Stroke is the third leading cause of death and the leading cause of adult disability in the United States. Each year in the US, 750,000 Americans suffer a symptomatic stroke, and over 11 million suffer an asymptomatic stroke. The central aim of this proposal is to demonstrate that paramedic initiation of the neuroprotective agent magnesium sulfate in the field is an efficacious and safe treatment for acute stroke. The proposal is a multicenter, randomized, double-blind, phase 3 clinical trial, using intention to treat analysis, of magnesium sulfate versus placebo among ambulance-transported patients with acute stroke. Study agent will be initiated within two hours of stroke onset in all enrolled individuals, and within one hour of onset in approximately one-half of enrolled individuals. A total of 1298 patients will be enrolled, 649 in each treatment arm. The dose of magnesium sulfate employed will be 4 gram IV loading dose over 15 minutes followed by 16 gram IV maintenance dose over 24 hours. The primary study hypothesis is that treatment with magnesium sulfate improves the long-term functional outcome of hyper-acute stroke patients. The primary study endpoint will be the difference in distribution of scores between magnesium sulfate and placebo groups on the modified Rankin Scale measure of global handicap, assessed 3 months poststroke. Secondary analyses will analyze treatment efficacy on endpoints indexing neurologic deficit, activities of daily living, global outcome, and quality of life, and in pre-specified patient subgroups, including patients with ischemic stroke, ischemic stroke co-treated with tissue plasminogen activator, ischemic stroke not co-treated with tissue plasminogen activator, intracerebral hemorrhage, patients treated within 15-60 minutes of symptom onset, and within 61-120 minutes of symptom onset. Successful conduct of the trial will serve as a pivotal test of the promising neuroprotective agent magnesium sulfate in acute stroke, and will also demonstrate for the first time that field enrollment and treatment of acute stroke patients is a practical and feasible strategy for phase 3 stroke trials, permitting enrollment of greater numbers of patients in hyper-acute time windows.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS044364-08
Application #
8233926
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
8
Fiscal Year
2011
Total Cost
$3,307,807
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Sanossian, Nerses; Fu, Katherine A; Liebeskind, David S et al. (2017) Utilization of Emergent Neuroimaging for Thrombolysis-Eligible Stroke Patients. J Neuroimaging 27:59-64
Sharma, Mohit; Helzner, Elizabeth; Sinert, Richard et al. (2016) Patient characteristics affecting stroke identification by emergency medical service providers in Brooklyn, New York. Intern Emerg Med 11:229-36
Kim, Dae-Hyun; Saver, Jeffrey L; Starkman, Sidney et al. (2016) Enrollment Yield and Reasons for Screen Failure in a Large Prehospital Stroke Trial. Stroke 47:232-5
Sanossian, Nerses; Liebeskind, David S; Eckstein, Marc et al. (2015) Routing Ambulances to Designated Centers Increases Access to Stroke Center Care and Enrollment in Prehospital Research. Stroke 46:2886-90
Kim, Seo Hyun; Saver, Jeffrey L (2015) Initial body temperature in ischemic stroke: nonpotentiation of tissue-type plasminogen activator benefit and inverse association with severity. Stroke 46:132-6
Brandler, Ethan S; Sharma, Mohit; McCullough, Flynn et al. (2015) Prehospital Stroke Identification: Factors Associated with Diagnostic Accuracy. J Stroke Cerebrovasc Dis 24:2161-6
Saver, Jeffrey L; Starkman, Sidney; Eckstein, Marc et al. (2015) Prehospital use of magnesium sulfate as neuroprotection in acute stroke. N Engl J Med 372:528-36
Saver, Jeffrey L; Starkman, Sidney; Eckstein, Marc et al. (2014) Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) phase 3 trial: Part 1 - rationale and general methods. Int J Stroke 9:215-9
Saver, Jeffrey L; Starkman, Sidney; Eckstein, Marc et al. (2014) Methodology of the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) phase 3 trial: Part 2 - prehospital study methods. Int J Stroke 9:220-5

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