Kevin N Sheth1, Jordan J Elm2, Lauren A Beslow3,4, Gordon K Sze5, W Taylor Kimberly6. 1. Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale University School of Medicine, 15 York Street, LCI 1003, New Haven, CT, 06510, USA. kevin.sheth@yale.edu. 2. Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA. 3. Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale University School of Medicine, 15 York Street, LCI 1003, New Haven, CT, 06510, USA. 4. Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA. 5. Department of Radiology, Yale University School of Medicine, New Haven, CT, USA. 6. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. wtkimberly@mgh.harvard.edu.
Abstract
BACKGROUND: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. METHODS: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 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was ≤10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. RESULTS: The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. CONCLUSIONS: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.
RCT Entities:
BACKGROUND: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. METHODS: 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 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was ≤10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. RESULTS: The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac- and glucose-related serious adverse events. CONCLUSIONS: 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.
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