Clinical trial NCT00485342: RIBAJUSTE Clinical Trial Investigating the Efficacy and Safety of Dose Adaptation of Ribavirin
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Hepatitis C
Keywords: Chronic hepatitis C,Genotype1,Naïf,bitherapy,Ribavirin adaptation,ribavirin AUC
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2007-06-12
Enrollment: 236
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: 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
timeFrame: 72 weeks
Secondary outcomes:
measure: Efficacy endpoints
timeFrame: 72 weeks
measure: safety endpoints
timeFrame: 72 weeks
measure: Economic endpoints
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Lyon
country: France
facility: Marianne Maynard
Study officials:
affiliation: Hospices Civils de Lyon
name: Christian Trépo, MD
role: PRINCIPAL_INVESTIGATOR
References: