Safety and Efficacy of Adjunctive Intra-arterial Tenecteplase following Successful Thrombectomy in Patients with Large Vessel Occlusion: Study Rationale and Design of A Phase 1/2 Randomized Clinical Trial

Abstract

Background: Adjunct intra-arterial thrombolysis has been shown to potentially improve clinical outcomes in patients with large vessel occlusion (LVO) stroke who have undergone successful endovascular thrombectomy (EVT). Tenecteplase, known for its enhanced fibrin specificity and extended activity duration, may be a better choice than alteplase for intra-arterial thrombolysis. However, the optimal dose, safety and efficacy of intra-arterial tenecteplase remain unclear. Objective: To evaluate the optimal dose, safety and efficacy of adjunctive intra-arterial tenecteplase following successful EVT in LVO patients. Methods and design: This study is a two-part, phase Ib/IIa, multicenter, open-label, 14+8 dose-escalation (Part I) and dose-expansion (Part II) trial conducted in China involving patients LVO patients who achieved successful EVT (defined as the expanded Thrombolysis in Cerebral Infarction [eTICI] grade of 2b50 or higher) within 24 hours of last known well. In Part Ib, the dose escalation will be conducted in up to four tiers of 14+8 patients, starting at 0.03125 mg/kg, to a planned maximum of 0.1875mg/kg, and the primary outcome is symptomatic intracranial hemorrhage within 24 hours. In Part IIa, 157 patients will be randomized among two selected safe doses and a placebo, and the primary outcome will be the proportion of patients with nondisabled outcome (modified Rankin Scale score of 0 to 1) at 90 days. Discussions: This pivotal trial will provide important data on adjunctive intra-arterial tenecteplase following successful EVT in patients with acute ischemic stroke due to LVO and may support advance of treatment standards.