Steroid Withdrawal in Pediatric Kidney Transplant Recipients

Condition(s) targeted: End-Stage Renal Disease

Intervention: Basiliximab. (Drug); Cyclosporine. (Drug); Tacrolimus. (Drug); Sirolimus. (Drug); Methylprednisolone. (Drug); Prednisone. (Drug); Bactrim. (Drug)

Phase: N/A

Status: Active, not recruiting

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

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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study measures whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

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

Study design: Treatment, Double-Blind

Primary outcome: Growth, measured as change in standardized height from 6 month to 2.5 years post-transplant

Secondary outcome:

Graft and patient survival

biopsy-proven acute rejection

renal function, measured by serum creatinine and the calculated creatinine clearances

hypertension

cushingoid features

systolic and diastolic blood pressure levels

fasting lipid profile

Detailed description: 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.

Minimum age: N/A. Maximum age: 20 Years. Gender(s): Both.

Criteria:

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.

Mara Bauman, Rockville, Maryland 20850, United States

Starting date: January 2001
Last updated: April 2, 2007