Safety of Immunosuppression Minimization in Children and Adolescents After Kidney Transplantation
|Kidney Failure, Chronic Kidney Transplantation Immunosuppression||Drug: Sirolimus Drug: MMF or Azathioprine||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
|Official Title:||Immunosuppression Minimization to Single Drug Therapy With Sirolimus (Rapamune) in Pediatric Transplantation|
- Per-person incidence of acute rejection episodes and death or graft loss [ Time Frame: Throughout study ]
- Incidence of chronic allograft dysfunction [ Time Frame: Throughout study ]
- Incidence of sub-clinical rejection [ Time Frame: Throughout study ]
- Incidence of hospitalizations [ Time Frame: Throughout study ]
- Incidence of surgical complications [ Time Frame: Throughout study ]
- Resumption of MMF or other therapy [ Time Frame: Throughout study ]
- Incidence, severity, and treatment of anemia, hypertension, hyperlipidemia, proteinuria, thrombocytopenia, and leukopenia [ Time Frame: Throughout study ]
- Incidence, severity, and treatment of opportunistic infections [ Time Frame: Throughout study ]
- Incidence of biopsy proven PTLD [ Time Frame: Throughout study ]
- Renal function assessed by measured GFR [ Time Frame: At baseline, week 48 and week 96 ]
- Development of donor-specific or non-specific anti-HLA antibodies [ Time Frame: Throughout study ]
- Evolution of immune response in cellular, humoral, and molecular assays from baseline through week 96 [ Time Frame: Throughout study ]
|Study Start Date:||May 2009|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Participants who have been maintained on MMF at study entry will start the study on 600 mg/m2 MMF orally daily. Participants who have been maintained on Azathioprine due to MMF intolerance will receive 1 mg/kg Azathioprine orally daily.
Participants will continue receiving sirolimus throughout the study. However, MMF or Azathioprine will be withdrawn gradually over a period of at least 6 months. Dosage will be reduced by 25% initially and by 25% every subsequent 2 months resulting in complete withdrawal by 6 months.
Oral tablets or liquid taken every 12 hours. Dosage adjusted to attain target trough levels of 8-12 ng/mL. Participants who have maintained such levels at study entry on once daily dosage will be permitted to continue on once daily dosing.
Other Name: Rapamycin, RapamuneDrug: MMF or Azathioprine
600 mg/m2 MMF taken orally daily or Azathioprine orally daily. Dosage of Azathioprine is dependent on weight. MMF or Azathioprine will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.
Improvements in surgical techniques, donor selection, immunosuppression practices, and the enhanced experience of specialized pediatric transplant teams have all led to marked improvements in patient and kidney graft survival in infants and young children Long-term graft survival rates decrease in adolescents 11 to 17 years of age. Several studies have suggested this decrease may be the result of noncompliance with immunosuppressive medications in this age group. Therefore, protocols that minimize the use of immunosuppressive medications, while retaining kidney function are necessary for improving graft and patient survival in children. The purpose of this study is to determine the safety of sirolimus monotherapy for long-term immunosuppression in children and adolescents after kidney transplantation.
This study will enroll 10 participants who previously completed the CCTPT-PC01 study. The accrual period is scheduled for 12 months. The study follow-up period will last 96 weeks. Patients from the CCTPT-PC01 study have been maintained on sirolimus and mycophenolate mofetil (MMF) since 2-3 months post transplant. Enrolled participants receiving (MMF) or Azathioprine at study entry will have their doses withdrawn gradually over a period of 6 months. Dosage will be reduced by 25% initially and by 25% every 2 months resulting in complete withdrawal by 6 months.
This study will consist of 11 study visits after screening and study entry. Study visits will occur at weeks 1, 8, 16, 24, 32, 40, 48, 60, 72, 84, and 96. A physical exam, vital signs, sirolimus levels, as well as blood and urine collection will occur at all visits. A renal biopsy will be performed at week 96.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00768729
|United States, California|
|Children's Hospital of Central California|
|Madera, California, United States|
|UCSF Children's Hospital|
|San Francisco, California, United States|
|United States, Massachusetts|
|Children's Hospital, Boston|
|Boston, Massachusetts, United States|
|United States, Pennsylvania|
|Children's Hospital, Philadelphia|
|Philadelphia, Pennsylvania, United States|
|United States, Washington|
|Children's Hospital and Regional Medical Center, Seattle|
|Seattle, Washington, United States|
|Study Chair:||William H. Harmon, MD||Boston Children’s Hospital|