RIBAJUSTE Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin - Full Text View

Purpose

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

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: Peg-interferon alpha 2a and ribavin Drug: ribavirin with adaptation dose	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Ribavirin Interferon Alfa-2a Peginterferon Alfa-2a

U.S. FDA Resources

Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:

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 [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Efficacy endpoints [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
Comparaison of the "test" and "standard" strategies by a medico-economic analysis

Estimated Enrollment:	236
Study Start Date:	April 2006
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: 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)	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
Experimental: 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.	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

Arms

Assigned Interventions

No Intervention: 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)

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

Experimental: 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.

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

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00485342

Contacts

Contact: Marianne Maynard, MD	33 4 72 41 30 88	marianne.maynard-muet@chu-lyon.fr
Contact: Véronique LOUSTAUD-RATTI, MD	33 5 55 05 66 84	veronique.loustaud-ratti@unilim.fr

Locations

France
Marianne Maynard	Recruiting
Lyon, France, 69002
Contact: Marianne Maynard, MD 33 4 72 41 30 88 marianne.maynard-muet@chu-lyon.fr
Principal Investigator: Christian Trépo, MD

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

Principal Investigator:

Christian Trépo, MD

Hospices Civils de Lyon

More Information

No publications provided

Responsible Party:	Hospices Civils de Lyon
ClinicalTrials.gov Identifier:	NCT00485342 History of Changes
Other Study ID Numbers:	2005-400
Study First Received:	June 8, 2007
Last Updated:	January 6, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:

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

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a

Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites

ClinicalTrials.gov processed this record on May 19, 2013