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Liver Fibrosis in Patients Transplanted for Hepatitis C Receiving Either Cyclosporine Microemulsion or Tacrolimus

2011年12月2日 更新者：Novartis Pharmaceuticals

A Multicenter, Randomized, Open-label Study to Compare the Development of Liver Fibrosis at 12 Months After Transplantation for Hepatitis C Cirrhosis in Patients Receiving Either Cyclosporine Microemulsion or Tacrolimus

Following a transplant for hepatitis C cirrhosis, the infection comes back in 70-90% of cases and over time causes fibrosis and eventually cirrhosis of the new liver. The aim of this study was to see if the frequency of liver fibrosis was different with cyclosporine microemulsion than tacrolimus

調査の概要

状態

終了しました

条件

介入・治療

研究の種類

介入

入学 (実際)

361

段階

  • フェーズ 4

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
    • New Jersey
      • East Hanover、New Jersey、アメリカ
        • Novartis Investigative Site
  • スイス
      • Zurich、スイス、8091
        • Novartis Investigational Site

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

18年～75年 (大人、高齢者)

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

  • Reason for transplant is end-stage liver disease due to hepatitis C cirrhosis
  • Patients receiving a first liver transplant from a deceased or living donor
  • Patients in whom biopsies will be possible

Exclusion criteria

  • Recipients of a liver from an hepatitis C virus positive (HCV+), human immunodeficiency virus positive (HIV+) or hepatitis B virus positive (HBV+) donor
  • Patients with any severe coexisting disease or suffering any unstable medical condition or co-infected with HBV or HIV
  • Patients with co-existing alcoholic disease who have not been abstinent for at least 6 months
  • Transplanted for liver cancer exceeding a pre-defined size
  • Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply

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：防止
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
アクティブコンパレータ：Cyclosporin A

The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.

Before enrolling the first patient, each center chose the adjunct immunosuppressive (IS) regimen between:

  • Steroids administered and tapered as per local practice
  • interleukin-2 receptor (IL-2R) antagonists + mycophenolic acid (MPA): Induction with IL-2R antagonists; Dosages were as per center practice. Patients received mycophenolic acid (MPA) no later than 24 hours after reperfusion of the graft. Dosages were as per local practice.

The regimen selected by the center was to be given to all patients enrolled in the trial from this center.
薬：Cyclosporine A
Initial dose of 10-15mg/kg/day either orally, via a nasogastric (NG) tube or intravenously (i.v.) within the first 24 hours post-transplantation.
他の名前：
  • ネオラル
アクティブコンパレータ：Tacrolimus

Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout study period. Throughout the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain C0 tacrolimus concentrations within target ranges.

Before enrolling the first patient, each center chose adjunct immunosuppressive (IS) regimen between:

  • Steroids administered and tapered as per local practice
  • interleukin-2 receptor (IL-2R) antagonists + mycophenolic acid (MPA): Induction with IL-2R antagonists; Dosages were as per center practice. Patients received mycophenolic acid (MPA) no later than 24 hours after reperfusion of the graft. Dosages were as per local practice.

The regimen selected by center was to be given to all patients enrolled in trial from this center.
薬：Tacrolimus
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses either orally or via a nasogastric (NG) tube or intravenously (i.v).

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
メジャーの説明
時間枠
Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant
時間枠：1 year post-transplant
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. Logistic regression on the presence of IK>=2 was applied based on central biopsy readings only.
1 year post-transplant

二次結果の測定

結果測定
メジャーの説明
時間枠
Number of Participants With Combined Endpoint of Death or Graft Loss or Fibrosis Score (FS) ≥ 2
時間枠：1 year post-transplant
The number of participants with combined end point of death or graft loss or presented with a Ishak-Knodell fibrosis score (FS) ≥2 was calculated. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had liver retransplant or died. Assessment of hepatic fibrosis was performed with liver biopsies read centrally. Ishak-Knodell FS was used to stage liver disease; 0=none; 1=portal fibrosis (some); 2=portal fibrosis (most); 3=bridging fibrosis (few); 4=bridging fibrosis (many); 5=Incomplete cirrhosis; 6=cirrhosis. Higher score indicates greater fibrosis.
1 year post-transplant
Number of Participants With Fibrosing Cholestatic Hepatitis
時間枠：1 year post-transplantation
Fibrosing cholestatic hepatitis (FCH) is characterized by progressive jaundice with a rapid decline in liver function leading to liver failure, most often associated with markedly elevated viral levels detected in the bloodstream (e.g. more than 20 times pre-liver transplantation levels) and in the liver tissue as well. The presence of FCH was reported based on the diagnosis given by the investigator.
1 year post-transplantation
Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation
時間枠：1 year post-transplant
Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.
1 year post-transplant
Number of Participants With Treated Acute Rejection, Biopsy Proven Acute Rejection (BPAR), and Sub-clinical Rejection
時間枠：1 year post-transplant
Treated acute rejection is defined as an acute rejection, clinically suspected, whether biopsy-proven or not, which has been treated and confirmed by the investigator according to the response to therapy. BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. A sub-clinical rejection was defined as a rejection identified by center driven biopsy, i.e. a biopsy performed routinely at some pre-defined time points after transplantation as per center practice in the absence of any clinical signs of rejection.
1 year post-transplant
Number of Participants With Combined Endpoint of Death or Graft Loss or Biopsy Proven Acute Rejection (BPAR)
時間枠：1 year post-transplant
BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.
1 year post-transplant
Number of Participants With Death or Re-transplantation Due to Recurrence of Hepatitis C Cirrhosis
時間枠：1 year post-transplant
Cirrhosis was resulted due to the recurrence of the hepatitis C virus infection in the transplanted liver.
1 year post-transplant
Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant (Intent to Treat Population)
時間枠：1 year post-transplant
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis.
1 year post-transplant
Mean Value of Liver Function Tests at 1 Year Post-transplantation
時間枠：1 year post-transplant

The mean value (in Units per liter, IU/L) of following tests were calculated at 1 year post-transplant:

  • Serum glutamic pyruvic transaminase (SGPT)
  • Serum Glutamic Oxaloacetic Transaminase (SGOT)
  • Bilirubin
  • Alkaline Phosphate
  • γ-Glutamyltransferase (GGT)
1 year post-transplant
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
時間枠：Pre-transplant (Day 1), Day , Day 8, Day 29, Month 6 and 12 post- transplant
HCV RNA was measured (IU/µL)centrally pre-transplant (Day 1) and at 48 hours (Day 3), Day 8 and 29, Month 6 and 12 post-transplant and concomitantly to any additional biopsies performed.
Pre-transplant (Day 1), Day , Day 8, Day 29, Month 6 and 12 post- transplant
Percentage of Participants With an Increase of at Least 1 Stage in Fibrosis
時間枠：Between 1 and 2 years
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. An increase of at least 1 stage demonstrated a worsening of the disease, i.e. the transition from one score to the next higher one.
Between 1 and 2 years
Mean Fibrosis Score
時間枠：At 1and 2 years and its evolution over time
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. The mean score was equivalent to mean of IK at 1 and 2 years (evolution over time).
At 1and 2 years and its evolution over time

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

Novartis Pharmaceuticals

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

2006年1月1日

一次修了 (実際)

2010年9月1日

試験登録日

最初に提出

2005年11月30日

QC基準を満たした最初の提出物

2005年11月30日

最初の投稿 (見積もり)

2005年12月1日

学習記録の更新

投稿された最後の更新 (見積もり)

2011年12月6日

QC基準を満たした最後の更新が送信されました

2011年12月2日

最終確認日

2011年12月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • COLO400A2426

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