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

NCT00485342 | Unknown Phase 3 DMC

• 1 other identifier: 2005-400
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

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

Keywords

Chronic hepatitis C,Genotype1,Naïf,bitherapy,Ribavirin adaptation,ribavirin AUC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Efficacy endpoints

  72 weeks

• safety endpoints

  72 weeks

• Economic endpoints

  72 weeks

Study Arms (2)

standard dose

NO INTERVENTION

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)

Drug: Peg-interferon alpha 2a and ribavin

adjusted dose

EXPERIMENTAL

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.

Drug: ribavirin with adaptation dose

Interventions

Peg-interferon alpha 2a and ribavin 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

standard dose

ribavirin with adaptation dose 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

adjusted dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years \>Age \>= 18 years
• 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

You may not qualify if:

• 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
• Chronic cardiac failure (grade III or IV - NYHA classification)
• Previous history or risk of venous thrombosis

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Marianne Maynard

Lyon, 69002, France

RECRUITING

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Christian Trépo, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marianne Maynard, MD

CONTACT

33 4 72 41 30 88; marianne.maynard-muet@chu-lyon.fr

Véronique LOUSTAUD-RATTI, MD

CONTACT

33 5 55 05 66 84; veronique.loustaud-ratti@unilim.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2007
• First Posted: June 12, 2007
• Study Start: April 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: January 9, 2012

Record last verified: 2012-01

Locations

FR (1)