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 of intravenous glyburide for the prevention of edema after large hemispheric stroke. The results from this effort led to a national, randomized, 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 preparing the CHARM trial, a randomized, multi-center, double-blind Phase 3 trial, which will be conducted globally.
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).
Glyburide is associated with attenuated vasogenic edema in stroke patients2013
- Kimberly WT, Battey TWK, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ and Sheth KN. Neurocrit Care, 20:193-201 (2014).