title: 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 infection.
abstract: OBJECTIVE
  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 microg/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.
authors.affiliation: Department of Internal Medicine IV, Medical University, Vienna, Austria. peter.ferenci@meduniwien.ac.at
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Formann
authors.forename: Hermann
authors.initials: H
authors.lastname: Laferl
authors.forename: Michael
authors.initials: M
authors.lastname: Gschwantler
authors.forename: Franz
authors.initials: F
authors.lastname: Hackl
authors.forename: Harald
authors.initials: H
authors.lastname: Brunner
authors.forename: Rainer
authors.initials: R
authors.lastname: Hubmann
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.forename: Petra
authors.initials: P
authors.lastname: Steindl-Munda
authors.forename: Harald H
authors.initials: HH
authors.lastname: Kessler
authors.forename: Anton
authors.initials: A
authors.lastname: Klingler
authors.forename: Alfred
authors.initials: A
authors.lastname: Gangl
mesh_terms: D000328:Adult; D000547:Amantadine / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011788:Quality of Life; D012367:RNA, Viral / Q000235:genetics*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C100416:peginterferon alfa-2a