The first potential treatment for strokes that result from bleeding in the brain is under study at the Medical College of Georgia.
MCG is one of about 100 sites worldwide looking at whether patients with this type of stroke - often resulting from the rupture of fragile arteries branching off the main arteries of the brain - can benefit from rapid delivery of a factor that is part of the body's natural clotting process.
Intracerebral hemorrhage accounts for up to 15 percent of the 750,000 strokes that occur annually in the United States, says Dr. Christiana E. Hall, MCG neurologist and a principal investigator on the NovoSeven® study.
"The biggest risk factor for these hemorrhages is hypertension, which we have a big problem with in the South," says Dr. Hall. "We are seeing young men and women in their 40s come in with these types of strokes when it's usually a disease of those 60 and older. These are mothers and fathers with children they are raising and they have this life-altering or lethal condition just come out of the blue.
"What we think happens, in the setting of long-standing untreated hypertension, is very small penetrating vessels in the deep parts of the brain that are bombarded with high pressures undergo changes. They thicken, develop tiny little out-pouches that destabilize them and make them weaker. Then one day one of these tiny penetrators just gives out and bleeds into the brain tissue," she says.
The bleeding essentially stretches and tears brain tissue, irreparably dissecting vital communication structures between brain cells. "It can disrupt huge bundles of fibers that carry information," says Dr. Hall. "Modern neuroimaging shows it also seems to have an effect more distant than just where you see the hemorrhage."
Patients can experience one-sided paralysis; coma; locked-in syndrome where they are fully conscious but paralyzed from the eyes down; or death as the blood spreads into brain tissue. Without treatment, bleeding and destruction may continue for several hours.
Treatment efforts to date, including medical therapies such as other clotting agents and surgery, generally haven't improved outcomes, Dr. Hall says. She hopes NovoSeven®, or recombinant activated factor VIIa, will.
Activated factor VIIa is a substance certain hemophilia patients may not have enough of. In fact the Food and Drug Administration has approved it for hemophiliacs who develop antibodies to other treatments, Dr. Hall says. It looks promising for intracerebral hemorrhage patients as well because it works at sites where there is tissue factor, which is exposed at sites of blood vessel injury.
Much like tissue plasminogen activator, or tPA, the first drug FDA approved to treat clot-based or ischemic strokes, activated factor VIIa for hemorrhage needs to be given as soon as possible after the onset of symptoms to minimize damage and maximize recovery, Dr. Hall says.
"We know that nearly 40% of these hemorrhages continue to grow and may grow significantly larger during the early hours after they start," she says. "The larger the hemorrhage, the more life-threatening or disabling it becomes. The whole idea behind the study is to intervene early to stop bleeding, halt hemorrhage growth, and thus make possible better outcomes."
The study protocol requires that patients receive a computerized tomography scan within three hours after symptom onset. Symptoms include sudden problems with weakness, particularly on one side of the body; confusion or trouble talking or comprehending; difficulty seeing out of one or both eyes; trouble with balance and coordination; and severe headaches.
After the CT scan helps determine the source and size of the hemorrhage, the stroke team has an hour to infuse the liquid that team members hope will stop the damage. "We understand that every minute this hemorrhage may be expanding so we will give the treatment at the earliest possible moment," Dr. Hall says.
One day after treatment, a second CT scan shows the final size of the hemorrhage at 24 hours and helps document how the drug worked. Blood samples also are taken and neurological exams, are performed.
MCG Medical Center receives about one to two patients per week with the type of stroke that could qualify for the study, she says. The MCG stroke team also is able to help treat patients at eight hospitals in rural Georgia via an Internet-based examination system developed at MCG. Patients with hemorrhage evaluated at those remote sites also will be considered for the study but will need to be rapidly transported to MCG to receive the drug, Dr. Hall says. Currently the MCG team works with health care providers at the distant hospitals to give tPA.
The study, comparing two doses of activated factor VIIa to placebo, will enroll 675 patients worldwide. Patients must be 18 or older and have a primary hemorrhage of almost any size and location. However, those who present with poor neurological exams, such as those already in a coma, cannot be enrolled.
"It's not the final answer but it's a first step," Dr. Hall says. "If it's successful, this is going to be the first treatment for any aspect of intracerebral hemorrhage that has ever been shown to make a difference for these patients."