Quick magnesium treatment fails to improve stroke outcomes, but study has silver lining
In the first study of its kind, a consortium led by UCLA physicians found that giving stroke patients intravenous magnesium within an hour of the onset of symptoms does not improve stroke outcomes.
However, the 8-year trial did find that with the help of paramedics in the field, intravenous medications can frequently be administered to stroke victims within that so-called "golden hour," during which they have the best chance to survive and avoid debilitating, long-term neurological damage.
The latter finding is a "game-changer," said Dr. Jeffrey Saver, director of the UCLA Stroke Center and a professor of neurology at the David Geffen School of Medicine at UCLA. Saver served as co-principal investigator on the research, which was presented Feb. 13 at the American Stroke Association's International Stroke Conference.
"Stroke is a true emergency condition. For every minute that goes by without restoration of blood flow, 2 million nerve cells are lost," Saver said. "Since time lost is brain lost, we wanted to develop a method that let us get potentially brain-saving drugs to the patient in the earliest moments of onset of the stroke. If these patients don't get protective drugs until two, three or four hours later, irreversible brain damage has already occurred."
While the Phase 3 clinical trial found that magnesium does not improve stroke-related disability, the search is now on for new drugs and treatments that can be administered in the field to improve long-term outcomes. The infrastructure to treat patients quickly was created by this study is in place, and that is a major accomplishment, Saver said.
The trial, called Field Administration of Stroke Therapy–Magnesium, or FAST–MAG, involved collaboration among 315 ambulances, 40 emergency medical-service agencies, 60 receiving hospitals and 2,988 paramedics in Los Angeles and Orange counties. Conducted between 2005 and 2013, the study showed that 74 percent of the 1,700 study patients were treated in the first hour, with the magnesium administered within a median time of 45 minutes.
"With this study, we were able to reach the threatened brain faster than ever before," said co-principal investigator Dr. Sidney Starkman, co-director of the UCLA Stroke Center and professor of emergency medicine and neurology at the Geffen School. "The study has really opened up opportunities to treat patients in the pre-hospital setting in the earliest minutes after symptoms appear."
Starkman said that the study would not have been possible without the approval and confidence of the California and local emergency medical-service agencies and the administrations of the participating hospitals.
Today, the only immediate treatment for strokes caused by blockage of blood vessels is the clot-busting drug tissue plasminogen activator (tPA). But tPA cannot be given until the patients arrive at the hospital and undergo a CT scan to rule out bleeding in the brain. Giving tPA in an ambulance without a CT scan first is not an option because it could harm patients whose strokes are caused by brain bleeds, Saver said. However, neuroprotective drugs can be administered in the field because they're safe for both blockage and the bleeding strokes.
For the FAST–MAG trial, magnesium was chosen because it was shown to dilate blood vessels in the brain in animal studies, increasing blood flow. It also countered the damaging calcium build up that occurs in cells deprived of oxygen. It was already approved to treat medical conditions in people, and it was known to have a good safety profile.
Saver said FAST–MAG researchers are extremely indebted to the nearly 3,000 paramedics involved in the study, as well as the emergency medicine physicians, neurologists, neurosurgeons and nurses who participated.
"Now we are tasked with finding a different agent or combination of agents that can improve stroke outcomes within that golden hour," Saver said. "We developed a treatment platform that works and can be used around the world to test promising agents. FAST–MAG has opened a new, earlier-than-ever window for treatment that has the potential to significantly improve outcomes for the hundreds of thousands of people each year who suffer a stroke."
The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, sponsored the FAST–MAG study.
"NINDS is extremely grateful to the investigators, emergency medical technicians and patients who participated in this landmark study demonstrating how to test therapies in stroke patients before they arrive at the hospital," said Dr. Walter Koroshetz, deputy director of NINDS. "NINDS has just set up a new national stroke trials network which can incorporate the lessons learned in FAST–MAG, but also increase the likelihood that the treatments we test will improve patients' lives."
Stroke is the fourth leading cause of death in the nation and a major cause of adult disability. About 800,000 people in the U.S. have a stroke each year. One American dies from a stroke every four minutes, on average.
The UCLA Department of Neurology, with over 100 faculty members, encompasses more than 20 disease-related research programs, along with large clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks in the top two among its peers nationwide in National Institutes of Health funding.