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

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• 作者：Peter Ferenci ; Elisabeth Formann ; Hermann Laferl ; Michael Gschwantler ; Franz Hackl ; Harald Brunner ; Rainer Hubmann ; Christian Datz ; Rudolf Stauber ; Petra Steindl-Munda et al.
• 刊名：Journal of Hepatology
• 出版年：2006
• 出版时间：February 2006
• 年：2006
• 卷：44
• 期：2
• 页码：275-282
• 全文大小：182 K

文摘

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 naïve 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-log₁₀; II, 0.8–1.39-log₁₀; III, <0.8-log₁₀; 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 μg/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 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.