title: No beneficial effect of all-trans retinoic acid in previous non-responder patients with chronic hepatitis C: the ATRACTION study, a phase II randomised trial.
abstract: BACKGROUND
  Preclinical data suggested all-trans retinoic acid (tretinoin) as a potential antiviral agent against chronic hepatitis C infection.
  
  
  OBJECTIVE
  To assess efficacy, safety, and tolerability of tretinoin in combination with peg-interferon and ribavirin in genotype-1 infected patients with prior non-response.
  
  
  METHODS
  We performed an open-label multicentre clinical trial. Patients were randomised to either receive additional tretinoin (45mg/m(2)/day) for 12 weeks (arm A), or peg-interferon and ribavirin alone (arm B). Primary endpoint was the slope of the third phase of viral decline (Mδ) as determined in an established kinetic model known to correlate with treatment outcome. Secondary endpoints were additional kinetic parameters, viral response rates, safety, and tolerability.
  
  
  RESULTS
  27 patients in arm A and 30 patients in arm B were treated per protocol until week 12. Viral kinetic parameters did not differ. Rates of early virological response (>2log10 drop at week 12) were similar (10/27 versus 11/30 patients). In arm A, patients experienced a higher rate and intensity of adverse events, most commonly skin and mucosal dryness, and headache.
  
  
  CONCLUSIONS
  Addition of tretinoin was safe and acceptably well tolerated. However, it did not influence viral kinetics and thus cannot be further considered as a treatment option.
authors.affiliation: Ist Medical Department, University Hospital Mainz, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.forename: Jens M
authors.initials: JM
authors.lastname: Kittner
authors.forename: Jörg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Dietmar M
authors.initials: DM
authors.lastname: Klass
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisenbach
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Rainer
authors.initials: R
authors.lastname: Günther
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Roger
authors.initials: R
authors.lastname: Gösseringer
authors.forename: Anne
authors.initials: A
authors.lastname: Ehrlich
authors.forename: Konrad
authors.initials: K
authors.lastname: Neumann
authors.forename: Daniel
authors.initials: D
authors.lastname: Wachtlin
authors.forename: Martin F
authors.initials: MF
authors.lastname: Sprinzl
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Wulf O
authors.initials: WO
authors.lastname: Böcher
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D014212:Tretinoin / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014212:Tretinoin; C100416:peginterferon alfa-2a