title: Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART).
abstract: BACKGROUND
  The benefits of routine prophylaxis vs. on-demand treatment with factor VIII products have not been evaluated in controlled clinical trials in older patients with hemophilia A.
  
  
  OBJECTIVE
  To report results from a preplanned analysis of data from the first year of the 3-year SPINART study, which compares routine prophylaxis with on-demand treatment with sucrose-formulated recombinant FVIII (rFVIII-FS).
  
  
  METHODS
  SPINART is an open-label, randomized, controlled, parallel-group, multinational trial. Males aged 12-50 years with severe hemophilia A, ≥ 150 days of exposure to FVIII, no FVIII inhibitors, no prophylaxis for > 12 consecutive months in the past 5 years and 6-24 bleeding episodes in the preceding 6 months were randomized 1 : 1 to rFVIII-FS prophylaxis (25 IU kg(-1) , three times weekly) or on-demand treatment. The primary efficacy endpoint, number of total bleeding episodes in the intent-to-treat population, was analyzed after the last patient had completed 1 year of follow-up. A negative binomial model was used for the primary endpoint analysis; analysis of variance was used for confirmatory analysis of annualized bleeding rates.
  
  
  RESULTS
  Eighty-four patients were enrolled and analyzed (n = 42 per group; mean age, 30.6 years; median treatment duration, 1.7 years). The median number of total bleeding episodes and total bleeding episodes per year were significantly lower with prophylaxis than with on-demand treatment (total, 0 vs. 54.5; total per year, 0 vs. 27.9; both P < 0.0001). No treatment-related adverse events occurred, and no patients developed FVIII inhibitors.
  
  
  CONCLUSIONS
  Routine prophylaxis with rFVIII-FS leads to a significant reduction in bleeding as compared with on-demand treatment. Adverse events were consistent with the established rFVIII-FS safety profile.
authors.affiliation: Department of Pediatrics, Hemophilia and Thrombosis Center, University of Colorado, Aurora, CO 80045, USA. marilyn.manco-johnson@ucdenver.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Manco-Johnson
authors.forename: C L
authors.initials: CL
authors.lastname: Kempton
authors.forename: M T
authors.initials: MT
authors.lastname: Reding
authors.forename: T
authors.initials: T
authors.lastname: Lissitchkov
authors.forename: S
authors.initials: S
authors.lastname: Goranov
authors.forename: L
authors.initials: L
authors.lastname: Gercheva
authors.forename: L
authors.initials: L
authors.lastname: Rusen
authors.forename: M
authors.initials: M
authors.lastname: Ghinea
authors.forename: V
authors.initials: V
authors.lastname: Uscatescu
authors.forename: V
authors.initials: V
authors.lastname: Rescia
authors.forename: W
authors.initials: W
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000737:chemistry / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D007391:International Cooperation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013395:Sucrose / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C438308:recombinant FVIII, sugar formulated; D013395:Sucrose; D005169:Factor VIII
keywords: hemophilia A; on demand; prophylaxis; sucrose-formulated recombinant factor VIII