Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.

Abstract

Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction. GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusion-weighted image lesion between 82 and 300cm(3) who are 18-80years of age. The target time from symptom onset to start of study infusion was ≤10h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72h. The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies.