High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      The rate of sustained virological response (SVR) in patients with chronic hepatitis C,
      genotype 3, high viral load and without rapid virological response (RNA-HCV negative at week
      4) is low. Standard of care of these patients include treatment with weekly peginterferon
      plus 800 mg/day of ribavirin (RBV). Extended treatment to 48 weeks does not provide more
      clinical benefit than the standard duration. The main hypothesis is that higher dose of
      ribavirin may be better in terms of SVR than the standard dose.
    

Detailed description: 
      Aims:

        1. Efficacy 1.1) Rate of RNA-HCV negative at week 4 and 24 in each arm. 1.2) Rate of SVR in
           each arm.

        2. Safety 2.1) Rate of adverse effects in each arm.

      Design: Randomized controlled trial.

      Patients will be randomly allocated into three arms:

      Arm A : Peginterferon α-2a (180 μg/week)SC. plus Ribavirin (800 mg/day) p.o. over 24 weeks.

      Arm B: Peginterferon α-2a (180 μg/week) plus Ribavirin (1600 mg/day) with support of Epoetin
      β (450 IU/kg/week) SC over 4 weeks:

      B1.- If RNA-HCV undetectable at week 4, standard of care will be continued (Peginterferon
      α-2a, 180 μg/wee plus Ribavirin (800 mg/day) over 20 additional weeks).

      B2.- If RNA-HCV were detectable at week 4, treatment will be continued with peginterferon
      α-2a (180 μg/week) plus RBV(1,600 mg/day) plus Epoetin β (450 UI/kg/week) over 20 additional
      weeks.

      Sample size: 111 patients. To increase the SVR from 50% to 75%. Beta: 0.1; alfa: 0.05; Loss:
      15%.

      Randomization will be 1:2, 37 patients in Group A and 74 patients in group B.
    

Intervention name(s): Peginterferon alfa 2 A; Peginterferon alfa 2 A, ribavirin + Epo Beta; ribavirin; ribavirin; Peginterferon alfa 2; ribavirin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 800 mg/day po (Control Group) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epoetin β (450 IU/kg/week) SC over 4 weeks (Arm B1) Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day po plus Epo beta 450 UI over four weeks (Arm B1) If RNA-HCV positive at week 4, Peginterferon alfa 2 A 180 mcg/week SC plus Ribavirin 1,600 mg/day plus Epo beta 450 UI to keep Hb>12 g/dL if required over 20 additional weeks (Arm B2); Ribavirin 1,600 mg/day plus peginterferon alfa 2A 180 mcg/week plus Epo beta 450 IU/Kg/day to maintain Hb>12g/dl over 4 or 24 weeks; RBV 1600 mg/day 24 weeks; ribavirin 800 mg/day for 24 weeks; Peginterferon alfa 2 a 180 mcg/week for 4 weeks and then peginterferon alfa 2A for 20 weeks; RBV 1600 mg/day 4 weeks and then ribavirin 800 mg/day 20 weeks
Other intervention name(s): Pegasys; Pegasys; peginterferon alfa 2 a; Epoetin beta; Pegasys; Pegasys; Pegasys
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a; Interferon-alpha
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Hepatitis C; Genotype 3; High viral load