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
Overview
- Phase
- Phase 3
- Intervention
- Peg-interferon alpha 2a and ribavin
- Conditions
- Chronic Hepatitis C
- Sponsor
- Hospices Civils de Lyon
- Enrollment
- 236
- Locations
- 1
- Primary Endpoint
- 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
- Last Updated
- 14 years ago
Overview
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
Investigators
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:
Arms & Interventions
standard dose
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)
Intervention: Peg-interferon alpha 2a and ribavin
adjusted dose
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: ribavirin with adaptation dose
Outcomes
Primary Outcomes
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 Outcomes
- Efficacy endpoints(72 weeks)
- safety endpoints(72 weeks)
- Economic endpoints(72 weeks)