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Aurora, Colorado 80045

  • Stage Renal Disease

Purpose:

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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.


Study summary:

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.


Criteria:

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


Study is Available At:


Original ID:

DAIT SW01


NCT ID:

NCT00023244


Secondary ID:


Study Acronym:


Brief Title:

Steroid Withdrawal in Pediatric Kidney Transplant Recipients


Official Title:

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


Overall Status:

Terminated


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

N/A


Maximum Age:

20 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Diseases (NIAID)


Oversight Authority:

  • United States: Federal Government
  • United States: Food and Drug Administration


Reasons Why Stopped:

Effective August 13, 2004: Unanticipated hig


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification: S


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

274


Enrollment Type:

Actual


Overall Contact Information

Official Name:William Harmon, MD
Principal Investigator
Boston Children’s Hospital

Study Dates

Start Date:January 2001
Completion Date:June 2005
Completion Type:Actual
Primary Completion Date:June 2005
Primary Completion Type:Actual
Verification Date:October 2016
Last Changed Date:October 19, 2016
First Received Date:August 29, 2001

Study Outcomes

Outcome Type: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
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Graft and patient survival
Time Frame:Throughout study
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:Biopsy-proven acute rejection
Time Frame:Throughout study
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Renal function, measured by serum creatinine and the calculated creatinine clearances
Time Frame:Throughout study
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Hypertension
Time Frame:Throughout study
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Cushingoid features
Time Frame:Throughout study
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Systolic and diastolic blood pressure levels
Time Frame:Throughout study
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Fasting lipid profile
Time Frame:Throughout study
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:Basiliximab
Description: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.
Arm Name:Corticosteroid (steroid) withdrawal
Other Name:Simulect
Intervention Type:Drug
Name:Cyclosporine
Description: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).
Arm Name:Corticosteroid (steroid) withdrawal
Other Name:CsA
Intervention Type:Drug
Name:Tacrolimus
Description: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.
Arm Name:Corticosteroid (steroid) withdrawal
Intervention Type:Drug
Name:Sirolimus
Description: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.
Arm Name:Corticosteroid (steroid) withdrawal
Intervention Type:Drug
Name:Methylprednisolone
Description:Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
Arm Name:Corticosteroid (steroid) withdrawal
Intervention Type:Drug
Name:Prednisone
Description: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.
Arm Name:Corticosteroid (steroid) withdrawal
Intervention Type:Drug
Name:Bactrim
Description: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).
Arm Name:Corticosteroid (steroid) withdrawal
Other Name:TMP SMX

Study Arms

Study Arm Type:Experimental
Arm Name:Corticosteroid (steroid) withdrawal
Description: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 medicati
Study Arm Type:Active Comparator
Arm Name:Control Treatment
Description: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 medicati

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)
Agency Class:Other
Agency Type:Collaborator
Agency Name:Cooperative Clinical Trials in Pediatric Transplantation

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Magee JC. Steroids in pediatric kidney transplantation: a balancing act in progress. Am J Transplant. 2010 Jan;10(1):6-7. doi: 10.1111/j.1600-6143.2009.02923.x. Epub 2009 Dec 17.
PMID:19958331
Reference Type:Reference
Citation:Li L, Chang A, Naesens M, Kambham N, Waskerwitz J, Martin J, Wong C, Alexander S, Grimm P, Concepcion W, Salvatierra O, Sarwal MM. Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits. Am J Transplant. 2009 Jun;9(6):1362-72. doi: 10.1111/j.1600-6143.2009.02640.x. Epub 2009 May 13.
PMID:19459814
Reference Type:Results Reference
Citation:Benfield MR, Bartosh S, Ikle D, Warshaw B, Bridges N, Morrison Y, Harmon W. A randomized double-blind, placebo controlled trial of steroid withdrawal after pediatric renal transplantation. Am J Transplant. 2010 Jan;10(1):81-8. doi: 10.1111/j.1600-6143.2009.02767.x. Epub 2009 Jul 28.
PMID:19663893
Reference Type:Results Reference
Citation:McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, Wyatt R, Arar M, Liereman D, Bridges N, Harmon W; CCTPT Study Group. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May;8(5):984-9. doi: 10.1111/j.1600-6143.2008.02167.x.
PMID:18416737

Data Source: ClinicalTrials.gov

Date Processed: April 07, 2020

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