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

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。这项多中心研究将采用随机、开放标签、平行分组设计。受试者将被随机(1：1)接受传统的基于类固醇的免疫抑制方案(类固醇、标准Daclizumab诱导、Prograf和CellCept)或非类固醇免疫抑制方案(延长Daclizumab直到移植后6个月、Prograf和CellCept)。这项研究的主要疗效终点是1年后标准化身高的变化。主要的安全终点是活检证实的急性排斥反应12个月的发生率。患者应计目标是在所有参与中心的18个月应计期间内，130名患者，每组65名。来自儿童医院的预计患者数量为15人。NIH认为130人的总数足以实现研究目标。随访期3年。主要的入选标准是：1)年龄小于21岁；2)接受首次肾移植。主要的排除标准是：1)移植前6个月内接受类固醇治疗；2)怀孕或哺乳；3)接受研究药物。受试者招募过程：所有在儿童医院接受肾移植的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，都将有机会参与。如果他们拒绝，将使用标准的免疫抑制方案。两个手臂的所有治疗都将遵循现行的护理做法标准。所有受试者都将在移植时、移植后6个月、12个月和24个月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。这是大多数中心护理标准的偏差。然而，由于临床方面的考虑，儿童医院的大多数肾移植患者在移植后的头两年里都要接受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.