Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C (SUSTAIN)

May 5, 2015 updated by: Novartis Pharmaceuticals

A Multi-center, Randomized, Open Label, Controlled Study to Compare the Sustained Virological Response During Treatment With Neoral or Tacrolimus in Maintenance Liver Transplant Recipients Treated With Pegylated Interferon and Ribavirin for Recurrent Hepatitis C

This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruxelles, Belgium, 1070
        • Novartis Investigative Site
  • Brazil
    • CE
      • Fortaleza, CE, Brazil, 60430-270
        • Novartis Investigative Site
    • SP
      • São Paulo, SP, Brazil, 04023-900
        • Novartis Investigative Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • Novartis Investigative Site
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Novartis Investigative Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0W3
        • Novartis Investigative Site
    • Ontario
      • London, Ontario, Canada, N6A 4G5
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M5G 2C4
        • Novartis Investigative Site
  • Colombia
      • Bogotá, Colombia
        • Novartis Investigative Site
    • Cundinamarca
      • Bogotá, Cundinamarca, Colombia, 110111
        • Novartis Investigative Site
  • France
      • Creteil, France, 94000
        • Novartis Investigative Site
      • Lyon Cedex 04, France, 69317
        • Novartis Investigative Site
      • Montpellier, France, 34295
        • Novartis Investigative Site
      • Paris, France, 75012
        • Novartis Investigative Site
      • Toulouse Cedex 4, France, 31054
        • Novartis Investigative Site
      • Villejuif, France, 94800
        • Novartis Investigative Site
  • Germany
      • Frankfurt, Germany, 60590
        • Novartis Investigative Site
      • Hamburg, Germany, 20246
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
      • Muenchen, Germany, 81377
        • Novartis Investigative Site
  • Italy
    • BO
      • Bologna, BO, Italy, 40138
        • Novartis Investigative Site
    • PD
      • Padova, PD, Italy, 35128
        • Novartis Investigative Site
    • UD
      • Udine, UD, Italy, 33100
        • Novartis Investigative Site
  • Korea, Republic of
    • Korea
      • Seoul, Korea, Korea, Republic of, 137-701
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republic of, 120-752
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republic of, 110 744
        • Novartis Investigative Site
      • Seoul, Korea, Korea, Republic of, 135-710
        • Novartis Investigative Site
  • Russian Federation
      • Moscow, Russian Federation, 123182
        • Novartis Investigative Site
      • Moscow, Russian Federation, 129010
        • Novartis Investigative Site
  • Spain
    • Asturias
      • Oviedo, Asturias, Spain, 33006
        • Novartis Investigative Site
    • Castilla y Leon
      • Valladolid, Castilla y Leon, Spain, 47012
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
    • Galicia
      • Santiago de Compostela, Galicia, Spain, 15706
        • Novartis Investigative Site
  • Switzerland
      • Zurich, Switzerland, 8091
        • Novartis Investigative Site
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TT
        • Novartis Investigative Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Novartis Investigative Site
    • California
      • Palo Alto, California, United States, 95128
        • Novartis Investigative Site
      • San Francisco, California, United States, 94143-2205
        • Novartis Investigative Site
    • Florida
      • Gainesville, Florida, United States, 32610
        • Novartis Investigative Site
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7211
        • Novartis Investigative Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Novartis Investigative Site
    • Texas
      • Houston, Texas, United States, 77030
        • Novartis Investigative Site
      • Houston, Texas, United States, 77030-2400
        • Novartis Investigative Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Liver transplantation performed at least 6 months and up to 5 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
  • Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at least 6 months prior randomization
  • Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at screening
  • Indication of treatment with Peg-IFN and ribavirin due to histological evidence of chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to 4 months prior to randomization.

Exclusion criteria:

  • Serum creatinine >150 μmol/L (1.6 7 mg/dL) or eGFR < 50 ml/min (4-variable Modification of Diet in Renal Disease [MDRD Cockcroft-Gault formula])
  • Multi-organ transplant recipients
  • Recent episode of steroid-treated acute rejection (AR) within 3 months prior to randomization, or >1 episode of steroid-treated AR in the last 6 months, or any number of steroid-resistant AR episodes in the last 6 months including evidence of chronic rejection or ductopenia
  • Evidence of conditions that could cause graft dysfunction other than HCV infection
  • Patients with signs of decompensated liver disease, defined as presence of ascites, variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin <3.5g/dL or, total direct bilirubin >1.5mg/dL or, INR >1.5)
  • Co-infection with HIV or Hepatitis B (defined as HBsAg-positive) at screening
  • Use of mTOR inhibitors (everolimus or sirolimus) in the 6 months prior to screening
  • Antiviral treatment for HCV administered at any time after liver transplantation
  • Patients on daily doses of corticosteroids higher than 5 mg/day
  • Patients with fibrosing cholestatic hepatitis
  • Patients with current diagnosis of malignancies, including lymphoproliferative disorders
  • Patients with platelet count <70,000/mm3 or neutrophiles <1,500/mm3
  • History of HCC outside Milan criteria based on radiology or UCSF criteria based on analysis of the explant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoral
Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
Drug: cyclosporin (Neoral)
Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges
Active Comparator: tacrolimus
Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.
Drug: tacrolimus (Prograf)
Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus
Time Frame: Week 24
The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components
Time Frame: Week 80
Efficacy failure (biopsy proven acute rejection (BPAR), graft loss, or death
Week 80
Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline)
Time Frame: Week 80
Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite, Participants showing an increase of Ishak Knodell fibrosis score by at least one level (increase of ≥1)
Week 80
Number of Participants of Rapid Viral Response (RVR)
Time Frame: Week 4
RVR defined as non-detectable HCV RNA 4 weeks after initiation of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Week 4
Number of Participants of Early Viral Response (EVR)
Time Frame: Week 12
EVR defined as non-detectable HCV RNA or a ≥2 logs reduction of HCV RNA at 12 weeks after initiation of antiviral treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Week 12
Number of Participants for the End of Treatment Response (ETR)
Time Frame: Week 80
ETR defined as non-detectable HCV RNA at the completion of AV treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Week 80
Number of Participants of True Non-responder Rate
Time Frame: Week 80
Defined as failure to achieve at least a 2 log reduction of Hepatitis C virus (HCV) RNA. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Week 80
Number of Participants for Relapse Rate
Time Frame: Week 24
Defined as reappearance of detectable Hepatitis C Virus (HCV) RNA at 24 weeks after completion of antiviral treatment when HCV RNA was undetectable at the end of treatment. The HCV RNA detection limit was <15 IU/ml (<1.18 log IU/ml)
Week 24
Number of Participants With Dose Reduction or Discontinuation of Antiviral (AV) Therapy Due to Poor Tolerability at Any Time During the Study for Any Reason
Time Frame: Week 80
Defined as number of patients with dose reduction or discontinuation of AV therapy due to poor tolerability
Week 80

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

May 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

July 13, 2009

First Submitted That Met QC Criteria

July 13, 2009

First Posted (Estimate)

July 14, 2009

Study Record Updates

Last Update Posted (Estimate)

May 22, 2015

Last Update Submitted That Met QC Criteria

May 5, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COLO400A2430
  • 2009-010806-12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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