NCT00141037

Steroid-Free Versus Steroid-Based Immunosuppression in Pediatric Renal (Kidney) Transplantation

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 130 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Kidney Diseases
• Kidney Transplantation
• Kidney Transplant
• Renal Transplantation
• Renal Transplant

Interventions

Type	Name	Description
DRUG	Daclizumab	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)
DRUG	Mycophenolate mofetil (MMF)	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.
DRUG	Prednisone	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.
DRUG	Tacrolimus	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.
DRUG	Ganciclovir	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.
DRUG	Valganciclovir	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.
DRUG	Trimethoprim and sulfamethoxazole	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.

Timeline

• Start date: 2004-03-01
• Primary completion: 2006-09-01
• Completion: 2010-11-01
• First posted: 2005-09-01
• Last updated: 2016-11-29
• Results posted: 2013-07-11

Locations

12 sites across 1 country: United States