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

Abstract

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. 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. Following trial initiation, a supply shortage of the investigational product hindered recruitment. When supply resumed, phase 3 evidence had emerged supporting tenecteplase use within 4.5 hours of stroke onset, including large vessel occlusion. ETERNAL-LVO was, therefore, terminated early. Two hundred forty-two participants (median age: 73 years, 43% female, 79% undergoing EVT) were included in the modified intention-to-treat analysis; 120 received tenecteplase and 122 received standard care. No difference in the primary outcome was observed between the tenecteplase (n=44, 37%) and standard care (n=52, 43%; adjusted risk ratio, 0.90 [95% CI, 0.66-1.21]; <i>P</i>=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. 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. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04454788.