Randomized, Multi-Center Comparative Trial of Tacrolimus w/Steroids and Standard Daclizumab Induction vs a Novel Steroid-Free Tacrolimus Based Immunosuppression Protocol w/ Extended Daclizumab Induction in Pediatric Renal Transplantation
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 130
- Locations
- 12
- Primary Endpoint
- The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation
Study Overview
Brief Summary
Over the last 40 years, corticosteroids (steroids) have been an important part of drug regimens used to prevent organ rejection and to maintain the immune health of individuals who have received organ transplants. Unfortunately, the negative physical effects of steroids can be severe, especially in children. The purpose of this study is to determine the safety and effectiveness of a steroid-free treatment regimen for children and adolescents who have received kidney (renal) transplants.
Detailed Description
Corticosteroids (steroids) have been a cornerstone of immunosuppressive therapy for kidney (renal) transplantation for over 40 years. However, poor growth and bone loss caused by the use of steroids are devastating to pediatric kidney recipients. The negative physical implications of steroid use also greatly impacts patients' compliance to their prescribed steroid-containing regimens.
The development of a steroid-free regimen for post-transplant pediatric patients is sorely needed. This study will evaluate the safety and efficacy of a steroid-free based treatment regimen in children and adolescents who have received kidney transplants, compared to a standard of care steroid-based regimen. Participants in this study will be pediatric patients with end-stage kidney disease who will undergo kidney transplantation at the start of the study.
Patients will participate in this study for 3 years. Participants will be randomized (1:1) to one of two groups. The study includes 23 study visits over 3 years. A physical exam, medication history, adverse events reporting, blood pressure readings, growth assessment, and blood collection will occur at most visits. At the time of transplantation, participants will have a kidney biopsy. Participants will also undergo cataract screening within 4 months of transplantation.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Primary recipient of a kidney transplant
- •Meets site-specific transplant criteria
- •Panel Reactive Antibody (PRA) of 20% or less
- •Willing to use acceptable forms of contraception
- •Parent or guardian willing to provide informed consent, if applicable
Exclusion Criteria
- •Previous treatment with steroids within 6 months prior to transplantation
- •Received en-bloc kidney or other kidney that does not meet protocol-specified requirements
- •Received an organ from an human leukocyte antigen (HLA) identical donor or a non-heart-beating donor
- •Received a solid organ other than a kidney
- •Received a bone marrow or hematopoietic stem cell transplant
- •Received a repeat kidney transplant
- •Currently receiving an investigational pharmacologic or biologic agent
- •Human Immunodeficiency virus (HIV) infected or infected with another immunodeficiency virus
- •Hypersensitivity to murine products or the study drugs or their formulations
- •Inability to measure height accurately
- •Pregnant or breastfeeding
Arms & Interventions
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Daclizumab (Drug)
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Mycophenolate mofetil (MMF) (Drug)
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Prednisone (Drug)
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Tacrolimus (Drug)
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Ganciclovir (Drug)
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Valganciclovir (Drug)
Steroid-Based Immunosuppression
Subjects will receive prednisone immunosuppression (10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing <40kg and 1.5 mg/kg/day in subjects weighing >40 kg) and proceed with a prednisone taper according to the trial's protocol.
Intervention: Trimethoprim and sulfamethoxazole (Drug)
Steroid-Free Immunosuppression
Subjects will receive extended daclizumab induction until the sixth month post-transplant (2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11 and months 4, 5, and 6).
Intervention: Daclizumab (Drug)
Steroid-Free Immunosuppression
Subjects will receive extended daclizumab induction until the sixth month post-transplant (2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11 and months 4, 5, and 6).
Intervention: Mycophenolate mofetil (MMF) (Drug)
Steroid-Free Immunosuppression
Subjects will receive extended daclizumab induction until the sixth month post-transplant (2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11 and months 4, 5, and 6).
Intervention: Tacrolimus (Drug)
Steroid-Free Immunosuppression
Subjects will receive extended daclizumab induction until the sixth month post-transplant (2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11 and months 4, 5, and 6).
Intervention: Ganciclovir (Drug)
Steroid-Free Immunosuppression
Subjects will receive extended daclizumab induction until the sixth month post-transplant (2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11 and months 4, 5, and 6).
Intervention: Valganciclovir (Drug)
Steroid-Free Immunosuppression
Subjects will receive extended daclizumab induction until the sixth month post-transplant (2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11 and months 4, 5, and 6).
Intervention: Trimethoprim and sulfamethoxazole (Drug)
Outcomes
Primary Outcomes
The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation
Time Frame: One year post kidney transplantation procedure
Standardized Z-scores were computed following a formula using an age- and gender-specific calculation provided by the NHANES III 2000 Growth Data set. The Z-score system expresses anthropometric values of height as several standard deviations (SDs) below (e.g., a negative value) or above (a positive value) the reference mean or median value. In this study the measure was used to test whether there is a difference in the change in height between the treatment groups: Steroid-Based versus Steroid-Free
Comparison by Treatment Assignment in the Number of Biopsy-Proven Acute Rejections Within 12 Months Post Kidney Transplantation
Time Frame: Up to one year post kidney transplantation procedure
Biopsy-proven acute renal (kidney) rejection \[1, 2\]. 1. Diagnosis of acute rejection was made by renal biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection\[2\] 2. Ref: Racusen LC et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999
Secondary Outcomes
No secondary outcomes reported