Prospective Randomized Double Blind Placebo Controlled Trial of Rifaximin 550mg PO Twice Daily for Three Months to Prevent Recurrent Fibrosis in Liver Transplant Recipients With Chronic Hepatitis C Virus Infection
试验速览
- 阶段
- 2 期
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Significant recurrence of Hepatitis C
研究概览
简要总结
The purpose of this study is to determine if the administration of a poorly-absorbable antibiotic (rifaximin) for the first three months after liver transplant will reduce the amount of fibrosis (or scarring of the liver) in liver transplant patients with recurrent hepatitis C virus (HCV) by lowering serum lipopolysaccharide (LPS), a protein in blood that comes from the bacteria in intestines and may cause scarring in the liver.
Approximately 60 subjects will participate in this study. Subjects will be part of the study for approximately 1 year post transplant.
详细描述
Hepatitis C virus (HCV) is the most common chronic liver infection and remains the leading indication for liver transplantation (LT). Although LT is a cure for cirrhosis of the liver, it does not always cure HCV infection or reinfection of post-transplanted liver. Post-LT recurrent HCV can lead to accelerated liver fibrosis. Chronic exposure to lipopolysaccharide (LPS) from gut-derived bacteria has shown to be at elevated levels in patients with cirrhosis due to HCV compared to normal controls. Therefore, the investigators hypothesize that LPS contributes to cause of liver fibrosis, specifically in patients with post-LT recurrent HCV, and this effect maybe modified with the poorly absorbed antibiotic, rifaximin, which alter the gut flora of the patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must provide written informed consent before any study assessment is performed
- •Age ≥ 18 years
- •Willing and able to sign informed consent
- •Chronic HCV infection with viremia
- •Listed for liver transplantation
- •Demonstrate ability to take oral medications prior to randomization (post LT)
排除标准
- •Age < 18 years old
- •Unwilling/able to sign informed consent
- •Cleared HCV infection (and therefore not at risk for recurrent HCV)
- •Human immunodeficiency virus (HIV) co-infection
- •Hepatitis B (HBV) co-infection
- •Participation in another interventional clinical trial
- •Females of childbearing (reproductive) potential must have a negative serum pregnancy test at Screening and agree to use an acceptable method of contraception throughout their participation in the study
- •Subjects with history of hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any of the components of rifaximin
- •Subjects with history of tuberculosis infection or has received treatment for tuberculosis infection. If subject has previous positive test for tuberculosis antigen then they must have current negative chest x-ray to be eligible
- •Subject has diarrhea and positive Clostridium difficile (C. difficile) toxin via stool examination during Screening period. NOTE: Stool examination for C. difficile toxin will be performed on subjects who have diarrhea during the screening period. Results of stool tests should be confirmed as negative prior to randomization
研究组 & 干预措施
Rifaximin Arm
Rifaximin will be initiated post-LT, once the subject is able to tolerate oral medications/diet. Rifaximin will be dosed at 550mg twice daily for 90 days (+/- 10 days) post-LT.
干预措施: Rifaximin (Drug)
Placebo Control Arm
Rifaximin placebo will be initiated post-LT, once the subject is able to tolerate oral medications/diet. Rifaximin placebo will be taken twice daily for 90 days (+/- 10 days) post-LT.
干预措施: Placebo (Drug)
结局指标
主要结局
Significant recurrence of Hepatitis C
时间窗: One year post liver transplant
Significant recurrence of hepatitis C at one year post-LT defined as at least stage 2 fibrosis, fibrosing cholestatic hepatitis or death/graft failure due to HCV.
次要结局
- Measurement of Serum LPS(3 months and 12 months post liver transplant)
- Measurement of mRNA markers of the fibrosis cascade(3 months and 12 months post liver transplant)
- Number of adverse events (severe and non-serious)(Up to 30 days post study participation)
研究者
Elizabeth C. Verna
Assistant Professor of Medicine
Columbia University