NIH study demonstrates feasibility of getting drugs to stroke patients faster
There is no time to waste when it comes to stroke. The more time that passes between stroke onset and treatment, the worse the outcome is for the patient. A study designed to test the benefits of early administration of magnesium sulfate suggests that stroke patients may not have to wait until they get to the hospital for treatment — paramedics may be able to start therapy as soon as stroke is suspected. Although the drug did not improve outcome in stroke patients, the study demonstrated the feasibility of early therapy in the ambulance. The results were published in the New England Journal of Medicine and the study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
Ambulance racing to the emergency room
“This study shows that it is possible to get treatments to stroke patients even before they arrive at a hospital. Because a blocked blood vessel causes brain damage over minutes to hours this pre-hospital approach to treatment is sure to be adopted and refined in future clinical research studies. Ultra-early brain salvage in stroke patients will someday surely reduce the tremendous burden of disability and death due to stroke,” said Walter Koroshetz, M.D., acting director of NINDS.
Jeffrey Saver, M.D., director of the University of California, Los Angeles Comprehensive Stroke Center, and his colleagues developed a novel approach to conducting a stroke clinical trial. They wanted to know if it was possible to shorten the time between stroke onset and treatment by having paramedics administer stroke therapies as soon as stroke is suspected. In most stroke trials, patients tend to receive initial treatment after undergoing tests at a hospital, which may be hours after the stroke began.
The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Phase 3 Trial was a multi-center, randomized, placebo-controlled clinical study. In this study, 1700 patients who were suspected of having had a stroke were given magnesium sulfate or a placebo by paramedics within two hours of stroke onset.
Paramedics used a version of the Los Angeles Prehospital Stroke Screen developed by the Investigators to rapidly and accurately identify potential stroke patients. Paramedics then contacted a neurologist via cellphone to further determine if a patient should be included in the study. After this contact, the patients or their representatives provided permission to the study doctor to participate in the trial.
This study indicated that patients were able to receive a study drug faster than in other stroke trials. Analysis revealed that 74.3 percent of patients received a study intervention within 60 minutes of stroke onset.
“The most important finding of this study was that medication could be delivered within the ‘golden hour’ of first onset of stroke symptoms when there is the greatest amount of brain to save. That means the prehospital paramedic delivery of drug system that was developed in FASTMAG could become a platform for testing additional drugs and devices in the future,” said Dr. Saver, lead author of the study.
In addition to testing the new protocol, the researchers wanted to see if a particular drug, magnesium sulfate, helped improve outcomes in patients 90 days after stroke. Magnesium sulfate has been shown to exhibit neuroprotective effects in animal models of stroke.
When the researchers analyzed the drug results, they found that magnesium sulfate was not better than placebo at reducing disability following stroke.
“Unfortunately the drug we tested turned out to be ineffective, but now there are many promising drugs and devices in the pipeline that can be tried with this novel protocol and the study has opened up a new window in which the interventions are most likely to be effective. There are several trials underway that are taking elements of the FASTMAG platform and applying it to test promising agents for neuroprotection,” said Dr. Saver.
“We believe this study represents a paradigm shift in the treatment of stroke and potentially numerous other neurological conditions,” said co-principal investigator Dr. Sidney Starkman, co-director of the UCLA Stroke Center and professor of emergency medicine and neurology at the David Geffen School of Medicine at UCLA. “We’ve never done something this large that demonstrates that paramedics not only are eager to provide the best possible patient care, but also are capable of being invaluable partners in an intense, time-dependent clinical trial.”