TRIAL OF TACROLIMUS WITH STEROIDS AND DACLIZUMAB VS STEROID FREE TACROLIMUS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该方案旨在消除慢性类固醇使用的发病率，传统上伴随实体器官移植。本研究专门针对儿童肾移植人群，这是最具免疫原性的实体器官群体之一，在历史上，类固醇的避免一直因移植功能的丧失和偶尔的完全移植丧失而复杂化。仅使用类固醇并不能对儿童的生长产生积极影响，而且移植受者还会遭受高血压、高血脂、糖尿病、骨质流失、美容毁容和白内障的困扰——所有这些都与长期使用类固醇直接相关。本研究首次提出用延长daclizumab诱导替代类固醇，直至移植后6个月。Zenapax¿（daclizumab）将是本研究中用于评估的研究产品。一项试点研究的初步数据显示，与既往基于类固醇的对照组相比，移植后临床急性排斥反应发生率低，慢性同种异体移植肾病、高血压和高胆固醇血症发生率降低，生长模式正常（1,2）。该临床试验将是一项开放标记的多中心前瞻性试验，纳入130名0至21岁的儿童肾移植受者，随机（1:1）分为传统的基于类固醇的免疫抑制方案（类固醇，标准的达利珠单抗诱导，直到移植后第二个月，他克莫司和霉酚酸酯（MMF））和提议的无类固醇免疫抑制方案（延长达利珠单抗诱导，直到移植后第六个月，他克莫司和MMF）。方案活检、药物水平、免疫学、组织学和临床评估将在3年内进行监测。主要疗效终点为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生存的等效性、移植物功能、慢性同种异体肾病、高血压、高脂血症、骨髓抑制、感染和白内障。

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.