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Steroid Withdrawal in Pediatric Kidney Transplant Recipients

2016年10月19日 更新者：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 Doctors believe steroids might be safely withdrawn in patients that are receiving other maintenance therapies.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 This study evaluates whether steroid therapy can be withdrawn in a way that does not increase graft rejection.

調査の概要

状態

終了しました

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (実際)

274

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

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

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

1日～20年 (子、大人)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：ダブル

武器と介入

参加者グループ / アーム
介入・治療
実験的：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.
薬：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.
他の名前：
  • シムレクト
  • Anti-CD25 monoclonal antibody, chimeric
薬：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).
他の名前：
  • CsA
薬：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.
薬：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.
薬：Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
薬：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.
薬：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).
他の名前：
  • トリメトプリム/スルファメトキサゾール
  • TMP SMX
アクティブコンパレータ：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.
薬：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.
他の名前：
  • シムレクト
  • Anti-CD25 monoclonal antibody, chimeric
薬：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).
他の名前：
  • CsA
薬：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.
薬：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.
薬：Methylprednisolone
Administered at 10 mg/kg intravenously perioperatively and on postoperative day 1.
薬：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.
薬：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).
他の名前：
  • トリメトプリム/スルファメトキサゾール
  • TMP SMX

この研究は何を測定していますか？

主要な結果の測定

結果測定
時間枠
Growth, measured as change in standardized height from 6 month to 2.5 years post-transplantation
時間枠：At 6 months and 2.5 years post-transplant
At 6 months and 2.5 years post-transplant

二次結果の測定

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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

National Institute of Allergy and Infectious Diseases (NIAID)

協力者

Cooperative Clinical Trials in Pediatric Transplantation

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

便利なリンク

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始

2001年1月1日

一次修了 (実際)

2005年6月1日

研究の完了 (実際)

2005年6月1日

試験登録日

最初に提出

2001年8月29日

QC基準を満たした最初の提出物

2001年8月30日

最初の投稿 (見積もり)

2001年8月31日

学習記録の更新

投稿された最後の更新 (見積もり)

2016年10月21日

QC基準を満たした最後の更新が送信されました

2016年10月19日

最終確認日

2016年10月1日

詳しくは

本研究に関する用語

追加の関連 MeSH 用語

その他の研究ID番号

  • DAIT SW01

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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.

試験データ・資料

  1. 個人参加者データセット
    情報識別子：SDY133
    情報コメント：ImmPort study identifier is SDY133
  2. 研究プロトコル
    情報識別子：SDY133
    情報コメント：ImmPort study identifier is SDY133
  3. Study summary, -design,-demographics, -files et al.
    情報識別子：SDY133
    情報コメント：ImmPort study identifier is SDY133

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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