TRIAL OF TACROLIMUS WITH STEROIDS AND DACLIZUMAB VS STEROID FREE TACROLIMUS

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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.