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.

OBJECTIVES:

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).

PATIENTS/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: M J Manco-Johnson, C L Kempton, M T Reding, T Lissitchkov, S Goranov, L Gercheva, L Rusen, M Ghinea, V Uscatescu, V Rescia, W Hong
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 11 Issue 6 Pg. 1119-27 (Jun 2013) ISSN: 1538-7836 [Electronic] England
• PMID: 23528101 (Publication Type: Clinical Trial, Phase III, Clinical Trial, Phase IV, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 International Society on Thrombosis and Haemostasis.

Chemical References

• recombinant FVIII, sugar formulated
• Sucrose
• Factor VIII

Topics

• Adolescent
• Adult
• Drug Administration Schedule
• Factor VIII (chemistry, therapeutic use)
• Hemophilia A (drug therapy)
• Hemorrhage (drug therapy)
• Humans
• International Cooperation
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Quality of Life
• Sucrose (chemistry, therapeutic use)
• Treatment Outcome
• Young Adult