BACKGROUND: Malignant infarction is characterized by the formation of cerebral 
edema, and medical treatment is limited. Preclinical data suggest that 
glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We 
previously reported feasibility of the GAMES-Pilot study, a two-center 
prospective, open label, phase IIa trial of 10 subjects at high risk for 
malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 
cm(3) treated with RP-1127 (glyburide for injection). In this secondary 
analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing 
poor outcome when compared to controls.
METHODS: Controls suffering large hemispheric infarction were obtained from the 
EPITHET and MMI-MRI studies. We first screened subjects for controls with the 
same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to 
address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 
0-4, rate of decompressive craniectomy, and mortality were the primary clinical 
outcomes of interest.
RESULTS: The mean age of the GAMES cohort was 51 years and initial DWI volume 
was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar 
NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus 50% in controls 
p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43) and trend 
toward lower mortality (10 vs. 35%; p = 0.21).
CONCLUSIONS: In this pilot study, RP-1127-treated subjects showed better 
clinical outcomes when compared to historical controls. An adequately powered 
and randomized phase II trial of patients at risk for malignant infarction is 
needed to evaluate the potential efficacy of RP-1127.