RIBAJUSTE Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin
- Conditions
- Chronic Hepatitis C
- Interventions
- Drug: Peg-interferon alpha 2a and ribavin
- Registration Number
- NCT00485342
- Lead Sponsor
- Hospices Civils de Lyon
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 236
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description standard dose Peg-interferon alpha 2a and ribavin 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) adjusted dose ribavirin with adaptation 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.
- Primary Outcome Measures
Name Time Method 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 72 weeks
- Secondary Outcome Measures
Name Time Method Efficacy endpoints 72 weeks 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 72 weeks 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 72 weeks Comparaison of the "test" and "standard" strategies by a medico-economic analysis
Trial Locations
- Locations (1)
Marianne Maynard
🇫🇷Lyon, France