• Cerebrovascular Disease
• Neurology Clinical Trials

• Cerebrovascular Disease
• Neurology Clinical Trials
• Neurology

Magnesium sulfate administered to patients <2 hours after stroke fails to provide neuroprotection. The primary findings of the Field Administration of Stroke Therapy-Magnesium trial [FAST-MAG] were presented by Jeffrey L. Saver, MD, Stroke Center, University of California at Los Angeles, Los Angeles, California, USA.

Early intervention is critical for stroke care. Delayed time to treatment after onset of stroke symptoms can result in progressive neuron loss and diminished outcome [Lansberg MG et al. Stroke 2009; Saver JL. Stroke 2006; Saver JL et al. Stroke 2004]. The physiological and neuroprotective prowess of magnesium has been amply demonstrated in animal models of stroke. Prehospital administration of magnesium by emergency medical services (EMS) providers can accelerate treatment by nearly 2 hours [Saver JL et al. JAMA 2013; Saver JL et al. Stroke 2004]. Yet, patient benefits of this ‘in-field’ treatment are unclear.

The FAST-MAG trial was undertaken to explore whether paramedic administration of magnesium is effective and safe for treatment of acute stroke. The placebo-controlled, double-blind, randomized, Phase 3 trial from January 2005 through March 2013 involved 60 hospitals (952 physicians) and 40 EMS provider agencies (2988 paramedics) throughout Los Angeles and Orange Counties. The 1700 patients received 4 g magnesium sulfate (n=857) or placebo (n=843) within 2 hours of the onset of stroke symptoms. All patients received 16 g maintenance magnesium sulfate within 24 hours. Inclusion criteria were suspected stroke according to the Los Angeles Prehospital Stroke Screen, age 40 to 95 years, last known well time within 2 hours of treatment initiation, and deficit present for ≥15 minutes.

The primary endpoint was the mRS stroke disability score. Secondary endpoints were mRS 0–1 and 0–2, Barthel Index scores of daily living, NIHSS scores, and Stroke Impact Scale scores.

The study arms were comparable in a battery of baseline characteristics and neurological features. There was no difference in the time from onset of symptoms to administration of placebo or magnesium. This shows that the EMS system succeeded in giving drug early after stroke even if the treatment was not effective. The 3-month mRS scores were not significantly different for both arms (Table 1). None of the secondary endpoints differed appreciably between the study arms (Table 2).

Subgroup analyses failed to reveal benefits of magnesium depending on use/non-use of tissue plasminogen activator, treatment within 60 or 120 minutes, age, gender, race, and stroke severity. Serious adverse events occurred in 50.1% and 51.2% of patients in the placebo and treatment arm, respectively (p=0.66).

Possible explanations for the disappointing results include slow passage of magnesium across the blood-brain barrier and the inability of magnesium to prevent the ischemic cascade.

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