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

Abstract

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^®) 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 μg/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 μg/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 μg/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [n=2], 20 μg/kg [n=1], 40 μg/kg [n=1], and 80 μg/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.