Recombinant activated factor VII for acute intracerebral hemorrhage - US phase IIA trial

Background and Purpose: Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven(R)) for preventing early hematoma growth in acute ICH. Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 mu g/kg of rFVIIa (n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs). Results: Mean age was 65 years (range 34-91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia (n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 mu g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 mu g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [n = 2], 20 mu g/kg [n = 1], 40 mu g/kg [n = 1], and 80 mu g/kg [n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred. Conclusions: Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.