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

Primary Purpose

Hepatitis C

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Rifaximin

Placebo

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring Liver Transplant Recipient, Recurrent Fibrosis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Columbia University Medical Center - NYPH

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Rifaximin Arm

Placebo Control Arm

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT01603108

First Posted

April 26, 2012

Last Updated

April 21, 2016

Sponsor

Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT01603108

Brief Title

Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant

Acronym

Rifaximin

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 Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Unknown status

Study Start Date

March 2012 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

Keywords

Liver Transplant Recipient, Recurrent Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rifaximin Arm

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo Control Arm

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Rifaximin

Other Intervention Name(s)

Xifaxin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

No other name

Intervention Description

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.

Primary Outcome Measure Information:

Title

Significant recurrence of Hepatitis C

Description

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.

Time Frame

One year post liver transplant

Secondary Outcome Measure Information:

Title

Measurement of Serum LPS

Description

Comparison of serum LPS measurements between groups, to determine if the use of rifaximin is associated with reduction in serum LPS.

Time Frame

3 months and 12 months post liver transplant

Title

Measurement of mRNA markers of the fibrosis cascade

Description

Comparison of mRNA markers of the fibrosis cascade between groups in the 3 month and 1 year post-LT liver biopsies.

Time Frame

3 months and 12 months post liver transplant

Title

Number of adverse events (severe and non-serious)

Description

Time Frame

Up to 30 days post study participation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elizabeth Verna, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Medical Center - NYPH

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

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Rifaximin to Prevent Recurrent HCV-Related Fibrosis After Liver Transplant

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