ABSTRACT NUMBER: ESOC2026A2041 GM1 GANGLIOSIDE IN ACUTE ISCHEMIC STROKE: A RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER TRIAL

Abstract Background and aims Patients with acute ischemic stroke (AIS) who are ineligible for thrombolysis or thrombectomy lack proven neuroprotective therapies. GM1 ganglioside has neuroprotective and neurorestorative effects in preclinical studies. We tested whether adjunctive GM1 improves 90-day functional outcome in AIS without reperfusion treatment. Methods In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 33 tertiary hospitals in China (May 2020–July 2022), adults within 48 hours of AIS onset who did not receive reperfusion therapy were randomized 1:1 to intravenous GM1 ganglioside (100 mg/day) or placebo for 14 days. The primary endpoint was functional independence (modified Rankin Scale [mRS] ≤ 2) at 90 days in the full analysis set, analyzed using a center-stratified Cochran–Mantel–Haenszel test. Key secondary endpoints included the ordinal shift in the full mRS distribution and clinical/quality-of-life measures. Results Among 720 randomized patients (GM1, n = 360; placebo, n = 360), the full analysis set included 714 patients. At 90 days, mRS ≤ 2 occurred in 270/343 (78.7%) in the GM1 group versus 230/345 (66.7%) in the placebo group (absolute rate difference 13.1%; 95.52% CI, 6.3–19.9; P = 0.0004). The overall mRS distribution favored GM1 (P = 0.0019). Adverse events were similar between groups (73.1% vs 78.7%); serious adverse events occurred in 5.9% vs 6.4%, with no new safety signals. Conclusions In AIS patients ineligible for reperfusion therapy, GM1 initiated within 48 hours improved 90-day functional independence without increasing adverse events, supporting GM1 as a promising therapy for this large untreated population. Conflict of interest Zefeng Tan, nothing to diclose.