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

Chronic Hepatitis C Clinical Trial

— RIBAJUSTE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00485342
• Other study ID #: 2005-400
• Status: Recruiting
• Phase: Phase 3
• First received: June 8, 2007
• Last updated: January 6, 2012
• Start date: April 2006
• Est. completion date: March 2013

Study information

• Verified date: January 2012
• Source: Hospices Civils de Lyon
• Contact: Marianne Maynard, MD
• Phone: 33 4 72 41 30 88
• Email: marianne.maynard-muet[@]chu-lyon.fr
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 236
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
France	Marianne Maynard	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Efficacy endpoints	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.	72 weeks	No
Secondary	safety endpoints	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.	72 weeks	Yes
Secondary	Economic endpoints	Comparaison of the "test" and "standard" strategies by a medico-economic analysis	72 weeks	No