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

Civil Hospices of Lyon

Status and phase: Unknown; Phase 3

Conditions: Chronic Hepatitis C

Treatments: Drug: ribavirin with adaptation dose; Drug: Peg-interferon alpha 2a and ribavin

Study type: Interventional

Funder types: Other

Identifiers

NCT00485342

2005-400

Details and patient eligibility

About

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

Enrollment: 236 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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236 participants in 2 patient groups

standard dose

No Intervention group

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)

Treatment:

Drug: Peg-interferon alpha 2a and ribavin

adjusted dose

Experimental group

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.

Treatment:

Drug: ribavirin with adaptation dose