Intravenous Silibinin in Combination With Peg-interferon and Ribavirin in Nonresponders

Study Overview
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Brief Summary
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By chance the investigators found that iv. silibinin has a potent antiviral effect against the hepatitis C virus. Based on the results of the dose finding study (published) te optima dosing schedule is explored.This study will be evaluate whether the highest active dose given for the optimal time combined with standard of care will result in a sustained virologic response (=cure of hepatitis C).

Detailed Description
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Since the publication of the first data the optimal dosing schedule is investigated

Official Title
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Multicenter Study To Evaluate The Efficacy Of Silymarin In Addition To Combination-Therapy With Pegylated Interferon Alfa 2a (Peg-Ifn Alfa 2a) And Ribavirin In Patients With Chronic Hepatitis C

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Silibinin
* Drug: Silibinin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nonresponders to full dose PEG-IFN/RBV therapy Liver biopsy within the last 2 year Exclusion Criteria: Intolerance to one of the study drugs Coinfection with HIV/HBV

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: on treatment nonresponders<br>naive patients with null response to peginterferon/ribavirin at week 12 or partial response at week 24 | Drug: Silibinin<br>* 20 mg/kg Silibinin iv /d /21 days, antiviral combination therapy will be continued<br>|
| Experimental: Nonresponders to previous antiviral combination therapy<br>Nonresponders defined by viral status at weeks 4,12, and 24 of previous peginterferon/ribavirin combination therapy | Drug: Silibinin<br>* comparison of different dosing schedule of Silibinin infusions (20 mg/kg/d infused over 2 hours) A: 3x5days B: 14 days C: 21 days D: 28 days sequential the infusion duration will be shortened - 2 hours, then 1 hr and then 1/2 hr/infusion<br>* Other names: Silibinin infusions (20 mg/kg/d infused over 2 hours)given for 21 (either Monday -Friday or daily) or 28 days, continuation of antiviral combination therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| viral response at week 24 |  | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sustained virologic response |  | week 72 | 
| Safety | start to end of treatment | week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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silibinin, chronic hepatitis C, peginterferon, ribavirin, nonresponders, efficacy of iv. silibinin, safety