Intracerebral hemorrhage accounts for up to 15 percent of the 750,000 strokes that occur annually in the United States, says Christiana E. Hall, MCG ( Medical College of Georgia ) neurologist and a principal investigator on the NovoSeven study.

" The biggest risk factor for these hemorrhages is hypertension”, says Hall.

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 Hall.

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, 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, 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, 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," 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.

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.

Source: Medical College of Georgia, 2006


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