Official Title: “A Double-Blind Randomized Trial of Steroid Withdrawal in Sirolimus- and Cyclosporine-Treated Primary Transplant Recipients”

The purpose of this study is to examine the effects of withdrawing steroids on graft rejection and kidney functions in kidney transplant recipients. 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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study measures whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment

Study Primary Completion Date: June 2005

Children receiving renal transplants face distressing issues in post-transplantation including growth retardation directly attributable to corticosteroids. 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 milieu without incurring the risk of increased incidence of acute 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. Immunosuppression 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-CMV therapy is given for all recipients of a CMV positive kidney. At 6 months post-transplant all patients who have not had an episode of acute rejection undergo a 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 immunosuppressant 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 biopsy and managed with methylprednisolone treatment. Patients are followed for 3 years for analysis of growth rate, blood pressure, lipid profile and renal function as measured by serum creatinine and calculated creatinine clearances. Post-transplant 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 center.

Intervention(s) in this Clinical Trial

• Drug: Basiliximab
  • Administered as a bolus intravenous injection. The first dose is given pre-operatively, the second dose is given on day four following the operation. Dosage is determined by individual weight.
• Drug: Cyclosporine
  • Administered orally or intravenously.Dosage is per recommendation and is to be maintained throughout the study.
• Drug: Tacrolimus
  • May be administered as an alternative to cyclosporine. Dosage is per recommendation and is to be maintained throughout the study.
• Drug: Sirolimus
  • Administered orally in either tablet or liquid form. Treatment begins on Post-op Day 1 and is maintained throughout the study.
• Drug: Methylprednisolone
  • Administered intravenously both peri-operatively and on Post-Op Day 1.
• Drug: Prednisone
  • 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.
• Drug: Bactrim
  • Administered three times a week beginning on Post-Op Day 1 for 180 days

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Participants receiving corticosteroids
• Placebo Comparator: B
  • Participants not receiving corticosteroids

Primary Measures

• Growth, measured as change in standardized height from 6 month to 2.5 years post-transplant
  • Time Frame: At 6 months and 2.5 years post-transplant
    Safety Issue?: No

Secondary Measures

• Graft and patient survival
  • Time Frame: Throughout study
    Safety Issue?: Yes
• Biopsy-proven acute rejection
  • Time Frame: Throughout study
    Safety Issue?: No
• Renal function, measured by serum creatinine and the calculated creatinine clearances
  • Time Frame: Throughout study
    Safety Issue?: No
• Hypertension
  • Time Frame: Throughout study
    Safety Issue?: No
• Cushingoid features
  • Time Frame: Throughout study
    Safety Issue?: No
• Systolic and diastolic blood pressure levels
  • Time Frame: Throughout study
    Safety Issue?: No
• Fasting lipid profile
  • Time Frame: Throughout study
    Safety Issue?: No

Inclusion Criteria

Patients may be eligible for this study if they:

• Are 0 to 20 years old.
• Are receiving the first living- (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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 20 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00023244

Study ID Number: DAIT SW01

ClinicalTrials.gov Identifier: NCT00023244

Health Authority: United States: Federal Government