title: Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial.
abstract: A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval = 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups.
  
  
  CONCLUSIONS
  Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.
authors.affiliation: Hepatic Hemodynamic Laboratory, Hospital Clinic and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Spain. jbosch@clinic.ub.es
authors.forename: Jaime
authors.initials: J
authors.lastname: Bosch
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.forename: Agustín
authors.initials: A
authors.lastname: Albillos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carbonell
authors.forename: Julius
authors.initials: J
authors.lastname: Spicak
authors.forename: Julien
authors.initials: J
authors.lastname: Massard
authors.forename: Gennaro
authors.initials: G
authors.lastname: D'Amico
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: Roberto
authors.initials: R
authors.lastname: de Franchis
authors.forename: Søren
authors.initials: S
authors.lastname: Fabricius
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D015942:Factor VIIa / Q000627:therapeutic use*; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos; D011994:Recombinant Proteins / Q000627:therapeutic use; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa