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Impact of an Antibiotic (Rifaximin) on Liver Scarring in HIV-Infected Patients With Liver Disease

Primary Purpose

HIV, Hepatitis C

Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Rifaximin
Sponsored by
Douglas T. Dieterich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV focused on measuring HIV, hepatitis C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged over 18 years old that can give an informed consent
  • HIV-infected patients with hepatitis C associated liver disease demonstrated by a fibroscan score above 8 kiloPascals
  • HCV infected patients with liver disease demonstrated by a fibroscan score above 8 kiloPascals
  • Patients placed on rifaximin by their physician for a mild hepatic encephalopathy

Exclusion Criteria:

  • Any patient unable to give informed consent.
  • Patients on hepatitis C treatment
  • Patients allergic to rifaximin or rifamycin
  • Patients on any prolonged antibiotic treatment including patients on tuberculosis treatment.
  • Patients with history of Clostridium difficile infection
  • Uncontrolled HIV infection: CD4 less than 200 or detectable viral load Patients need to be on a stable ART regimen for at least one month.
  • Patient on a HIV regimen including an unboosted protease inhibitor.
  • Acute hepatitis of any cause.
  • Child C cirrhosis
  • Patients on dialysis
  • Pregnant women or childbearing age women not accepting to use an effective contraceptive method Acceptable methods are double barrier methods (condom with spermicide jelly or diaphragm with spermicide), hormonal methods (oral contraceptives, patches or medroxyprogesterone acetate), or an intrauterine device with a documented failure rate of less than 1% per year. Females who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (total cessation of menses for >1 year) will not be considered "females of childbearing potential."
  • Usual exclusion criteria for FibroScan (pregnancy, BMI over 40, ascites, pacemaker or defibrillator).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    rifaximin

    Arm Description

    All patients will be taking rifaximin 550 mg twice daily

    Outcomes

    Primary Outcome Measures

    Liver fibrosis progression as measured by transient elastography
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Liver fibrosis progression as measured by transient elastography
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Liver fibrosis progression as measured by transient elastography
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Liver fibrosis progression as measured by transient elastography
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Liver fibrosis progression as measured by transient elastography
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.

    Secondary Outcome Measures

    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    sCD14 is a surrogate marker of bacterial translocation
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    sCD14 is a surrogate marker of bacterial translocation
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    sCD14 is a surrogate marker of bacterial translocation
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    sCD14 is a surrogate marker of bacterial translocation
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    sCD14 is a surrogate marker of bacterial translocation
    Safety of prolonged use of rifaximin in HIV patients taking many other medications

    Full Information

    First Posted
    July 30, 2012
    Last Updated
    September 25, 2015
    Sponsor
    Douglas T. Dieterich
    Collaborators
    Bausch Health Americas, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01654939
    Brief Title
    Impact of an Antibiotic (Rifaximin) on Liver Scarring in HIV-Infected Patients With Liver Disease
    Official Title
    Impact of Rifaximin on Liver Fibrosis in HIV-Infected Patients With Liver Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2015
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    October 2012 (undefined)
    Primary Completion Date
    September 2014 (Actual)
    Study Completion Date
    September 2015 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Douglas T. Dieterich
    Collaborators
    Bausch Health Americas, Inc.

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    For HIV-infected patients who have access to treatment, liver diseases are a major cause of morbidity and mortality. Hepatitis C is the most frequently encountered liver condition in this population. Both diseases allow a higher level of poisonous substances (toxins) normally produced by the bacteria present in the gut to enter the bloodstream. This leads to a chronic inflammatory state, which results in faster development of liver scars (fibrosis) and ultimately, end stage disease (cirrhosis). To prevent this from happening, the use of antibiotics has been attempted to reduce the quantity of gut flora in the hopes of lowering the amount of toxins produced. These trials have shown promising results, but the antibiotics studied had major side effects and were not designed for continuous use. Rifaximin is a non absorbable antibiotic with very few side effects. It is already used for long periods of time in cirrhotic patients to treat the effects of cirrhosis on the brain (encephalopathy). This project will try to determine if rifaximin, by reducing the level of toxins produced by the bacteria in the gut, can improve the evolution of liver fibrosis in HIV-infected patients with hepatitis C. In this pilot study, ten patients with HIV and HCV infection will be followed for one year. In addition, 10 patients with HCV mono infection will also be followed. Both populations will be included if they are starting on rifaximin, for its currently approved FDA indication (hepatic encephalopathy).
    Detailed Description
    Many studies have already proved the deleterious effects of LPS on HIV and hepatic diseases evolution. There has never been a concerted effort to prevent the progression of liver disease in these patients. To date, the only treatment is initiation of antiretroviral therapy. Rifaximin could be an easy and well tolerated way to improve the outcome of liver disease in HIV-infected patients. We hypothesize that it could help to slow down the progression of liver disease at any stage in these patients. This is a pilot study. A total of twenty patients placed on rifaximin by their physician for a mild hepatic encephalopathy will be monitored over a period of one year. The evaluation of the fibrosis will be done through transient elastography every 3 months. Bacterial translocation will be evaluated through the dosing of soluble CD14. The safety of the prolonged use of rifaximin in patients will also be assessed.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV, Hepatitis C
    Keywords
    HIV, hepatitis C

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 4
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    rifaximin
    Arm Type
    Experimental
    Arm Description
    All patients will be taking rifaximin 550 mg twice daily
    Intervention Type
    Drug
    Intervention Name(s)
    Rifaximin
    Other Intervention Name(s)
    XIFAXAN
    Intervention Description
    All patients will be taking rifaximin 550 mg twice daily for one year for a diagnosis of hepatic encephalopathy
    Primary Outcome Measure Information:
    Title
    Liver fibrosis progression as measured by transient elastography
    Description
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Time Frame
    Baseline
    Title
    Liver fibrosis progression as measured by transient elastography
    Description
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Time Frame
    3 months
    Title
    Liver fibrosis progression as measured by transient elastography
    Description
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Time Frame
    6 months
    Title
    Liver fibrosis progression as measured by transient elastography
    Description
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Time Frame
    9 months
    Title
    Liver fibrosis progression as measured by transient elastography
    Description
    Transient elastography is a non invasive way to measure liver stiffness. It is not FDA-approved and is used as a research tool in this study.
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    Description
    sCD14 is a surrogate marker of bacterial translocation
    Time Frame
    Baseline
    Title
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    Description
    sCD14 is a surrogate marker of bacterial translocation
    Time Frame
    1 month
    Title
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    Description
    sCD14 is a surrogate marker of bacterial translocation
    Time Frame
    3 months
    Title
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    Description
    sCD14 is a surrogate marker of bacterial translocation
    Time Frame
    6 months
    Title
    Levels of sCD14 in HIV-infected patients with liver disease and HCV infected patients taking rifaximin
    Description
    sCD14 is a surrogate marker of bacterial translocation
    Time Frame
    12 months
    Title
    Safety of prolonged use of rifaximin in HIV patients taking many other medications
    Time Frame
    up to 12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients aged over 18 years old that can give an informed consent HIV-infected patients with hepatitis C associated liver disease demonstrated by a fibroscan score above 8 kiloPascals HCV infected patients with liver disease demonstrated by a fibroscan score above 8 kiloPascals Patients placed on rifaximin by their physician for a mild hepatic encephalopathy Exclusion Criteria: Any patient unable to give informed consent. Patients on hepatitis C treatment Patients allergic to rifaximin or rifamycin Patients on any prolonged antibiotic treatment including patients on tuberculosis treatment. Patients with history of Clostridium difficile infection Uncontrolled HIV infection: CD4 less than 200 or detectable viral load Patients need to be on a stable ART regimen for at least one month. Patient on a HIV regimen including an unboosted protease inhibitor. Acute hepatitis of any cause. Child C cirrhosis Patients on dialysis Pregnant women or childbearing age women not accepting to use an effective contraceptive method Acceptable methods are double barrier methods (condom with spermicide jelly or diaphragm with spermicide), hormonal methods (oral contraceptives, patches or medroxyprogesterone acetate), or an intrauterine device with a documented failure rate of less than 1% per year. Females who have been surgically sterilized (e.g., hysterectomy or bilateral tubal ligation) or who are postmenopausal (total cessation of menses for >1 year) will not be considered "females of childbearing potential." Usual exclusion criteria for FibroScan (pregnancy, BMI over 40, ascites, pacemaker or defibrillator).
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Douglas T Dieterich, MD
    Organizational Affiliation
    Icahn School of Medicine at Mount Sinai
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Impact of an Antibiotic (Rifaximin) on Liver Scarring in HIV-Infected Patients With Liver Disease

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