Plasma Ribavirin Assay During Combination Therapy for Chronic Hepatitis C

September 13, 2005 updated by: Hopital A Michallon

Diagnostic Value of Plasma Ribavirin Assay During the Combination Therapy " Pegylated Interferon + Ribavirin " in Chronic Hepatitis C.

Investigation of the usefullness of therapeutical drug monitoring of ribavirin for dose adaptation during combination therapy of chronic hepatitis C patients.

The correlation between ribavirin plasma concentration levels at week 4 (steady state) and early virological response (HCV-RNA decay from baseline to week 12) is to be tested in 40 patients approximately.

Study Overview

Detailed Description

  1. Background and rational The serum concentrationS of ribavirin commonly range from 1 to 5 in patients during the combination treatment " interferon+ribavirin " (Larrat et al. 2003). However, the bioavailibility of ribavirin is not considered in the current recommendation for this treatment.

    The aim of this study is to demonstrate that the adaptation " à la carte " of ribavirin posology according to its serum concentration could improve the efficacy and the tolerance of the hepatitis C combination therapy.

  2. Study design This study is a prospective clinical pharmacology trial in patients on combination treatment for a chronic hepatitis C with genotype 1 or 4 virus.

    The evaluation will concern the serum ribavirin concentration during the first three months of treatment and its correlation with the evolution of hemoglobin (toxicity marker) or viral load (efficacy marker).

    After the 3 months of the study, a adaptation of posology based on serum ribavirin level will be offer to the patients for the rest of the treatment period. A control of the ribavirin level one month after the dose adaptation will be performed.

  3. Study treatments This trial is not a treatment evaluation. All the patients will receive the same treatment with PegInterferon alfa-2a and ribavirin according to the registered recommendations for use.
  4. Target population The study population will consist of patients with genotype 1 or 4 chronic hepatitis C and for which a combination therapy is indicated.
  5. Main selection criteria Patients with chronic hepatitis C related to genotype 1 or 4 virus and for which a combination therapy is needed will be eligible. Patients with co-infection (either VHB or VIH) or with concomitant treatments expected to interact with the endpoints (hemoglobin, viral load, serum ribavirin) will be excluded.
  6. Judgement endpoints

    There will be intermediate endpoints :

    • blood hemoglobin concentration whom reduction during the 4 first weeks of treatment is a marker of toxicicty of the drug (induction of an hemolytic anemiae)
    • viral load whom reduction of at least 2 log after 12 weeks of treatment is correlated with the sustained virologic response to treatment
    • serum level of ribavirin for which it is expected a correlation with the two previous biological markers

    The primary judgement endpoint will be the statistical correlation as following :

    • the serum concentration of ribavirine at the plateau of pharmacokinetics (J28(S4))
    • the change of the hemoglobin concentration from D0 to D28(S4)
    • the change of hemoglobin concentration between D0 and D84(S12)
  7. Secondary endpoints The thresholds of efficacy and toxicity of ribavirin will be determined by comparison of responder/non responder patients (as predicted by viral load change) and patients with/without toxicity. A correlation between the evolution of these two markers will be calculated.

Study Type

Interventional

Enrollment

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Grenoble, France, 38043
        • university hospital ; HGE dpt

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with chronic hepatitis C related to genotype 1 or 4 virus and for which a combination therapy is needed will be eligible.

Exclusion Criteria:

  • Patients with co-infection (either VHB or VIH) or with concomitant treatments expected to interact with the endpoints (hemoglobin, viral load, serum ribavirin) will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
relationship between plasma ribavirin concentration and early virological response

Secondary Outcome Measures

Outcome Measure
safety
relationship between plasma ribavirin concentration and hemoglobin drop
dose effect of ribavirin on ribavirin plasma concentration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jean Pierre ZARSKI, MD, university hospital of Grenoble (France)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2003

Study Completion

July 1, 2004

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 21, 2005

Study Record Updates

Last Update Posted (Estimate)

September 21, 2005

Last Update Submitted That Met QC Criteria

September 13, 2005

Last Verified

September 1, 2004

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Hepatitis C

Clinical Trials on therapeutic drug monitoring of ribavirin and dose adaptation

Subscribe