Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant (Rifaximin)

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Rifaximin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center - NYPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Elizabeth Verna, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: April 26, 2012
• First Submitted That Met QC Criteria: May 21, 2012
• First Posted (Estimate): May 22, 2012

Study Record Updates

• Last Update Posted (Estimate): April 22, 2016
• Last Update Submitted That Met QC Criteria: April 21, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Liver Transplant Recipient; Recurrent Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Fibrosis; Hepatitis; Hepatitis C; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: AAAI4155