IV glyburide for the prevention of brain edema

Conduct clinical trials

Our primary focus in clinical trials is the prevention of cerebral edema, testing the hypothesis that the sulfonylurea receptor 1 (Sur1) mediates edema formation after stroke. The clinical development of the Sur1 inhibitor, intravenous glyburide, began with a Phase 2a pilot clinical trial (GAMES-Pilot Trial), which evaluated the safety and efficacy for the prevention of edema after large hemispheric stroke. The results from this effort led to a national, multi-center, double-blind Phase 2b trial in patients with large hemispheric stroke who were likely to develop edema, GAMES-RP. As the national co-PI and biomarker coordinating center, we found evidence that intravenous glyburide may reduce brain edema. There was also a reduction in mortality and a trend toward more favorable neurological outcome. In order to definitively test efficacy, we are now conducting the CHARM trial, a randomized, multi-center, double-blind Phase 3 trial, which is enrolling patients globally.

Related Publications:

Hypoxanthine is a Pharmacodynamic Marker of Ischemic Brain Edema Modified by Glibenclamide
Irvine HJ, Acharjee A, Wolcott Z, Ament Z, Hinson HE, Molyneaux BJ, Simard JM, Sheth KN, Kimberly WT. Hypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide. Cell Rep Med, 3:100654 (2022). view PDF
Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction
Vorasayan P, Bevers MB, Beslow LA, Sze G, Molyneaux BJ, Hinson HE, Simard JM, von Kummer R, Sheth KN, Kimberly WT. Stroke, 50:3021-3027 (2019). view PDF
Effect of intravenous glyburide on adjudicated edema endpoints in the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial
Kimberly WT, Bevers MB, von Kummer R, Demchuk AM, Romero JM, Elm JJ, Hinson HE, Molyneaux BJ, Simard JM and Sheth KN. Neurology, 91:e2163-e2169 (2018). view PDF
Long-Term Outcomes in Patients Aged ≤70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction
Sheth KN, Petersen NH, Cheung K, Elm JJ, Hinson HE, Molyneaux BJ, Beslow LA, Sze GK, Simard JM and Kimberly WT. Stroke, 49:1457-1463 (2018). view PDF
Effect of intravenous glyburide (RP-1127) on brain swelling after large hemispheric infarction: A phase 2 randomized, double-blind, placebo-controlled clinical trial
Sheth KN, Elm JJ, Molyneaux BJ, Hinson H, Beslow LA, Sze GK, Ostwaldt A-C, del Zoppo GJ, Simard JM, Jacobson S and Kimberly WT. Lancet Neurol, 15:1160-1169 (2016). view PDF