TY - JOUR
T1 - 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)
AU - Manco-Johnson, M. J.
AU - Kempton, C. L.
AU - Reding, M. T.
AU - Lissitchkov, T.
AU - Goranov, S.
AU - Gercheva, L.
AU - Rusen, L.
AU - Ghinea, M.
AU - Uscatescu, V.
AU - Rescia, V.
AU - Hong, W.
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
KW - Hemophilia A
KW - On demand
KW - Prophylaxis
KW - Sucrose-formulated recombinant factor VIII
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U2 - 10.1111/jth.12202
DO - 10.1111/jth.12202
M3 - Article
C2 - 23528101
AN - SCOPUS:84883798278
SN - 1538-7933
VL - 11
SP - 1119
EP - 1127
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 6
ER -