CLINICAL TRIAL: TRIAL OF TACROLIMUS WITH STEROIDS AND DACLIZUMAB VS STEROID FREE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究针对儿童肾移植人群，这些人群在历史上因移植功能丧失和偶尔的移植物完全丧失而使避免类固醇变得复杂。单独减少类固醇并不能对儿童的生长产生积极的影响，移植受者患有高血压、高血脂、糖尿病、骨质流失、美容毁容和白内障-所有这些都与长期使用类固醇直接相关。这项研究建议用daclizumab延长诱导的方法取代类固醇，直到移植后第六个月。 Zenapax将是本研究中用于评价的试验药物。初步研究的初步数据表明，与历史类固醇对照组相比，临床急性排斥反应的发生率较低，慢性移植物肾病、高血压和高胆固醇血症减少，移植后生长模式正常。本临床试验将是一项开放标签、多中心、前瞻性试验，纳入130例儿童肾移植受者。将在3年内监测方案活检、药物水平、免疫学、组织学和临床评估。主要疗效终点为1年时标准身高变化的差异。主要安全性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、移植物功能、慢性同种异体移植物肾病、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 study targets the pediatric kidney transplant population 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 an approach of prolonged induction with daclizumab, until the sixth post-transplant month. Zenapax 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. This clinical trial will be an open label multi-center prospective trial of 130 pediatric renal transplant recipients. 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.