title: Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial.
abstract: Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.
authors.affiliation: Division of Gastroenterology & Hepatology, University Hospital, Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Helbling
authors.forename: Ivan
authors.initials: I
authors.lastname: Stamenic
authors.forename: Francesco
authors.initials: F
authors.lastname: Viani
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Gonvers
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Dufour
authors.forename: Jurg
authors.initials: J
authors.lastname: Reichen
authors.forename: Gieri
authors.initials: G
authors.lastname: Cathomas
authors.forename: Michael
authors.initials: M
authors.lastname: Steuerwald
authors.forename: Jan
authors.initials: J
authors.lastname: Borovicka
authors.forename: Markus
authors.initials: M
authors.lastname: Sagmeister
authors.forename: Eberhard L
authors.initials: EL
authors.lastname: Renner
mesh_terms: D000328:Adult; D000547:Amantadine / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010919:Placebos; D011994:Recombinant Proteins; D000547:Amantadine