Background: Patients with large hemispheric infarction are at high risk for cerebral edema and death. Here we report pre-specified adjudicated edema endpoints in the GAMES-RP trial.
Objective: The primary objective of this pre-specified analysis was to evaluate the effect of intravenous (IV) glyburide treatment on mortality and malignant edema.
Design: The GAMES-RP trial was a prospective, double blind, randomized, placebo-controlled phase 2 study. Blinded adjudicators assigned designations for hemorrhage and edema-related death using a priori definitions.
Population studied: Patients age 18 to 80 years who presented to 18 U.S. centers with baseline stroke lesion volumes between 82cc-300cc on MRI were randomized 1:1 to study drug or placebo within 10 hours from stroke onset. The per protocol group, which included all treated subjects with a baseline stroke lesion volume between 82cc and 300cc, was the primary analysis.
Outcome measure: The adjudication outcomes were mortality due to all causes, and death due to cerebral edema. Secondary adjudication outcomes included the incidence of parenchymal hematoma and incidence of malignant edema defined as an increase in NIHSS ≥4 were also compared between treatment arms.
Results: Subjects treated with intravenous glyburide had a trend toward lower all-cause mortality at one year (weighted log-rank test, p=0.052). Treatment with IV glyburide reduced the proportion of deaths due to cerebral edema [2.4% (N=1) with IV glyburide vs. 22.2% (N=8) with placebo, p=0.007). The frequency of parenchymal hematoma was not statistically different between treatment arms [2.4% (N=1) in IV glyburide versus 5.6% (N=2) in placebo, p=0.60]. The incidence of malignant edema was also similar [46.3% (N=19) in RP-1127 versus 47.2% (N=17) in placebo].
Conclusions: Our data provide supporting evidence that intravenous glyburide may reduce edema-related deaths, but not malignant edema defined as an increase of ≥4 points in the NIHSS score. Future study is required to confirm the effect of IV glyburide on clinical outcome.