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Low Dose Peginterferon and Ribavirin Therapy for Patients With Chronic Hepatitis C Infected With Genotype 2 or 3

Phase 4
18 Years
Not Enrolling
Hepatitis C

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Trial Information

Low Dose Peginterferon and Ribavirin Therapy for Patients With Chronic Hepatitis C Infected With Genotype 2 or 3

Sixty patients with chronic hepatitis C infected with HCV genotype 2 or 3 will be treated
using the combination of either low- or standard dose peginterferon and ribavirin for 24
weeks, with re-treatment using the standard doses and a longer duration (48 weeks) for those
who do not respond to or relapse after initial low dose therapy.

Adult patients with chronic hepatitis C who have HCV genotype 2 or 3 and previously have not
received anti-viral treatment will be given peginterferon alfa-2a (90 or 180 micrograms
weekly by injection) and ribavirin (800 mg daily by mouth). Patients will be monitored at
2- to 4-week intervals for side effects, compliance, complete blood counts, liver
biochemical tests and HCV RNA. Patients becoming HCV RNA negative by week 12 will be
considered on-treatment responders, continue therapy to week 24, and be monitored thereafter
for another 24 weeks. Patients who do not become HCV RNA negative by week 12 as well as
patients who relapse after therapy will be retreated with 180 micrograms of peginterferon
weekly and 800 mg of ribavirin for another 48 weeks.

The primary outcome will be sustained loss of HCV RNA at 24 weeks after low- or
standard-dose combination therapy. Secondary outcomes include viral kinetics and side
effects. Because of preliminary results in the initial 31 patients enrolled in this study,
the dose of peginterferon was changed from 90 to 180 micrograms weekly for the remaining 29
patients to be enrolled, allowing for a direct comparison of efficacy, viral kinetics and
side effects of standard- vs low-dose peginterferon therapy.

This study will evaluate the relative efficacy and safety of the standard versus lower doses
of peginterferon with ribavirin in patients with chronic hepatitis C and HCV genotype 2 or

Inclusion Criteria


Age above 18 years, male or female.

Presence of anti-HCV in serum.

Positive HCV RNA determination in serum.

HCV genotype 2 or 3 as determined by Inno LiPa assay or by direct sequencing. Patients
with mixed genotypes will not be eligible if they have genotypes other than 2 or 3.

Written informed consent.


Previous treatment with interferon alpha or peginterferon.

Decompensated liver disease, as marked by bilirubin greater than 4 mg/dL, albumin less
than 3.0 g/dL, prothrombin time greater than 2 sec prolonged, or history of bleeding
esophageal varices, ascites or hepatic encephalopathy.

Patients with ALT levels greater than 1000 U/L (greater than 25 times ULN) 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 such women, inability
to practice adequate contraception, defined as vasectomy in men, tubal ligation in women,
or use of condoms and spermicidal, or birth control pills, or an intrauterine device.

Significant systemic or major illnesses other than liver disease, including congestive
heart failure, renal failure (creatinine clearance less than 50 ml/min), organ
transplantation, serious psychiatric disease not controlled by psychotropic agents, and
angina pectoris.

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.

Pre-existing, severe bone marrow compromise; anemia (hematocrit less than 30%),
neutropenia (less than 1000 neutrophils/microliter) or thrombocytopenia (less than 70,000

History of hemolytic anemia.

Evidence of another form of liver disease in addition to hepatitis C (for example
hepatitis B, autoimmune liver disease, Wilson's disease, alcoholic liver disease).

Active substance abuse, such as alcohol, inhaled or injection drugs within the previous
six months.

Evidence of hepatocellular carcinoma: either alfa-fetoprotein (AFP) levels greater than 50
ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study) demonstrating
a mass suggestive of liver cancer.

Clinical gout.

HIV infection.

Quiescent or active, serious autoimmune disease such as lupus erythematosus, ulcerative
colitis, Crohn's disease or rheumatoid arthritis that in the opinion of the investigators
might be exacerbated by therapy with alfa interferon.

The use of immunosuppressive medications, including corticosteroids in doses of 10 mg of
prednisone or its equivalent and higher.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Virological Response (Intention to Treat)

Outcome Description:

Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.

Outcome Time Frame:

6 months after stopping therapy

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

March 2003

Completion Date:

June 2010

Related Keywords:

  • Hepatitis C
  • Hepatitis C Virus
  • Antiviral Agents
  • Hemolysis
  • Neutropenia
  • Cirrhosis
  • Hemolytic Anemia
  • Viral Hepatitis
  • Ribavirin
  • Alfa Interferon
  • Pegylated Interferon
  • Hepatitis C
  • HCV
  • Hepatitis
  • Hepatitis A
  • Hepatitis, Chronic
  • Hepatitis C
  • Hepatitis C, Chronic



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892