High Dose Versus Standard Dose of Ribavirin in Patients With Chronic Hepatitis C, Genotype 3

Aims:

• Efficacy 1.1) Rate of RNA-HCV negative at week 4 and 24 in each arm. 1.2) Rate of SVR in each arm.
• 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.

Inclusion criteria

• HCV Genotype 3
• RNA-HCV > > 600.000 IU/ml.
• Compromise to use contraceptive measures on treatment until 6 months after the end of treatment.

Exclusion criteria

• Pregnant or breastfeeding females.
• Concurrent treatment with antineoplastic or immunomodulatory agents, including corticosteroids or radiation therapy over the last 6 months before starting the trial
• Treatment with investigational drugs < 6 weeks before starting the trial
• Chronic liver disease other than hepatitis C.
• Evidence of hepatocellular carcinoma.
• Evidence of carcinoma hepatocellular
• Decompensated liver disease
• Baseline Neutrophil count < 1500/cc; or Platelet count < 90,000/cc
• Baseline Hemoglobin <12 g/dL in females o <13 g/dL in males.
• Increased risk of anemia(Eg, thalassemia, spherocytosis..).
• Ischemic heart disease or cerebrovascular disease.
• Serum creatinine >1.5 times upper limit of normality.
• History of severe psychiatric conditions (Major antidepressives or neuroleptic drugs required for major depression or psychosis), suicide attempts or psychiatric disability .
• History of convulsive disorders.
• Immunological conditions.
• Chronic Obstructive Lung Disease with limited functionality
• Severe heart disease or congestive cardiac insufficiency cardiopathy grave.
• Advanced atherosclerosis
• Solid organ or bone marrow transplant.