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 Keyword(s):
None
Condition(s):
Chronic Hepatitis C
Investigational Drug(s):
Ribavirin
Investigational Device(s):
None
Intervention(s):
None
Supporting Site:
N/A

Contact(s):
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@...

Citation(s):
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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