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

Condition(s) targeted: Kidney Diseases; Kidney Transplantation; Kidney Transplant; Renal Transplantation; Renal Transplant

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

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Minnie Sarwal, MD, PhD, Study Chair, Affiliation: California Pacific Medical Center
Oscar Salvatierra, MD, Principal Investigator, Affiliation: Pediatric Kidney Transplant Program, Stanford University Medical Center, Stanford Hospital and Clinics

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation

Comparison by Treatment Assignment in the Number of Biopsy-Proven Acute Rejections Within 12 Months Post Kidney Transplantation

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.

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

Criteria:

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

University of Alabama - Pediatric Nephrology, Birmingham, Alabama 35233, United States

Maxine Dunitz Children's Health Center Cedars-Sinai, Los Angeles, California 90048, United States

UCLA - Department of Pediatrics, Division of Nephrology, Los Angeles, California 90095-1752, United States

Stanford University Medical Center, Lucile Packard Children's Hospital, Palo Alto, California 94304, United States

UCSF Children's Hospital, San Francisco, California 94143, United States

University of Florida - Pediatric Nephrology, Gainesville, Florida 32610-0296, United States

Children's Hospital of New Orleans-Department of Pediatric Nephrology, New Orleans, Louisiana 70118, United States

Children's Hospital Boston - Division of Nephrology, Boston, Massachusetts 02115, United States

University of Michigan Medical Center, C.S. Mott Children's Hospital- Division of Nephrology & Transplantation, Ann Arbor, Michigan 48109, United States

Children's Mercy Hospital - Department of Nephrology, Kansas City, Missouri 64108, United States

The Children's Hospital of Philadelphia-Department of Nephrology, Philadelphia, Pennsylvania 19104, United States

Children's Hospital & Regional Medical Center - Division of Nephrology, Seattle, Washington 98105, United States

Related publications:

Cole E, Landsberg D, Russell D, Zaltzman J, Kiberd B, Caravaggio C, Vasquez AR, Halloran P. A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients. Transplantation. 2001 Sep 15;72(5):845-50.

Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O Jr. Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation. 2003 Nov 15;76(9):1331-9.

Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol. 2005 Mar;20(3):418-26. Epub 2005 Feb 3. Review.

Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation: can it be achieved? Paediatr Drugs. 2004;6(5):273-87. Review.

Starting date: March 2004
Last updated: July 11, 2013