UCLA leads clinical trial of promising new stroke drug
By Jennifer Lauren Lee
Oct. 13, 2003 9:00 p.m.
The National Institutes of Health awarded the UCLA Stroke Center
a $16 million grant earlier this month to be used in the clinical
trial of a new treatment for acute strokes.
Unlike the standard FDA-approved “clot-busting”
drugs, which clear out blocked blood vessels to the brain, the new
treatment uses magnesium sulfate to protect brain cells directly
from the harmful effects of stroke.
“A lot of neuroprotective drugs have been tested before in
neurostroke trials,” said Dr. Jeffrey Saver, professor and
director of the UCLA Department of Neurology, and the principal
investigator for the study. “All have failed.”
Instead, this trial will test whether the brain-protecting
magnesium sulfate will be more effective if administered during the
critical first two hours after a stroke, said Dr. Sidney Starkman,
professor of emergency medicine and neurology at UCLA and
co-principal investigator of the study.
“This is the first large trial having paramedics give
drugs for stroke to patients on site, in time for (them) to
work,” Saver said. “Twelve (to) 26 hours after the
stroke, most of the damage is done – and then it’s too late
to intervene.”
According to Saver, a stroke, which is caused by a rupture or
blockage of a blood vessel to the brain, deprives brain cells of
oxygen-rich blood and kills them within five to six minutes.
But reduced blood flow to the areas surrounding that blockage
allows cells to survive for a few minutes to hours.
“The golden hour is the first hour,” Saver said.
“The more time lost, the more brain is lost.”
As headquarters for the study, UCLA will coordinate an effort
involving 330 paramedics from the Los Angeles Fire Department and
up to 80 receiving hospitals in the Los Angeles area, Saver
said.
Other key figures in the trial study include co-principal
investigators Dr. Marc Eckstein, medical director of the Los
Angeles City Fire Department, and Dr. Chelsea Kidwell, co-director
of the UCLA Stroke Center.
The trial will involve 1,298 patients over a four-year period in
a randomized, double-blind,
placebo-controlled study.
Paramedics at the scene will use the novel method of contacting
a trial physician by cell phone to get the consent of the stroke
victims or their family members to be enrolled in the study.
The FDA-approved clot-busting drug currently in use, tissue
plasminogen activator, helps one in three of the patients who get
it – but only 1 to 2 percent of acute stroke victims receive the
drug, since it is dangerous for hemorrhaging patients and may only
be administered in the hospital after a CAT scan, Saver said.
Magnesium sulfate is safer and can be administered right away.
It helps the brain cells tolerate a lower blood flow, inducing a
sort of chemical hibernation that would extend the time window
until patients could get the currently approved drug, Saver
said.
In addition to increasing blood flow to the brain, magnesium
sulfate blocks calcium from entering and destroying brain cells,
thereby slowing down the process of brain death that accompanies
stroke.
The compound has also been used for 75 years to treat patients
with eclampsia, a condition particular to pregnant women that
includes seizures and agitation, Saver said.
The initial pilot study, which ran from May 2000 to January
2002, had encouraging results, with some of the stroke patients
exhibiting a dramatic recovery in 24 hours.
“The pilot trial showed that paramedics can recognize
stroke accurately and safely start magnesium sulfate in the
field,” Eckstein stated in a recent press release.
“Now, we need to perform the large pivotal trial to determine
definitively if early magnesium sulfate improves patient
outcome.”
Stroke is the third leading cause of death in the United States
after heart disease and cancer, Saver said.
There are more than 40,000 stroke victims per year in the L.A.
metropolitan area.
Symptoms of stroke include sudden weakness, change in vision, or
difficulty speaking or walking.
According to Starkman, the consolidated effort of so many local
hospitals with the county Emergency Medical Services could make
this trial more efficient than if it were spread across many U.S.
cities.
“If you’re having a stroke,” Starkman said,
“you want to be in L.A.”
