title: No beneficial effects of amantadine in treatment of chronic hepatitis C patients.
abstract: BACKGROUND
  Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial.
  
  
  OBJECTIVE
  We aimed to examine whether such policy enhances sustained viral response in treatment-naïve patients.
  
  
  METHODS
  297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5 microg/kg/week up to 26 weeks and thereafter, 1.0 microg/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24.
  
  
  RESULTS
  49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p=0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response.
  
  
  CONCLUSIONS
  Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: van Soest
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Schaar
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.forename: Richard A
authors.initials: RA
authors.lastname: de Vries
authors.forename: Nancy A
authors.initials: NA
authors.lastname: van Ooteghem
authors.forename: Bart
authors.initials: B
authors.lastname: van Hoek
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Jan M
authors.initials: JM
authors.lastname: Vrolijk
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Lieverse
authors.forename: Peter
authors.initials: P
authors.lastname: Houben
authors.forename: Annet
authors.initials: A
authors.lastname: van der Sluys Veer
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Marguerite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Karel J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: Greet J
authors.initials: GJ
authors.lastname: Boland
mesh_terms: D000328:Adult; D000547:Amantadine / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D057194:Intention to Treat Analysis; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C417083:peginterferon alfa-2b