TY - JOUR
T1 - Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial
AU - Kimberly, W. Taylor
AU - Bevers, Matthew B.
AU - Von Kummer, Rudiger
AU - Demchuk, Andrew M.
AU - Romero, Javier M.
AU - Elm, Jordan J.
AU - Hinson, Holly E.
AU - Molyneaux, Bradley J.
AU - Simard, J. Marc
AU - Sheth, Kevin N.
N1 - Funding Information:
The GAMES-RP Trial was funded by Remedy Pharmaceuticals, Inc. J.M.S. is supported by grants from NHLBI (R01 HL082517) and NINDS (R01 NS060801). W.T.K. is supported by grants from NINDS (K23 NS076597, R01 NS099209), AHA (14GRNT19060044, AHA 17CSA 33550004), and the Andrew David Heitman Neurovascular Research Foundation. As the compound owner, Biogen was provided the opportunity to review this manuscript. The authors maintained full control of all content.
PY - 2018/12/4
Y1 - 2018/12/4
N2 - Objective In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMESRP) Trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints. Methods Blinded adjudicators assigned designations for hemorrhagic transformation, neurologic deterioration, malignant edema, and edema-related death to patients from the GAMES-RP phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment on additional markers of edema and clinical deterioration were examined. Results In the per-protocol sample, 41 patients received glyburide and 36 received placebo. There was no difference in the frequency of hemorrhagic transformation (n = 24 [58.5%] in IV glyburide vs n = 23 [63.9%] in placebo, p = 0.91) or the incidence of malignant edema (n = 19 [46%] in IVglyburide vs n = 17 [47%] in placebo, p = 0.94). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (n = 1 [2.4%] with IV glyburide vs n = 8 [22.2%]with placebo, p = 0.01). In the subset of patients with malignant edema, those treated with IV glyburide had lessmidline shift (p < 0.01) and reduced MMP-9 (matrixmetalloproteinase 9) levels (p < 0.01). The glyburide treatment group had lower rate of NIH Stroke Scale (NIHSS) increase of ≥4 during the infusion period (n = 7 [37%] in IV glyburide vs n = 12 [71%] in placebo, p = 0.043), and of change in level of alertness (NIHSS subscore 1a; n = 11 [58%] vs n = 15 [94%], p = 0.016). Conclusion IV glyburide was associated with improvements in midline shift, level of alertness, and NIHSS, and there were fewer deaths attributed to edema. Additional studies of IV glyburide in large hemispheric infarction are warranted to corroborate these findings.
AB - Objective In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMESRP) Trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints. Methods Blinded adjudicators assigned designations for hemorrhagic transformation, neurologic deterioration, malignant edema, and edema-related death to patients from the GAMES-RP phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment on additional markers of edema and clinical deterioration were examined. Results In the per-protocol sample, 41 patients received glyburide and 36 received placebo. There was no difference in the frequency of hemorrhagic transformation (n = 24 [58.5%] in IV glyburide vs n = 23 [63.9%] in placebo, p = 0.91) or the incidence of malignant edema (n = 19 [46%] in IVglyburide vs n = 17 [47%] in placebo, p = 0.94). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (n = 1 [2.4%] with IV glyburide vs n = 8 [22.2%]with placebo, p = 0.01). In the subset of patients with malignant edema, those treated with IV glyburide had lessmidline shift (p < 0.01) and reduced MMP-9 (matrixmetalloproteinase 9) levels (p < 0.01). The glyburide treatment group had lower rate of NIH Stroke Scale (NIHSS) increase of ≥4 during the infusion period (n = 7 [37%] in IV glyburide vs n = 12 [71%] in placebo, p = 0.043), and of change in level of alertness (NIHSS subscore 1a; n = 11 [58%] vs n = 15 [94%], p = 0.016). Conclusion IV glyburide was associated with improvements in midline shift, level of alertness, and NIHSS, and there were fewer deaths attributed to edema. Additional studies of IV glyburide in large hemispheric infarction are warranted to corroborate these findings.
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U2 - 10.1212/WNL.0000000000006618
DO - 10.1212/WNL.0000000000006618
M3 - Article
C2 - 30446594
AN - SCOPUS:85058909186
VL - 91
SP - E2163-E2169
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 23
ER -