Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial

Stella Kidwell, Kennedy R. Lees, Keith W. Muir, Christopher Chen, Stephen M. Davis, Deidre A. De Silva, Christopher J. Weir, Sidney Starkman, Jeffry R. Alger, Jeffrey L. Saver

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background and Purpose-: Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth. Methods-: IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed. Results-: Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume. Conclusions-: Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.

Original languageEnglish (US)
Pages (from-to)1704-1709
Number of pages6
JournalStroke
Volume40
Issue number5
DOIs
StatePublished - May 1 2009
Externally publishedYes

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Magnesium
Stroke
Growth
Placebos
Glucose
Magnetic Resonance Spectroscopy
Therapeutics
Animal Models
Clinical Trials

Keywords

  • Diffusion-weighted imaging
  • Glucose
  • Magnesium
  • Magnetic resonance imaging
  • Surrogate endpoint

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Kidwell, S., Lees, K. R., Muir, K. W., Chen, C., Davis, S. M., De Silva, D. A., ... Saver, J. L. (2009). Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial. Stroke, 40(5), 1704-1709. https://doi.org/10.1161/STROKEAHA.108.537613

Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial. / Kidwell, Stella; Lees, Kennedy R.; Muir, Keith W.; Chen, Christopher; Davis, Stephen M.; De Silva, Deidre A.; Weir, Christopher J.; Starkman, Sidney; Alger, Jeffry R.; Saver, Jeffrey L.

In: Stroke, Vol. 40, No. 5, 01.05.2009, p. 1704-1709.

Research output: Contribution to journalArticle

Kidwell, S, Lees, KR, Muir, KW, Chen, C, Davis, SM, De Silva, DA, Weir, CJ, Starkman, S, Alger, JR & Saver, JL 2009, 'Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial', Stroke, vol. 40, no. 5, pp. 1704-1709. https://doi.org/10.1161/STROKEAHA.108.537613
Kidwell, Stella ; Lees, Kennedy R. ; Muir, Keith W. ; Chen, Christopher ; Davis, Stephen M. ; De Silva, Deidre A. ; Weir, Christopher J. ; Starkman, Sidney ; Alger, Jeffry R. ; Saver, Jeffrey L. / Results of the MRI substudy of the intravenous magnesium efficacy in stroke trial. In: Stroke. 2009 ; Vol. 40, No. 5. pp. 1704-1709.
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AU - De Silva, Deidre A.

AU - Weir, Christopher J.

AU - Starkman, Sidney

AU - Alger, Jeffry R.

AU - Saver, Jeffrey L.

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AB - Background and Purpose-: Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth. Methods-: IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline diffusion-weighted imaging and day 90 fluid-attenuated inversion recovery image lesions. Patients who died were imputed the largest infarct growth observed. Results-: Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth, P=0.639; median percentage growth, P=0.616; proportion with any growth, P=0.212) between the 46 treated with magnesium and 44 with placebo. Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment, but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume. Conclusions-: Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this 12-hour time window stroke study.

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