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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Kidney Transplantation; Kidney Diseases; Kidney Transplant; Renal Transplantation; Renal Transplant

Treatments: Drug: Daclizumab; Drug: Tacrolimus; Drug: Valganciclovir; Drug: Prednisone; Drug: Mycophenolate mofetil (MMF); Drug: Ganciclovir; Drug: Trimethoprim and sulfamethoxazole

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00141037

DAIT SNS01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 130 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

Steroid-Based Immunosuppression

Active Comparator group

Description:

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.

Treatment:

Drug: Trimethoprim and sulfamethoxazole

Drug: Ganciclovir

Drug: Mycophenolate mofetil (MMF)

Drug: Prednisone

Drug: Valganciclovir

Drug: Tacrolimus

Drug: Daclizumab

Steroid-Free Immunosuppression

Experimental group

Description:

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).

Treatment:

Drug: Trimethoprim and sulfamethoxazole

Drug: Ganciclovir

Drug: Mycophenolate mofetil (MMF)

Drug: Valganciclovir

Drug: Tacrolimus

Drug: Daclizumab