title: Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial.
abstract: Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00803309.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heidrich
authors.affiliation: Gastroenterological Practice, Frankfurt, Germany.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Cordes
authors.affiliation: Department of Internal Medicine II, University of Würzburg, Würzburg, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Klinker
authors.affiliation: Medical Practice, Leberzentrum, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Möller
authors.affiliation: Center for Addiction-Medicine, Hepatology and HIV, Praxiszentrum Kaiserdamm, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Naumann
authors.affiliation: Praxiszentrum Gastroenterologie, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rössle
authors.affiliation: Department of Internal Medicine, Hospital Altötting-Burghausen, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kraus
authors.affiliation: Medical Practice, Hannover, Germany.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Böker
authors.affiliation: Medical Practice, Minden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Roggel
authors.affiliation: Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
authors.affiliation: IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St Georg, Hamburg, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stoehr
authors.affiliation: Medical Practice, Stuttgart, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trein
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Hardtke
authors.affiliation: Institute of Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gonnermann
authors.affiliation: Institute of Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; HepNet Study-House, German Liver Foundation, Hannover, Germany; German Center for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
mesh_terms: D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D012254:Ribavirin