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)
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)
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DOI：
10.1111/jth.12202
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发表时间：
2013-06-01
影响因子：
10.4
通讯作者：
Hong, W.
中科院分区：
文献类型：
--
作者：
Manco-Johnson, M. J.;Kempton, C. L.;Hong, W.
背景在老年血友病患者中，常规预防与按需治疗凝血因子VIII产品的益处尚未在对照临床试验中进行评估。A.目的报告3年SPINART研究第一年数据的预先计划分析结果，该研究比较了常规预防与按需治疗蔗糖配制的重组FVIII患者/方法SPINART是一项开放标签、随机、对照、平行组、多国试验。年龄在12- 50岁的男性重度血友病A患者，暴露于FVIII 150天，无FVIII抑制剂，在过去5年中连续12个月未接受预防性治疗，在过去6个月内发生6-24次出血事件，以1：1的比例随机接受rFVIII-FS预防性治疗（25 IU kg（-1），每周3次）或按需治疗。在末例患者完成1年随访后，分析主要疗效终点，即意向治疗人群中的总出血事件数量。负二项模型用于主要终点分析;方差分析用于年出血率的验证性分析。ResultsEighty-four例患者入组并进行分析（n=42每组;平均年龄，30.6岁;中位治疗持续时间，1.7年）。预防性治疗组总出血事件和每年总出血事件的中位数显著低于按需治疗组（总出血事件，0 vs. 54.5;每年总出血事件，0 vs. 27.9;均P
BackgroundThe benefits of routine prophylaxis vs. on-demand treatment with factorVIII products have not been evaluated in controlled clinical trials in older patients with hemophiliaA.ObjectivesTo 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/MethodsSPINART is an open-label, randomized, controlled, parallel-group, multinational trial. Males aged 12-50years with severe hemophiliaA, 150 days of exposure to FVIII, no FVIII inhibitors, no prophylaxis for >12 consecutive months in the past 5years and 6-24 bleeding episodes in the preceding 6months were randomized 1:1 to rFVIII-FS prophylaxis (25IUkg(-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 1year 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.ResultsEighty-four patients were enrolled and analyzed (n=42 per group; mean age, 30.6years; median treatment duration, 1.7years). 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