Recombinant activated factor VII for acute intracerebral hemorrhage: US phase IIA trial.
OBJECTIVE
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 microg/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 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg 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.
Mayer
Stephan A
SA
Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY, USA. sam14@columbia.edu
Brun
Nikolai C
NC
Broderick
Joseph
J
Davis
Stephen M
SM
Diringer
Michael N
MN
Skolnick
Brett E
BE
Steiner
Thorsten
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005167:Factor VII / Q000008:administration & dosage* / Q000009:adverse effects; D015942:Factor VIIa; D005240:Feasibility Studies; D005260:Female; D006406:Hematoma / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014481:United States
D006490:Hemostatics; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa