Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin
Condition: Chronic Hepatitis C; Hemodialysis
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Pegylated interferon alfa-2a and ribavirin; Pegylated interferon alfa-2a and ribavirin
Intervention description: Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 48 weeks; Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 135 ug/week plus ribavirin (Copegus, F. Hoffman-LaRoche) 200 mg/day for 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: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
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. 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%.

      Although dialysis patients have a higher SVR rate to conventional IFN or pegylated IFN
      monotherapy than patients with normal renal function for HCV therapy. More than half of these
      patients are relapsers or non-responders to IFN monotherapy. Retreatment of HCV-patients with
      normal renal function by combined pegylated IFN alfa plus ribavirin who fail to response to
      IFN monotherapy has achieved a SVR rate of 28%. Based on the long-term favorable outcome in
      dialysis patients who eradicate HCV, the aim of the study is to evaluate the efficacy and
      safety of retreatment by pegylated IFN alfa-2a plus low dose ribavirin in dialysis patients
      who fail to achieve HCV eradication by conventional or pegylated IFN alfa.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Non-responders or relapsers of dialysis patients to conventional interferon or
             pegylated interferon monotherapy

          -  Age 18~65 years old

          -  Creatinine clearance (Ccr) < 10 ml/min/1.73 m2

          -  Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months

          -  Detectable serum quantitative HCV-RNA (Cobas Taqman HCV Monitor v2.0, Roche
             Diagnostics) with dynamic range 25- 391000000 IU/ml

        Exclusion Criteria:

          -  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