LOS ANGELES—Treatment with t-PA decreases mortality in patients with intraventricular hemorrhage (IVH), according to a study described at the International Stroke Conference 2016. The treatment also reduces disability among patients with high-volume bleeds. In addition, flushing blood from the brain using an extraventricular drain increases the likelihood that a patient will return home and live independently, said the researchers.
Brain hemorrhages are a major problem in the United States and cause more disability than ischemic strokes do, said Daniel Hanley Jr, MD, the Jeffrey and Harriet Legum Professor of Acute Care Neurological Medicine and Director of the Brain Injury Outcomes Program at the Johns Hopkins University School of Medicine in Baltimore. Dr. Hanley and colleagues conducted a phase III, randomized, double-blind trial to determine whether reduction of IVH from a routinely placed extraventricular drain, along with administration of t-PA, affects functional outcomes in patients with large IVH and small intracerebral hemorrhage (ICH).
Daniel Hanley Jr, MD
Patients Received t-PA or Saline
Eligible patients were between ages 18 and 80 with an ICH volume of 30 cm3 or less and had had an extraventricular drain placed. Patients with an underlying etiology other than hypertension were excluded. Participants were randomized to 1 mg of t-PA or saline administered through a brain catheter every eight hours. Patients were monitored remotely in real time to ensure proper catheter placement. As many as 12 doses of treatment were administered. Patients were followed up at day 30 and day 180. A panel of experts blinded to patients’ treatment allocations adjudicated their results.
The study’s primary end point was the percentage of patients with a modified Rankin Scale (mRS) score of 0 to 3 at 180 days. The secondary end points included all-cause mortality at 180 days; the amount of residual blood, in relation to mRS, at 180 days; and safety at 30 days.
In all, 249 patients received t-PA, and 251 patients received saline. The population’s median age was 59, and 44% of participants were female. Approximately 61% of participants were white, and 34% were African American. The researchers noted no significant differences between the two treatment groups. Participants received treatment for a mean of 2.6 days.
Intervention Reduced Mortality
Compared with the control group, approximately 3% more participants in the t-PA group had an mRS of 0 to 3 at 180 days (45% vs 48%). The investigators had hypothesized a difference of 13%, however. The mortality rate was 19% among patients who received t-PA, compared with 29% among controls.
The percentage of patients in nursing homes or long-term care facilities at 180 days did not differ significantly between groups. Compared with controls, 10% more people in the t-PA group (nearly half of the group) were discharged home or to a rehabilitation facility. Approximately 2% of patients in each group were in an acute-care hospital at 180 days.
Data analysis indicated that t-PA was safer than saline, said Dr. Hanley. The rate of symptomatic bleeding was similar between treatment groups, but the rate of serious adverse events was 13% lower in the t-PA group (49% vs 62%). The researchers also noted a trend toward lower rates of bacterial ventriculitis and meningitis in the t-PA group.
Patients With Larger Clots Benefited More
Approximately 45% of participants had an IVH volume of less than 20 mL. Those participants did not benefit from treatment, said Issam Awad, MD, John Harper Seeley Professor of Surgery at the University of Chicago Medicine. The likelihood of a good outcome was increased by approximately 20%, however, among patients with an IVH volume greater than 20 mL, compared with patients with smaller IVH volumes.
Issam Awad, MD
Dr. Awad found that the efficiency of clot removal was strongly correlated with outcome. “The more blood you remove, the greater the likelihood of good functional outcome,” he said. “This was strongly significant in the larger clots…. If you remove 85% of the clot, you have almost two times the likelihood of a good outcome.” If 90% of the clot is removed, the likelihood of good outcome increases by a factor of 2.25.
“You remove much more [of the] clot if your catheter is in the clot,” Dr. Awad continued. “This [method] is very different from how neurosurgeons currently do the procedure. You have to change the way you put the catheter [in] if you want to maximize the benefit of this procedure.” Clot removal also was significantly more efficient when two catheters were used, compared with one. “More efficient IVH clearance can be accomplished with new catheter strategies,” said Dr. Awad.