Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant

Sponsor

Columbia University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01603108

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Rifaximin Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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. Other Names: Xifaxin
Placebo Comparator: 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.	Drug: Placebo 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. Other Names: No other name

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.

Other Names:

Xifaxin

Placebo Comparator: 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.

Drug: Placebo

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.

Other Names:

No other name

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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