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

• ClinicalTrials.gov Identifier: NCT00059332
• Recruitment Status: Completed
• First Posted: April 24, 2003
• Results First Posted: August 21, 2015
• Last Update Posted: August 21, 2015
• Sponsor: Jeffrey L. Saver
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Jeffrey L. Saver, University of California, Los Angeles

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cerebrovascular Accident	Drug: Magnesium Sulfate; Drug: Normal Saline	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2005
• Actual Primary Completion Date: March 2013
• Actual Study Completion Date: March 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Magnesium Sulfate; 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; 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.; Other Name: MA 135 magnesium sulfate heptahydrate
Placebo Comparator: Normal saline; 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; 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.; Other Name: SO155 sodium chloride

Outcome Measures

Primary Outcome Measures :

1. Modified Rankin Scale [ Time Frame: 3 months after stroke onset ]

   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

   1. No significant disability despite symptoms; able to carry out all usual duties and activities
   2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
   3. Moderate disability; requiring some help, but able to walk without assistance
   4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
   5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention
   6. Dead

Secondary Outcome Measures :

1. Modified Rankin Score of 0 or 1 [ Time Frame: 3 months ]
   Minimal or no disability based on the modified Rankin score
2. Modified Rankin Score ≤2 [ Time Frame: 3 months ]
   Functional independence based on modified Rankin score
3. NIH Stroke Scale [ Time Frame: 3 months ]

   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

4. Barthel Index [ Time Frame: 3 months ]

   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)

5. Stroke Impact Scale [ Time Frame: 3 months ]

   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.

   1. Physical problems
   2. Memory and thinking
   3. Mood and emotions
   4. Communication, reading and understanding
   5. Daily activities
   6. Mobility at home and in the community
   7. Affected hand use
   8. Hobbies and activities participation
6. Serious Adverse Events [ Time Frame: 3 months ]
7. Symptomatic Intracranial Hemorrhage [ Time Frame: 3 month ]
8. Mortality [ Time Frame: 3 months ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

The Clinical Coordinating Center is: UCLA School of Medicine, 710 Westwood Plaza

Los Angeles, California, United States, 90095

Sponsors and Collaborators

Jeffrey L. Saver

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Jeffrey Saver, M.D.; UCLA School of Medicine, Study Overall Principal Investigator
• Principal Investigator: Sidney Starkman, M.D.; UCLA Stroke Center, Co-Principal Investigator
• Principal Investigator: Marc Eckstein, M.D.; Los Angeles City Emergency Medical Service, Co-Principal Investigator
• Principal Investigator: Samuel Stratton, MD; Los Angeles and Orange County Emergency Medical Services Agencies, Co-Principal Investigator
• Principal Investigator: Frank Pratt, MD; Los Angeles County Emergency Medical Service, Co-Principal Investigator

More Information

Additional Information:

The official FAST-MAG Clinical Trial website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Naidech AM, Shkirkova K, Villablanca JP, Sanossian N, Liebeskind DS, Sharma L, Eckstein M, Stratton S, Conwit R, Hamilton S, Saver JL; FAST-MAG Investigators and Coordinators. Magnesium Sulfate and Hematoma Expansion: An Ancillary Analysis of the FAST-MAG Randomized Trial. Stroke. 2022 May;53(5):1516-1519. doi: 10.1161/STROKEAHA.121.037999. Epub 2022 Apr 5.

Shkirkova K, Wang TT, Vartanyan L, Liebeskind DS, Eckstein M, Starkman S, Stratton S, Pratt FD, Hamilton S, Kim-Tenser M, Conwit R, Saver JL, Sanossian N. Quality of Acute Stroke Care at Primary Stroke Centers Before and After Certification in Comparison to Never-Certified Hospitals. Front Neurol. 2020 Jan 22;10:1396. doi: 10.3389/fneur.2019.01396. eCollection 2019.

Shkirkova K, Schuberg S, Balouzian E, Starkman S, Eckstein M, Stratton S, Pratt FD, Hamilton S, Sharma L, Liebeskind DS, Conwit R, Saver JL, Sanossian N; FAST-MAG Investigators and Coordinators. Paramedic Global Impression of Change During Prehospital Evaluation and Transport for Acute Stroke. Stroke. 2020 Mar;51(3):784-791. doi: 10.1161/STROKEAHA.119.026392. Epub 2020 Jan 20.

Shkirkova K, Saver JL, Starkman S, Wong G, Weng J, Hamilton S, Liebeskind DS, Eckstein M, Stratton S, Pratt F, Conwit R, Sanossian N; FAST-MAG Trial Coordinators and Investigators. Frequency, Predictors, and Outcomes of Prehospital and Early Postarrival Neurological Deterioration in Acute Stroke: Exploratory Analysis of the FAST-MAG Randomized Clinical Trial. JAMA Neurol. 2018 Nov 1;75(11):1364-1374. doi: 10.1001/jamaneurol.2018.1893.

Chung PW, Kim JT, Sanossian N, Starkmann S, Hamilton S, Gornbein J, Conwit R, Eckstein M, Pratt F, Stratton S, Liebeskind DS, Saver JL; FAST-MAG Investigators and Coordinators. Association Between Hyperacute Stage Blood Pressure Variability and Outcome in Patients With Spontaneous Intracerebral Hemorrhage. Stroke. 2018 Feb;49(2):348-354. doi: 10.1161/STROKEAHA.117.017701. Epub 2018 Jan 4.

Sanossian N, Rosenberg L, Liebeskind DS, Starkman S, Eckstein M, Stratton S, Pratt FD, Hamilton S, Kim-Tenser M, Sharma LK, Restrepo L, Valdes-Suieras M, Conwit R, Saver JL; FAST-MAG Investigators and Coordinators. A Dedicated Spanish Language Line Increases Enrollment of Hispanics Into Prehospital Clinical Research. Stroke. 2017 May;48(5):1389-1391. doi: 10.1161/STROKEAHA.117.014745. Epub 2017 Apr 7.

Sanossian N, Apibunyopas KC, Liebeskind DS, Starkman S, Burgos AM, Conwit R, Eckstein M, Pratt F, Stratton S, Hamilton S, Saver JL; FAST-MAG (Field Administration of Stroke Therapy-Magnesium) Investigators and Coordinators. Characteristics and Outcomes of Very Elderly Enrolled in a Prehospital Stroke Research Study. Stroke. 2016 Nov;47(11):2737-2741. doi: 10.1161/STROKEAHA.116.013318. Epub 2016 Sep 27.

Kim DH, Saver JL, Starkman S, Liebeskind DS, Ali LK, Restrepo L, Kim-Tenser M, Valdes-Sueiras M, Eckstein M, Pratt F, Stratton S, Hamilton S, Conwit R, Sanossian N; Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial Nurse-Coordinators and Investigators. Enrollment Yield and Reasons for Screen Failure in a Large Prehospital Stroke Trial. Stroke. 2016 Jan;47(1):232-5. doi: 10.1161/STROKEAHA.115.011687. Epub 2015 Dec 10.

Sanossian N, Liebeskind DS, Eckstein M, Starkman S, Stratton S, Pratt FD, Koenig W, Hamilton S, Kim-Tenser M, Conwit R, Saver JL; FAST-MAG Investigators and Coordinators. Routing Ambulances to Designated Centers Increases Access to Stroke Center Care and Enrollment in Prehospital Research. Stroke. 2015 Oct;46(10):2886-90. doi: 10.1161/STROKEAHA.115.010264. Epub 2015 Aug 11.

Saver JL, Starkman S, Eckstein M, Stratton SJ, Pratt FD, Hamilton S, Conwit R, Liebeskind DS, Sung G, Kramer I, Moreau G, Goldweber R, Sanossian N; FAST-MAG Investigators and Coordinators. Prehospital use of magnesium sulfate as neuroprotection in acute stroke. N Engl J Med. 2015 Feb 5;372(6):528-36. doi: 10.1056/NEJMoa1408827.

• Responsible Party: Jeffrey L. Saver, Professor of Neurology, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00059332
• Other Study ID Numbers: U01NS044364 ( U.S. NIH Grant/Contract ); U01NS044364 ( U.S. NIH Grant/Contract )
• First Posted: April 24, 2003
• Results First Posted: August 21, 2015
• Last Update Posted: August 21, 2015
• Last Verified: June 2015

Keywords provided by Jeffrey L. Saver, University of California, Los Angeles:

stroke; brain attack; magnesium sulfate; neuroprotection; prehospital care; emergency medical services

Additional relevant MeSH terms:

Magnesium Sulfate; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Anti-Arrhythmia Agents; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Tocolytic Agents; Reproductive Control Agents