Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Rifaximin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rifaximin Arm<br>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. | Drug: Rifaximin<br>* 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.<br>* Other names: Xifaxin;|
| Placebo Comparator: Placebo Control Arm<br>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. | Drug: Placebo<br>* Rifaximin placebo will be initiated post LT, once the subject is able to tolerate oral medications/diet. Rifaximin placebo dosed at 550 mg twice daily for 90 days (+/10 days) post LT.<br>* Other names: No other name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Significant recurrence of Hepatitis C | 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. | One year post liver transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Serum LPS | Comparison of serum LPS measurements between groups, to determine if the use of rifaximin is associated with reduction in serum LPS. | 3 months and 12 months post liver transplant | 
| Measurement of mRNA markers of the fibrosis cascade | Comparison of mRNA markers of the fibrosis cascade between groups in the 3 month and 1 year post-LT liver biopsies. | 3 months and 12 months post liver transplant | 
| Number of adverse events (severe and non-serious) | 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. | Up to 30 days post study participation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Transplant Recipient, Recurrent Fibrosis