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| Sponsored by: |
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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study measures whether steroid therapy can be withdrawn in a way that does not increase graft rejection.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 |
| 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
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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.
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
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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.
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
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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 |
Inclusion Criteria
Patients may be eligible for this study if they:
Exclusion Criteria
Patients will not be eligible for this study if they:
Contacts and Locations More Information
| 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 |
|
Sirolimus Anti-Inflammatory Agents Prednisone Renal Insufficiency Cyclosporine Immunologic Factors Methylprednisolone Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Benzocaine Kidney Failure, Chronic Antiemetics Trimethoprim-Sulfamethoxazole Combination Prednisolone acetate Tacrolimus |
Hormones Neuroprotective Agents Cyclosporins Anti-Bacterial Agents Urologic Diseases Antifungal Agents Kidney Diseases Methylprednisolone Hemisuccinate Antineoplastic Agents, Hormonal Methylprednisolone acetate Glucocorticoids Immunosuppressive Agents Basiliximab Renal Insufficiency, Chronic Prednisolone |
|
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 |
