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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01846663
Recruitment Status : Recruiting
First Posted : May 3, 2013
Last Update Posted : April 27, 2017
Information provided by (Responsible Party):
Valeant Pharmaceuticals International, Inc.

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

Condition or disease Intervention/treatment Phase
Hepatic Encephalopathy Drug: Placebo Drug: Rifaximin Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 3, 2013
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Rifaximin

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 Name: 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

Primary Outcome Measures :
  1. Time to first Hepatic Encephalopathy(HE) breakthrough episode [ Time Frame: 6 Months ]

Secondary Outcome Measures :
  1. Time to first HE-related hospitalization [ Time Frame: 6 Months ]
  2. All Cause Mortality [ Time Frame: 6 Months ]

Other Outcome Measures:
  1. Adverse Events [ Time Frame: 6 Months ]
  2. Assessment of Quality of Life [ Time Frame: 6 Months ]
  3. Laboratory Parameters (changes in hematology, blood chemistry and urinalysis test results) [ Time Frame: 6 Months ]
  4. Vital Signs (changes in blood pressure and heart rate) [ Time Frame: 6 Months ]
  5. Electrocardiograms (12 lead ECG findings) [ Time Frame: 6 months ]
  6. Neurologic Function (Critical Flicker Frequency (CFF) Test) [ Time Frame: 6 Months ]
    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).

  7. Pharmacokinetics [ Time Frame: 6 months ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01846663

Contact: Erica Bullock 919-862-1854

  Hide Study Locations
United States, Alabama
The University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294-0111
Contact: Megan Pickering    205-934-1224      
Principal Investigator: Brendan McGuire, MD         
United States, Arizona
Banner Research Recruiting
Phoenix, Arizona, United States, 85016
Contact: Kelly Enders    602-839-6211      
Principal Investigator: Ester Little, MD         
University Of Arizona Liver Research Institute Recruiting
Tucson, Arizona, United States, 85724
Contact: Julie Johnson    520-626-1208      
Principal Investigator: Shahid Habib, MD         
United States, California
Southern California Liver Centers Recruiting
Coronado, California, United States, 92118
Contact: Monson Petrea    619-522-0330 ext 222      
Principal Investigator: Tarek Hassanein, MD         
UCSD Clinical & Translational Research Institute Recruiting
La Jolla, California, United States, 92037
Contact: Sharon Quigley    858-657-5147      
Principal Investigator: Michael Mendler, MD         
Loma Linda University Medical Center Transplantation Institute Recruiting
Loma Linda, California, United States, 92324
Contact: Diane Scavone    909-558-3636 ext 33634      
Principal Investigator: Thomas Amankonah, MD         
University of Southern Califorina Keck School Of Medicine Recruiting
Los Angeles, California, United States, 90033
Contact: Pui Yan    323-442-8152      
Principal Investigator: Linda Sher, MD         
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Jennifer Luckett    310-423-5453      
Principal Investigator: Vinay Sundaram, MD         
Inland Empire Liver Foundation Recruiting
Rialto, California, United States, 92377
Contact: Tina Mercado    909-883-2999   
Contact: Isma Hafeez    909-883-2999   
Principal Investigator: Zeid Kayali, MD         
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Haley Isberg    303-724-6559      
Principal Investigator: Lisa Forman, MD         
United States, Connecticut
Salix Site Terminated
New Haven, Connecticut, United States, 06520
United States, Florida
Salix Site Not yet recruiting
Tampa, Florida, United States, 33606
United States, Georgia
Piedmont Atlanta Hospital Recruiting
Atlanta, Georgia, United States, 30309
Contact: Becky Slawik    404-605-3212      
Principal Investigator: Lance Stein, MD         
United States, Illinois
Northwestern University-Comprehensive Transplant Center Recruiting
Chicago, Illinois, United States, 60611
Contact: Grace Rivera    312-926-0658      
Principal Investigator: Josh Levitsky, MD         
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Diana Giczewski    312-563-3919      
Principal Investigator: Nikunj Shah, MD         
United States, Louisiana
Tulane Abdominal Transplant Research Office Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Joni Murray    504-988-6902      
Principal Investigator: Luis Balart, MD         
United States, Minnesota
Mayo Clinic Completed
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Debra Kemp    314-362-3839      
Principal Investigator: Jackie Fleckenstein, MD         
United States, New York
New York University School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Christelle Sommervil    212-263-8391      
Principal Investigator: Lewis Teperman, MD         
United States, Oregon
Salix Site Not yet recruiting
Portland, Oregon, United States, 97239
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37212-1610
Contact: Tonya Givens    615-936-1745      
Principal Investigator: Michael Porayko, MD         
United States, Texas
The Liver Institute at Methodist Dallas Medical Center Recruiting
Dallas, Texas, United States, 75203
Contact: Zena Cooper    214-947-4463      
Principal Investigator: Parvez Mantry, MD         
Brook Army Medical Center Completed
Fort Sam Houston, Texas, United States, 78234
Salix Site Terminated
Galveston, Texas, United States, 77555
The Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Susan Dorman    713-441-6316      
Principal Investigator: Howard Monsour, Jr., MD         
United States, Virginia
McGuire VA Medical Center Recruiting
Richmond, Virginia, United States, 23249
Contact: Edith Gavis, RN    804-675-5584   
Principal Investigator: Jasmohan Bajaj, MD         
VCU/MCV Health Systems Recruiting
Richmond, Virginia, United States, 23298
Contact: Stephanie Taylor, RN    804-828-9311      
Principal Investigator: Arun Sanyal, MD         
United States, Washington
Swedish Medical Center Completed
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Valeant Pharmaceuticals International, Inc.
Study Director: Enoch Bortey, Ph.D. Valeant Pharmaceuticals International, Inc.

Responsible Party: Valeant Pharmaceuticals International, Inc. Identifier: NCT01846663     History of Changes
Other Study ID Numbers: RFHE4043
First Posted: May 3, 2013    Key Record Dates
Last Update Posted: April 27, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Valeant Pharmaceuticals International, Inc.:
Hepatic Encephalopathy
Liver Failure
Hepatic Insufficiency
Liver Diseases
Brain Diseases

Additional relevant MeSH terms:
Brain Diseases
Hepatic Encephalopathy
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Metabolic Diseases
Anti-Infective Agents
Gastrointestinal Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents