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.

Author(s): Ferenci P, Formann E, Laferl H, Gschwantler M, Hackl F, Brunner H, Hubmann R, Datz C, Stauber R, Steindl-Munda P, Kessler HH, Klingler A, Gangl A, For The Austrian Hepatitis Study Group

Affiliation(s): Department of Internal Medicine IV, Medical University, Vienna, Austria.

Publication date & source: 2006-02, J Hepatol., 44(2):275-82. Epub 2005 Nov 7.

Publication type:

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 1 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 I, 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) 180mug/week plus ribavirin 1000-1200mg/day and were randomized to receive amantadine 100mg 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 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.