Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin for Treatment-Naïve Hemodialysis Patients With Chronic Hepatitis C
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Peginterferon alfa-2a and ribavirin; Peginterferon alfa-2a
Intervention description: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 24 to 48 weeks (genotype 1: 48 weeks, genotype 2: 24 weeks); Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week for 24 to 48 weeks (genotype 1: 48 weeks, genotype 2: 24 weeks)
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 377.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Chronic hepatitis C; Hemodialysis; Interferon; Ribavirin

Summary:

      Chronic hepatitis C virus (HCV) infection is common in dialysis patients. Interferon
      (IFN)-based treatment for chronic hepatitis C has been the mainstay therapy in
      immunocompetent patients. In dialysis patients, treatment with conventional or pegylated
      interferon has also received much attention recently. Two meta-analyses evaluating the
      efficacy and safety of conventional IFN alfa monotherapy showed that the sustained virologic
      response (SVR) rates were 37% and 33%, respectively; and the corresponding dropout rates were
      17% and 29.6%, respectively.The efficacy and safety of pegylated IFN alfa-2a and 2b in
      treating dialysis patients showed conflicting results, with a more favorable outcome of
      patients treated with pegylated IFN alfa-2a (135-180 μg/week: SVR 33-75%, well tolerated)
      than those treated with pegylated IFN alfa-2b (0.5-1.0 μg/week: SVR 12.5%, poorly tolerated.
      Currently, IFN-based therapy to treatment HCV infection should be initiated in dialysis
      stages, because the use of IFN in RT patients harbors high risks of acute graft rejection,and
      have low response rates under the concomitant use of immunosuppressive agents.

      Ribavirin, which has been used in combination with IFN to treat chronic hepatitis C in the
      general patients and achieve a higher SVR rate than IFN monotherapy, is considered
      contraindicated in dialysis patients with chronic hepatitis C due to the risk of severe
      hemolytic anemia. However, some pilot studies evaluating combined conventional IFN alfa plus
      low dose ribavirin (170-300 mg/day) showed SVR rates of 17%-66% after 24-48 weeks of
      treatment. In addition, a recent study including 6 patients with combination of pegylated IFN
      alfa plus low dose ribavirin also showed a SVR rate of 50%. In this study, treatment with
      pegylated IFN alfa-2a plus low dose ribavirin achieved a higher SVR rate that that with
      pegylated IFN alfa-2b plus low dose ribavirin (100% vs. 25%).

      Based on the long-term favorable outcome in dialysis patients who eradicate HCV, and the
      superior response of pegylated IFN alfa-2a plus low dose ribavirin to pegylated IFN alfa-2b
      plus low dose ribavirin in treating dialysis patients with chronic hepatitis C, the aim of
      the study is to evaluate the efficacy and safety of pegylated IFN alfa-2a plus low dose
      ribavirin versus pegylated interferon alfa-2a alone in treatment naïve dialysis patients with
      chronic hepatitis C.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-65 years old

          -  Creatinine clearance (Ccr) < 15 ml/min/1.73 m2

          -  Anti-HCV (Abbott HCV EIA 3.0, Abbott Diagnostic, Chicago, IL) positive > 6 months

          -  Detectable serum quantitative HCV-RNA (Cobas Taqman HCV test, version 2, Roche
             Diagnostics) with a dynamic range of 25-391000000 IU/ml

        Exclusion Criteria:

          -  Receiving interferon-based therapy for chronic hepatitis C

          -  Severe anemia (hemoglobin < 10 g/dL) or hemoglobinopathy

          -  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)

          -  Autoimmune liver disease

          -  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