Rates of functional recovery with the active tPA treatment far surpassed those achieved with standard “supportive” therapy that essentially gives clots a chance to shrink on their own.
In the study, ICH patients who randomly received the minimally invasive surgery to deliver a drug designed to dissolve their golf ball-sized clots went home from the hospital an average of 38 days sooner than those receiving supportive therapy. In addition to the health benefits, the tPA therapy and resulting shortened hospital stay led to a savings of an estimated $44,000 per patient, the researchers say.
“These early results, if replicable, would produce a large, meaningful human benefit and would lead to a major change in practice,” says Mario Zuccarello, MD, Frank H. Mayfield Professor and Chairman of the Department of Neurosurgery at UC and principal co-investigator of the study. “The changes would produce a return on research investment as large as those defined for the most productive NIH trials.”
Often the result of uncontrolled blood pressure, ICH is marked by bleeding from a blood vessel in the brain that causes a clot to form. The clot builds up pressure in the brain and leaches inflammatory chemicals that can cause irreversible brain damage, often leading to death or extreme disability. The standard of care for ICH patients is general supportive care, usually in an ICU, that includes intense blood pressure control, artificial ventilation, drugs to control swelling and watchful waiting for the clot to dissipate on its own. Invasive surgery is reserved for patients who deteriorate.
Although ICH accounts for only 15 percent of all strokes, it affects 70,000 to 100,000 Americans each year. The more common type of stroke is ischemic, which results from a blockage in a blood vessel. ICH has long been considered surgically untreatable under most circumstances, and roughly 50 percent of people who have such a stroke die from it.
The drug tPA (tissue plasminogen activator), which is used to dissolve clots in patients suffering from ischemic stroke, to dissolve clots in the lung and to treat those formed by heart attacks involving major blood vessels, has historically not been considered appropriate for treating hemorrhagic stroke.
“This is the most promising treatment that has come along in the last 30 or 40 years for people who have suffered hemorrhagic stroke,” says Daniel F. Hanley, MD, principal co-investigator and professor of neurology at Johns Hopkins.
Hanley presented the study’s findings today at the International Stroke Conference in Honolulu.
The Minimally Invasive Surgery plus tPA for Intracerebral Hemorrhage Evacuation (MISTIE) trial enrolled 123 patients at 25 sites in the United States, Canada and Europe. Sixteen of the study’s patients were enrolled at the UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health, making UC and Virginia Commonwealth University the highest-enrolling centers.
Researchers hope the findings will lead to a larger study of 500 patients, which they say should provide enough information to determine definitively whether the intervention can transform the practice of caring for brain hemorrhage.
Surgeons at each study site performed the procedure by drilling a dime-sized hole in the patient’s skull close to the clot location. Using image-guidance technology, they guided the catheter through the hole and directly into the clot. The catheter was then used to drip small doses of tPA into the clot for several days, shrinking the clots roughly 20 percent per day. Those patients who underwent supportive therapy saw their clots shrink by about 5 percent per day.
“The procedure is safe, simple, rapid and easy to implement,” says Zuccarello, a neurosurgeon with the Mayfield Clinic. “It has the potential to bring widespread benefits to patients while greatly reducing health care costs.”
The study found that after one year, those who underwent the minimally invasive procedure were 14 percent more likely to be back to nearly full functioning, with only minor limitations. And they found that, across all levels of functioning, patients continued to improve and to do better than those undergoing standard therapy, even a year after their strokes. For example, 13 percent fewer subjects were in long-term nursing care if they were in the group receiving minimally invasive surgery early after their brain hemorrhage.
“We found that, after a year, the healing process is continuing to occur in a differentiated manner, favoring those who had their blood clots removed as opposed to those who didn’t,” Hanley says. “The recovery time for a golf ball-sized clot is very long, but recovery can be to high levels of independence, including going back to work. There appear to be drawbacks to leaving the clot in the brain over the long term.”
The research was supported by the National Institute of Neurological Disorders and Stroke.
Zuccarello has no financial interest in Codman & Shurtleff Inc., which manufactures the drains used in the MISTIE trial.