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Steroid Withdrawal in Pediatric Kidney Transplant Recipients

2016년 10월 19일 업데이트: National Institute of Allergy and Infectious Diseases (NIAID)

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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

연구 개요

상태

종료됨

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (실제)

274

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 멕시코
    • Distrito Federal
      • Mexico City, Distrito Federal, 멕시코, 06720
        • Hospital Infantil de Mexico
  • 미국
    • Alabama
      • Birmingham, Alabama, 미국, 35233
        • University of Alabama
    • California
      • San Diego, California, 미국, 92103
        • UCSD Medical Center
    • Colorado
      • Aurora, Colorado, 미국, 80045
        • Denver Children's Hospital
    • Florida
      • Jacksonville, Florida, 미국, 32209
        • University of Florida Health Science Center
    • Georgia
      • Atlanta, Georgia, 미국, 30322
        • Emory Children's Center
    • Louisiana
      • New Orleans, Louisiana, 미국, 70112
        • Tulane University Medical Center
    • Maryland
      • Baltimore, Maryland, 미국, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, 미국, 02115
        • Children's Hospital of Boston
    • New Mexico
      • Albuquerque, New Mexico, 미국, 87131
        • University of New Mexico Health Science Center
    • New York
      • Buffalo, New York, 미국, 14222
        • The Children's Hospital of Buffalo
      • Valhalla, New York, 미국, 10595
        • Westchester Medical Center
    • Ohio
      • Cleveland, Ohio, 미국, 44106
        • Rainbow Babies and Childrens Hospital
      • Cleveland, Ohio, 미국, 44106
        • University Hospitals of Cleveland
    • Pennsylvania
      • Hershey, Pennsylvania, 미국, 17033
        • Penn State College of Medicine
    • Tennessee
      • Memphis, Tennessee, 미국, 38103
        • LeBonheur Children's Medical Center
    • Texas
      • San Antonio, Texas, 미국, 78207
        • Christopher Goldsbury Center
    • Washington
      • Seattle, Washington, 미국, 98105
        • Children's Hospital and Regional Medical Center
    • Wisconsin
      • Madison, Wisconsin, 미국, 53705
        • University of Wisconsin

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

1일 (어린이, 성인)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 더블

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
의약품: 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.
다른 이름들:
  • 시뮬렉트
  • Anti-CD25 monoclonal antibody, chimeric
의약품: 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).
다른 이름들:
  • CSA
의약품: 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.
의약품: 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.
의약품: Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
의약품: 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.
의약품: 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).
다른 이름들:
  • 트리메토프림/설파메톡사졸
  • TMP SMX
활성 비교기: 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.
의약품: 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.
다른 이름들:
  • 시뮬렉트
  • Anti-CD25 monoclonal antibody, chimeric
의약품: 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).
다른 이름들:
  • CSA
의약품: 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.
의약품: 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.
의약품: Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
의약품: 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.
의약품: 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).
다른 이름들:
  • 트리메토프림/설파메톡사졸
  • TMP SMX

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
기간: At 6 months and 2.5 years post-transplant
At 6 months and 2.5 years post-transplant

2차 결과 측정

결과 측정
기간
Graft and patient survival
기간: Throughout study
Throughout study
Biopsy-proven acute rejection
기간: Throughout study
Throughout study
Renal function, measured by serum creatinine and the calculated creatinine clearances
기간: Throughout study
Throughout study
Hypertension
기간: Throughout study
Throughout study
Cushingoid features
기간: Throughout study
Throughout study
Systolic and diastolic blood pressure levels
기간: Throughout study
Throughout study
Fasting lipid profile
기간: Throughout study
Throughout study

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Institute of Allergy and Infectious Diseases (NIAID)

협력자

Cooperative Clinical Trials in Pediatric Transplantation

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

유용한 링크

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2001년 1월 1일

기본 완료 (실제)

2005년 6월 1일

연구 완료 (실제)

2005년 6월 1일

연구 등록 날짜

최초 제출

2001년 8월 29일

QC 기준을 충족하는 최초 제출

2001년 8월 30일

처음 게시됨 (추정)

2001년 8월 31일

연구 기록 업데이트

마지막 업데이트 게시됨 (추정)

2016년 10월 21일

QC 기준을 충족하는 마지막 업데이트 제출

2016년 10월 19일

마지막으로 확인됨

2016년 10월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

  • DAIT SW01

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

연구 데이터/문서

  1. 개별 참가자 데이터 세트
    정보 식별자: SDY133
    정보 댓글: ImmPort study identifier is SDY133
  2. 연구 프로토콜
    정보 식별자: SDY133
    정보 댓글: ImmPort study identifier is SDY133
  3. Study summary, -design,-demographics, -files et al.
    정보 식별자: SDY133
    정보 댓글: ImmPort study identifier is SDY133

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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