title: Randomised, double blind, placebo controlled trial of interferon, ribavirin, and amantadine versus interferon, ribavirin, and placebo in treatment naïve patients with chronic hepatitis C.
abstract: OBJECTIVE
  In this study, we compared the efficacy of triple therapy (interferon alfa, ribavirin, and amantadine) with standard therapy (interferon alfa and ribavirin) in treatment naïve patients with chronic hepatitis C virus (HCV).
  
  
  METHODS
  In this prospective, randomised, double blind, placebo controlled, multicentre study, 85 patients (amantadine group) received a three drug regimen of interferon alfa-2b 3 million units three times per week, ribavirin 1000-1200 mg daily in divided doses, and amantadine 100 mg twice daily, and 86 patients (placebo group) received interferon alfa-2b, ribavirin, and identical placebo. Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction (PCR). All patients were followed for 24 weeks after completion of treatment. The primary end point was undetectable HCV-RNA by PCR at 24 weeks (sustained viral clearance) after completion of treatment.
  
  
  RESULTS
  At the end of treatment, HCV RNA clearance was seen in 32.9% of the amantadine group and 38.4% of the placebo group (p=0.3). Sustained virological response was seen in 24.7% of the amantadine group and in 27.9% of the placebo group by intention to treat analysis; response rate was 30.4% and 34.8%, respectively, in those who completed 24 weeks of treatment. Poor response was seen in both groups among cirrhotics, African-Americans, genotype 1, and those with a higher viral load. By multivariate analysis, genotype 1, high viral load, and low serum albumin were the only predictors of poor response. Addition of amantadine to the standard regimen did not result in any unexpected side effects.
  
  
  CONCLUSIONS
  Response to triple therapy of interferon alfa, ribavirin, and amantadine was similar to standard therapy of interferon alfa and ribavirin. Our results suggest that amantadine has no role in the management of HCV.
authors.affiliation: Division of Gastroenterology and Hepatology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. pjthuluv@jhmi.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Thuluvath
authors.forename: A
authors.initials: A
authors.lastname: Maheshwari
authors.forename: J
authors.initials: J
authors.lastname: Mehdi
authors.forename: K D
authors.initials: KD
authors.lastname: Fairbanks
authors.forename: L L-W
authors.initials: LL
authors.lastname: Wu
authors.forename: L G
authors.initials: LG
authors.lastname: Gelrud
authors.forename: M J
authors.initials: MJ
authors.lastname: Ryan
authors.forename: F A
authors.initials: FA
authors.lastname: Anania
authors.forename: I F
authors.initials: IF
authors.lastname: Lobis
authors.forename: M
authors.initials: M
authors.lastname: Black
mesh_terms: D000328:Adult; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000547:Amantadine