Kidney transplantation is often successful. However, despite aggressive anti-rejection drug therapy, some patients will reject their new kidney. This study is designed to test two anti-rejection approaches. Two medications in this study are currently used in children, but there is no information regarding which drug is safer or more effective. Survival rates in renal transplantation are unacceptably low. Therefore, there is a need for an improved post-transplant treatment, such as the induction therapy used in this study.
Renal transplantation is recognized as the treatment of choice for children with chronic renal failure. However, patient and graft survival rates in young children are unacceptably low. In preliminary studies, OKT3 (a monoclonal antibody) induction therapy received post transplant has been more successful than standard immunosuppression alone in improving graft survival. This study is designed to assess the impact of induction therapy on graft survival in pediatric kidney transplant patients. Patients are assigned to OKT3 induction or no induction in a 1:1 ratio. Randomization to oral cyclosporine of either Sandimmune or Neoral is also done in a 1:1 ratio. Group 1 receives OKT3 intraoperatively followed by Neoral. Group 2 receives OKT3 intraoperatively followed by Sandimmune. OKT3 is administered at 2.5 mg (if weight less than 30 kg) or 5 mg (if weight above 30 kg) per day for a maximum of 14 days. Group 3 receives IV cyclosporine followed by Neoral. Group 4 receives IV cyclosporine followed by Sandimmune. Oral cyclosporine is administered in a masked preparation. The dose for Sandimmune and Neoral is the same; patients 6 years of age and older begin at a dose of 15 mg/kg/day and patients under 6 years of age receive 500 mg/m2/day. Patients will receive concomitant medications including steroids (IV and po), Nifedipine, anti-CMV therapy, Bactrim, Azathioprine or Mycophenolate Mofetil. Kidney function, incidence of viral infection, graft survival, and incidence of malignancy will be measured to assess the role of OKT3 induction and the role of rejection in graft failure. Graft function will be evaluated at 1-, 2-, and 4-year intervals.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Administered both during and after transplantation in IV form. Dosage determined by individual weight and given for a maximum of 14 days.
Administered orally as either sandimmune or neoral at a dose determined by weight. Patients 6 years of age and older begin at a dose of 15 mg/kg/day and patients under 6 years of age receive 500 mg/m2/day, for the duration of the study.
Administered intravenously (IV) both during and after transplantation at a dosage determined by individual age.
Ilene Blechman-Krom
Rockville, Maryland, United States
To determine one-year graft function, as measured by graft survival and serum creatinine of children undergoing OKT3 induction versus no induction
Time frame: At 1 year
To compare the efficacy of Sandimmune and Neoral with respect to graft function
Time frame: Throughout study
Two and four-year graft functions
Time frame: At 2 and 4 years
Safety with respect to viral infections and malignancies in children undergoing a renal transplant
Time frame: Throughout study
Frequency and severity of rejection episodes
Time frame: Throughout study
Time to first rejection
Time frame: Throughout study
Length and frequency of hospitalization
Time frame: Throughout study
Nature of acute cellular rejection at a molecular level
Time frame: Throughout study
Nature of "heightened immune response" of younger children by studying gene expression in surveillance biopsies
Time frame: Throughout study
Correlate intragraft events during rejection with cytokine profile in the peripheral blood
Time frame: Throughout study
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Masking
DOUBLE
Enrollment
292