title: Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial.
abstract: The antiviral efficacy of amantadine in patients with chronic hepatitis C is controversial. In this randomized, prospective, placebo-controlled, multicenter trial, triple therapy with interferon alfa (IFN-alpha)-2a plus ribavirin and amantadine (amantadine group) was compared with combination therapy IFN-alpha plus ribavirin (control group). Four hundred previously untreated patients with histologically proven chronic hepatitis C were randomly allocated to treatment with amantadine sulphate (100 mg twice daily orally) or a matched placebo together with IFN-alpha induction plus ribavirin (1,000-1,200 mg/day orally) for 48 weeks. The primary end point was sustained virologic response (SVR) defined as undetectable serum hepatitis C virus (HCV) RNA (<100 copies/mL) 24 weeks after the end of treatment. SVR was observed in 52% of the amantadine group and in 43.5% of the control group (P =.11). Among patients with HCV genotype 1 infection, the corresponding SVR rates were 39% and 31%, respectively. The virologic on-treatment response rate in week 24 was significantly higher in the amantadine group as compared with the control group (70% vs. 59%, respectively, P =.016). This beneficial effect was mainly related to HCV type 1-infected patients (63% vs. 47%, respectively, P =.012). Independent factors associated with SVR, according to multiple logistic regression analysis, were amantadine treatment, low baseline HCV RNA, platelet counts (>/=250/nL), pretreatment ALT quotient >/=3, and GGT level (<28 U/L) as well as HCV genotypes other than 1. In conclusion, although we could not demonstrate a significant advantage of the triple regimen in univariate analysis, multivariate analysis offers arguments that amantadine should be considered as a potential anti-HCV drug in future studies.
authors.affiliation: Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Universitätsklinikum Charité, Campus Virchow-Klinikum, Humboldt-Universität, Berlin, Germany. thomas.berg@charite.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Bernd
authors.initials: B
authors.lastname: Kronenberger
authors.forename: Holger
authors.initials: H
authors.lastname: Hinrichsen
authors.forename: Tilman
authors.initials: T
authors.lastname: Gerlach
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Tobias
authors.initials: T
authors.lastname: Goeser
authors.forename: Samer
authors.initials: S
authors.lastname: Nasser
authors.forename: Karsten
authors.initials: K
authors.lastname: Wursthorn
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Pape
authors.forename: Uwe
authors.initials: U
authors.lastname: Hopf
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010919:Placebos; D011994:Recombinant Proteins; D012254:Ribavirin; D000547:Amantadine; D000410:Alanine Transaminase