Background: Prior evidence suggests that younger patients are at increased risk for the deleterious consequences associated with edema after large hemispheric infarction (LHI). GAMES-RP was a double-blind, randomized, placebo controlled phase 2 study. Patients presenting to 18 centers with baseline infarct volumes between 82 and 300 cm3 on MRI were randomized 1:1 within 10 hours of symptom onset. Although the primary analysis, which included decompressive craniectomy as part of a composite endpoint, suggested no difference between groups, there was a trend toward decreased mortality for patients treated with IV glyburide.
Objective: Exploratory analyses of the GAMES-RP trial suggested that overall trend of decreased mortality for patients treated with IV glyburide may be more pronounced with younger patients. We hypothesized that patients age 70 and under who were treated with IV glyburide would have improved long term outcomes compared to placebo.
Methods: This exploratory analysis included the subset of patients aged < 70 who met the Per-Protocol definition: IV glyburide (n=35) and placebo (n=30). We analyzed 12-month mortality, functional outcome by analysis of the modified Rankin Scale (mRS), functional improvement on the Barthel Index (BI), and quality of life using the EQ-5D. Differences were analyzed using Fisher’s exact test except for shift analysis, which used a two sided Mann-Whitney test.
Results: Subjects treated with IV glyburide had lower mortality at 12 months (14% vs 40%, p=0.025, OR 4.00). Shift analysis revealed a trend towards improved functional outcome in IV glyburide treated patients (OR 2.24; p=0.080), higher score on the BI (mean 60.1; SD 37.9 vs mean 39.5; SD 40.1, p=0.03), and higher score on the EQ-5D (mean 0.49; SD 0.31 vs mean 0.33; SD 0.32, p=0.04).
Conclusion: This post-hoc analysis suggests that patients under 70, who may be at highest risk for poor outcomes secondary to edema after large hemispheric infarction, may have improved survival, better functional outcome and improved quality of life following treatment with IV glyburide. A prospective study is required in this population in order to definitively establish that IV glyburide can improve outcome. Registry: NCT01794182