A minimally invasive surgical procedure that enables direct local delivery of tissue plasminogen activator to the blood clot in patients with intracerebral hemorrhage safely resulted in markedly improved functional ability, greater independence, and dramatically lower costs than conventional medical management at 1 year of follow-up, in the randomized multicenter MISTIE trial.
"The procedure is simple, rapid, and easy to generalize. There is now real hope we have a treatment for the last form of stroke that doesn’t have a treatment: brain hemorrhage," Dr. Daniel F. Hanley said at the International Stroke Conference sponsored by the American Stroke Association.
That being said, MISTIE (Minimally Invasive Surgery plus rTPA for Intracerebral Hemorrhage Evacuation) was a modestly sized, phase II proof-of-concept study, the concept being that reducing clot size should improve outcomes in patients with intracerebral hemorrhage (ICH). Based on the encouraging 1-year MISTIE results, the plan is to ramp up to a 500-patient definitive phase III trial, said Dr. Hanley, professor of neurology and director of the brain injury outcomes division at Johns Hopkins University, Baltimore.
The trial involved 96 patients with ICH at 26 hospitals who were randomized to the minimally invasive surgical procedure or medical management. The "most startling" finding to emerge from the trial, in Dr. Hanley’s view, was that the benefits of the surgical intervention documented at 6 months’ follow-up and reported at last year’s International Stroke Conference are even greater at 1 year.
"The benefits of surgery are expanding over time," the neurologist observed. "It takes a long time to resolve brain injury, even though we’re getting the majority of the clot out in the first 3 days."
The procedure entails cutting a dime-sized hole in the patient’s skull, snaking a catheter through it and into the bulk of the clot, then delivering a dose of tissue plasminogen activator (TPA) every 8 hours for 2-3 days. As TPA dissolves the clot, the material is evacuated through the catheter. The surgical procedure took an average of 42 minutes compared with 3 hours, typically, for a craniotomy.
Among the key findings from the MISTIE 1-year update:
• Non-ICU hospital length of stay averaged 38 days less in the surgically managed group.
• The cost of acute care averaged $44,000 less per patient, a 35% reduction, compared with medical management.
• At 1 year, 21% of patients in the medically managed group were in a nursing home, compared with just 8% of the surgically managed group.
• The average Stroke Impact Scale mobility score in the surgical group doubled from 40 at 6 months to 80 at 1 year while plateauing at about 20 between days 80 and 90 in the medically managed patients. A score of 80 on this scale means a patient can do what he wants most of the time; a score of 20 means he seldom can
• The average Stroke Impact Scale activities of daily living score similarly showed progressive, roughly linear improvement in the surgical group between 6 months and 1 year while plateauing at a low performance level at 90-180 days in the medically managed group.
• The proportion of patients with functional independence as defined by a modified Rankin score of 0-2 was an absolute 14% greater in surgically managed compared with medically managed patients at 1 year.
The average baseline clot volume was 46 mL. The surgical goal was to remove 60% of the clot volume; this was achieved in 72% of treated patients. On average 28 mL of clot were removed over a period of 3 days.
"The surgeons are consistently able to achieve 20- to 40-mL reductions in clot volume. Twenty-nine surgeons have done the procedure, and we don’t see a learning curve. That’s good. It means this is a pretty simple procedure to do. In point of fact, the training consisted of a single 1-hour conference with the lead neurosurgeon and a short self-learning computer program," according to Dr. Hanley.
Roughly 60% of patients whose clot volume was reduced to less than 10 mL had functional independence as reflected in a modified Rankin score of 0-2 at 180 days, compared with a 10% rate in those with a residual clot volume in excess of 35 mL.
Outcomes were similar regardless of whether the surgery was done within 36 hours after stroke onset or later.
"To me it looks like the time consideration for this surgery is going to be permissive. That’s very important for the 1 million people in the world each year who have an ICH," the neurologist noted.