"Although treatment with recombinant activated factor VII (rFVIIa) can reduce hematoma growth in patients with intracerebral hemorrhage, it does not improve survival or functional outcomes, according to a report in
The New England Journal of Medicine for May 15.
The authors note that intracerebral hemorrhage is the most serious type of stroke with roughly 40 per cent of patients dying within 30 days and most of the survivors being left with marked disability. In large part, this morbidity and mortality stems from a lack of proven agents to treat the condition.
In an earlier study, Dr. Stephan A. Mayer, from Columbia University in New York, and colleagues had found that rFVIIa therapy not only reduced hematoma growth, but also improved survival and function at 90 days. The goal of the current phase 3 trial was to confirm these findings.
The new study involved 841 patients who were randomized to receive rFVIIa at one of two doses (20 or 80 micrograms/kg) or placebo within four hours of stroke onset. The main outcome measure was "poor outcome," defined as severe disability, based on the modified Rankin scale, or death at 90 days.
Treatment with the higher dose of rFVIIa did significantly reduce hemorrhage volume relative to placebo, the findings show. Still, the percentage of patients with a poor outcome in the rFVIIa 80 microgram/kg group, 29 per cent, was actually slightly (but not significantly) higher than the percentages in the placebo and rFVIIa 20 micrograms/kg groups, 24 and 26 per cent, respectively.
Serious thromboembolic events occurred with comparable frequency in each group, but arterial events were more common with higher dose rFVIIa than with placebo: nine vs. four per cent (p = 0.04).
In a related editorial, Dr. Stanley Tuhrim, from Mount Sinai School of Medicine in New York, comments that "although failing to show a clinical benefit, the trials of rFVIIa in the treatment of acute intracerebral hemorrhage have demonstrated the ability of rFVIIa to limit hematoma growth while increasing the risk of arterial thrombosis only minimally."
He adds that proper patient selection may be the key to achieving a favorable risk/benefit ratio with rFVIIa and other hematoma-limiting agents currently being studied."
