Impact of Nitazoxanide on Virologic Responses in Chronic HCV Infected Patients With Genotype 4: A Placebo-controlled Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Assessment of efficacy of Nitazoxanide as an add-on therapy in terms of achieving a sustained virologic response
研究概览
简要总结
The main objective of antiviral therapy of patients with chronic hepatitis C (CHC) is the sustained elimination of the hepatitis C virus (HCV). The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks according to HCV genotype.
However, this approach is not sufficient to substantially improve the sustained virologic response (SVR) rates. Therefore, new therapies are needed to treat patients with hepatitis C virus (HCV) infection. Nitazoxanide (NTZ), originally used to treat cryptosporidium parvum infection, recently was shown to have an unexpected antiviral activity in the HCV replicon system and in chronically infected patients.
The aim of this work is to study impact of nitazoxanide therapy in addition to peginterferon/ribavirin combination on virologic responses in patients with chronic hepatitis C genotype 4.
Patients will be enrolled in this study and will be randomly assigned in a 1:1 ratio into 2 groups:
Group A: comprises 100 CHC patients who will receive the standard of care treatment, peginterferon-alf 2a plus weight-based ribavirin for 48 weeks.
Group B: comprises 100 CHC patients who will receive nitazoxanide monotherapy at a dose of 500 mg twice daily for 12 weeks as a lead-in phase followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a, and weight-based ribavirin for 48 weeks.
Data will be collected and statistical analysis will be done comparing the groups regarding response to antiviral therapy. Final results will be discussed and compared to similar studies published in peer reviewed journals and international conferences.
详细描述
Chronic hepatitis C virus (CHC) infects approximately 170 million individuals worldwide. Egypt has the highest hepatitis C virus prevalence in the world (overall prevalence is 12% among the general population, and up to 40% in persons above 40 years of age and is more in rural areas.
Approximately, 90% of hepatitis C patients in Egypt are infected with HCV genotype 4.
The main objective of antiviral therapy of patients with chronic hepatitis C is the sustained elimination of the hepatitis C virus (HCV).
The standard of care for the treatment of chronic hepatitis C is a 24- to 48- week course of peginterferon plus ribavirin, depending on genotype.
Overall, approximately, half of the patients can be cured by SOC. For patients with genotype 4, the sustained virologic response (SVR) rate with 48 weeks of therapy ranges from 50 to 60 %. Based on baseline viral load and the speed of virologic response during treatment, individualization of treatment duration is possible. However, this approach is not sufficient to substantially improve the sustained virologic response (SVR) rates. A significant proportion of treated patients thus either fail to respond or relapse following an initial response and a substantial number of patients are unable to tolerate treatment. There is at present no alternative therapy for these patients and thus a need for new drugs for the treatment of chronic hepatitis C.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 and <
- •Liver biopsy showing chronic hepatitis with significant fibrosis using Ishak scoring system.
- •Compensated liver disease; serum bilirubin < 1.5 mg/dl, INR no more than 1.5, serum albumin > 3.4, platelet count >75,000 mm, and no evidence of hepatic decompensation (hepatic encephalopathy or ascites).
- •Acceptable hematological and biochemical indices (hemoglobin 13g/dl for men and 12 g/dl for women; neutrophil count 1500/mm3 or more and serum creatinine <1.5 mg/dl.
- •Willing to be treated and to adhere to treatment requirements
排除标准
- •Major uncontrolled depressive illness.
- •Solid organ transplantation.
- •Autoimmune conditions, known to be exacerbated by peginterferon and ribavirin.
- •Untreated thyroid disease.
- •Pregnant or unwilling to comply with adequate contraception.
- •Severe concurrent medical disease such as severe hypertension, heart failure, significant coronary heart disease, poorly controlled diabetes, chronic obstructive pulmonary disease.
- •Known hypersensitivity to drugs used to treat HCV.
研究组 & 干预措施
placebo
• Group A: comprises 100 chronic hepatitis patients who will receive placebo twice daily orally with food for an average of 12 weeks followed by the standard of care treatment, peginterferon Alfa 2a once weekly and weight-based ribavirin 1000 or 1200 mg/day (based on body weight < 75 kg or ≥ 75 kg, respectively) in divided doses plus placebo twice daily for 48 weeks.
All patients in this group will have an HCV RNA within 3 months before initiation of therapy, in addition to ALT levels, CBC and other routine liver function tests.
干预措施: Placebo (Drug)
Nitazoxanide
• Group B: comprises 100 CHC patients who will receive oral Nitazoxanide 500 mg twice daily with food for an average of 12 weeks as a part of monotherapy lead-in phase followed by triple therapy, nitazoxanide 500 mg twice daily plus peginterferon alfa-2a (once weekly), and weight-based ribavirin (1000-1200 mg daily) for 48 weeks.
All patients in this group will have an HCV RNA within 3 months before initiation of therapy, in addition to ALT levels, CBC and other routine liver function tests.
干预措施: Nitazoxanide (Drug)
结局指标
主要结局
Assessment of efficacy of Nitazoxanide as an add-on therapy in terms of achieving a sustained virologic response
时间窗: 180 ± 7 days after the end of triple therapy, the preliminary data will be available at least 2 years after the beginning of the study (September 2012)
Patients in the 2 group who will continue on triple therapy till achieving an end-of-treatment response (after 48 weeks from the start of triple therapy), will have their viral load measured 6 months thereafter for assessment of sustained virologic response. patients in whom the virus is undetectble will be regarded as achieving a sustained virologic response.
次要结局
- Assessment of early virologic response(90 ± 7 days from the start of triple therapy)
- Assessment of end-of-treatment response(48± one week from the start of triple therapy)
- assessment of rapid virologic response(28-35 days from the start of triple therapy)
- Safety of Nitazoxanide(Throughout the study and up to 90 days after the end of triple therapy)
- Assessment of the efficacy of Nitazoxanide monotherapy following the lead-in phase(90± 7 days from the start of the lead_in phase)
研究者
Mohamed Kohla
Lecturer of Hepatology
National Liver Institute, Egypt