Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction

Pongpat Vorasayan, Matthew B. Bevers, Lauren A. Beslow, Gordon Sze, Bradley J. Molyneaux, Holly E. Hinson, J. Marc Simard, Rüdiger von Kummer, Kevin N. Sheth, W. Taylor Kimberly

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background and Purpose- Prior studies have shown a linear relationship between computed tomography (CT)-derived radiodensity and water uptake, or brain edema, within stroke lesions. To test the hypothesis that intravenous glibenclamide (glyburide; BIIB093) reduces ischemic brain water uptake, we quantified the lesional net water uptake (NWU) on serial CT scans from patients enrolled in the phase 2 GAMES-RP Trial (Glyburide Advantage in Malignant Edema and Stroke). Methods- This was a post hoc exploratory analysis of the GAMES-RP study. Noncontrast CT scans performed between admission and day 7 (n=264) were analyzed in the GAMES-RP modified intention-to-treat sample. Quantitative change in CT radiodensity (ie, NWU) and midline shift (MLS) was measured. The gray and white matter NWU were also examined separately. Repeated-measures mixed-effects models were used to assess the effect of intravenous glibenclamide on MLS or NWU. Results- A median of 3 CT scans (interquartile range, 2-4) were performed per patient during the first 7 days after stroke. In a repeated-measures regression model, greater NWU was associated with increased MLS (β=0.23; 95% CI, 0.20-0.26; P<0.001). Treatment with intravenous glibenclamide was associated with reduced NWU (β=-2.80; 95% CI, -5.07 to -0.53; P=0.016) and reduced MLS (β=-1.50; 95% CI, -2.71 to -0.28; P=0.016). Treatment with intravenous glibenclamide reduced both gray and white matter water uptake. In mediation analysis, gray matter NWU (β=0.15; 95% CI, 0.11-0.20; P<0.001) contributed to a greater proportion of MLS mass effect, as compared with white matter NWU (β=0.08; 95% CI, 0.03-0.13; P=0.001). Conclusions- In this phase 2 post hoc analysis, intravenous glibenclamide reduced both water accumulation and mass effect after large hemispheric infarction. This study demonstrates NWU is a quantitative and modifiable biomarker of ischemic brain edema accumulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

Original languageEnglish (US)
Pages (from-to)3021-3027
Number of pages7
JournalStroke
Volume50
Issue number11
DOIs
StatePublished - Nov 1 2019

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Glyburide
Infarction
Water
Tomography
Stroke
Brain Edema
Edema
Biomarkers

Keywords

  • brain edema
  • glyburide
  • humans
  • infarction
  • white matter

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Vorasayan, P., Bevers, M. B., Beslow, L. A., Sze, G., Molyneaux, B. J., Hinson, H. E., ... Kimberly, W. T. (2019). Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction. Stroke, 50(11), 3021-3027. https://doi.org/10.1161/STROKEAHA.119.026036

Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction. / Vorasayan, Pongpat; Bevers, Matthew B.; Beslow, Lauren A.; Sze, Gordon; Molyneaux, Bradley J.; Hinson, Holly E.; Simard, J. Marc; von Kummer, Rüdiger; Sheth, Kevin N.; Kimberly, W. Taylor.

In: Stroke, Vol. 50, No. 11, 01.11.2019, p. 3021-3027.

Research output: Contribution to journalArticle

Vorasayan, P, Bevers, MB, Beslow, LA, Sze, G, Molyneaux, BJ, Hinson, HE, Simard, JM, von Kummer, R, Sheth, KN & Kimberly, WT 2019, 'Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction', Stroke, vol. 50, no. 11, pp. 3021-3027. https://doi.org/10.1161/STROKEAHA.119.026036
Vorasayan, Pongpat ; Bevers, Matthew B. ; Beslow, Lauren A. ; Sze, Gordon ; Molyneaux, Bradley J. ; Hinson, Holly E. ; Simard, J. Marc ; von Kummer, Rüdiger ; Sheth, Kevin N. ; Kimberly, W. Taylor. / Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction. In: Stroke. 2019 ; Vol. 50, No. 11. pp. 3021-3027.
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abstract = "Background and Purpose- Prior studies have shown a linear relationship between computed tomography (CT)-derived radiodensity and water uptake, or brain edema, within stroke lesions. To test the hypothesis that intravenous glibenclamide (glyburide; BIIB093) reduces ischemic brain water uptake, we quantified the lesional net water uptake (NWU) on serial CT scans from patients enrolled in the phase 2 GAMES-RP Trial (Glyburide Advantage in Malignant Edema and Stroke). Methods- This was a post hoc exploratory analysis of the GAMES-RP study. Noncontrast CT scans performed between admission and day 7 (n=264) were analyzed in the GAMES-RP modified intention-to-treat sample. Quantitative change in CT radiodensity (ie, NWU) and midline shift (MLS) was measured. The gray and white matter NWU were also examined separately. Repeated-measures mixed-effects models were used to assess the effect of intravenous glibenclamide on MLS or NWU. Results- A median of 3 CT scans (interquartile range, 2-4) were performed per patient during the first 7 days after stroke. In a repeated-measures regression model, greater NWU was associated with increased MLS (β=0.23; 95{\%} CI, 0.20-0.26; P<0.001). Treatment with intravenous glibenclamide was associated with reduced NWU (β=-2.80; 95{\%} CI, -5.07 to -0.53; P=0.016) and reduced MLS (β=-1.50; 95{\%} CI, -2.71 to -0.28; P=0.016). Treatment with intravenous glibenclamide reduced both gray and white matter water uptake. In mediation analysis, gray matter NWU (β=0.15; 95{\%} CI, 0.11-0.20; P<0.001) contributed to a greater proportion of MLS mass effect, as compared with white matter NWU (β=0.08; 95{\%} CI, 0.03-0.13; P=0.001). Conclusions- In this phase 2 post hoc analysis, intravenous glibenclamide reduced both water accumulation and mass effect after large hemispheric infarction. This study demonstrates NWU is a quantitative and modifiable biomarker of ischemic brain edema accumulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.",
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AU - Vorasayan, Pongpat

AU - Bevers, Matthew B.

AU - Beslow, Lauren A.

AU - Sze, Gordon

AU - Molyneaux, Bradley J.

AU - Hinson, Holly E.

AU - Simard, J. Marc

AU - von Kummer, Rüdiger

AU - Sheth, Kevin N.

AU - Kimberly, W. Taylor

PY - 2019/11/1

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N2 - Background and Purpose- Prior studies have shown a linear relationship between computed tomography (CT)-derived radiodensity and water uptake, or brain edema, within stroke lesions. To test the hypothesis that intravenous glibenclamide (glyburide; BIIB093) reduces ischemic brain water uptake, we quantified the lesional net water uptake (NWU) on serial CT scans from patients enrolled in the phase 2 GAMES-RP Trial (Glyburide Advantage in Malignant Edema and Stroke). Methods- This was a post hoc exploratory analysis of the GAMES-RP study. Noncontrast CT scans performed between admission and day 7 (n=264) were analyzed in the GAMES-RP modified intention-to-treat sample. Quantitative change in CT radiodensity (ie, NWU) and midline shift (MLS) was measured. The gray and white matter NWU were also examined separately. Repeated-measures mixed-effects models were used to assess the effect of intravenous glibenclamide on MLS or NWU. Results- A median of 3 CT scans (interquartile range, 2-4) were performed per patient during the first 7 days after stroke. In a repeated-measures regression model, greater NWU was associated with increased MLS (β=0.23; 95% CI, 0.20-0.26; P<0.001). Treatment with intravenous glibenclamide was associated with reduced NWU (β=-2.80; 95% CI, -5.07 to -0.53; P=0.016) and reduced MLS (β=-1.50; 95% CI, -2.71 to -0.28; P=0.016). Treatment with intravenous glibenclamide reduced both gray and white matter water uptake. In mediation analysis, gray matter NWU (β=0.15; 95% CI, 0.11-0.20; P<0.001) contributed to a greater proportion of MLS mass effect, as compared with white matter NWU (β=0.08; 95% CI, 0.03-0.13; P=0.001). Conclusions- In this phase 2 post hoc analysis, intravenous glibenclamide reduced both water accumulation and mass effect after large hemispheric infarction. This study demonstrates NWU is a quantitative and modifiable biomarker of ischemic brain edema accumulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

AB - Background and Purpose- Prior studies have shown a linear relationship between computed tomography (CT)-derived radiodensity and water uptake, or brain edema, within stroke lesions. To test the hypothesis that intravenous glibenclamide (glyburide; BIIB093) reduces ischemic brain water uptake, we quantified the lesional net water uptake (NWU) on serial CT scans from patients enrolled in the phase 2 GAMES-RP Trial (Glyburide Advantage in Malignant Edema and Stroke). Methods- This was a post hoc exploratory analysis of the GAMES-RP study. Noncontrast CT scans performed between admission and day 7 (n=264) were analyzed in the GAMES-RP modified intention-to-treat sample. Quantitative change in CT radiodensity (ie, NWU) and midline shift (MLS) was measured. The gray and white matter NWU were also examined separately. Repeated-measures mixed-effects models were used to assess the effect of intravenous glibenclamide on MLS or NWU. Results- A median of 3 CT scans (interquartile range, 2-4) were performed per patient during the first 7 days after stroke. In a repeated-measures regression model, greater NWU was associated with increased MLS (β=0.23; 95% CI, 0.20-0.26; P<0.001). Treatment with intravenous glibenclamide was associated with reduced NWU (β=-2.80; 95% CI, -5.07 to -0.53; P=0.016) and reduced MLS (β=-1.50; 95% CI, -2.71 to -0.28; P=0.016). Treatment with intravenous glibenclamide reduced both gray and white matter water uptake. In mediation analysis, gray matter NWU (β=0.15; 95% CI, 0.11-0.20; P<0.001) contributed to a greater proportion of MLS mass effect, as compared with white matter NWU (β=0.08; 95% CI, 0.03-0.13; P=0.001). Conclusions- In this phase 2 post hoc analysis, intravenous glibenclamide reduced both water accumulation and mass effect after large hemispheric infarction. This study demonstrates NWU is a quantitative and modifiable biomarker of ischemic brain edema accumulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.

KW - brain edema

KW - glyburide

KW - humans

KW - infarction

KW - white matter

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