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.
Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction2019
Effect of intravenous glyburide on adjudicated edema endpoints in the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial2018
Long-Term Outcomes in Patients Aged ≤70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction2018
Effect of intravenous glyburide (RP-1127) on brain swelling after large hemispheric infarction: A phase 2 randomized, double-blind, placebo-controlled clinical trial2016
Pilot study of intravenous glyburide in patients with a large ischemic stroke2014
- Sheth KN*, Kimberly WT*, Elm JJ, Kent TA, Mandava P, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, Simard JM and Stern BJ. Stroke, 45:281-283 (2014).