Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial

Hepatology. 2002 Feb;35(2):447-54. doi: 10.1053/jhep.2002.31168.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amantadine / adverse effects
  • Amantadine / economics
  • Amantadine / therapeutic use*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / economics
  • Antiviral Agents / therapeutic use*
  • Cost-Benefit Analysis
  • Double-Blind Method
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / economics
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Placebos
  • Recombinant Proteins
  • Treatment Outcome


  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Placebos
  • Recombinant Proteins
  • Amantadine