Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Columbia University
Sponsor:
Information provided by (Responsible Party):
Robert Brown, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01603108
First received: April 26, 2012
Last updated: August 8, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Hepatitis C Virus
Liver Transplant Recipient
Recurrent Fibrosis
Drug: Rifaximin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Significant recurrence of Hepatitis C [ Time Frame: One year post liver transplant ] [ Designated as safety issue: No ]
    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:
  • Serum LPS measurements [ Time Frame: 3 and 12 months post liver transplant ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 months and 12 months post liver transplant ] [ Designated as safety issue: No ]
    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 and severe adverse events [ Time Frame: Up to 30 days post study participation. ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 60
Study Start Date: March 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 dosed at 550 mg twice daily for 90 days (+/10 days) post LT.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • Subject has renal insufficiency requiring routine dialysis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01603108

Contacts
Contact: Theresa Lukose, Pharm D. 212-305-3839 tt2103@columbia.edu

Locations
United States, New York
Columbia University Medical Center - NYPH Recruiting
New York, New York, United States, 10032
Contact: Robert S Brown, MD    212-305-0662    rb464@columbia.edu   
Contact: Theresa Lukose, Pharm D    212-305-3839    tt2103@columbia.edu   
Principal Investigator: Robert S Brown, MD         
Principal Investigator: Elizabeth C Verna, MD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Robert S Brown, MD, MPH Columbia University
  More Information

No publications provided

Responsible Party: Robert Brown, MD, Principal Investigator, Columbia University
ClinicalTrials.gov Identifier: NCT01603108     History of Changes
Other Study ID Numbers: AAAI4155
Study First Received: April 26, 2012
Last Updated: August 8, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Fibrosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Rifaximin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 18, 2014