Randomized, controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C

J Hepatol. 2003 Oct;39(4):606-13. doi: 10.1016/s0168-8278(03)00298-8.

Abstract

Background/aims: Efficacy and safety of interferon-alpha (IFN-alpha)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C.

Methods: Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-alpha alone or in combination with ribavirin or amantadine were treated with IFN-alpha 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000-1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24.

Results: An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 (P<0.001), low viremia (P=0.011) and only one previous antiviral treatment (P=0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-alpha/ribavirin alone (25 versus 18%, P=0.172).

Conclusions: The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-alpha/ribavirin alone, in particular in patients with low baseline viremia.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Amantadine / administration & dosage
  • Amantadine / adverse effects
  • Amantadine / therapeutic use*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Ribavirin / administration & dosage
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

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