Study Stopped
Effective August 13, 2004: Unanticipated high incidence of post-transplant lymphoproliferative disorder
Steroid Withdrawal in Pediatric Kidney Transplant Recipients
A Double-Blind Randomized Trial of Steroid Withdrawal in Sirolimus- and Cyclosporine-Treated Primary Transplant Recipients
1 other identifier
interventional
274
2 countries
19
Brief Summary
The purpose of this study is to examine the effects of withdrawing steroids on graft rejection and kidney functions in kidney transplant recipients between the ages of 0 and 20 years (prior to their 21st birthday). Graft survival has improved in recent years in children with kidney transplants. One bad side effect of steroid maintenance therapy has been growth retardation. Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies. If steroids are removed, children might catch up in their growth and also might have fewer side effects of other kinds. This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2001
Typical duration for phase_2
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2001
CompletedFirst Submitted
Initial submission to the registry
August 29, 2001
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2005
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2005
CompletedOctober 21, 2016
October 1, 2016
4.4 years
August 29, 2001
October 19, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
At 6 months and 2.5 years post-transplant
Secondary Outcomes (7)
Graft and patient survival
Throughout study
Biopsy-proven acute rejection
Throughout study
Renal function, measured by serum creatinine and the calculated creatinine clearances
Throughout study
Hypertension
Throughout study
Cushingoid features
Throughout study
- +2 more secondary outcomes
Study Arms (2)
Corticosteroid (steroid) withdrawal
EXPERIMENTALAll enrolled subjects who have not experienced an episode of acute rejection or other event resulting in removal from the study in the first 6 months after transplantation will undergo a protocol-driven biopsy at 6 months. Subjects with no clinical or histologic evidence of rejection will be eligible to be randomized and treated in a double-blinded (e.g., masked-neither subject nor health care providers will know treatment being received) fashion while continuing other immunosuppressive medications. Subjects in this arm will undergo complete steroid withdrawal by the end of 12 months post-transplant.
Control Treatment
ACTIVE COMPARATORAll enrolled subjects who have not experienced an episode of acute rejection or other event resulting in removal from the study in the first 6 months after transplantation will undergo a protocol-driven biopsy at 6 months. Subjects with no clinical or histologic evidence of rejection will be eligible to be randomized and treated in a double-blinded (e.g., masked-neither subject nor health care providers will know treatment being received) fashion while continuing other immunosuppressive medications. Subjects in this arm will be maintained on low-dose (0.15 mg/kg/day) daily steroids.
Interventions
Administered as a bolus intravenous injection. The first dose is given pre-operatively, the second dose is given on post-transplant day four. Dosage is determined by individual weight.
Participants receiving cyclosporine microemulsion formula (in lieu of tacrolimus) will have the dose adjusted to maintain a whole blood trough Abbott TDx assay monoclonal level of 175-400 ng/mL (or an equivalent high pressure liquid chromatography (HPLC) level) for the first 2 weeks after transplant. The dose will subsequently be tapered to maintain a trough level of 175-300 ng/mL from week 3 to month 3, and 50-250 ng/mL from month 3 through the end of the study at month 36 (year 3).
Participants receiving tacrolimus (in lieu of Cyclosporine) will have the dose adjusted to maintain a whole blood trough level between 10 and 15 ng/mL for the first 4weeks after transplant. Trough levels will be maintained between 5 and 10 ng/mL thereafter throughout the duration of the study.
Participants take daily (orally, either as tablets or as liquid) starting on postoperative day 1 at a dose of 6 mg/m2 and will be adjusted to maintain a trough level of 10-20 ng/mL throughout the study.
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
Administered orally beginning on Post-Op Day 2 and maintained for all participants until day 180. Randomization will determine whether patients will maintain this treatment following day 180.
All subjects will receive TMP SMX (Bactrim), pneumocystis jiroveci (carinii) prophylaxis, beginning on postoperative day 1 and continuing for 6 months following transplant. Dosage: 10 mg/kg taken orally three times weekly (maximum dose 160 mg).
Eligibility Criteria
You may qualify if:
- Patients may be eligible for this study if they:
- Are between the ages of 0 and 20 years (prior to their 21st birthday)
- Are receiving their first living related (e.g.,kidney from a relative or unrelated donor) or cadaver donor transplant
- Are willing to practice an acceptable method of birth control during the study, if women able to have children
You may not qualify if:
- Patients will not be eligible for this study if they:
- Have received multiple organs
- Have received 2 or more transplants
- Have an active infection (including tuberculosis), or cancer
- Have used an experimental agent within 4 weeks of transplantation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
University of Alabama
Birmingham, Alabama, 35233, United States
UCSD Medical Center
San Diego, California, 92103, United States
Denver Children's Hospital
Aurora, Colorado, 80045, United States
University of Florida Health Science Center
Jacksonville, Florida, 32209, United States
Emory Children's Center
Atlanta, Georgia, 30322, United States
Tulane University Medical Center
New Orleans, Louisiana, 70112, United States
University of Maryland Medical Center
Baltimore, Maryland, 21201, United States
Children's Hospital of Boston
Boston, Massachusetts, 02115, United States
University of New Mexico Health Science Center
Albuquerque, New Mexico, 87131, United States
The Children's Hospital of Buffalo
Buffalo, New York, 14222, United States
Westchester Medical Center
Valhalla, New York, 10595, United States
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106, United States
University Hospitals of Cleveland
Cleveland, Ohio, 44106, United States
Penn State College of Medicine
Hershey, Pennsylvania, 17033, United States
LeBonheur Children's Medical Center
Memphis, Tennessee, 38103, United States
Christopher Goldsbury Center
San Antonio, Texas, 78207, United States
Children's Hospital and Regional Medical Center
Seattle, Washington, 98105, United States
University of Wisconsin
Madison, Wisconsin, 53705, United States
Hospital Infantil de Mexico
Mexico City, Mexico City, 06720, Mexico
Related Publications (4)
Magee JC. Steroids in pediatric kidney transplantation: a balancing act in progress. Am J Transplant. 2010 Jan;10(1):6-7. doi: 10.1111/j.1600-6143.2009.02923.x. Epub 2009 Dec 17. No abstract available.
PMID: 19958331BACKGROUNDLi L, Chang A, Naesens M, Kambham N, Waskerwitz J, Martin J, Wong C, Alexander S, Grimm P, Concepcion W, Salvatierra O, Sarwal MM. Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits. Am J Transplant. 2009 Jun;9(6):1362-72. doi: 10.1111/j.1600-6143.2009.02640.x. Epub 2009 May 13.
PMID: 19459814BACKGROUNDBenfield MR, Bartosh S, Ikle D, Warshaw B, Bridges N, Morrison Y, Harmon W. A randomized double-blind, placebo controlled trial of steroid withdrawal after pediatric renal transplantation. Am J Transplant. 2010 Jan;10(1):81-8. doi: 10.1111/j.1600-6143.2009.02767.x. Epub 2009 Jul 28.
PMID: 19663893RESULTMcDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W; CCTPT Study Group. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May;8(5):984-9. doi: 10.1111/j.1600-6143.2008.02167.x.
PMID: 18416737RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
William Harmon, MD
Boston Children's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 29, 2001
First Posted
August 31, 2001
Study Start
January 1, 2001
Primary Completion
June 1, 2005
Study Completion
June 1, 2005
Last Updated
October 21, 2016
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.