title: Recombinant factor VIIa analog (vatreptacog alfa [activated])  for treatment of joint bleeds in hemophilia patients with  inhibitors: a randomized controlled trial.
abstract: BACKGROUND
  A recombinant factor VIIa analog (NN1731; vatreptacog alfa [activated]) was developed to provide safe, rapid and sustained resolution of bleeds in patients with hemophilia and inhibitors.
  
  
  METHODS
  This global, prospective, randomized, double-blinded, active-controlled, dose-escalation trial evaluated and compared one to three doses of vatreptacog alfa at 5, 10, 20, 40, and 80 lg kg(-1) with one to three doses of recombinant FVIIa (rFVIIa) at 90 lg kg(-1) in the treatment of acute joint bleeds in hemophilia patients with inhibitors. The primary endpoint comprised adverse events; secondary endpoints were evaluations of immunogenicity, pharmacokinetics, and efficacy.
  
  
  CONCLUSIONS
  Overall, 96 joint bleeds in 51 patients (> 12 years of age) were dosed. Vatreptacog alfa was well tolerated, with a low frequency of adverse events. No immunogenic or thrombotic events related to vatreptacog alfa were reported. A high efficacy rate of vatreptacog alfa in controlling acute joint bleeds was observed; 98% of bleeds were controlled within 9 h of the initial dose in a combined evaluation of 20–80 lg kg(-1) vatreptacog alfa. The efficacy rate observed for rFVIIa (90%) is consistent with data from published clinical trials. The trial was not powered to compare efficacy, and further trials are needed to investigate the efficacy of vatreptacog alfa as compared with that of rFVIIa. The trial was registered at ClinicalTrials.gov (
  
  
  BACKGROUND
  NCT00486278).
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, São Paulo, Brazil. erich@unicamp.br
authors.forename: Erich V
authors.initials: EV
authors.lastname: de Paula
authors.forename: Kaan
authors.initials: K
authors.lastname: Kavakli
authors.forename: Johnny
authors.initials: J
authors.lastname: Mahlangu
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Ayob
authors.forename: Steven R
authors.initials: SR
authors.lastname: Lentz
authors.forename: Massimo
authors.initials: M
authors.lastname: Morfini
authors.forename: László
authors.initials: L
authors.lastname: Nemes
authors.forename: Silva Z
authors.initials: SZ
authors.lastname: Šalek
authors.forename: Midori
authors.initials: M
authors.lastname: Shima
authors.forename: Jerzy
authors.initials: J
authors.lastname: Windyga
authors.forename: Silke
authors.initials: S
authors.lastname: Ehrenforth
authors.forename: Ampaiwan
authors.initials: A
authors.lastname: Chuansumrit
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015942:Factor VIIa / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006395:Hemarthrosis / Q000188:drug therapy*; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa