title: Safety and efficacy of viramidine versus ribavirin in ViSER2: randomized, double-blind study in therapy-naive hepatitis C patients.
abstract: OBJECTIVE
  Pegylated interferon (peg-IFN) plus ribavirin (standard of care for chronic hepatitis C virus [HCV]), can cause dose-limiting anemia in up to 22% of patients. Viramidine is associated with a lower incidence of anemia because of its liver-targeting properties.
  
  
  METHODS
  The efficacy and safety of viramidine versus ribavirin plus peg-IFN alfa-2a was assessed in patients with HCV. Randomized patients received peg-IFN alfa-2a 180 mcg with viramidine 600 mg twice daily or weight-based doses of ribavirin 1000 or 1200 mg/day. Treatment duration was based on HCV ribonucleic acid (RNA) genotype: genotype 2/3 and non-2/3 patients were treated for 24 and 48 weeks, respectively. The primary efficacy end point was the non-inferiority of viramidine versus ribavirin (proportion of patients achieving sustained virologic response at week 24). The primary safety end point was the proportion of patients experiencing a hemoglobin event.
  
  
  RESULTS
  In total, 962 patients received peg-IFN alfa-2a with viramidine (n=644) or ribavirin (n=318). Sustained virologic response was achieved in 40% of viramidine-treated patients and 55% of ribavirin-treated patients (difference of proportions 0.150 [95% CI, 0.09, 0.21]). Improved efficacy was seen with higher viramidine exposure on a mg/kg basis. Viramidine was significantly superior to ribavirin in hemoglobin event rates (54% vs. 80%; p<0.001). Adverse event rates were similar between groups except for diarrhea (viramidine 29.5%; ribavirin 15.7%; p<0.0001).
  
  
  CONCLUSIONS
  Viramidine 600 mg BID did not meet the primary efficacy non-inferiority end point but met the safety end point. Determination of a viramidine dosage that would yield superior efficacy over ribavirin is needed.
authors.affiliation: Hôpital Beaujon, Clichy, France. patrick.marcellin@bjn.ap-hop-paris.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gish
authors.forename: Norman
authors.initials: N
authors.lastname: Gitlin
authors.forename: Jamie
authors.initials: J
authors.lastname: Heise
authors.forename: Deanine G
authors.initials: DG
authors.lastname: Halliman
authors.forename: Eric
authors.initials: E
authors.lastname: Chun
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
mesh_terms: D000328:Adult; D000740:Anemia / Q000453:epidemiology / Q000517:prevention & control; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003967:Diarrhea / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a; C026956:taribavirin