Interferon Treatment for Patients With Chronic Hepatitis C and End Stage Renal Disease
Condition: Chronic Hepatitis C; End Stage Renal Disease
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      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: 
      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.
    

Intervention name(s): Peginterferon alfa-2a; Interferon alfa-2a
Intervention type(s): Drug; Drug
Intervention description(s): Peginterferon alfa-2a 135 ug/week for 24 weeks; Interferon alfa-2a 3 MU tiw for 24 weeks
Other intervention name(s): Pegasus 135 ug/syringe; Roferon 3 MU/syringe
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Hepatitis C; End stage renal disease; Hemodialysis; Interferon; Pegylated interferon