Data from: Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial

Objective: In this secondary analysis of the GAMES-RP trial, we report the
effect of IV glyburide on adjudicated, edema-related endpoints. Methods:
Blinded adjudicators assigned designations for hemorrhagic transformation,
neurological deterioration, malignant edema and edema-related death to
patients from the GAMES-RP Phase II randomized controlled trial of IV
glyburide for large hemispheric infarct. Rates of these endpoints were
compared between treatment arms in the per-protocol sample. In those
participants with malignant edema, the effects of treatment on additional
markers of edema and clinical determiration were examined. Results: In the
per-protocol sample, 41 patients received glyburide and 36 received
placebo. There was no difference in the frequency of hemorrhagic
transformation [n=24 (58.5%) in IV glyburide versus n=23 (63.9%) in
placebo, p=0.91], or the incidence of malignant edema [n=19 (46%) in IV
glyburide versus n=17 (47%) in placebo, p=0.94]. However, treatment with
IV glyburide was associated with a reduced proportion of deaths attributed
to cerebral edema [n=1 (2.4%) with IV glyburide vs. n=8 (22.2%) with
placebo, p=0.01)]. In the subset of patients with malignant edema, those
treated with IV glyburide had less midline shift (p<0.01) and
reduced MMP-9 levels (p<0.01). The glyburide treatment group had
lower rate of NIHSS increase of ≥4 during the infusion period [n=7 (37%)
in IV glyburide versus n=12 (71%) in placebo, p=0.043], and of change in
level of alertness [NIHSS subscore 1a; n=11 (58%) versus n=15 (94%),
p=0.016] . Conclusions: IV glyburide was associated with improvements in
midline shift, level of alertness and NIHSS, and there were fewer deaths
attributed to edema. Additional studies of IV glyburide in large
hemispheric infarction are warranted to corroborate these findings.
NCT01794182. Level of Evidence: This study provides Class II evidence that
for patients with large hemispheric infarction, IV glyburide improves some
edema-related endpoints.