Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage.
OBJECTIVE
Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VII (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH.


METHODS
In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 microg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios.


RESULTS
Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-microg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred.


CONCLUSIONS
This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
Mayer
Stephan A
SA
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA. sam14@columbia.edu
Brun
Nikolai C
NC
Broderick
Joseph
J
Davis
Stephen
S
Diringer
Michael N
MN
Skolnick
Brett E
BE
Steiner
Thorsten
T
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D001929:Brain Edema / Q000000981:diagnostic imaging; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004311:Double-Blind Method; D015942:Factor VIIa / Q000009:adverse effects* / Q000235:genetics / Q000627:therapeutic use; D005260:Female; D006406:Hematoma / Q000517:prevention & control; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed
D006490:Hemostatics; D011994:Recombinant Proteins; D015942:Factor VIIa