Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin. with or without amantadine in treatment-naive patients with-chronic hepatitis C genotype 1 infection

Background/Aims: Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients. Using a novel design, amantadine was studied in naive genotype I patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin. Methods: Patients enrolled in this randomized, placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity (stratum 1, 24-h HCV-RNA decline >1.4-log(10); II, 0.8-1.39-log(10); III, <0.8-log(10); a reliable means of identifying nonresponders to interferon/ribavirin) and fibrosis grade (F0/1/2 vs. F3/4) at baseline. All patients received peginterferon alfa-2a (40KD) 180 mu g/week plus ribavirin 1000-1200 mg/day and were randomized to receive amantadine 100 mg twice daily (N = 114) or placebo (N = 95) for 48 weeks. Results: Week-24 virological response rates in strata II and III, the primary outcome, were similar in patients treated with amantadine (63.7%) or placebo (65.7%), as were sustained virological response rates at week 72 (46.5 and 51.6%, respectively). Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo. Interferon sensitivity was the only significant predictor of treatment outcome. Conclusions: Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype I patients. Virological response was almost exclusively determined by interferon sensitivity at baseline. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.