Trial of Peg-interferon Plus Epoetin-alfa for Treatment of Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine if the use of epoetin-alpha will allow patients with chronic hepatitis C virus infection to be treated with higher doses of peginterferon-alpha-2b and ribavirin, thus increasing chances at lower viral levels and raising sustained virologic response.

Detailed Description
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Chronic infection with hepatitis C virus (HCV) leads to cirrhosis, hepatocellular carcinoma and liver failure. The treatment for end stage liver disease is hepatic transplantation. It is therefore important the patients with chronic HCV infection be recognized and treated before they develop advanced disease. The most effective therapy for patients with chronic HCV appears to be the combination of peginterferon-alpha-2b (PEG-Intron) plus ribavirin. Overall, 54% of patients treated with these medications achieve sustained virologic response. Response to therapy is greatly enhanced in those patients who can tolerate this therapy and remain on treatment without the need for dose reduction. The single most common reason for reducing the dose of ribavirin is anemia. Ribavirin causes a dose dependent hemolytic anemia and this side effect is believed to be exacerbated by the marrow suppressive effects of interferon. Preliminary studies have suggested that anemia can be overcome with the use of erythropoetin. The present pilot study will test the hypothesis that treatment with Epoetin-alph will allow patients with chronic HCV to utilize higher doses of ribavirin along with PEG-Intron therapy and that this will lead to a more rapid decline in HCV RNA titer and an increase in sustained virologic response.

Official Title
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An Open-label, Randomized Pilot Study to Compare the Effectiveness of Peginterferon-alfa-2b Plus Ribavirin to Peginterferon-alfa-2b Plus Epoetin-alfa and Two Doses of Ribavirin in the Treatment of Chronic Hepatitis C Virus Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Peginterferon-alpha-2b (PEG-Intron)
* Drug: Ribavirin
* Drug: Epoetin-alpha (Procrit)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV RNA positive in serum HCV genotype 1 Liver histology consistent with chronic HCV performed within 24 months prior to starting medication in this study Exclusion Criteria: Previous interferon treatment Any other cause for liver disease Hemoglobin >10 gm/dl WBC >3,000/cubic mm Platelet count > 80,000/cubic mm Serum albumin < 3.5 gm.dl Conjugated serum bilirubin > 2.0 mg/dl INR > 1.5 Positive HIV test Refusal to use adequate contraception in female subjects or the spouse.sexual partners of male subjects An elevation in TSH (thyroid stimulating hormone). Patients with a pre-existing thyroid disorder may enter the study if their TSH level can be maintained within the normal range. Women who are pregnant or breast feeding. A history of decompensated liver disease defined as presence of ascites, bleeding esophageal or gastric varices or hepatic encephalopathy. Patients with active alcohol/drug use. Patients with active psychiatric disorders which might be exacerbated by interferon therapy including schizophrenia and severe depression. Use of any immune suppressive medications within 3 months of starting interferon therapy. A history of cardiac disease to include recent myocardial infarction or angina. Patients with previous exposure to Procrit, Aranesp, GA_EPO, or any other Epoetin formulations, within 6 months prior to enrollment in this study. Patients with known sensitivity to mammalian cell-derived products. Patients with known hypersensitivity to human albumin. Patients unable to provide informed consent. Any other medical condition which the primary investigator feels might be exacerbated or jeopardise the patient's participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD | Drug: Peginterferon-alpha-2b (PEG-Intron)<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>Drug: Ribavirin<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>|
| Active Comparator: 2<br>PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. | Drug: Peginterferon-alpha-2b (PEG-Intron)<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>Drug: Ribavirin<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>Drug: Epoetin-alpha (Procrit)<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>|
| Active Comparator: 3<br>PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. | Drug: Peginterferon-alpha-2b (PEG-Intron)<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>Drug: Ribavirin<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus ribavirin  13.3 mg/kg QD PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>Drug: Epoetin-alpha (Procrit)<br>* PEG-interferon-alpha-2b 1.5 μg/kg QW plus standard dose ribavirin,  13.3 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week. PEG-interferon-alpha-2b 1.5 μg/kg QW plus high dose ribavirin,  15.2 mg/kg QD, plus erythropoetin (PROCRIT®) 40,000 U/week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean dose of ribavirin utilized in each of the 3 treatment arms will be compared. |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in each group who required a dose reduction of ribavirin |  | 18 months | 
| Rate of virologic response and sustained virologic response observed in each group |  | 18 months | 
| Rate of decline in HCV RNA titer in each group |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Peginterferon, Ribavirin, Procrit, Epoetin-alpha