Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease

March 5, 2008 updated by: National Taiwan University Hospital

A Pilot Study in Comparing the Efficacy and Safety of Peginterferon Alfa-2a and Interferon Alfa-2a in Treating Patients With End Stage Renal Disease and Chronic Hepatitis C

The treatment response with conventional interferon alpha alone in patients with end stage renal disease and chronic hepatitis C is about 33-39%. However, the drop-out rate is 17-29.6%. Pegylated interferon alpha, a newly developed form of interferon with superior pharmacokinetic profiles, has not been used to treatment these patients. We expect the better treatment response treated with peginterferon alpha than conventional interferon. In addition, we also observe the safety of the two drugs during the study. The goal of the study is to compare the efficacy and safety of the two different treatment regimens in patients with chronic hepatitis C and end stage renal disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis C virus (HCV) infection is common among patients with end stage renal disease (ESRD), with the reported prevalence ranging from 8 to 20% in dialysis patients in developed world. In Taiwan, the estimated prevalence of HCV infection in patients with ESRD who maintain hemodialysis ranges from 20 to 24.7%. Although most studies have provided mild to moderate disease activity and a high proportion of normal alanine aminotransferase (ALT) levels, the frequency of bridging hepatic fibrosis or cirrhosis ranges from 5 to 32%. Several studies have shown that chronic hepatitis C adversely affects the survival in patients with ESRD. After renal transplantation, recipients with HCV have an increased risk of liver-related mortality and morbidity compared with those without HCV. Therefore, eradication of HCV can improve clinical outcome in dialysis patients as well as in patients awaiting renal transplantation.

Combined interferon and ribavirin is the standard therapy in HCV-infected patients with normal renal function. However, ribavirin, which is cleared by the kidneys, may cause severe hemolytic anemia and be dangerous in dialysis patients. Two recent meta-analyses showed that the sustained virological responses were (SVR) 39% and 33%; the drop-out rate were 17% and 29.6% in HCV-infected dialysis patients treated with interferon-alpha 3 MU thrice weekly of varied duration. The response and the drop-out rate were higher than that reported in HCV-infected patients with normal renal function (SVR of 7-16% by interferon-alpha 3 MU thrice weekly for 24 weeks; drop-out rate of 5-9%) due to a lower interferon clearance rate.

Peginterferon alpha-2a (40KD) is a modified form of interferon alpha-2a consisting of a branched polyethylene glycol (PEG) chain covalently bound to interferon alpha-2a. A better response of peginterferon alpha-2a than interferon alpha-2a has been demonstrated in HCV-infected patients with normal renal function, either combined with ribavirin or not, due to the superior pharmacokinetic profiles. The clearance of peginterferon alpha-2a for ESRD patients was about 30-40% lower than that in healthy subjects. A similarly pharmacokinetic profile of peginterferon alpha-2a is observed with 135 μg weekly in dialysis patients compared with 180μg weekly in patients with normal renal function.

We expect that peginterferon alpha-2a is superior to interferon alpha-2a in achieving an increased SVR and decreased drop-out rate in dialysis patients. The goal of the study is to compare the efficacy and safety of the two different treatment regimens in patients with chronic hepatitis C and end stage renal disease.

Study Type

Interventional

Enrollment (Actual)

50

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

  • Taiwan
      • Douliou, Taiwan
        • National Taiwan University Hospital, Yun-Lin branch

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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age between 18 to 65 years old
  • Creatinine clearance (Ccr) < 10 ml/min/1.73 m2
  • Receiving regular hemodialysis
  • Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months
  • Detectable serum HCV-RNA (Cobas Amplicor HCV Monitor v2.0, Roche Molecular Systems, Pleasanton, CA) with dynamic range 600~<500,000 IU/ml

Exclusion Criteria:

  • Neutropenia (neutrophil count, <1,500/mm3)
  • Thrombocytopenia (platelet <90,000/ mm3)
  • Co-infection with HBV or HIV
  • Chronic alcohol abuse (daily consumption > 20 g/day)
  • Decompensated liver disease (Child classification B or C)
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to have contraception

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
Active Comparator: 1
Peginterferon alfa-2a (Pegasys, Hoffmann-LaRoche) 135 ug/week for 24 weeks
Drug: Peginterferon alfa-2a
Peginterferon alfa-2a 135 ug/week for 24 weeks
Other Names:
  • Pegasus 135 ug/syringe
Active Comparator: 2
Interferon alfa-2a (Roferon, Hoffmann-LaRoche) 3 MU tiw for 24 weeks
Drug: Interferon alfa-2a
Interferon alfa-2a 3 MU tiw for 24 weeks
Other Names:
  • Roferon 3 MU/syringe

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Sustained histological response and sustained virological response 6 months after the completion of the intervention
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
The overall tolerance of the two different regimens and the comparison of the rates of side effects
Time Frame: 1 year
1 year

Collaborators and Investigators

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

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Chen-Hua Liu, M.D., Department of Internal Medicine, National Taiwan Univeristy Hospital, Yun-Lin Branch

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2005

Primary Completion (Actual)

June 1, 2006

Study Completion (Actual)

January 1, 2007

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

March 6, 2008

Last Update Submitted That Met QC Criteria

March 5, 2008

Last Verified

June 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 940209

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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