Efficacy and safety of tirofiban after intravenous tenecteplase for acute ischemic stroke: the multicenter, randomized, placebo-controlled, double-blind, INSTANT trial protocol

Abstract Background It is very common that symptoms do not improve or even worsen after intravenous thrombolysis (IVT) in acute ischemic stroke. However, it remains unknown whether early administration of tirofiban after IVT may improve clinical outcomes. Objective This trial aims to assess the efficacy and safety of early administration of tirofiban after intravenous thrombolysis with Tenecteplase in acute ischemic stroke within 24 hours of symptom onset. Methods and design The INSTANT trial is an investigator-initiated, randomized, placebo-controlled, double-blind, multicenter trial. Up to 310 patients with acute non-large/medium-sized vascular occlusion and non-atrial fibrillation stroke who are treated with intravenous tenecteplase will be consecutively randomized to intravenous tirofiban or placebo in a 1:1 ratio over two years across 50 intravenous thrombolysis-capable stroke centers in China. Subjects will be treated with intravenous tirofiban or placebo at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for up to 47.5 hours. Outcomes The primary efficacy outcome is the proportion of patients with excellent functional outcomes (defined as a score of 0-1 on the modified Rankin scale (mRS)) at 90 days. The secondary outcome is the proportion of patients achieving functional independence, defined as a mRS score of 0-2 at 90 days. Safety outcomes include symptomatic intracranial hemorrhage within 48 hours and mortality at 90 days. Discussion This randomized, double-blind, placebo-controlled trial will provide data regarding the role of early antiplatelet therapy with intravenous tirofiban after IVT. Trial registry number ChiCTR2300074368 ( www.chictr.org.cn ).