Steroid Withdrawal in Pediatric Kidney Transplant Recipients

This study has been terminated.
(Effective August 13, 2004: Due to an unanticipated high incidence of post-transplant lymphoproliferative disorder)
Sponsor:
Collaborator:
Cooperative Clinical Trials in Pediatric Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00023244
First received: August 29, 2001
Last updated: October 26, 2012
Last verified: October 2012

August 29, 2001
October 26, 2012
January 2001
June 2005   (final data collection date for primary outcome measure)
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation [ Time Frame: At 6 months and 2.5 years post-transplant ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00023244 on ClinicalTrials.gov Archive Site
  • Graft and patient survival [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Biopsy-proven acute rejection [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Renal function, measured by serum creatinine and the calculated creatinine clearances [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Hypertension [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Cushingoid features [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Systolic and diastolic blood pressure levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Fasting lipid profile [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Steroid Withdrawal in Pediatric Kidney Transplant Recipients
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 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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
End-Stage Renal Disease
  • Drug: Basiliximab
    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.
    Other Names:
    • Simulect
    • Anti-CD25 monoclonal antibody, chimeric
  • Drug: Cyclosporine
    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).
    Other Name: CsA
  • Drug: Tacrolimus
    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.
  • Drug: Sirolimus
    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.
  • Drug: Methylprednisolone
    Administered at 10 mg/kg intravenously perioperatively and on postoperative 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
    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).
    Other Names:
    • TMP SMX
    • trimethoprim/sulfamethoxazole
  • Experimental: Corticosteroid (steroid) withdrawal
    All 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.
    Interventions:
    • Drug: Basiliximab
    • Drug: Cyclosporine
    • Drug: Tacrolimus
    • Drug: Sirolimus
    • Drug: Methylprednisolone
    • Drug: Prednisone
    • Drug: Bactrim
  • Active Comparator: Control Treatment
    All 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:
    • Drug: Basiliximab
    • Drug: Cyclosporine
    • Drug: Tacrolimus
    • Drug: Sirolimus
    • Drug: Methylprednisolone
    • Drug: Prednisone
    • Drug: Bactrim

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
274
June 2005
June 2005   (final data collection date for primary outcome measure)

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
Both
up to 20 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Mexico
 
NCT00023244
DAIT SW01
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Cooperative Clinical Trials in Pediatric Transplantation
Principal Investigator: William Harmon, MD Children's Hospital Boston
National Institute of Allergy and Infectious Diseases (NIAID)
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP