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

NCT ID: NCT00485342

Last Updated: 2012-01-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2013-03-31

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

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: NO_INTERVENTION

Peg-interferon alpha 2a and ribavin

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

ribavirin with adaptation dose

Intervention Type: DRUG

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

Interventions

Peg-interferon alpha 2a and ribavin

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

ribavirin with adaptation dose

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Trépo, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Marianne Maynard

Lyon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Marianne Maynard, MD

Role: CONTACT

marianne.maynard-muet@chu-lyon.fr

33 4 72 41 30 88

Véronique LOUSTAUD-RATTI, MD

Role: CONTACT

veronique.loustaud-ratti@unilim.fr

33 5 55 05 66 84

Facility Contacts

Marianne Maynard, MD

Role: primary

marianne.maynard-muet@chu-lyon.fr

33 4 72 41 30 88

Other Identifiers

2005-400

Identifier Type: -

Identifier Source: org_study_id