Preclinical studies of traumatic brain injury (TBI) show that Glyburide reduces edema and hemorrhagic progression of contusions. We conducted a small Phase 2, three-institution, randomized placebo-controlled trial of subjects with TBI, to assess the safety and efficacy of intravenous (IV) Glyburide. Twenty-eight subjects were randomized and underwent a 72-hour infusion of IV Glyburide or placebo, beginning within 10 hours of trauma. Of the 28 subjects, 25 had Glasgow Coma Scale scores of 6-10, and 14 had contusions. There were no differences in adverse or severe adverse events between groups. The MRI percent change at 72-168 hours from screening/baseline was compared between the Glyburide and Placebo groups. Analysis of contusions (7 per group) showed that lesion volumes (hemorrhage plus edema) increased 1036% with placebo vs. 136% with Glyburide (P=0.15), and that hemorrhage volumes increased 11.6% with placebo but decreased 29.6% with Glyburide (P=0.62). Three diffusion MRI measures of edema were quantified: mean diffusivity (MD), free water (FW), and tissue MD (MDt), corresponding to overall, extracellular and intracellular water, respectively. The percent change with time for each measure was compared in lesions (n=14) vs. uninjured white matter (n=24) in subjects receiving placebo (n=20) or Glyburide (n=18). For placebo, the percent change in lesions for all 3 measures was significantly different compared to uninjured white matter (ANOVA, P<0.02), consistent with worsening of edema in untreated contusions. In contrast, for Glyburide, the percent change in lesions for all 3 measures was not significantly different compared to uninjured white matter. Further study of IV Glyburide in contusion-TBI is warranted.
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