Efficacy of Tenecteplase in Large Vessel Occlusion Stroke Within 24 Hours of Symptom Onset: The ETERNAL-LVO Randomized Controlled Trial

BACKGROUND: To assess the efficacy and safety of tenecteplase in patients presenting within 24 hours of symptom onset with a large vessel occlusion and target mismatch on perfusion computed tomography. METHODS: ETERNAL-LVO (Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients With Large Vessel Occlusion) was a prospective, randomized, open-label, blinded end point, phase 3, superiority trial where adult participants with a large vessel occlusion, presenting within 24 hours of onset with salvageable tissue on computed tomography perfusion, were randomized to tenecteplase 0.25 mg/kg or standard care across 11 primary and comprehensive stroke centers in Australia. The primary outcome was the modified Rankin Scale score of 0 to 1 or return to baseline at 90 days via a modified Poisson regression model. Secondary outcomes include the modified Rankin Scale, considered as an ordinal variable, and symptomatic intracerebral hemorrhage. RESULTS: =0.48). No significant differences in an ordinal analysis of the modified Rankin Scale were observed between the 2 treatment groups. In a planned per-protocol analysis, the odds of improvement by 1 point in the modified Rankin Scale were doubled in the tenecteplase-treated transfer subgroup compared with standard care transfer patients (odds ratio, 2.61 [95% CI, 1.07-6.40]). Symptomatic intracerebral hemorrhage occurred in 5 (4%) participants assigned to tenecteplase and was present in 1 (1%) participant assigned to standard care. CONCLUSIONS: Treatment with tenecteplase did not increase the likelihood of a favorable functional outcome, but early stoppage of the study prevents definitive conclusions from being drawn. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04454788.