Clinical trial NCT00141037: Steroid-Free Versus Steroid-Based Immunosuppression in Pediatric Renal (Kidney) Transplantation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Kidney Diseases
Kidney Transplantation
Kidney Transplant
Renal Transplantation
Renal Transplant
Keywords: Organ Rejection
Corticosteroids
Child
Adolescent
Immunosuppression
Steroids
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Astellas Pharma Inc
name: Hoffmann-La Roche
First posted: 2005-09-01
Enrollment: 130
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation
timeFrame: One year post kidney transplantation procedure
measure: Comparison by Treatment Assignment in the Number of Biopsy-Proven Acute Rejections Within 12 Months Post Kidney Transplantation
timeFrame: Up to one year post kidney transplantation procedure
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Pediatric Nephrology
state: Alabama
city: Los Angeles
country: United States
facility: Maxine Dunitz Children's Health Center Cedars-Sinai
state: California
city: Los Angeles
country: United States
facility: UCLA - Department of Pediatrics, Division of Nephrology
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center, Lucile Packard Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Children's Hospital
state: California
city: Gainesville
country: United States
facility: University of Florida - Pediatric Nephrology
state: Florida
city: New Orleans
country: United States
facility: Children's Hospital of New Orleans-Department of Pediatric Nephrology
state: Louisiana
city: Boston
country: United States
facility: Children's Hospital Boston - Division of Nephrology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center, C.S. Mott Children's Hospital- Division of Nephrology & Transplantation
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospital - Department of Nephrology
state: Missouri
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia-Department of Nephrology
state: Pennsylvania
city: Seattle
country: United States
facility: Children's Hospital & Regional Medical Center - Division of Nephrology
state: Washington
Study officials:
affiliation: California Pacific Medical Center
name: Minnie Sarwal, MD, PhD
role: STUDY_CHAIR
affiliation: Pediatric Kidney Transplant Program, Stanford University Medical Center, Stanford Hospital and Clinics
name: Oscar Salvatierra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1097/00007890-200109150-00018.
citation: 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. doi: 10.1097/01.TP.0000092950.54184.67.
citation: Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation. Pediatr Nephrol. 2005 Mar;20(3):418-26. doi: 10.1007/s00467-004-1786-4. Epub 2005 Feb 3.
citation: Vidhun JR, Sarwal MM. Corticosteroid avoidance in pediatric renal transplantation: can it be achieved? Paediatr Drugs. 2004;6(5):273-87. doi: 10.2165/00148581-200406050-00002.
citation: Sarwal MM, Ettenger RB, Dharnidharka V, Benfield M, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Tang L, Liu J, Li L, Naesens M, Sigdel T, Waskerwitz J, Salvatierra O. Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up. Am J Transplant. 2012 Oct;12(10):2719-29. doi: 10.1111/j.1600-6143.2012.04145.x. Epub 2012 Jun 13.
citation: Naesens M, Salvatierra O, Benfield M, Ettenger RB, Dharnidharka V, Harmon W, Mathias R, Sarwal MM; SNS01-NIH-CCTPT Multicenter Trial. Subclinical inflammation and chronic renal allograft injury in a randomized trial on steroid avoidance in pediatric kidney transplantation. Am J Transplant. 2012 Oct;12(10):2730-43. doi: 10.1111/j.1600-6143.2012.04144.x. Epub 2012 Jun 13.
citation: Li L, Khatri P, Sigdel TK, Tran T, Ying L, Vitalone MJ, Chen A, Hsieh S, Dai H, Zhang M, Naesens M, Zarkhin V, Sansanwal P, Chen R, Mindrinos M, Xiao W, Benfield M, Ettenger RB, Dharnidharka V, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Davis R, Butte AJ, Salvatierra O, Sarwal MM. A peripheral blood diagnostic test for acute rejection in renal transplantation. Am J Transplant. 2012 Oct;12(10):2710-8. doi: 10.1111/j.1600-6143.2012.04253.x.