Abstract Body: Introduction: The benefit of tenecteplase in the treatment of large vessel occlusion (LVO) patients presenting within 24 hours of symptom onset remains unclear.
Aims: To assess the effectiveness and safety of tenecteplase, compared to standard of care, in patients presenting within the first 24 hours of symptom onset, with a LVO and target mismatch on perfusion CT.
Methods: The “Extending the time window for Tenecteplase by Effective Reperfusion of peNumbrAL tissue in patients with Large Vessel Occlusion” (ETERNAL-LVO) trial is a prospective, randomized, open-label, blinded endpoint, phase 3, parallel group, superiority trial with covariate-adjusted 1:1 randomization, and adaptive sample size re-estimation. Patients with an anterior circulation LVO stroke, who present within 24 hours of stroke onset or last known well with a target mismatch on CTP or MRI, were randomized to tenecteplase (0.25 mg/kg) or standard of care (alteplase 0.90 mg/kg or conservative management, clinician choice) prior to undergoing endovascular thrombectomy. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) of 0-1 (no disability) or return to baseline mRS at 3 months. Secondary and safety outcomes included the proportion of patients with a mRS of 0-2, an ordinal analysis of the mRS, the proportion of patients with symptomatic intracerebral hemorrhage at 24-72 hour follow-up imaging, and the proportion of patients with death due to any cause. An estimated total sample size of 740 patients, equally distributed between two study arms, would yield 80% power to detect an absolute difference of at least 10% in proportion of patients achieving the primary outcome.
Results: At an interim analysis, the majority of patients were found to have been randomized in the early (<4.5 hour) window. Given the current evidence for tenecteplase in this timeframe, the steering committee felt that there was no longer adequate equipoise to continue the trial. The trial was stopped with 244 patients randomized and results will be available for the International Stroke Conference 2025 in Los Angeles, California.
Discussion: The ETERNAL-LVO trial will contribute to the evidence for tenecteplase in both the early and extended time window. Specifically, this trial evaluates tenecteplase in a patient population who have access to endovascular therapy but may incur delays to endovascular therapy or require transfer from a primary to a comprehensive stroke center.