High-Dose Ribavirin and Peginterferon to Treat Chronic Hepatitis C Genotype 1
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Peginterferon; Ribavirin
Intervention MeSH terms: Ribavirin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Non-Responder; Relapser; High Dose Ribavirin; Peginterferon; Chronic Hepatitis C

Summary:

      This study will evaluate the effectiveness of an experimental treatment regimen for hepatitis
      C (HCV). Standard treatment consists of combination therapy with ribavirin, taken by mouth
      twice a day, and Peginterferon, injected under the skin once a week. Hepatitis C genotypes 2
      and 3 have a high success rate with this regimen, while genotype 1 is more difficult to
      treat. This study will determine if patients with genotype 1 respond better to treatment that
      uses a higher dose of ribavirin than the standard approved dose of 1,000 to 1,200 mg daily.

      Patients 18 years of age and older with chronic hepatitis C genotype 1 who have not been
      successfully treated with a standard course of Peginterferon and ribavirin may be eligible
      for this study. Participants eligible will receive Peginterferon plus twice the standard dose
      of ribavirin (2,000 to 2,400 mg daily) for 48 weeks. In addition to treatment, all patients
      receive undergo the following:

      Before Treatment:

        -  Medical history and physical examination, symptom questionnaires, blood tests, urine
           collection, chest x-ray, electrocardiogram, liver ultrasound, Fibroscan (ultrasound to
           measure stiffness of the liver) and pregnancy test for women who are able to have
           children.

        -  Patients with other medical conditions or special risk factors may have further
           evaluations before starting treatment. These may include, for example, eye evaluation
           for patients with diabetes, exercise stress test for people over age 40 or who have risk
           factors for heart disease and psychiatric evaluation for people who have depression or
           anxiety disorder.

      During Treatment

        -  Periodic blood tests to monitor blood counts and viral levels.

        -  Outpatient clinic visits every 4 weeks for the duration of the study for laboratory
           tests and review of symptoms and treatment side effects. Physical examinations and urine
           tests are done every 12 weeks.

      Following Completion of Treatment

      About 1 1/2 years after starting treatment, subjects are re-evaluated as they were at the
      start of treatment.

      ...
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Age 18 years or above, male or female

        Documented relapse or non-response to a prior adequate course of peginterferon and
        ribavirin

        Genotype 1 HCV as determined by probe specific hybridization (Inno-Lipa assay).

        Written informed consent.

        EXCLUSION CRITERIA:

        Age greater than 65 years

        If cirrhosis is present, decompensated liver disease, as marked by serum bilirubin greater
        than 4 mg percent, albumin less than 3.0 gm percent, prothrombin time greater than 2 sec
        prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy.

        Serum Alanine transaminase (ALT) or Aspartate transaminase (AST) levels greater than 1000
        U/L (greater than 25 times the ULN). Such patients will not be enrolled but may be followed
        until three determinations are below this level.

        Pregnancy or, in women of child bearing potential or in spouses of pregnant women,
        inability to practice adequate contraception, defined as vasectomy in men, tubal ligation
        in women, or use of condoms and spermicide, or birth control pills, or an intrauterine
        device.

        Breastfeeding.

        Significant systemic or major illnesses including congestive heart failure, organ
        transplantation, serious psychiatric disease or depression, human immunodeficiency virus
        (HIV) infection, and angina pectoris.

        Previous intolerance of weight based ribavirin dose (1,000-1,200 mg daily) including need
        for dose reduction, use of erythropoietin or serious adverse event attributable to
        ribavirin use.

        Renal insufficiency (creatinine clearance less than 60 ml/min) or renal failure

        Pre existing anemia (hematocrit less than 34 percent) or known history of hemolytic anemia.

        Uncontrolled hypertension or diabetes mellitus

        Other antiviral therapy within the last 6 months.

        Immunosuppressive therapy with either corticosteroids (more than 5 mg of prednisone daily)
        or major immunosuppressive agents (such as azathioprine or 6-mercaptopurine).

        Evidence of another form of liver disease in addition to viral hepatitis (for example
        autoimmune liver disease, Wilson disease, alcoholic liver disease, hemochromatosis, alpha 1
        antitrypsin deficiency).

        Evidence of coronary artery disease or cerebral vascular disease, including abnormalities
        on exercise stress testing in patients with defined risk factors who will be screened for
        evidence of underlying coronary artery disease.

        Active substance abuse, such as alcohol, inhaled or injection drugs within the previous
        year.

        Evidence of hepatocellular carcinoma; either alpha-fetoprotein (AFP) levels greater than
        200 ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study)
        demonstrating a mass suggestive of liver cancer.

        Clinical gout.

        Active, serious autoimmune disease, such as lupus erythematosis, ulcerative colitis, Crohn
        s disease or rheumatoid arthritis that in the opinion of the investigators might be
        exacerbated by therapy with peginterferon.

        Uncontrolled thyroid disease

        Evidence if severe retinopathy or clinically relevant ophthalmological disorder (only
        patients with pre-existing hypertension or diabetes will undergo an ophthalmological
        assessment).