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
1 other identifier
interventional
130
1 country
12
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2004
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2004
CompletedFirst Submitted
Initial submission to the registry
August 1, 2005
CompletedFirst Posted
Study publicly available on registry
September 1, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2010
CompletedResults Posted
Study results publicly available
July 11, 2013
CompletedNovember 29, 2016
October 1, 2016
2.5 years
August 1, 2005
May 21, 2013
October 19, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation
Standardized Z-scores were computed following a formula using an age- and gender-specific calculation provided by the NHANES III 2000 Growth Data set. The Z-score system expresses anthropometric values of height as several standard deviations (SDs) below (e.g., a negative value) or above (a positive value) the reference mean or median value. In this study the measure was used to test whether there is a difference in the change in height between the treatment groups: Steroid-Based versus Steroid-Free
One year post kidney transplantation procedure
Comparison by Treatment Assignment in the Number of Biopsy-Proven Acute Rejections Within 12 Months Post Kidney Transplantation
Biopsy-proven acute renal (kidney) rejection \[1, 2\]. 1. Diagnosis of acute rejection was made by renal biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection\[2\] 2. Ref: Racusen LC et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999
Up to one year post kidney transplantation procedure
Study Arms (2)
Steroid-Based Immunosuppression
ACTIVE COMPARATORSubjects 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.
Steroid-Free Immunosuppression
EXPERIMENTALSubjects 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).
Interventions
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)
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.
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.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)lead
- Astellas Pharma Inccollaborator
- Hoffmann-La Rochecollaborator
Study Sites (12)
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 (7)
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.
PMID: 11571448BACKGROUNDSarwal 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.
PMID: 14627912BACKGROUNDVidhun 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.
PMID: 15690189BACKGROUNDVidhun 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.
PMID: 15449967BACKGROUNDSarwal 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.
PMID: 22694755RESULTNaesens 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.
PMID: 22694733RESULTLi 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.
PMID: 23009139RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
1. The results cannot be generalized and daclizumab has since been withdrawn from the United States market (business-related, not due to any safety issues). 2. The study was not powered to definitively evaluate small differences in rejection rate.
Results Point of Contact
- Title
- Director, Clinical Research Program
- Organization
- DAIT/NIAID
Study Officials
- STUDY CHAIR
Minnie Sarwal, MD, PhD
California Pacific Medical Center
- PRINCIPAL INVESTIGATOR
Oscar Salvatierra, MD
Pediatric Kidney Transplant Program, Stanford University Medical Center, Stanford Hospital and Clinics
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 1, 2005
First Posted
September 1, 2005
Study Start
March 1, 2004
Primary Completion
September 1, 2006
Study Completion
November 1, 2010
Last Updated
November 29, 2016
Results First Posted
July 11, 2013
Record last verified: 2016-10
Data Sharing
- IPD Sharing
- Will share
Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.