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
试验速览
- 阶段
- 3 期
- 入组人数
- 236
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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)
干预措施: Peg-interferon alpha 2a and ribavin (Drug)
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.
干预措施: ribavirin with adaptation dose (Drug)
结局指标
主要结局
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
时间窗: 72 weeks
次要结局
- Efficacy endpoints(72 weeks)
- safety endpoints(72 weeks)
- Economic endpoints(72 weeks)