized that generating evidence on tenecteplase is important for potential regulatory approval and broader clinical adoption in Japan.
The investigator-initiated, multicenter, open-label trial included patients with acute ischemic stroke due to large-vessel occlusion who were eligible for intravenous thrombolysis within 4.5 hours of symptom onset and planned for mechanical thrombectomy. A total of 221 patients were randomized between August 2022 and March 2025, with 218 included in the final analysis (107 receiving tenecteplase and 111 receiving alteplase).
The primary endpoint was substantial reperfusion on the initial angiogram, while secondary assessments included 90-day functional outcomes, symptomatic intracranial hemorrhage within 24–36 hours, and 90-day mortality.
The trial revealed the following findings:
- Substantial reperfusion before thrombectomy was achieved more often in the tenecteplase group than in the alteplase group.
- Early reperfusion occurred in 10.3% of patients treated with tenecteplase compared with 3.6% of those who received alteplase.
- The difference in early reperfusion rates met the trial’s predefined criterion for superiority in favor of tenecteplase.
- Patients treated with tenecteplase showed a trend toward better functional outcomes at 90 days, although the difference was not statistically significant.
- Symptomatic intracranial hemorrhage within 24–36 hours occurred in 2.8% of patients in the tenecteplase group and 1.8% in the alteplase group.
- Mortality at 90 days was 6.5% among patients receiving tenecteplase and 9.9% among those receiving alteplase.
- Overall safety outcomes were comparable between the tenecteplase and alteplase groups.
Based on these findings, the researchers concluded that standard-dose tenecteplase administered before thrombectomy improves the likelihood of early vessel reperfusion compared with low-dose alteplase without increasing the risk of major adverse outcomes.
The results suggest that tenecteplase may represent a promising thrombolytic alternative in regions where low-dose alteplase remains the standard treatment for acute ischemic stroke caused by large-vessel occlusion.
Reference:
Inoue M, Hirano T, Fukuda-Doi M, et al. Standard-Dose Tenecteplase vs Low-Dose Alteplase for Acute Ischemic Stroke From Large-Vessel Occlusion: A Randomized Clinical Trial. JAMA Neurol. Published online June 01, 2026. doi:10.1001/jamaneurol.2026.1590
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