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
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Chronic hepatitis C virus (HCV) infection is common in dialysis patients, with the reported
      prevalence varying from 3% to 80% worldwide. (1-3) Although these patients usually have mild
      symptoms and moderate elevation of alanine transaminase levels, recent international
      collaborative survey and prospective studies found that anti-HCV seropositivity and positive
      HCV RNA were risk factors for mortality and hepatocellular carcinoma (HCC). (4-7)
      Furthermore, progressive hepatic fibrosis, poor patient and graft survival were observer in
      dialysis patients with HCV infection who undergo renal transplantation (RT), suggesting
      immunosuppression following RT may worsen the course of hepatic fibrosis and renal graft
      function. (8-13) These lines of evidence indicate that HCV infection in the dialysis
      population is an important issue to be tackled.

      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.(14,15) 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),
      (16-21) which may result from different pharmacokinetic profiles between these two pegylated
      IFNs. 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,(22,23) and have low response rates under the concomitant use of immunosuppressive
      agents. (24,25) 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. (26-28) 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%. (29) 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 in treatment naïve dialysis patients with chronic hepatitis C.
    

Intervention name(s): Peginterferon alfa-2a and ribavirin; Peginterferon alfa-2a
Intervention type(s): Drug; Drug
Intervention description(s): 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)
Other intervention name(s): Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche); Ribavirin (Copegus, F. Hoffman-LaRoche); Pegylated interferon alfa-2a (Pegasys, F. Hoffman-LaRoche)
Intervention MeSH terms: Interferons; Ribavirin; 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; Hemodialysis; Interferon; Ribavirin