Suppressing the Immune System With or Without Steroids in Children Who Have Received Kidney Transplants - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Astellas Pharma Inc Hoffmann-La Roche
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00141037

Purpose

Over the last 40 years, corticosteroids have been an important part of drug regimens used to prevent organ rejection and maintain the immune health of people who have received organ transplants. Unfortunately, the negative physical effects of corticosteroids can be severe, especially in children. The purpose of this study is to determine the safety and effectiveness of a corticosteroid-free treatment regimen for children and adolescents who have received kidney transplants.

Condition	Intervention
Kidney Diseases Kidney Transplantation	Drug: Daclizumab Drug: Mycophenolate mofetil Drug: Prednisone Drug: Tacrolimus

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Prednisone Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Corticosteroids Tacrolimus anhydrous Dacliximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Multi-Center Comparative Trial of Tacrolimus With Steroids and Standard Daclizumab Induction Versus a Novel Steroid-Free Tacrolimus Based Immunosuppression Protocol With Extended Daclizumab Induction in Pediatric Renal Transplantation

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Efficacy, as measured by the difference in the change of standardized height at 1 year [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
safety, as measured by the rate at 12 months of biopsy-proven acute rejection [ Time Frame: At 1 year ] [ Designated as safety issue: Yes ]

Enrollment:	130
Study Start Date:	November 2005
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Subjects will undergo a treatment regimen that includes prednisone	Drug: Daclizumab Steroid based arm: 1 mg/kg per-transplant followed by 1 mg/kg at weeks 2, 4, 6, and 8 Steroid-free arm: 2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11, and months 4, 5, and 6 Drug: Mycophenolate mofetil Typically administered in 2-3 divided doses both before and after transplant, and generally given at least until week two. Exact dosage is per recommendation. Drug: Prednisone Administered as 10 mg/kg before transplant. Following transplant, regimen is adjusted to 2mg/kg/day in subjects weighing <40 kg, or 1.5 mg/kg/day in subjects weighing >40 kg. Drug: Tacrolimus For recipients older than 5 years it is administered orally before transplant at a dose of 0.1 mg/kg twice daily for living donor recipients, or 0.1 mg/kg once daily for cadaveric donor recipients. For recipients under 5 years, dosing will be 0.15 mg/kg twice daily for living donor recipients, or 0.15 mg/kg once daily for cadaveric donor recipients. Post-transplant the oral dose will be 0.07 mg/kg twice daily adjusted per recommendation to achieve target levels.
B: Active Comparator Subjects will undergo a treatment regimen absent of prednisone	Drug: Daclizumab Steroid based arm: 1 mg/kg per-transplant followed by 1 mg/kg at weeks 2, 4, 6, and 8 Steroid-free arm: 2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11, and months 4, 5, and 6 Drug: Mycophenolate mofetil Typically administered in 2-3 divided doses both before and after transplant, and generally given at least until week two. Exact dosage is per recommendation. Drug: Tacrolimus For recipients older than 5 years it is administered orally before transplant at a dose of 0.1 mg/kg twice daily for living donor recipients, or 0.1 mg/kg once daily for cadaveric donor recipients. For recipients under 5 years, dosing will be 0.15 mg/kg twice daily for living donor recipients, or 0.15 mg/kg once daily for cadaveric donor recipients. Post-transplant the oral dose will be 0.07 mg/kg twice daily adjusted per recommendation to achieve target levels.

Arms

Assigned Interventions

A: Experimental

Subjects will undergo a treatment regimen that includes prednisone

Drug: Daclizumab

Steroid based arm: 1 mg/kg per-transplant followed by 1 mg/kg at weeks 2, 4, 6, and 8

Steroid-free arm: 2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11, and months 4, 5, and 6

Drug: Mycophenolate mofetil

Typically administered in 2-3 divided doses both before and after transplant, and generally given at least until week two. Exact dosage is per recommendation.

Drug: Prednisone

Administered as 10 mg/kg before transplant. Following transplant, regimen is adjusted to 2mg/kg/day in subjects weighing <40 kg, or 1.5 mg/kg/day in subjects weighing >40 kg.

Drug: Tacrolimus

For recipients older than 5 years it is administered orally before transplant at a dose of 0.1 mg/kg twice daily for living donor recipients, or 0.1 mg/kg once daily for cadaveric donor recipients. For recipients under 5 years, dosing will be 0.15 mg/kg twice daily for living donor recipients, or 0.15 mg/kg once daily for cadaveric donor recipients. Post-transplant the oral dose will be 0.07 mg/kg twice daily adjusted per recommendation to achieve target levels.

B: Active Comparator

Subjects will undergo a treatment regimen absent of prednisone

Drug: Daclizumab

Steroid based arm: 1 mg/kg per-transplant followed by 1 mg/kg at weeks 2, 4, 6, and 8

Steroid-free arm: 2 mg/kg pre-transplant followed by 1 mg/kg at weeks 2, 4, 6, 8, 11, and months 4, 5, and 6

Drug: Mycophenolate mofetil

Typically administered in 2-3 divided doses both before and after transplant, and generally given at least until week two. Exact dosage is per recommendation.

Drug: Tacrolimus

For recipients older than 5 years it is administered orally before transplant at a dose of 0.1 mg/kg twice daily for living donor recipients, or 0.1 mg/kg once daily for cadaveric donor recipients. For recipients under 5 years, dosing will be 0.15 mg/kg twice daily for living donor recipients, or 0.15 mg/kg once daily for cadaveric donor recipients. Post-transplant the oral dose will be 0.07 mg/kg twice daily adjusted per recommendation to achieve target levels.

Detailed Description:

Corticosteroids have been a cornerstone of immunosuppressive therapy for kidney transplantation for over 40 years. However, poor growth and bone loss caused by the use of corticosteroids are devastating to pediatric kidney recipients. The negative physical implications of corticosteroid use also greatly impacts patients' compliance to their prescribed corticosteroid-containing regimens. The development of a corticosteroid-free regimen for post-transplant pediatric patients is sorely needed. This study will evaluate the safety and efficacy of a corticosteroid-free treatment regimen in children and adolescents who have received kidney transplants, compared to a standard of care regimen including corticosteroids. 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 randomly assigned to one of two groups. Group 1 patients will receive daclizumab, tacrolimus, mycophenolate mofetil (MMF), and prednisone. Group 1 patients will receive daclizumab prior to transplantation and at Weeks 2, 4, 6, and 8 after transplantation. Group 1 patients will receive prednisone at the time of transplantation and will undergo gradual prednisone tapering post-transplant. Group 2 patients will receive daclizumab, tacrolimus, MMF, but no prednisone. Group 2 patients will receive daclizumab prior to transplantation, at Weeks 2, 4, 6, 8, and 11, and at Months 4, 5 and 6 after transplantation. To prevent opportunistic infections, all patients will receive prophylactic medications beginning after transplantation.

There will be 23 study visits during the 3-year study. 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, patients will have a kidney biopsy. Patients will also undergo cataract screening within 4 months of transplantation.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00141037

Locations

United States, Alabama
University of Alabama - Pediatric Nephrology
Birmingham, Alabama, United States, 35233
United States, California
UCLA - Department of Pediatrics, Division of Nephrology
Los Angeles, California, United States, 90095-1752
Stanford University Medical Center, Lucile Packard Children's Hospital
Palo Alto, California, United States, 94304
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
UCSD - Department of Pediatrics
San Diego, California, United States, 94143
UCSF Children's Hospital
San Francisco, California, United States, 94143
United States, Florida
University of Florida - Pediatric Nephrology
Gainesville, Florida, United States, 32610-0296
United States, Louisiana
Children's Hospital of New Orleans-Department of Pediatric Nephrology
New Orleans, Louisiana, United States, 70118
United States, Massachusetts
Children's Hospital Boston - Division of Nephrology
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Medical Center, C.S. Mott Children's Hospital- Division of Nephrology & Transplantation
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Children's Mercy Hospital - Department of Nephrology
Kansas City, Missouri, United States, 64108
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-3285
United States, Pennsylvania
The Children's Hospital of Philadelphia-Department of Nephrology
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Hospital/Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital & Regional Medical Center - Division of Nephrology
Seattle, Washington, United States, 98105
Canada, Quebec
Montreal Children's Hospital, McGill University Health Centre
Montreal, Quebec, Canada, H3H 1P3

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Astellas Pharma Inc

Hoffmann-La Roche

Investigators

Study Chair:	Minnie Sarwal, MD, PhD	Stanford University
Principal Investigator:	Oscar Salvatierra, MD	Pediatric Kidney Transplant Program, Stanford University Medical Center, Stanford Hospital and Clinics

More Information

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.

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

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT SNS01
Study First Received:	August 1, 2005
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00141037
Health Authority:	United States: Food and Drug Administration

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

Organ Rejection
Corticosteroids
Child
Adolescent
Immunosuppression

Study placed in the following topic categories:

Prednisone
Urologic Diseases
Daclizumab

Mycophenolate mofetil
Tacrolimus
Kidney Diseases

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Immunologic Factors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists
Immunosuppressive Agents
Hormones
Glucocorticoids
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 13, 2009