Abstract Body: INTRODUCTION
Recent large core stroke trials show a benefit for endovascular treatment (EVT) of acute ischemic stroke up to approximately 125 mL. Consequently, clinical trials evaluating neuroprotection in EVT populations may best test proof of concept under this volume threshold. The 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
The objective of this analysis was to examine the treatment effect of IV glyburide in EVT patients with baseline infarcts up to 125 mL.

METHODS
CHARM subjects who were enrolled with CTP or DWI volume 80-125 mL and underwent EVT were included in this analysis. The primary endpoint was a shift analysis on the 90-day modified Rankin Scale (mRS) and included participants aged ≤70 years who received any study drug. Independent variables included age, sex, baseline NIHSS, world region, and tPA. We also examined the frequency of decompressive craniectomy and the amount of midline shift (mm) by treatment group.

RESULTS
For a total of 34 subjects (mean age 56 years, 32% female, baseline NIHSS 20, 41% received thrombolysis), the time to thrombectomy was 4.5±2.0 hours and time to study drug was 9.6±1.4 hours. glyburide-treated patients received study drug later than placebo by an average of 1 hour (P=0.036). The baseline infarct volume was 94±20 mL, which did not differ by treatment arm. glyburide-treated subjects had a favorable outcome (n=18, cOR 7.13, 95%CI 1.51-33.7, P=0.013) relative to placebo (see figure). 90-day mortality occurred less frequently in glyburide treated subjects compared to placebo (5.6% vs 31%, P=0.05). There were no decompressive craniectomies in glyburide treated patients, whereas there were 4 decompressions among the placebo-treated subjects (P=0.021). The mean midline shift was 4.2 ± 2.5 mm in IV glyburide-treated subjects and 7.6 ± 5.5 mm among placebo-treated subjects (P=0.024).

CONCLUSIONS
There is evidence of benefit for IV glyburide in large core EVT treated subjects with a baseline stroke volume ≤125 mL. Although IV glyburide may also have benefit among non-EVT treated subjects, the evolving standard of care of EVT for large core stroke indicates that an efficient, feasible trial design should focus on EVT patients.