Intravenous Glyburide in Medical and Endovascular‐Treated Large‐Core Stroke: A Subgroup Analysis of the CHARM Randomized Clinical Trial

Objective The Glibenclamide for Large Hemispheric Infarction Analyzing mRS and Mortality (CHARM) trial enrolled participants with large hemispheric infarction, randomized to a placebo or intravenous glyburide. Our objective in this post‐hoc study was to evaluate the relationship between baseline stroke volume and the potential efficacy of i.v. glyburide. Methods Participants enrolled in CHARM and aged ≤70 years were included if a <125 ml ischemic core lesion volume was measured by computed tomography perfusion or diffusion magnetic resonance imaging. The primary endpoint was a shift analysis on the 90‐day modified Rankin Scale. Independent variables included age, sex, baseline National Institutes of Health Stroke Scale, world region, tissue plasminogen activator, and endovascular thrombectomy. Results A total of 147 participants with a baseline large‐core stroke volume <125 ml were available for this analysis (mean age 58 years, 37% women, baseline National Institutes of Health Stroke Scale 18, and the time to study drug was 9.1 ± 2.1 h). The median baseline core volume of 92 mL (IQR 81–107 ml) did not differ by treatment arm. The i.v. glyburide‐treated participants had a favorable shift in outcome relative to the placebo (adjusted common odds ratio 2.11, 95% CI 1.10–4.01, p = 0.02). In patients who underwent endovascular thrombectomy, i.v. glyburide‐treated subjects had a favorable outcome (adjusted common odds ratio 8.19, 95% CI 1.60–42.0, p = 0.01), fewer decompressive craniectomies (0% vs 25%, P = 0.02), less midline shift (4.2 ± 2.5 mm vs 7.6 ± 5.5 mm, p = 0.02), and lower 90‐day mortality (5.6% vs 31%, p = 0.05) compared with the placebo, respectively. Interpretation This post‐hoc analysis of the CHARM trial provides hypothesis‐generating evidence that i.v. glyburide may improve outcome in large‐core stroke <125 ml, especially among endovascular thrombectomy‐treated patients. These results require confirmation in a prospective randomized clinical trial. ANN NEUROL 2025