Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design.
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.
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.
Kevin N
KN
Sheth
Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA.
Jordan J
JJ
Elm
Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale University School of Medicine, 15 York Street, LCI 1003, New Haven, CT, 06510, USA.|Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Lauren A
LA
Beslow
Department of Radiology, Yale University School of Medicine, New Haven, CT, USA.
Gordon K
GK
Sze
Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. wtkimberly@mgh.harvard.edu.
W Taylor
WT
Kimberly
D000328:Adult; D000368:Aged; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D020520:Brain Infarction / Q000150:complications* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies
D007004:Hypoglycemic Agents; D005905:Glyburide
Cerebral edema; Clinical trials; Ischemic stroke; Large stroke; MRI; Malignant infarction