TRIAL OF TACROLIMUS WITH STEROIDS AND DACLIZUMAB VS STEROID FREE TACROLIMUS

他克罗莫司加类固醇和达利珠单抗对比无类固醇他克莫司的试验

• 批准号: 7605461
• 负责人: Vikas R. Dharnidharka
• 金额: $ 2.41万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-23 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605461
• 关键词: Acute; Age-Years; Biopsy; Bone Marrow Suppression; Cataract; Child; Childhood; Chronic; Chronic rejection of renal transplant; Clinical; Clinical Trials; Clinical assessments; Computer Retrieval of Information on Scientific Projects Database; Cosmetics; Daclizumab; Data; Diabetes Mellitus; End Point; Evaluation; Funding; Graft Survival; Grant; Growth; Height; Hyperlipidemia; Hypertension; Immunosuppression; Incidence; Infection; Institution; Kidney Transplantation; Label; Lipids; Monitor; Morbidity - disease rate; Mycophenolate Mofetil/Tacrolimus; Organ; Organ Transplantation; Patients; Pattern; Pharmaceutical Preparations; Pilot Projects; Population; Protocols documentation; Randomized; Research; Research Personnel; Resources; Roche brand of daclizumab; Safety; Solid; Source; Standards of Weights and Measures; Steroids; Tacrolimus; Therapeutic immunosuppression; Transplant Recipients; Transplantation; United States National Institutes of Health; base; bone loss; graft function; hypercholesterolemia; immunogenic; prospective

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.

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， 因此可以在其他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。 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。本研究专门针对儿童肾移植人群，这是免疫原性最强的实体器官组之一，在历史上，由于移植功能丧失和偶尔的移植物完全丧失，避免使用类固醇一直很复杂。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。这项研究建议用第一种用daclizumab延长诱导的方法取代类固醇，直到移植后第六个月。Zenapax？（daclizumab）将作为本研究中用于评价的试验药物。一项初步研究的初步数据表明，与历史上基于类固醇的对照组相比，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（1，2）。本临床试验将是一项开放标签多中心前瞻性试验，130名0至21岁的儿童肾移植受者随机（1：1）接受传统的基于类固醇的免疫抑制方案（类固醇、标准达克珠单抗诱导直至移植后第2个月、他克莫司和吗替麦考酚酯（MMF））与拟定的无类固醇免疫抑制方案（延长达克珠单抗诱导直至移植后第6个月、他克莫司和MMF）。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。