title: Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.
abstract: BACKGROUND
  Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV).
  
  
  OBJECTIVE
  To assess the impact of high doses of RBV on SVR in patients with G3 and HVL.
  
  
  METHODS
  Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13).
  
  
  RESULTS
  RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%.
  
  
  CONCLUSIONS
  G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (Clin Trials Gov NCT00830609).
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain. Electronic address: cfernandez@fhalcorcon.es.
authors.forename: Conrado M
authors.initials: CM
authors.lastname: Fernández-Rodríguez
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Morillas
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Masnou
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Navarro
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Bárcena
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: González
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Martín-Martín
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Poyato
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Miquel-Planas
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Jorquera
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Casanovas
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Salmerón
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Solà
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Alonso
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Planas
authors.affiliation: Hospital Universitario Fundacion Alcorcon, Unit of Gastroenterology and Hepatology, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000188:drug therapy / Q000821:virology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: Chronic hepatitis C; Genotype 3; HCV; Hepatitis crónica C; Rapid virological response; Respuesta virológica rápida; Respuesta virológica sostenida; Ribavirin; Ribavirina; Sustained virological response; VHC; VHC genotipo 3