Extending the Time Window for Tenecteplase by Effective Reperfusion of Penumbral Tissue in Patients with Large Vessel Occlusion (ETERNAL-LVO): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial.

Abstract

Rationale: The benefit of tenecteplase in the treatment of large vessel occlusion (LVO) patients presenting within 24 hours of symptom onset remains unclear.

Aim: 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 and design: 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, will be randomized to tenecteplase (0.25 mg/kg) or standard of care (alteplase 0.90 mg/kg or conservative management at clinician discretion) prior to undergoing endovascular therapy.

Study outcomes: The primary outcome is 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 include the proportion of patients with a mRS of 0-2 at 3 months, an ordinal analysis of the mRS at 3 months, the proportion of patients with symptomatic intracerebral haemorrhage (sICH), the proportion of patients with death due to any cause, and the proportion of patients with mRS 5-6 at 3 months (severe disability or death).

Discussion: The ETERNAL-LVO trial will build upon the current evidence for tenecteplase in the >4.5-hour window. Specifically, this trial will evaluate tenecteplase in a patient population who have access to endovascular therapy but may incur delays to endovascular therapy commencement or require transfer from a primary to a comprehensive stroke center.

Trials registration: ClincialTrials.gov: NCT04454788.