Retreatment of Dialysis Patients With Chronic Hepatitis C With Pegylated Interferon Alfa-2a Plus Low Dose Ribavirin

• Status: Completed
• Trial end date: 2008-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Collaborators: Department of Health, Executive Yuan, R.O.C. (Taiwan); National Science Council, Taiwan
• Treatments: Interferon alpha-2; Interferon-alpha; Interferons; Peginterferon alfa-2a; Ribavirin

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