Protocol Number: 99-DK-0042

Title:

Long-Term Therapy with Ribavirin for Chronic Hepatitis C

Number:

99-DK-0042

Summary:

Chronic hepatitis C is a disease of the liver caused by the hepatitis C virus. The disease can be serious and even fatal. Approximately 25% of patients with chronic hepatitis C will develop cirrhosis and some of these patients will develop cancer of the liver or liver failure.

Presently the disease is treated with a combination of alpha interferon or peginterferon (antiviral and immune stimulating drugs) and ribavirin (an antiviral drug). Alpha interferon is given by injection three times a week whereas peginterferon is given by injection only once a week. Ribavirin is given as a tablet by mouth twice a day. The combination therapy is given for 6 to months. About half of the patients given these medications will receive a lasting benefit and many patients do not respond well to the combination therapy.

This study will select up to 50 patients will chronic hepatitis C who have not responded to combination therapy or who could not stand the side effects associated with interferon or peginterferon therapy. These subjects will be evaluated and undergo liver biopsy to determine their present liver condition. If selected as subjects they will be started on single drug therapy with ribavirin. The drug will be given orally twice a day at a dose based on the patient's body weight.

The patients will be followed on an out-patient basis. They will we asked to return for regular check-ups and blood tests every 2 to 8 weeks for the duration of the study. After 6 months, the medication will be stopped or adjusted based on the results of the subject's blood tests (liver enzymes). A response is considered if a decrease of 50% or more of the initial liver enzyme (alanine aminotransferase, ALT) is noted. A complete response will be considered if liver enzymes return to normal levels.

Therapy will be discontinued after 6 months if patients do not respond. However, patients that respond to the single drug therapy will continue to receive the medication at a decreased dose. The patients will remain on an appropriate dose for up to 8 years with repeat liver biopsies at 2, 4 and 8 years to assess progress.

This study will determine if long-term therapy with ribavirin is safe and effective.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Age above 18 years, male or female.

Elevated alanine (ALT) or asparate (AST) aminotransferase activities averaging at least twice the upper limit of normal on three determinations taken at least one month apart during the previous 6 months. The mean of these three determinations will be defined as "baseline" ALT and AST levels.

Presence of anti-HCV and HCV RNA in serum tested at least once during the previous six months.

Evidence of chronic hepatitis on liver biopsy done within the previous 12 months with a histology activity index of at least 6 (out of a maximum of 22).

Contraindications to the use of alpha interferon, either in the form of specific contraindications to its use (depression, psychiatric illness, neurological impairment, severe thrombocytopenia, autoimmune disease), or the history of severe side effects or intolerance during a previous course of alpha interferon, or lack of a sustained virological (sustained lost of HCV RNA from serum for more than six months after stopping treatment) response to an adequate course (6 months) of the combination of alpha interferon and ribavirin or (after September 1, 2003) the combination of peginterferon and ribavirin.

Written informed consent.

INCLUSION CRITERIA FOR PATIENTS IN 98-DK-0003:

An important group of patients who were enrolled in the current study, were patients who participated in the Clinical Research Protocol 98-DK-0003 (Combination of alpha interferon with long-term ribavirin for patients with chronic hepatitis C) and who did not have a sustained virological response to this treatment. These patients were eligible to enroll into the current study once they had finished the therapy and follow up period in that trial. These patients fit the inclusion criteria listed above with one exception: some patients were receiving ribavirin monotherapy as a part of their participation in 98-DK-0003. These patients were eligible to be immediately enrolled into this study without a medication-free period in between.

EXCLUSION CRITERIA:

Pregancy or, in women of childbearing potential, inability to practice adequate contraception. Men with spouses or sexual partners of childbearing potential also be excluded if they are unable to practice adequate contraception.

Significant systemic illnesses other than liver disease, including a history of congestive heart failure, cerebral vascular disease, renal failure (creatinine clearance less than 50 ml/min), and angina pectoris.

Patients with an abnormal stress test or carotid untrasound will not be enrolled into this study.

Pre-existing anemia (hematocrit less than 32%) or known history of hemolytic anemia.

Interferon or immunosuppressive therapy within the last 6 months.

Evidence of another form of liver disease in addition to viral hepatitis, such as autoimmune or alcoholic liver disease.

Active or recent (within one year) alcohol or drug abuse or psychiatric illness that is likely to interfere with compliance and requirements for safety monitoring during this study.

Special Instructions: Currently Not Provided

Keywords:

Ribavirin

Liver Disease

Antiviral Agent

Cirrhosis

Chronic Hepatitis

Iron

Viral Hepatitis

Hepatitis C Virus

Hemolytic Anemia

Hemolysis

Recruitment Keywords:

None

Conditions:

Chronic Hepatitis C

Investigational Drug(s):

Ribavirin

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Hepatitis C: the clinical spectrum of disease

Hepatitis C and hepatocellular carcinoma

Ten-year follow up after interferon-alpha therapy for chronic hepatitis C

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