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
Study type: Interventional
Phase: Phase 2

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.

      ...
    

Detailed description: 
      Up to 60 patients with chronic hepatitis C genotype 1 infection who were previously treated
      with standard doses of peginterferon and ribavirin (1000 to 1200 mg daily) but who did not
      have a virological response (non-responders: n=35) or who relapsed after therapy (relapsers:
      n = 25) will be re-treated using peginterferon and higher doses of ribavirin (2000 to 2400 mg
      daily). After medical evaluation, documentation of eligibility and written informed consent,
      patients will be started on therapy with standard doses of peginterferon alfa-2a (180 micro g
      per week) and twice the standard dose of ribavirin (2000 mg daily for patients less than 75
      kg; 2400 mg daily for patients greater than or equal to 75 kg). Viral kinetics will be
      evaluated on the basis of changes in HCV RNA levels during the first 24 weeks of therapy with
      blood sampling done on days 0, 1, and 2 and weeks 1, 2, 3, 4, 8, 12, 16, 20 and 24. Patients
      who fail to decrease levels of HCV RNA by more than 2 log(10) IU/ml by week 12 will be
      considered non-responders and therapy will stop. Similarly, patients who do not become HCV
      RNA negative (less than 10 IU) by week 24 will also be considered non-responders and therapy
      will be discontinued. Patients who do become HCV RNA negative during the first 24 weeks of
      therapy will continue for 48 weeks and be followed for at least 24 weeks thereafter. The
      primary end-point of this study will be a sustained virological response (SVR), which is
      defined by the absence of detectable HCV RNA in serum on treatment and for at least 24 weeks
      after stopping therapy. The SVR rate for re-treatment using conventional doses of
      peginterferon and ribavirin is expected to be less than 5 percent. The estimated rate of SVR
      using peginterferon with high doses of ribavirin is 50 percent for patients with a previous
      relapse and 25 percent for those with a previous non-response. A sample size of 35 patients
      would be needed to achieve statistical significance based upon these estimates of response
      rates for non-responders and 25 patients for relapsers. If none of the first ten
      non-responder patients treated in this protocol achieve an SVR, no more non-responder
      patients will be enrolled and this part of the study will be terminated early. Patients also
      will be monitored closely for side effects of therapy, the major one for ribavirin being
      anemia. Patients who develop anemia will be treated with darbepoietin to maintain a
      hemoglobin level above 10 gm percent. This pilot study is expected to demonstrate whether use
      of high doses of ribavirin is an option for patients who fail to have an adequate response to
      conventional doses of peginterferon and ribavirin for chronic hepatitis C.
    

Intervention name(s): Peginterferon; Ribavirin
Intervention type(s): Drug; Drug
Intervention MeSH terms: Ribavirin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non-Responder; Relapser; High Dose Ribavirin; Peginterferon; Chronic Hepatitis C