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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Hepatitis C, End Stage Renal Disease

Intervention / Treatment
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* Drug: Peginterferon alfa-2a
* Drug: Interferon alfa-2a


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Peginterferon alfa-2a (Pegasys, Hoffmann-LaRoche) 135 ug/week for 24 weeks | Drug: Peginterferon alfa-2a<br>* Peginterferon alfa-2a 135 ug/week for 24 weeks<br>* Other names: Pegasus 135 ug/syringe;|
| Active Comparator: 2<br>Interferon alfa-2a (Roferon, Hoffmann-LaRoche) 3 MU tiw for 24 weeks | Drug: Interferon alfa-2a<br>* Interferon alfa-2a 3 MU tiw for 24 weeks<br>* Other names: Roferon 3 MU/syringe;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, End stage renal disease, Hemodialysis, Interferon, Pegylated interferon