TRIAL OF TACROLIMUS WITH STEROIDS AND DACLIZUMAB VS STEROID FREE TACROLIMUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。该方案旨在消除传统上伴随实体器官移植的慢性类固醇使用的发病率。这项研究专门针对儿童肾移植人群，这是免疫原性最强的固体器官群体之一，历史上，移植功能丧失和偶尔完全失去移植物使避免类固醇治疗变得复杂。仅靠减少类固醇对儿童的生长发育没有产生积极影响，移植受者患有高血压、高血脂、糖尿病、骨丢失、整容毁容和白内障--所有这些都与长期使用类固醇直接相关。这项研究建议首次使用Daclizumab延长诱导时间以取代类固醇，直到移植后6个月。Zenapax(Daclizumab)将作为本研究的研究产品进行评价。一项初步研究的初步数据显示，与以往使用类固醇的对照组(1，2)相比，移植后临床急性排斥反应发生率低，慢性移植物肾病、高血压和高胆固醇血症减少，生长模式正常。这项临床试验将是一项开放标签的多中心前瞻性试验，对象为130名0至21岁的儿童肾移植受者，随机(1：1)采用传统的以类固醇为基础的免疫抑制方案(类固醇，移植后第二个月前的标准达克珠单抗诱导，他克莫司和霉酚酸酯(MMF))与建议的非类固醇免疫抑制方案(将达克珠单抗诱导延长至移植后6个月，他克莫司和MMF)。方案活组织检查、药物水平、免疫学、组织学和临床评估将在3年内进行监测。主要疗效终点将是1年后标准化身高变化的差异。主要安全终点将是活检证实的急性排斥反应的等效性。次要终点将包括患者和移植物存活率、移植物功能、慢性移植物肾病、高血压、高脂血症、骨髓抑制、感染和白内障的等效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This protocol aims to remove the morbidity of chronic steroid usage that has traditionally accompanied solid organ transplantation. This study specifically targets the pediatric kidney transplant population, one of the most immunogenic solid organ groups, where steroid avoidance has been historically complicated by loss of transplant function and occasionally outright graft loss. Steroid minimization alone has failed to make a positive impact on growth in children, and transplant recipients suffer from hypertension, high lipids, diabetes, bone loss, cosmetic disfigurement and cataracts - all directly related to chronic steroid use. This study proposes to replace steroids with a first ever approach of prolonged induction with daclizumab, until the sixth post-transplant month. Zenapax¿ (daclizumab) will be the investigational product for evaluation in this study. Preliminary data from a pilot study demonstrated low incidence of clinical acute rejections, a reduction in chronic allograft nephropathy, hypertension and hypercholesterolemia and normal growth patterns post¿transplantation, as compared with historical steroid-based controls (1, 2). This clinical trial will be an open label multi-center prospective trial of 130 pediatric renal transplant recipients, 0 to 21 years of age, randomized (1:1) to a traditional steroid-based immunosuppression protocol (steroids, standard daclizumab induction until the second post transplant month, tacrolimus and Mycophenolate Mofetil (MMF)) verses a steroid-free immunosuppression protocol proposed (prolonged daclizumab induction until the sixth post transplant month, tacrolimus and MMF). Protocol biopsies, drug levels, immunological, histological and clinical assessments will be monitored over a 3-year period. The primary efficacy endpoint will be the difference in the change in standardized height at 1 year. The primary safety endpoint will be equivalency for biopsy proven acute rejection. The secondary endpoints will include equivalency of patient and graft survival, graft function, chronic allograft nephropathy, hypertension, hyperlipidemia, bone marrow suppression, infection, and cataracts.