Efficacy, Safety, And Pharmacokinetics Of Rifaximin In Subjects With Severe Hepatic Impairment And Hepatic Encephalopathy

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial To Evaluate The Efficacy, Safety, And Pharmacokinetics Of Rifaximin 550 Mg In Subjects With Severe Hepatic Impairment And Overt Hepatic Encephalopathy

The purpose of the study is to evaluate the safety of Rifaximin or placebo in subjects with severe hepatic impairment and Hepatic Encephalopathy.

Study Overview

• Status: Terminated
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Rifaximin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0111
      • The University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Banner Research
    • Tucson, Arizona, United States, 85724
      • University Of Arizona Liver Research Institute
  • California
    • Coronado, California, United States, 92118
      • Southern California Liver Centers
    • La Jolla, California, United States, 92037
      • UCSD Clinical & Translational Research Institute
    • Loma Linda, California, United States, 92324
      • Loma Linda University Medical Center Transplantation Institute
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern Califorina Keck School Of Medicine
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Salix Site
  • Florida
    • Tampa, Florida, United States, 33606
      • Salix Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University-Comprehensive Transplant Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Abdominal Transplant Research Office
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Salix Site
  • Tennessee
    • Nashville, Tennessee, United States, 37212-1610
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
    • Fort Sam Houston, Texas, United States, 78234
      • Brook Army Medical Center
    • Galveston, Texas, United States, 77555
      • Salix Site
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
    • Richmond, Virginia, United States, 23298
      • VCU/MCV Health Systems
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or non-pregnant, non-breast feeding female ≥ 18 years old
• In remission from demonstrated overt HE
• Had ≥1 episode of overt HE associated with liver disease within the last 6 months
• MELD score of ≥ 19
• Has a close family member or other personal contact who is familiar with the subject's HE, can provide continuing oversight to the subject and is willing to be available to the subject during the conduct of the trial

Exclusion Criteria:

• HIV
• History of tuberculosis infection
• Chronic respiratory insufficiency
• Current infection and receiving antibiotics
• Renal insufficiency requiring dialysis
• Active spontaneous bacterial peritonitis infection
• Intestinal obstruction or has inflammatory bowel disease
• Active malignancy within the last 5 years
• Current GI bleeding or has had a GI hemorrhage within past 3 months
• Anemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifaximin; Rifaximin, oral, 550 mg BID, 6 months of treatment	Drug: Rifaximin; Rifaximin, oral, 550 mg BID, 6 months treatment; Other Names: XIFAXAN® Tablets
Placebo Comparator: Placebo; Placebo, oral, 0 mg BID, 6 months of treatment	Drug: Placebo; Placebo, oral, 0 mg BID, 6 months of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With Hepatic Encephalopathy (HE) Breakthrough Episode	6 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With HE-related Hospitalization	6 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events		6 Months
Assessment of Quality of Life		6 Months
Laboratory Parameters (changes in hematology, blood chemistry and urinalysis test results)		6 Months
Vital Signs (changes in blood pressure and heart rate)		6 Months
Electrocardiograms (12 lead ECG findings)		6 months
Neurologic Function (Critical Flicker Frequency (CFF) Test)	The CFF is the frequency at which the subject observes a constant light transition to a flickering light and will be measured in Hertz (Hz).	6 Months
Pharmacokinetics	The pharmacokinetics outcome measures are peak and trough plasma concentrations of rifaximin and rifaximin metabolite at Visit 3 (Day 28) and Visit 8 (Day 168); and additional determinations of rifaximin and rifaximin metabolite plasma concentrations at Visits 4 (Day 56), 5 (Day 84), 6 (Day 120), and 7 (Day 140) for all subjects.	6 months

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Study Director: Varsha Bhatt, Ph.D., Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2013
• Primary Completion (Actual): February 22, 2016
• Study Completion (Actual): February 22, 2016

Study Registration Dates

• First Submitted: April 24, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimated): May 3, 2013

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cirrhosis; Liver Diseases; Brain Diseases; Rifaximin; Hepatic Encephalopathy; Liver Failure; Hepatic Insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: RFHE4043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES