Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial

Study Overview
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Brief Summary
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The goal of this study is to evaluate the effectiveness and safety of field-initiated magnesium sulfate in improving the long-term functional outcome of patients with acute stroke.

Detailed Description
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Stroke is the third leading cause of death and the leading cause of adult disability in the United States. Each year, more than 750,000 Americans suffer a symptomatic stroke. Currently, tissue plasminogen activator (rt-PA) is the only approved treatment for acute ischemic stroke; however, its usefulness is limited because most patients cannot reach medical attention within the necessary 3-hour time window. In addition, rt-PA cannot be given in the field because it is contraindicated for treatment of patients with brain hemorrhage. The purpose of this multi-center, randomized, double-blind trial is to demonstrate that paramedic initiation of the neuroprotective agent magnesium sulfate in the field is an effective and safe treatment for acute stroke. This study will analyze magnesium sulfate, an experimental therapy for stroke, versus placebo among ambulance-transported patients with acute stroke. This trial will also demonstrate that paramedics can safely, effectively, and rapidly start neuroprotective therapies for stroke.

Official Title
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Field Administration of Stroke Therapy-Magnesium Trial: A Randomized, Double-Blind, Placebo Controlled Trial of Neuroprotective Magnesium Sulfate Therapy for Acute Stroke Initiated Within 2 Hours of Onset by Paramedics in the Field

Conditions
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Cerebrovascular Accident

Intervention / Treatment
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* Drug: Magnesium Sulfate
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Suspected stroke identified by the Los Angeles Prehospital Stroke Screen Age 40-95, inclusive Last known well time within 2 hours of treatment initiation Deficit present for >/= 15 minutes Exclusion Criteria: Coma Rapidly improving neurologic deficit Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound the neurological or functional outcome evaluations Systolic Blood Pressure (SBP) < 90 or > 220 Known severe renal dysfunction (on dialysis or known chronic creatinine > 3.0) Severe respiratory distress (O2 sat < 90% or respiratory rate < 12 or >/= 24) Known second or third degree heart block with no pacemaker in place Major head trauma in the last 24 hours Recent stroke within prior 30 days Patient unable to give informed consent and no available on scene consent or assent provider

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Magnesium Sulfate<br>Magnesium sulfate (Mg) was administered intravenously with a 15 minute bolus load followed by a 24 hour infusion. The bolus-loading dose consisted of 4 grams Mg in 54 ml normal saline. The maintenance infusion contained 16 grams Mg diluted in 240 ml 0.9% normal saline, infused at 10 ml/hr for 24 hours. Paramedics in the field initiated the bolus-loading dose, administered at 216 ml/hr over 15 minutes through a rate controlled IV infusion set. The maintenance infusion was initiated in hospital immediately upon completion of the loading dose. | Drug: Magnesium Sulfate<br>* Paramedics initiate a loading dose of 4 grams magnesium sulfate IV over 15 minutes, followed after hospital arrival by a maintenance infusion of 16 grams magnesium sulfate IV over 24 hours.<br>* Other names: MA 135 magnesium sulfate heptahydrate;|
| Placebo Comparator: Normal saline<br>Normal saline was administered intravenously with a 15 minute bolus load followed by a 24 hour infusion. Paramedics in the field initiated the bolus-loading dose of 54 ml normal saline, administered at 216 ml/hr over 15 minutes through a rate controlled IV infusion set. The maintenance infusion was initiated in hospital immediately upon completion of the loading dose at 10 ml/hr for 24 hours. | Drug: Normal Saline<br>* Paramedics initiate a loading dose of placebo normal saline IV over 15 minutes, followed after hospital arrival by a maintenance infusion of placebo normal saline IV over 24 hours.<br>* Other names: SO155 sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale | Modified Rankin Scales (mRS) is a measure of global disability. Total Scale range is 0-6, with lower values indicating better outcomes. 0 No symptoms at all No significant disability despite symptoms; able to carry out all usual duties and activities Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance Moderate disability; requiring some help, but able to walk without assistance Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Severe disability; bedridden, incontinent and requiring constant nursing care and attention Dead | 3 months after stroke onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Score of 0 or 1 | Minimal or no disability based on the modified Rankin score | 3 months | 
| Modified Rankin Score ≤2 | Functional independence based on modified Rankin score | 3 months | 
| NIH Stroke Scale | The National Institute of Health Stroke Scale (NIHSS) is a measure of neurologic deficit. Total Score range 0-42, with higher scores indicating greater severity. The 11 domains assessed are: 1a-c Level of consciousness 2. Best Gaze 3. Visual 4. Facial Palsy 5a. Motor left arm 5b. Motor right arm 6a. Motor left leg 6b. Motor right leg 7. Limb Ataxia 8. Sensory 9. Best Language 10. Dysarthria 11. Extinction and Inattention | 3 months | 
| Barthel Index | The Barthel Index is a measure of activities of daily living. Total score is calculated by addition of subscale scores. Total score range is 0-100, with higher scores indicating better outcomes. The ten subitems are: FEEDING (Subscale range is 0-10) BATHING (Subscale range is 0-5) GROOMING (Subscale range is 0-5) DRESSING (Subscale range is 0-10) BOWELS (Subscale range is 0-10) BLADDER (Subscale range is 0-10) TOILET USE (Subscale range is 0-10) TRANSFERS (Subscale range is 0-15) MOBILITY (Subscale range is 0-15) STAIRS (Subscale range is 0-10) | 3 months | 
| Stroke Impact Scale | The Stroke Impact Scale (SIS) is a measure of stroke-specific quality of life. The scale assesses 8 domains. Scores for each domain range from 0-100, with higher scores indicating better outcomes. Physical problems Memory and thinking Mood and emotions Communication, reading and understanding Daily activities Mobility at home and in the community Affected hand use Hobbies and activities participation | 3 months | 
| Serious Adverse Events |  | 3 months | 
| Symptomatic Intracranial Hemorrhage |  | 3 month | 
| Mortality |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, brain attack, magnesium sulfate, neuroprotection, prehospital care, emergency medical services