Clinical trial NCT00023244: Steroid Withdrawal in Pediatric Kidney Transplant Recipients
Official title: A Double-Blind Randomized Trial of Steroid Withdrawal in Sirolimus- and Cyclosporine-Treated Primary Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: End-Stage Renal Disease
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Cooperative Clinical Trials in Pediatric Transplantation
First posted: 2001-08-31
Enrollment: 274
Sex: ALL
Minimum age (years): 1
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

Detailed description: Children receiving kidney (renal) transplantation face distressing issues in post-transplantation including but not limited to growth retardation directly attributable to corticosteroids (steroids). It is hypothesized that robust immunosuppression with sirolimus and calcineurin inhibitors (cyclosporine or tacrolimus) in conjunction with induction therapy should enable successful steroid withdrawal. A steroid-free environment could lessen side effects by enabling a child to achieve catch-up growth, reducing the need for anti-hypertensive therapy, and reducing the risk of cardiovascular disease. This trial tests the objective of providing a steroid-free state without incurring the risk of increased incidence of acute transplant rejections.

Patients are enrolled prior to kidney transplantation and receive standard evaluations. Patients receive induction therapy with basiliximab preoperatively and on Day 4 after surgery. Immunosuppressive therapy begins with sirolimus and either cyclosporine or tacrolimus on Day 1 following surgery, and with corticosteroids the day of surgery. Infection prophylaxis with Bactrim is begun on Day 1 after surgery and center-specific anti-cytomegalovirus (CMV) therapy is given for all recipients of a CMV positive kidney. At 6 months post-transplantation, all patients who have not had an episode of acute rejection undergo a renal graft biopsy. Patients who are confirmed to be free of subclinical rejection are randomized to either undergo complete steroid withdrawal or continue maintenance on daily steroids. Patients receive either steroids or placebo, while continuing other immunosuppressive medications. Patients are segregated into weight groups for steroid withdrawal that occurs over months 7 to 13. Any acute rejection event during withdrawal is confirmed by renal biopsy and managed with methylprednisolone treatment. Patients are followed for 3 years post-transplantation for analysis of growth rate, blood pressure, lipid profile and renal function as measured by serum creatinine and calculated creatinine clearances. Post-transplantation clinic visits are weekly for the first 2 months, every 2 weeks until 13 months, weekly during Month 13, every 2 weeks through Month 18, and monthly until the study ends.

Patients who exhibit evidence of acute or subclinical rejection do not continue the steroid withdrawal trial and care is managed by their pediatric renal transplant center physicians.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
timeFrame: At 6 months and 2.5 years post-transplant
Secondary outcomes:
measure: Graft and patient survival
timeFrame: Throughout study
measure: Biopsy-proven acute rejection
timeFrame: Throughout study
measure: Renal function, measured by serum creatinine and the calculated creatinine clearances
timeFrame: Throughout study
measure: Hypertension
timeFrame: Throughout study
measure: Cushingoid features
timeFrame: Throughout study
measure: Systolic and diastolic blood pressure levels
timeFrame: Throughout study
measure: Fasting lipid profile
timeFrame: Throughout study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: Aurora
country: United States
facility: Denver Children's Hospital
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Children's Hospital of Boston
state: Massachusetts
city: Albuquerque
country: United States
facility: University of New Mexico Health Science Center
state: New Mexico
city: Buffalo
country: United States
facility: The Children's Hospital of Buffalo
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Memphis
country: United States
facility: LeBonheur Children's Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: Christopher Goldsbury Center
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico
state: Distrito Federal
Study officials:
affiliation: Boston Children's Hospital
name: William Harmon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Li 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.
citation: Benfield 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.
citation: McDonald 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.