title: Safety and feasibility of recombinant factor VIIa for acute intracerebral hemorrhage.
abstract: 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.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA. sam14@columbia.edu
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Mayer
authors.forename: Nikolai C
authors.initials: NC
authors.lastname: Brun
authors.forename: Joseph
authors.initials: J
authors.lastname: Broderick
authors.forename: Stephen
authors.initials: S
authors.lastname: Davis
authors.forename: Michael N
authors.initials: MN
authors.lastname: Diringer
authors.forename: Brett E
authors.initials: BE
authors.lastname: Skolnick
authors.forename: Thorsten
authors.initials: T
authors.lastname: Steiner
mesh_terms: 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
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; D015942:Factor VIIa