Dr. Kevin Sheth, one of the lead investigators in this trial and a member of the C3O Telemedicine’s clinical team has been researching avenues to reduce complications following an acute stroke. One major contributor to poor outcomes after a stroke is brain swelling and was found to be reduced by intravenous glyburide treatment according to phase 2 clinical trial. The information collected from the study is further used for other phases of clinical trial.
Accumulation of excess fluid in the brain may cause brain swelling. This usually occurs during stroke which is mainly due to a blockage in the blood supply to the brain. Swelling in the brain may increase pressure and pushes the brain out of the skull resulting in 50% of the mortality rate. Surgery procedures like hemicraniectomy ( removing a portion of the skull to reduce swelling) may not be possible with all patients and treatment using drugs may also be less effective.
According to previous animal studies, glyburide utilized in the treatment of diabetes was found to reduce brain swelling in stroke patients. The phase 2 clinical trial for glyburide was sponsored by Remedy Pharmaceuticals following a pilot study conducted by Kimberly and co-author Kevin Sheth, MD, Department of Neurology, Yale University School of Medicine, which reported that glyburide was found to be safe for stroke patients.
Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) trial was conducted in 18 hospitals across the United States. About 77 stroke patients were randomly assigned to continuous glyburide treatment or placebo for 72 hours.
The results were obtained from patients after 90 days, using a standardized stroke scale ranging from 0 to 4 indicating no symptoms to moderate and severe brain swelling. About 40% of the patients met the criteria and were able to survive without surgery.
Sheth said that the decision for performing surgery seems to be complicated and was noted only in cases where physicians decide based on the wishes of the patient or their family. And this was found to be the main reason for not reaching the endpoint of the clinical trial.
However, the results of the clinical trials were able to show a reduced degree of the midline shift in the brain by 40% after treatment with glyburide and was also able to reduce MM-9 biomarker which was associated with brain swelling in previous studies. These results will further be used in 2017 for phase 3 clinical trials.