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RIBAJUSTE Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin (RIBAJUSTE)

Primary Purpose

Chronic Hepatitis C

Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Peg-interferon alpha 2a and ribavin
ribavirin with adaptation dose
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Chronic hepatitis C,Genotype1,Naïf,bitherapy,Ribavirin adaptation,ribavirin AUC

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 65 years >Age >= 18 years
  • Chronic hepatitis C documented by PCR performed within 3 months and at liver biopsy within 18 months or with serum markers of fibrosis performed within 3 months before inclusion or FibroScan performed
  • Naive patients for who the physician decided to initiate a combination treatment of chronic hepatitis C with pegylated interferon alfa-2a plus ribavirine
  • Genotype VHC-1
  • Compensated liver disease (Child-Pugh <=6)
  • Negative HBsAg test and HIV-RNA test
  • Negative pregnancy test at baseline in women in age of procreation and efficient contraception all along the treatment period, and up to 7 months after discontinuation for women and men
  • Signed consent form
  • Patient with a social cover

Exclusion Criteria:

  • Non HCV liver disease
  • Non-1 HCV genotype
  • Organ transplant whatever the organ
  • Clinical or radiological evidence of liver carcinoma
  • Severe psychiatric disorder
  • Non compensated thyroid dysfunction
  • Woman pregnant or breast-feeding
  • Recent history of epilepsy (less than 6 months)
  • Absolute contraindications to one of the drug of combination therapy
  • Biological abnormalities at pre-treatment check-up, such as:

Neutropenia (<1500/mm³); Haemoglobinemia (<13 g/dL for men et <12 g/dL for women); Thrombopenia (<90 000/mm³);

  • Kidney failure (creatinine clearance>70 ml/min)
  • Hypersensitivity to epoetin or one of its excipients
  • Treatment by epoetin within 2 months prior inclusion
  • Chronic cardiac failure (grade III or IV - NYHA classification)
  • High blood pressure unwell-controlled (SBP > 180 mmHg during inclusion in spite of hypertension treatment)
  • Previous history or risk of venous thrombosis
  • Major surgery within the previous 3 months

Sites / Locations

  • Marianne MaynardRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

standard dose

adjusted dose

Arm Description

the "reference" strategy : Peg-interferon alpha 2a (180 µg/week) and ribavine (1000 mg/day if weight < 75 kg and 1200 mg/day if weight ≥ 75 kg)

individual dose adjustment of ribavirin dose at D7, based on ribavirin abbreviated AUC-0-4H , estimated itself by two independent methods: multiple linear regression and bayesien estimation based on three ribavirin concentration measurements obtained at 0.5H, 1H, 2H after the first intake of 600 mg at D0.

Outcomes

Primary Outcome Measures

Inter-group comparison of sustained virological response rates as defined by the proportion of subjects with a negative PCR HCV-RNA test at Week 72

Secondary Outcome Measures

Efficacy endpoints
To compare the virological response rate between the two groups: Rapid Virological Response (RVR) at W4, Early Virological Response (EVR) at W12, Virological Response at W24, and End-Of-Treatment response (EOT) at W48 ; To determine the relapse rate (between W48 and W72) and to determine the proportion of patients reaching the target trough ribavirin concentration of 2 mg/L at W4 or W8 after ribavirin dose adjustment in the first 7 days of treatment.
safety endpoints
To investigate the clinical and biological tolerability in patients with dose-adjusted ribavirin compared to those with standard ribavirin doses, the proportion of patients needing EPO co-prescription due to secondary anemia in each group, to estimate the rate of treatment discontinuation due to serious or other relevant adverse events in each group and to determine the proportion of subjects reaching ribavirin trough plasma concentrations considered as "toxic" (> 3.5 mg/L) at W4 and W8, in each arm.
Economic endpoints
Comparaison of the "test" and "standard" strategies by a medico-economic analysis

Full Information

First Posted
June 8, 2007
Last Updated
January 6, 2012
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT00485342
Brief Title
RIBAJUSTE Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin
Acronym
RIBAJUSTE
Official Title
Multicentric, Controlled and Randomised Open Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin Using Pharmacologic Measures of Ribavirin Exposition During Combination Peginterferon Alfa-2 and Ribavirin Treatment in Naive Patients With Chronic Hepatitis C of Genotype 1 on a First Combination Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Unknown status
Study Start Date
April 2006 (undefined)
Primary Completion Date
March 2013 (Anticipated)
Study Completion Date
March 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this study is to compare two therapeutical strategies concerning the combination therapy (peginterferon alfa-2a and ribavirin) in naïve patients with chronic hepatitis C of genotype 1. "Reference" strategy corresponding to standards of care recommended by the French consensus conference versus "Test" strategy corresponding to adaptation strategy of ribavirin dose during the first week according to AUC (area under the curve) of ribavirin plasmatic concentration after the first intake (Day 0) of 600 mg

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
Chronic hepatitis C,Genotype1,Naïf,bitherapy,Ribavirin adaptation,ribavirin AUC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
236 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
standard dose
Arm Type
No Intervention
Arm Description
the "reference" strategy : Peg-interferon alpha 2a (180 µg/week) and ribavine (1000 mg/day if weight < 75 kg and 1200 mg/day if weight ≥ 75 kg)
Arm Title
adjusted dose
Arm Type
Experimental
Arm Description
individual dose adjustment of ribavirin dose at D7, based on ribavirin abbreviated AUC-0-4H , estimated itself by two independent methods: multiple linear regression and bayesien estimation based on three ribavirin concentration measurements obtained at 0.5H, 1H, 2H after the first intake of 600 mg at D0.
Intervention Type
Drug
Intervention Name(s)
Peg-interferon alpha 2a and ribavin
Intervention Description
Date of ribavirin AUC : Day 0 (beginning of treatment) Bitherapy : Peg-interferon alpha 2a (180 µg/week) with ribavirin (1000 mg/day if weight < 75 kg and 1200 mg/day if weight ≥ 75 kg). Duration of treatment : 48 weeks Duration of study for patients : 72 weeks
Intervention Type
Drug
Intervention Name(s)
ribavirin with adaptation dose
Intervention Description
Date of ribavirin AUC : Day 0 (beginning of treatment) Bitherapy : Peg-interferon alpha 2a (180 µg/week) with ribavirin (dose adaptation) Dose adaptation : Day 7, dependant of result of AUC Ribavirin dose increments : 200 mg, 400 mg or 600 mg with a maximum of 50% of the initial dose (600 mg) applied every 4 days up to the adjusted dose proposed in order to reach the targeted AUC. The maximum daily dose will not exceed 3600 mg Duration of treatment : 48 weeks Duration of study for patients : 72 weeks
Primary Outcome Measure Information:
Title
Inter-group comparison of sustained virological response rates as defined by the proportion of subjects with a negative PCR HCV-RNA test at Week 72
Time Frame
72 weeks
Secondary Outcome Measure Information:
Title
Efficacy endpoints
Description
To compare the virological response rate between the two groups: Rapid Virological Response (RVR) at W4, Early Virological Response (EVR) at W12, Virological Response at W24, and End-Of-Treatment response (EOT) at W48 ; To determine the relapse rate (between W48 and W72) and to determine the proportion of patients reaching the target trough ribavirin concentration of 2 mg/L at W4 or W8 after ribavirin dose adjustment in the first 7 days of treatment.
Time Frame
72 weeks
Title
safety endpoints
Description
To investigate the clinical and biological tolerability in patients with dose-adjusted ribavirin compared to those with standard ribavirin doses, the proportion of patients needing EPO co-prescription due to secondary anemia in each group, to estimate the rate of treatment discontinuation due to serious or other relevant adverse events in each group and to determine the proportion of subjects reaching ribavirin trough plasma concentrations considered as "toxic" (> 3.5 mg/L) at W4 and W8, in each arm.
Time Frame
72 weeks
Title
Economic endpoints
Description
Comparaison of the "test" and "standard" strategies by a medico-economic analysis
Time Frame
72 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 65 years >Age >= 18 years Chronic hepatitis C documented by PCR performed within 3 months and at liver biopsy within 18 months or with serum markers of fibrosis performed within 3 months before inclusion or FibroScan performed Naive patients for who the physician decided to initiate a combination treatment of chronic hepatitis C with pegylated interferon alfa-2a plus ribavirine Genotype VHC-1 Compensated liver disease (Child-Pugh <=6) Negative HBsAg test and HIV-RNA test Negative pregnancy test at baseline in women in age of procreation and efficient contraception all along the treatment period, and up to 7 months after discontinuation for women and men Signed consent form Patient with a social cover Exclusion Criteria: Non HCV liver disease Non-1 HCV genotype Organ transplant whatever the organ Clinical or radiological evidence of liver carcinoma Severe psychiatric disorder Non compensated thyroid dysfunction Woman pregnant or breast-feeding Recent history of epilepsy (less than 6 months) Absolute contraindications to one of the drug of combination therapy Biological abnormalities at pre-treatment check-up, such as: Neutropenia (<1500/mm³); Haemoglobinemia (<13 g/dL for men et <12 g/dL for women); Thrombopenia (<90 000/mm³); Kidney failure (creatinine clearance>70 ml/min) Hypersensitivity to epoetin or one of its excipients Treatment by epoetin within 2 months prior inclusion Chronic cardiac failure (grade III or IV - NYHA classification) High blood pressure unwell-controlled (SBP > 180 mmHg during inclusion in spite of hypertension treatment) Previous history or risk of venous thrombosis Major surgery within the previous 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marianne Maynard, MD
Phone
33 4 72 41 30 88
Email
marianne.maynard-muet@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Véronique LOUSTAUD-RATTI, MD
Phone
33 5 55 05 66 84
Email
veronique.loustaud-ratti@unilim.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Trépo, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Marianne Maynard
City
Lyon
ZIP/Postal Code
69002
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marianne Maynard, MD
Phone
33 4 72 41 30 88
Email
marianne.maynard-muet@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Christian Trépo, MD

12. IPD Sharing Statement

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RIBAJUSTE Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin

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