Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant
- Registration Number
- NCT01603108
- Lead Sponsor
- Columbia University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 59
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rifaximin Arm Rifaximin 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. Placebo Control Arm Placebo 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.
- Primary Outcome Measures
Name Time Method Significant recurrence of Hepatitis C 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.
- Secondary Outcome Measures
Name Time Method Measurement of Serum LPS 3 months and 12 months post liver transplant Comparison of serum LPS measurements between groups, to determine if the use of rifaximin is associated with reduction in serum LPS.
Measurement of mRNA markers of the fibrosis cascade 3 months and 12 months post liver transplant Comparison of mRNA markers of the fibrosis cascade between groups in the 3 month and 1 year post-LT liver biopsies.
Number of adverse events (severe and non-serious) Up to 30 days post study participation Evaluation of the safety of Rifaximin compared to placebo in early post liver transplant patients, by assessing adverse events and severe adverse events experienced by the patients during the Rifaximin treatment course.
Trial Locations
- Locations (1)
Columbia University Medical Center - NYPH
🇺🇸New York, New York, United States