Conference Coverage
LOS ANGELES—Among patients with large anterior circulation acute ischemic stroke, IV glyburide given within 10 hours of symptom onset is safe and may provide benefits, according to phase II trial results presented at the International Stroke Conference 2016. There was a strong trend toward reduced mortality in patients who received glyburide, compared with placebo, as well as a trend toward improved functional outcome. In addition, the treatment significantly improved biomarkers of edema, including midline shift and levels of matrix metalloproteinase-9 in plasma. The trial did not meet its primary efficacy end point of avoidance of decompressive craniectomy and modified Rankin Scale score of 4 or less at 90 days, however.
“Our goal was to gain experience in this indication, develop an understanding of how the drug was working in patients, and, ultimately, guide the design for a pivotal phase III trial,” said W. Taylor Kimberly, MD, PhD, Associate Director of the Neuroscience Intensive Care Unit at Massachusetts General Hospital in Boston.
W. Taylor Kimberly, MD, PhD
Emergency decompressive craniectomy surgery is the only proven treatment for brain edema after stroke. Investigators are testing whether IV glyburide, also known as RP-1127, can reduce edema and associated secondary injury. To assess the safety and efficacy of IV glyburide, researchers conducted the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) trial.
The double-blind trial enrolled patients between ages 18 and 80 who had large anterior circulation acute ischemic stroke and who were able to undergo randomization within 10 hours of symptom onset. Baseline lesion volumes were between 82 cm3 and 300 cm3. Patients received the treatment as a bolus followed by a continuous 72-hour infusion. Investigators enrolled and treated 83 patients. Participants were followed up at 30 days, 90 days, six months, and 12 months.
In the placebo arm, as expected, the mortality rate was 36%, whereas in the IV glyburide arm, the mortality rate was 17%. In addition, there was a trend toward improved functional outcomes, as evaluated by shift analysis of modified Rankin Scale scores, with RP-1127. There was no difference in the frequency of adverse events between groups. Rates of decompressive craniectomy varied widely across the 18 trial sites, and standardizing the use of this surgical procedure may be challenging. Thus, the rate of decompressive craniectomy is not an ideal end point.
“We are enthusiastic about moving on to GAMES 3, where we intend to answer the question of whether this drug can improve clinical outcomes in this patient population,” Dr. Kimberly said.
—Jake Remaly