Steroid Withdrawal in Pediatric Kidney Transplant Recipients - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00023244

Purpose

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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study measures whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

Condition	Intervention
End-Stage Renal Disease	Drug: Basiliximab Drug: Cyclosporine Drug: Tacrolimus Drug: Sirolimus Drug: Methylprednisolone Drug: Prednisone Drug: Bactrim

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment
Official Title:	A Double-Blind Randomized Trial of Steroid Withdrawal in Sirolimus- and Cyclosporine-Treated Primary Transplant Recipients

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Prednisone Sirolimus Cyclosporine Cyclosporin Methylprednisolone Tacrolimus anhydrous Tacrolimus Basiliximab

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Enrollment:	600
Study Start Date:	January 2001
Estimated Primary Completion Date:	June 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Participants receiving corticosteroids	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
B: Placebo Comparator Participants not receiving corticosteroids	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

Assigned Interventions

A: Experimental

Participants receiving corticosteroids

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

B: Placebo Comparator

Participants not receiving corticosteroids

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

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.

Eligibility

Ages Eligible for Study:	up to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00023244

Locations

United States, Maryland
Mara Bauman
Rockville, Maryland, United States, 20850

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

More Information

No publications provided

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT SW01, SW01
Study First Received:	August 29, 2001
Last Updated:	September 26, 2008
ClinicalTrials.gov Identifier:	NCT00023244 History of Changes
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Sirolimus
Prednisone
Anti-Infective Agents
Renal Insufficiency
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Kidney Failure, Chronic
Antiemetics
Prednisolone acetate

Tacrolimus
Antibiotics, Antineoplastic
Hormones
Neuroprotective Agents
Cyclosporins
Anti-Bacterial Agents
Urologic Diseases
Therapeutic Uses
Antifungal Agents
Kidney Diseases
Dermatologic Agents
Methylprednisolone Hemisuccinate
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Methylprednisolone acetate

ClinicalTrials.gov processed this record on November 27, 2009