NEW ORLEANS – An investigative, minimally invasive surgery for reducing intracranial clot volume following an intracerebral hemorrhage showed promise in results from a phase II study.
In the controlled study, 54 patients who underwent clot removal by minimally-invasive surgery (MIS) had a 10% increased rate of achieving a modified Rankin Scale (mRS) score of 1-3 at 180 days, compared with 39 patients managed by conventional, medical therapy, Dr. Daniel F. Hanley said at the meeting.
"These data may establish a surgical goal for MIS of reducing clot burden to 15 mL or less by 3-4 days" after the intracerebral hemorrhage (ICH), said Dr. Hanley, a professor of neurology and neurosurgery at Johns Hopkins University in Baltimore. The study enrolled patients within a day of their ICH with a clot volume of at least 20 mL; the average volume for the 93 patients was 40 mL.
The next step will be a pivotal, controlled study planned to enroll 500 patients at 35-50 centers, with an expected study duration of 5 years. Dr. Hanley and his associates are seeking funding for the phase III trial from the National Institutes of Health.
The MISTIE (Minimally Invasive [Stereotactic] Surgery and rTPA for ICH Extraction) study used a combination of intracerebrally infused recombinant tissue plasminogen activator (rTPA) and placement of a cannula into a patient’s skull to remove thrombolysed clot, a method that "has been around" for several years, but never before underwent assessment as a standardized procedure and in a prospective, controlled study, Dr. Hanley said in an interview. "MIS is widely available, and could be practical to use on ICH patients" once it is clearly shown to be safe and effective.
The study enrolled patients at 35 international sites who were 18-75 years old and had a spontaneous, supratentorial ICH with a stable clot. They also had received rTPA within 54 hours of their first diagnostic CT examination. The mean age of the enrolled patients was 61 years, two-thirds were men, and the patients randomized to MIS received their initial rTPA treatment an average of 48 hours after the ICH began. During an initial phase of the study patients received 0.3 mg of rTPA, but during the later phase the dose increased to 1.0 mg, the amount that most of the MIS patients received.
Safety data showed that patients treated with MIS had a 7-day mortality rate of 2 and a 30-day mortality of 15%, compared with a rate of 8% at 30 days in the medically-treated control patients. Symptomatic bleeds occurred in two of the MIS patients and one of the controls, and a brain infection occurred in none of the MIS patients and in one control patient. During follow-up out to 180 days, mortality rates were virtually identical, about 20%, in both arms of the study, and dropouts also reached similar levels in both arms, about 45%.
During their first 4 days in the study, MIS patients had an average 65% reduction in their intracerebral clot volume, compared with no change in the control patients. The two-thirds reduction with MIS corresponded to an average 28 mL drop in volume. Twenty-four surgeons participated in the study, and the analysis showed very little surgeon-to-surgeon variation in their ability to achieve clot-volume reductions. Roughly two-thirds of the surgeons had never previously performed the procedure, but each surgeon treated a run-in patient before the study formally began.
The study’s primary outcome was mRS at 180 days, with data available for 50 MIS patients and 33 controls. No patients in either group had an mRS of 0. An mRS of 1 occurred in two MIS patients and none of the controls. An mRS of 1-3 occurred in about 35% of the MIS patients and about 25% of the controls.
An analysis of all patients showed a strong link between clot volume after 4 days in the study and 180-day outcomes. The prespecified goal of MIS was removal of at least 15 mL of clot, and surgeons achieved this in about a third of the MIS patients. When patients attained that level of clot reduction, they had a statistically significant, 3.7-fold increased rate of having an mRS of 1-3 at 180 days, compared with patients who did not reach this goal.
The impact of MIS on outcome was even stronger in patients who entered the study with larger clots. Among the subgroup with a clot burden of at least 50 mL, MIS led to a 17% increased rate of patients achieving an mRS of 1-3, compared with the controls, Dr. Hanley said. Among patients treated medically, those with a clot burden on entry of about 20 mL often had an mRS of 1-3 at 180 days, but among those who began with a clot of at least 30 mL, only three patients reached an mRS of 1-3.