Abstract Body: INTRODUCTION
The phase III CHARM trial evaluated the safety and efficacy of intravenous glyburide as a treatment for large hemispheric infarction (LHI) patients at high risk for cerebral edema.

HYPOTHESIS
We aimed to determine whether subjects who were treated with IV glyburide would have better 12-month outcomes than those who received placebo in the CHARM trial.

METHODS
The source population included all CHARM subjects who were enrolled and treated with IV glyburide or placebo and had a recorded 12-month outcome. For those subjects missing a 12-month outcome, multiple imputation including baseline covariates and the 90-day modified Rankin Scale (mRS) was used. Shift analysis was performed on the 12-month mRS using 5 categories, where 0-1 and 5-6 were each collapsed into a single category. Independent variables included age, sex, baseline NIHSS, world region, tPA, and thrombectomy. Based on prior analysis, we also examined subjects with a baseline stroke volume ≤125 mL.

RESULTS
The cohort included a total of 431 subjects (mean age 58±9 years, 33% female, baseline NIHSS 19 (16-22), 40% received thrombolysis), the median 90-day mRS was 5 (4-6) and the median 12-month mRS was 5 (3-6). A total of 90 subjects (21%) had missing 12-month outcomes (n=38 in glyburide and n=52 in placebo). The correlation between 90d and 12mo mRS was r=0.93, p<0.0001. At 12 months, IV glyburide was not associated with better functional outcome (cOR 1.09, 95% CI 0.73-1.62, p=0.68) in the primary analytic population. However, among the subgroup of subjects with a baseline stroke volume ≤125 mL (n=118), the IV glyburide treatment arm had a favorable effect, cOR 2.26, 95% CI 1.06-4.78, p=0.034 (see figure). This effect was also present among those treated with endovascular thrombectomy at baseline (n=34, cOR 5.52, 95% CI 1.05-28.9, p=0.043).

CONCLUSIONS
Long term outcomes in the CHARM trial suggests a potential for durable improvement in functional outcome in patients treated with IV glyburide among those with a baseline stroke volume ≤125 mL. Demonstration of clinical efficacy requires a dedicated trial focusing on this patient population.