The HepC Antiviral Long-Term Tx Against Cirrhosis (HALT-C) Trial: A Randomized Controlled Trial to Evaluate the Safety & Efficacy of Long-Term Peginterferon Alpha-2A for Tx of Chronic Hep C in Patients Who Failed to Respond to Previous Interferon Tx

Summary: Adult patients with chronic hepatitis will be enrolled in a multi-center study to evaluate the efficacy of long-term Pegylated Interferon in preventing the progression of liver fibrosis and/or the development of end-stage liver disease. Patients with chronic Hepatitis C who have failed prior Interferon therapy and who have advanced hepatic fibrosis (3+ to 6 on a scale of 0 to 6) will be eligible for enrollment in the protocol. After a medical evaluation and a liver biopsy, patients who qualify for entry into the study will initially receive a 24-week course of Pegylated Interferon (180 mcg/week) and Ribavirin (1000 to 1200 mg/day). During the initial 24-week period of combination therapy, patients will be seen in the outpatient medical clinic for medical interview, physical examinations and blood tests at 2 to 4 week intervals. At 24-weeks, patients will be classified as responders or non-responders based upon the result of HCV RNA testing of serum from the week 20 visit. Responders (HCV RNA negative in serum) will continue on the combination therapy for another 24 weeks (total treatment = 48 weeks). Non-responders (HCV RNA positive in serum) will be randomized to receive monotherapy with Pegylated Interferon (90 mcg/week) or no therapy for 31/2 more years. All non-responders will be readmitted for repeat medical evaluation and liver biopsy at two and four years. At the month 48 endpoint, Pegylated Interferon will be stopped. All patients will be seen for a final clinic visit in 6 months (study month 54).

The primary end point of the study will be the prevention of progression to cirrhosis and/or hepatic decompensation (development of ascites, variceal hemorrhage, spontaneous bacterial peritonitis and hepatic encephalopathy).

The 10 participating Clinical Centers will enroll 900 patients in the randomized phase of the trial. The Liver Diseases Section, NIDDK will plan to enroll between 80 to 100 patients. This will be an important study for defining the optimal management of patients with advanced hepatic fibrosis who have failed interferon therapy as these patients are at greatest risk for the development of cirrhosis, hepatic decompensation and hepatocellular carcinoma.

Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:

• Must be at least 18 years old.
• Positive serology for HCV antibody by a second generation or higher assay.
• Previous interferon preparation treatment utilized either alone or in combination with ribavirin, administered at a minimum dose of 3 mU three times weekly or equivalent, for at least 12 weeks.
• No interferon treatment in the 6 months prior to screen visit # 1.
• Need a documented, non-response to the most recent course of interferon therapy.
• AST or ALT elevation at least once within 6 months of the initial screening visit.
• Liver biopsy, performed at least 6 months following the last course of interferon and within 12 months prior to the baseline visit, to demonstrate, at least, Ishank stage 3 fibrosis.
• All women of child bearing age must be willing to use contraception during this 4 year study.
• All men must be willing to use contraception during the time they are treated with interferon-ribavirin combination therapy and 6 months thereafter.
• No liver histology consistent with any other co-existent cause of chronic liver disease.
• No Child-Turcotte-Pugh score greater than or equal to 7 points or any other history of ascites or hepatic encephalopathy.
• No documented history of bleeding from either esophageal or gastric varices.
• Platelet count of at least 75,000/mm(3)
• Neutrophil count of at least 1,500/mm(3)
• Hematocrit of at least 33%.
• Hemoglobin of at least 11gm/dL.
• No Alpha-fetoprotein greater than 200 ng/mL.
• No evidence of an hepatic mass lesion suspicious for hepatocellular carcinoma.
• No renal insufficiency defined by a serum creatinine greater than 1.5 mg/dL.
• No positive HIV test in the past 12 months.
• No uncontrolled diabetes.
• No hemophilia.
• No patients who have received organs, limbs or bone marrow transplant.
• No patients that require chronic medications such as immunosuppressive medications or Coumadin.
• No patients with active systemic autoimmune disorders.
• No patients with a diagnosed and/or treated malignancy in the past 5 years (except for localized squamous or basal cell cancers treated by local excision).
• No patients with serious cardiac, cerebrovascular or pulmonary disease that would preclude treatment with interferon and/or ribavirin.
• No patients with underlying hematologic abnormalities that would preclude treatment with interferon.
• No patients with a history of seizure disorder that hasn't been well controlled by medication in the past 2 years.
• No breast feeding women.
• No male partners of pregnant women.
• No patients with active alcohol abuse within the past 12 months.
• No patients who have used illegal drugs in the past 2 years.
• No patients with a history of major depression requiring a hospitalization or electroconvulsive therapy.
• No suicide attempt in the past 5 years.
• No schizophrenia or other psychotic disorders, bipolar illness requiring medication, or other severe or poorly-controlled psychiatric disorder that has led to repeated hospitalizations or poor compliance.
• No patients intolerant to previous interferon therapy.
• No patients unable to provide an informed consent.
• No patients unable or unwilling to undergo three liver biopsies over the 4 year trial period.
• No serum bilirubin above 2.5 mg/dL undue to Gilbert's syndrome.
• No patients participating in another clinical trial.
• No conditions, in the opinion of the investigator, that would make the subject unsuitable for enrollment, or could interfere with the subject participating in or completing the protocol.

Special Instructions: Currently Not Provided
Disease Category:  Infectious and Parasitic
Keywords:

• Prevention
• Hepatocellular Carcinoma
• Complications
• Natural History
• Fibrosis

Contacts:

Patient Recruitment and Public Liaison Office, CC.
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Long Distance Calls: 1-800-411-1222
Fax: (301) 480-9793
Electronic Mail:   prpl@mail.cc.nih.gov