Steroid-Free Versus Steroid-Based Immunosuppression in Pediatric Renal (Kidney) Transplantation
- Conditions
- Kidney TransplantRenal TransplantationKidney TransplantationKidney DiseasesRenal Transplant
- Interventions
- Registration Number
- NCT00141037
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Steroid-Based Immunosuppression Trimethoprim and sulfamethoxazole 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. Steroid-Based Immunosuppression Mycophenolate mofetil (MMF) 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. Steroid-Free Immunosuppression Mycophenolate mofetil (MMF) 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). Steroid-Free Immunosuppression Ganciclovir 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). Steroid-Free Immunosuppression Trimethoprim and sulfamethoxazole 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). Steroid-Based Immunosuppression Daclizumab 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. Steroid-Based Immunosuppression Prednisone 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. Steroid-Based Immunosuppression Tacrolimus 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. Steroid-Based Immunosuppression Ganciclovir 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. Steroid-Based Immunosuppression Valganciclovir 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. Steroid-Free Immunosuppression Daclizumab 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). Steroid-Free Immunosuppression Tacrolimus 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). Steroid-Free Immunosuppression Valganciclovir 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).
- Primary Outcome Measures
Name Time Method The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation 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 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 Outcome Measures
Name Time Method
Trial Locations
- Locations (12)
UCLA - Department of Pediatrics, Division of Nephrology
🇺🇸Los Angeles, California, United States
Children's Hospital Boston - Division of Nephrology
🇺🇸Boston, Massachusetts, United States
Children's Hospital of New Orleans-Department of Pediatric Nephrology
🇺🇸New Orleans, Louisiana, United States
Stanford University Medical Center, Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States
UCSF Children's Hospital
🇺🇸San Francisco, California, United States
Children's Hospital & Regional Medical Center - Division of Nephrology
🇺🇸Seattle, Washington, United States
Children's Mercy Hospital - Department of Nephrology
🇺🇸Kansas City, Missouri, United States
University of Alabama - Pediatric Nephrology
🇺🇸Birmingham, Alabama, United States
University of Florida - Pediatric Nephrology
🇺🇸Gainesville, Florida, United States
The Children's Hospital of Philadelphia-Department of Nephrology
🇺🇸Philadelphia, Pennsylvania, United States
Maxine Dunitz Children's Health Center Cedars-Sinai
🇺🇸Los Angeles, California, United States
University of Michigan Medical Center, C.S. Mott Children's Hospital- Division of Nephrology & Transplantation
🇺🇸Ann Arbor, Michigan, United States