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Protocol Details

High Dose Ribavirin in Combination with Peginterferon for Patients with Chronic Hepatitis C Genotype 1 Infection Who Have Failed to Respond or Relapsed after Standard Therapy

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

08-DK-0149

Sponsoring Institute

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

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: 65

Referral Letter Required

Yes

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Chronic Hepatitis C

Recruitment Keyword(s)

Chronic Hepatitis C;
Non-Responder

Condition(s)

Chronic Hepatitis C

Investigational Drug(s)

Ribavirin

Investigational Device(s)

None

Intervention(s)

Drug: Peginterferon
Drug: Ribavirin

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

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 eligibile 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.

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Eligibility

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).


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Citations:

Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000 Feb 15;132(4):296-305.

Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. Summary for patients in: Ann Intern Med. 2006 May 16;144(10):I20.

Nainan OV, Alter MJ, Kruszon-Moran D, Gao FX, Xia G, McQuillan G, Margolis HS. Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. Gastroenterology. 2006 Aug; 131(2):478-84.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Marc G. Ghany, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10 RM 10N248D
10 CENTER DR
BETHESDA MD 20814
(301) 402-5115
mg228m@nih.gov

Marc G. Ghany, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10 RM 10N248D
10 CENTER DR
BETHESDA MD 20814
(301) 402-5115
mg228m@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT00735969

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