Plasma Ribavirin Assay During Combination Therapy for Chronic Hepatitis C

This study has been terminated.
Sponsor:
Collaborators:
University Hospital, Grenoble
Central Hospital, Nancy, France
Information provided by:
Hopital A Michallon
ClinicalTrials.gov Identifier:
NCT00209755
First received: September 13, 2005
Last updated: NA
Last verified: September 2004
History: No changes posted
  Purpose

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.


Condition Intervention
Chronic Hepatitis C
Procedure: therapeutic drug monitoring of ribavirin and dose adaptation

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Diagnostic Value of Plasma Ribavirin Assay During the Combination Therapy « Pegylated Interferon + Ribavirin » in Chronic Hepatitis C.

Resource links provided by NLM:


Further study details as provided by Hopital A Michallon:

Primary Outcome Measures:
  • relationship between plasma ribavirin concentration and early virological response

Secondary Outcome Measures:
  • safety
  • relationship between plasma ribavirin concentration and hemoglobin drop
  • dose effect of ribavirin on ribavirin plasma concentration

Estimated Enrollment: 40
Study Start Date: October 2003
Estimated Study Completion Date: July 2004
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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00209755

Locations
France
university hospital ; HGE dpt
Grenoble, France, 38043
Sponsors and Collaborators
Hopital A Michallon
University Hospital, Grenoble
Central Hospital, Nancy, France
Investigators
Principal Investigator: Jean Pierre ZARSKI, MD university hospital of Grenoble (France)
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00209755     History of Changes
Other Study ID Numbers: ribatop - afssaps #031161, N.A.
Study First Received: September 13, 2005
Last Updated: September 13, 2005
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hopital A Michallon:
chronic hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014