Individualized Duration of Peg-interferon/Ribavirin Treatment of Hepatitis C

Study Overview
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Brief Summary
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The purpose of the study is to investigate if the duration of treatment of hepatitis C with pegylated interferon and ribavirin can be individualized on the basis of how fast the hepatitis C virus concentration in the blood decreases, and if this is more cost-efficient than standard treatment.

Detailed Description
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The current standard regimen for patients with chronic hepatitis C virus (HCV) infection, i.e., 48 weeks of pegylated interferon and ribavirin, needs to be further improved because of high costs and side-effects; in addition, the treatment is curative in only 50% of patients with genotype 1 of HCV. According to the current guidelines treatment with pegylated interferon and ribavirin is given for 24, 48 or 72 weeks depending on the time point when HCV-RNA becomes undetectable (week 4, 12 or 24). Patients with a very poor response may also be identified by applying a stopping rule at week 12 and 24. Still, most patients are treated for 48 weeks and a substantial number of those relapse after discontinuation. In this study, standard treatment is compared with tailored treatment, when the treatment duration is based on the time point when HCV RNA level is calculated to be 1 copy/mL, according measurements of HCV RNA on day 14, 21, 28 and 49. This arm also includes an earlier stopping rule: If the HCV RNA does not decline significantly between day 14 and 28, treatment is stopped after 5 weeks. The advantage of tailored treatment is hypothesised to be that unnecessary side-effects and costs are avoided by an earlier identification of non-response and a treatment duration that is optimised for each patient.

Official Title
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Tailored Treatment of Hepatitis C Genotype 1

Conditions
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Chronic Hepatitis C, Genotype 1

Intervention / Treatment
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* Drug: Peg-interferon-alfa2a (Pegasys)
* Drug: Ribavirin (Copegus)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Anti-HCV positive for > 6 months Genotype 1 Clinical indication for treatment, preferably a liver biopsy showing significant inflammation and/or fibrosis Negative pregnancy test (for fertile women) Exclusion Criteria: Pregnancy or breast-feeding Antiviral or immune modulating treatment the last 6 months Hepatitis B or HIV infection (HBsAg, anti-HIV) Other significant chronic liver disease History of bleeding esophageal varices or other signs of decompensation Neutrophiles < 1.0 x 109/L or platelets < 50 x 109/L. S-creatinine > 2 x ULN History of severe psychiatric disorder Autoimmune disease, severe heart disease, previous organ or stem cell transplantation, malignancy, thyroid disease, severe retinopathy Drug abuse, current or during the last year

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: Standard of care<br>Treatment with Pegasys 180 µg/week and ribavirin 1000/1200 mg per day. Treatment is given for 24, 48 or 72 weeks depending on the time point (week 4, 12 or 24) when HCV RNA becomes undetectable by the Cobas Taqman assay. If HCV RNA has not declined 2 logs by week 12 or is detectable at week 24, treatment is stopped. | Drug: Peg-interferon-alfa2a (Pegasys)<br>* Peg-interferon-alfa2a 180 µg per week<br>* Other names: Pegasys;Drug: Ribavirin (Copegus)<br>* Ribavirin 1000 or 1200 mg per day depending on if body weight is below or above 75 kg<br>|
| Experimental: Tailored treatment<br>Treatment with Pegasys 180 µg/week and ribavirin 1000/1200 mg per day. Treatment duration is flexible, 24-72 weeks, depending on the time point when the HCV RNA level is calculated to be 1 copy/mL. If the decline between day 14 and 28 is poor, treatment is stopped after 5 weeks. | Drug: Peg-interferon-alfa2a (Pegasys)<br>* Peg-interferon-alfa2a 180 µg per week<br>* Other names: Pegasys;Drug: Ribavirin (Copegus)<br>* Ribavirin 1000 or 1200 mg per day depending on if body weight is below or above 75 kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication dose per cured patient |  | 26 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response and relapse rate |  | 26 weeks after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C virus, Real-time PCR, Treatment