Phase 3 Trial Protocol Evaluating Intravenous Loberamisal for Acute Ischaemic Stroke ManagementTrial Plans to Test Loberamisal for Acute Ischaemic Stroke

BACKGROUND AND OBJECTIVES: Loberamisal, a novel agent that dissociates the post-synaptic density protein 95/neuronal nitric oxide synthase complex and potentiates the α2-containing γ-aminobutyric acid type A receptors, is a potential neuroprotectant that is effective in preclinical studies for acute ischaemic stroke. This trial aims to demonstrate the efficacy and safety of intravenous loberamisal in patients with acute ischaemic stroke (AIS) within 48 hours of onset. METHODS AND DESIGN: The LAIS (Loberamisal for Acute Ischaemic Stroke) trial is a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 trial. A total of 998 eligible patients will be randomly assigned to receive either loberamisal or placebo in a 1:1 ratio. OUTCOMES: The primary efficacy outcome is proportion of individuals achieving an excellent functional outcome, defined as modified Rankin Scale (mRS) 0-1 at 90 days. Secondary efficacy outcomes include favourable functional outcome (defined as an mRS score of 0 in patients with a baseline NIHSS score of 4 to 7; an mRS score of 0 to 1 in patients with a baseline NIHSS score of 8 to 14; and an mRS score of 0 to 2 in patients with a baseline NIHSS score of 15 to 25), distribution of mRS at 90 days, patients with ≥4 points reduction in National Institutes of Health Stroke Scale score from baseline at 10 days and 30 days, and Barthel Index ≥95 at 90 days. Safety outcomes were adverse events. Exploratory outcomes include the incidence of depressive and anxiety symptoms at 90 days. DISCUSSION: The LAIS trial will evaluate the potential of loberamisal as a novel neuroprotectant in acute ischaemic stroke. TRIAL REGISTRATION NUMBER: NCT06517173.