FOR-DMD:Double-blind randomized trial to optimize steroid regimen in Duchenne MD

描述(由申请人提供)：这项申请提出了一项多中心试验，比较长期使用皮质类固醇治疗杜氏肌营养不良症的男孩。皮质类固醇激素泼尼松对Duchenne营养不良患者的体力有18个月的益处，另一种皮质类固醇药物呋喃西林也可能是有益的。由于担心副作用和长期风险/益处，许多皮质类固醇方案一直在使用，导致实践中的差异很大。鉴于“2008年比较效力研究法”，这项研究尤其及时。这项拟议的随机对照试验将对3种最广泛使用的皮质类固醇方案进行比较，以解决以下实用假设：就功能和父母满意度而言，每日强的松和每日的呋喃西林都比间歇(强的松)有更大的益处。初步统计分析将基于多变量(3维)结果(起跳时间、用力肺活量和治疗满意度)和零假设的全局检验，即皮质类固醇方案在三种结果中的任何一种上没有差异，与替代方案在所有三种结果变量上不同(在同一方向上)，分别针对三种皮质类固醇方案中的三种成对比较中的每一种进行。第二个假设指出，每天服用地塞米松会比每天服用强的松有更好的副作用。这项试验将随机选择300名4-7岁的男孩，分别服用0.75 mg/kg/d的泼尼松、0.9 mg/kg/d的呋喃西林或0.75 mg/kg/d的泼尼松，为期10天，期间休息10天。次要结果变量将包括方案耐受性、其他计时功能测试、心功能、生活质量和不良事件概况。参与者将在两年内被招募，并被跟踪至少三年。研究方案包括治疗和预防Duchenne营养不良症和皮质类固醇所致的骨、心脏、呼吸、行为和库辛戈德并发症的标准化方案。这项试验将通过评估患者/父母对治疗的满意度来评估对肌肉力量的益处，从而评估3种方案中哪种方案是治疗Duchenne营养不良的最佳方案。这将为长期(8-10年)研究糖皮质激素方案的相对有效性和耐受性提供依据，主要结果变量为失去下地行走的时间。辅助研究将探索研究对象中不同表型和对皮质类固醇治疗反应的分子基础。

DESCRIPTION (provided by applicant): This application proposes a multicenter trial comparing long-term regimens of corticosteroids in boys with Duchenne muscular dystrophy. The corticosteroid prednisone is of established 18 months benefit to strength in Duchenne dystrophy, and another corticosteroid, deflazacort, may also be of benefit. Many corticosteroid regimens have been in use because of concerns regarding side effects and long-term risk/benefit, resulting in great variations in practice. The study is particularly timely in view of the "Comparative Effectiveness Research Act of 2008". The proposed randomized controlled trial will compare the 3 most widely used corticosteroid regimens to address the pragmatic hypothesis that both daily prednisone and daily deflazacort will be of greater benefit in terms of function and parent satisfaction than intermittent (prednisone). The primary statistical analysis will be based on a multivariate (3-dimensional) outcome (time to rise from the floor, forced vital capacity, and treatment satisfaction) and global tests of the null hypothesis that the corticosteroid regimens do not differ with regard to any of the three outcomes vs the alternative that they differ (in the same direction) for all 3 outcome variables, performed separately for each of the three pair-wise comparisons among the three corticosteroid regimens. A secondary hypothesis states that daily deflazacort will have a preferable side effect profile to that of daily prednisone. The trial will randomize 300 boys aged 4-7 years to 0.75 mg/kg/d prednisone; 0.9 mg/kg/d deflazacort; or 0.75 mg/kg/d prednisone for 10 days alternating with 10 days off. Secondary outcome variables will include regimen tolerance, other timed function tests; cardiac function, quality of life, and adverse event profile. Participants will be recruited over a 2 year period and followed for at least 3 years. The study protocol includes standardized regimens for treatment and prevention of bone, cardiac, respiratory, behavioral, and cushingoid complications of Duchenne dystrophy and corticosteroids. This trial will assess which of the 3 regimens is optimum for treatment of Duchenne dystrophy by assessing benefits to muscle strength in the context of patient/parent satisfaction with treatment. It will provide the basis for the long-term (8-10 year) study of the relative efficacy and tolerability of corticosteroid regimens with the primary outcome variable of time to loss of ambulation. Ancillary studies will explore the molecular basis for differing phenotypes and responses to corticosteroid treatment in study subjects.