SNS01: A RANDOMIZED, MULTI-CENTER COMPARITAVE TRIAL OF TACROLIMUS WITH STEROIDS

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。本多中心研究采用随机、开放标签、平行组设计。受试者将被随机分配（1:1）到传统的基于类固醇的免疫抑制方案（类固醇，标准的daclizumab诱导，Prograf和CellCept）或无类固醇免疫抑制方案（延长daclizumab至移植后6个月，Prograf和CellCept）。研究的主要疗效终点是1年后标准化身高的变化。主要安全终点是12个月活检证实的急性排斥反应的发生率。患者累积目标是在18个月的累积期内从所有参与中心获得130例患者，每组65例。预计儿童医院的病人人数为15人。总共130个被NIH认为足以达到研究的目标。随访时间为3年。主要入选标准为：1)年龄小于21岁；2)第一次接受肾脏移植。主要排除标准为：1)移植前6个月内接受类固醇治疗；2)怀孕或哺乳期；3)接受临床试验药物。受试者招募流程：所有在儿童医院接受肾脏移植且符合研究条件的患者，在向患者及其监护人解释用药方案后，将有机会参与研究。如果下降，将使用标准的免疫抑制方案。两组的所有治疗都将遵循目前的标准护理实践。在移植、移植后6、12和24个月，两组的所有受试者都将接受移植肾的经皮活检，以记录药物毒性和亚临床排斥反应。这是大多数中心的护理标准偏差。然而，由于临床原因，儿童医院的大多数肾移植患者在移植后的头两年接受了2-5次肾活检。

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 multi-center study will use randomized, open-label, parallel group design. Subjects will be randomized (1:1) to a traditional steroid-based immunosuppression regimen (steroids, standard daclizumab induction, Prograf and CellCept) or to a steroid-free immunosuppression regimen (prolonged daclizumab until the sixth month post-transplant, Prograf and CellCept). The primary efficacy endpoint of the study is change in standardized height at 1 year. The primary safety endpoint is the rate at 12 months of biopsy-proven acute rejection. Patient accrual goal is 130 patients, 65 in each group, during an 18 month accrual period from all participating centers. The anticipated number of patients from Children's Hospital is 15. The total number of 130 has been deemed sufficient by NIH to achieve the goals of the study. The duration of follow-up is 3 years. The major inclusion criteria are: 1) age less than 21 years; 2) receiving first kidney transplant. The major exclusion criteria are: 1) steroid treatment within 6 months prior to transplantation; 2) pregnant or lactating; 3) receiving investigational drugs. Subject recruitment process: all patients receiving kidney transplants at Children's Hospital who qualify for the study will be offered an opportunity to paticipate after the medication protocols are explained to the patients and their guardians. If they decline, the standard immunosuppressive protocol will be used. All treatments in both arms will follow current standard of care practices. All subjects in both arms will undergo a percutaneous biopsy of the transplant kidney at transplant, 6, 12, and 24 months after the transplant for documentation of drug toxicity and subclinical rejection. This is a deviation of standard of care in most centers. However, most kidney transplant patients at Children's Hospital undergo 2-5 kidney biopsies during the first 2 years after transplant because of clinical concerns.