Clinical trial NCT00141037
Conditions: Kidney Diseases Kidney Transplantation Kidney Transplant Renal Transplantation Renal Transplant
Keywords: Organ Rejection Corticosteroids Child Adolescent Immunosuppression Steroids
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2004-03-01; Completion date: 2010-11-01
Enrollment: 130 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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).
Interventions: intervention 1: Daclizumab intervention 2: Mycophenolate mofetil (MMF) intervention 3: Prednisone intervention 4: Tacrolimus intervention 5: Ganciclovir intervention 6: Valganciclovir intervention 7: Trimethoprim and sulfamethoxazole
Intervention descriptions: intervention 1: Steroid-Based Immunosuppression(Prednisone) arm: 1 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, and 8 (e.g., standard dose of daclizumab induction until the second month post-transplant)

Steroid-Free Immunosuppression (Extended daclizumab induction) arm: 2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11, and months 4, 5, and 6 (e.g., extended daclizumab induction until the sixth month post-transplant) intervention 2: Intravenous MMF was dosed at 1200 mg/m\^2/day in two divided doses preoperatively and for the first 48 hours postoperatively. Oral MMF was dosed at 600 to 900 mg/m\^2/day in two divided doses; the dose range allowed for dose titration according to tolerability and side effects of MMF. This regimen was used in both arms. intervention 3: Administered as 10 mg/kg peri-operatively followed by 2 mg/kg/day in subjects weighing \<40 kg and 1.5 mg/kg/day in subjects weighing \>40 kg. The prednisone dosing was tapered as follows: by the end of wks 1, 2, 4,6,12 and 16, dosages were 0.5, 0.4, 0.3, 0.2, 0.15 and 0.1 mg/kg/day, respectively. The prednisone dose of 0.1 mg/kg was achieved by no later than 6 months post-transplant. intervention 4: Taken orally from immediately preoperatively to those\>age 5 yrs. (starting dose= 0.1 mg/kg/dose twice daily (BID) for living donor recipients; 0.1 mg/kg/dose daily for deceased donor recipients).Subjects \<age 5 yrs. received drug from immediately preoperatively at 0.15 mg/kg/dose BID (two preoperative doses) for living donor recipients and 0.15 mg/kg/dose daily (one preoperative dose) for deceased donor recipients. Postoperatively: 0.07 mg/kg/dose BID w/adjustment to achieve target levels of 12-14 ng/mL (days 0-7), 10-12 ng/mL (wks. 2-8), 7-10 ng/mL (wks. 9-12) \&5-7 ng/mL \>= 12 wks. Evidence of drug toxicity on any protocol biopsy resulted in a further lowering of the drug target level to 4-6 ng/mL before yr 1 \& 3-5 ng/mL after yr 1 post-transplant. This regimen was used in both arms. intervention 5: Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Prophylaxis: All participants will receive intravenous ganciclovir 5 mg/kg/day beginning after transplantation until tolerating oral medications, at which time oral valganciclovir will be initiated and continued for a minimum of 100 days. intervention 6: Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Prophylaxis: All participants will receive intravenous ganciclovir 5 mg/kg/day beginning after transplantation until tolerating oral medications, at which time oral valganciclovir will be initiated and continued for a minimum of 100 days. intervention 7: Pneumocystis pneumonia (PCP)/Urinary Tract Infection (UTI) Prophylaxis: Trimethoprim/sulfamethoxazole (Septra®) 2 mg/kg by mouth will be administered daily at bedtime for a minimum period of the first 6 months post-transplant. If unable to tolerate Septra®, inhaled pentamidine (8 mg/kg to a maximum dose of 300 mg monthly) or Dapsone (2 mg/kg PO to a maximum dose of 100 mg/day) may be substituted for a minimum of the first 6 months post-transplant. For UTI prophylaxis, if Septra® is not tolerated, nitrofurantoin (Macrodantin®), 2.5 mg/kg/day, may be given at bedtime up to a maximum dose of 100 mg/day.

Protocol documents: