Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial

W. Taylor Kimberly, Matthew B. Bevers, Rüdiger von Kummer, Andrew M. Demchuk, Javier M. Romero, Jordan J. Elm, Holly Hinson, Bradley J. Molyneaux, J. Marc Simard, Kevin N. Sheth

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

OBJECTIVE: In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) 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 IV glyburide 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 less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 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. CLINICALTRIALSGOV IDENTIFIER: NCT01794182. LEVEL OF EVIDENCE: This study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.

Original languageEnglish (US)
Pages (from-to)e2163-e2169
JournalNeurology
Volume91
Issue number23
DOIs
StatePublished - Dec 4 2018

Fingerprint

Glyburide
Edema
Placebos
Stroke
Infarction
Brain Edema
Matrix Metalloproteinase 9
Therapeutics
Nervous System

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kimberly, W. T., Bevers, M. B., von Kummer, R., Demchuk, A. M., Romero, J. M., Elm, J. J., ... Sheth, K. N. (2018). Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial. Neurology, 91(23), e2163-e2169. https://doi.org/10.1212/WNL.0000000000006618

Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial. / Kimberly, W. Taylor; Bevers, Matthew B.; von Kummer, Rüdiger; Demchuk, Andrew M.; Romero, Javier M.; Elm, Jordan J.; Hinson, Holly; Molyneaux, Bradley J.; Simard, J. Marc; Sheth, Kevin N.

In: Neurology, Vol. 91, No. 23, 04.12.2018, p. e2163-e2169.

Research output: Contribution to journalArticle

Kimberly, WT, Bevers, MB, von Kummer, R, Demchuk, AM, Romero, JM, Elm, JJ, Hinson, H, Molyneaux, BJ, Simard, JM & Sheth, KN 2018, 'Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial', Neurology, vol. 91, no. 23, pp. e2163-e2169. https://doi.org/10.1212/WNL.0000000000006618
Kimberly WT, Bevers MB, von Kummer R, Demchuk AM, Romero JM, Elm JJ et al. Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial. Neurology. 2018 Dec 4;91(23):e2163-e2169. https://doi.org/10.1212/WNL.0000000000006618
Kimberly, W. Taylor ; Bevers, Matthew B. ; von Kummer, Rüdiger ; Demchuk, Andrew M. ; Romero, Javier M. ; Elm, Jordan J. ; Hinson, Holly ; Molyneaux, Bradley J. ; Simard, J. Marc ; Sheth, Kevin N. / Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial. In: Neurology. 2018 ; Vol. 91, No. 23. pp. e2163-e2169.
@article{bcd37fb4298c4ec999f787f66580dd8e,
title = "Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial",
abstract = "OBJECTIVE: In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) 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 IV glyburide 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 less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 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. CLINICALTRIALSGOV IDENTIFIER: NCT01794182. LEVEL OF EVIDENCE: This study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.",
author = "Kimberly, {W. Taylor} and Bevers, {Matthew B.} and {von Kummer}, R{\"u}diger and Demchuk, {Andrew M.} and Romero, {Javier M.} and Elm, {Jordan J.} and Holly Hinson and Molyneaux, {Bradley J.} and Simard, {J. Marc} and Sheth, {Kevin N.}",
year = "2018",
month = "12",
day = "4",
doi = "10.1212/WNL.0000000000006618",
language = "English (US)",
volume = "91",
pages = "e2163--e2169",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "23",

}

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, Rüdiger

AU - Demchuk, Andrew M.

AU - Romero, Javier M.

AU - Elm, Jordan J.

AU - Hinson, Holly

AU - Molyneaux, Bradley J.

AU - Simard, J. Marc

AU - Sheth, Kevin N.

PY - 2018/12/4

Y1 - 2018/12/4

N2 - OBJECTIVE: In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) 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 IV glyburide 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 less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 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. CLINICALTRIALSGOV IDENTIFIER: NCT01794182. LEVEL OF EVIDENCE: This study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.

AB - OBJECTIVE: In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) 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 IV glyburide 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 less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 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. CLINICALTRIALSGOV IDENTIFIER: NCT01794182. LEVEL OF EVIDENCE: This study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.

UR - http://www.scopus.com/inward/record.url?scp=85058909186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058909186&partnerID=8YFLogxK

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 -