Prehospital use of magnesium sulfate as neuroprotection in acute stroke

FAST-MAG Investigators and Coordinators

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

BACKGROUND: Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. METHODS: We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). RESULTS: Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P=0.95) or all serious adverse events. CONCLUSIONS: Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days.

Original languageEnglish (US)
Pages (from-to)528-536
Number of pages9
JournalNew England Journal of Medicine
Volume372
Issue number6
DOIs
StatePublished - Feb 5 2015

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Magnesium Sulfate
Stroke
Magnesium
Placebos
Neuroprotective Agents
Allied Health Personnel
Los Angeles
Neuroprotection
Intracranial Hemorrhages
Brain Ischemia
Pharmaceutical Preparations
Maintenance
Safety
Mortality
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

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Prehospital use of magnesium sulfate as neuroprotection in acute stroke. / FAST-MAG Investigators and Coordinators.

In: New England Journal of Medicine, Vol. 372, No. 6, 05.02.2015, p. 528-536.

Research output: Contribution to journalArticle

FAST-MAG Investigators and Coordinators. / Prehospital use of magnesium sulfate as neuroprotection in acute stroke. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 6. pp. 528-536.
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abstract = "BACKGROUND: Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. METHODS: We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). RESULTS: Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6{\%} were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3{\%} of patients, intracranial hemorrhage in 22.8{\%}, and a stroke-mimicking condition in 3.9{\%}. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3{\%} of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4{\%} in the magnesium group and 15.5{\%} in the placebo group, P=0.95) or all serious adverse events. CONCLUSIONS: Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days.",
author = "{FAST-MAG Investigators and Coordinators} and Saver, {Jeffrey L.} and Sidney Starkman and Marc Eckstein and Stratton, {Samuel J.} and Pratt, {Franklin D.} and Scott Hamilton and Robin Conwit and Liebeskind, {David S.} and Gene Sung and Ian Kramer and Gary Moreau and Robert Goldweber and Nerses Sanossian and A. Ali and K. Andruss and B. Beck and S. Chin and D. Conneen and D. Copeland and A. Crisan and L. Gale and G. Ganguly and Gonzalez, {J. E.} and P. Helfgott and H. Hovanessian and E. Jarema and M. Liu and Martin, {M. L.} and G. Meyer and H. Minassian and T. Nguyen and R. Rison and M. Salinas and A. Sato and R. Shapiro and Shook, {G. D.} and M. Suleiman and M. Thomas and R. Zoraster and A. Aguayo and K. Balauag and N. Coleman and S. Feudi and S. Henthorn and C. Anderegg and C. Barba and B. Burden and G. Bush and I. Carrillo-Nunez and Hartmut Gross",
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T1 - Prehospital use of magnesium sulfate as neuroprotection in acute stroke

AU - FAST-MAG Investigators and Coordinators

AU - Saver, Jeffrey L.

AU - Starkman, Sidney

AU - Eckstein, Marc

AU - Stratton, Samuel J.

AU - Pratt, Franklin D.

AU - Hamilton, Scott

AU - Conwit, Robin

AU - Liebeskind, David S.

AU - Sung, Gene

AU - Kramer, Ian

AU - Moreau, Gary

AU - Goldweber, Robert

AU - Sanossian, Nerses

AU - Ali, A.

AU - Andruss, K.

AU - Beck, B.

AU - Chin, S.

AU - Conneen, D.

AU - Copeland, D.

AU - Crisan, A.

AU - Gale, L.

AU - Ganguly, G.

AU - Gonzalez, J. E.

AU - Helfgott, P.

AU - Hovanessian, H.

AU - Jarema, E.

AU - Liu, M.

AU - Martin, M. L.

AU - Meyer, G.

AU - Minassian, H.

AU - Nguyen, T.

AU - Rison, R.

AU - Salinas, M.

AU - Sato, A.

AU - Shapiro, R.

AU - Shook, G. D.

AU - Suleiman, M.

AU - Thomas, M.

AU - Zoraster, R.

AU - Aguayo, A.

AU - Balauag, K.

AU - Coleman, N.

AU - Feudi, S.

AU - Henthorn, S.

AU - Anderegg, C.

AU - Barba, C.

AU - Burden, B.

AU - Bush, G.

AU - Carrillo-Nunez, I.

AU - Gross, Hartmut

PY - 2015/2/5

Y1 - 2015/2/5

N2 - BACKGROUND: Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. METHODS: We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). RESULTS: Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P=0.95) or all serious adverse events. CONCLUSIONS: Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days.

AB - BACKGROUND: Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents. METHODS: We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability). RESULTS: Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (±SD) age was 69±13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7±1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P=0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P=1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P=0.95) or all serious adverse events. CONCLUSIONS: Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days.

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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