The Safety/Efficacy of Rifaximin With/Without Lactulose in Participants With A History of Recurrent Hepatic Encephalopathy
A Multicenter, Randomized, Open-Label, Active-Controlled, Trial to Evaluate the Safety and Efficacy of Rifaximin 550 mg With and Without Lactulose in Subjects With a History of Recurrent Overt Hepatic Encephalopathy
1 other identifier
interventional
222
1 country
43
Brief Summary
The purpose of the study is to evaluate if rifaximin alone or rifaximin plus lactulose delays the onset of hepatic encephalopathy (HE) in participants with cirrhosis who have had a previous episode of HE.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jan 2013
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 8, 2013
CompletedFirst Submitted
Initial submission to the registry
April 16, 2013
CompletedFirst Posted
Study publicly available on registry
April 29, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 17, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 17, 2014
CompletedResults Posted
Study results publicly available
September 9, 2019
CompletedSeptember 9, 2019
September 1, 2019
1.9 years
April 16, 2013
August 15, 2019
September 6, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Reporting a First Breakthrough HE Episode
A breakthrough HE episode was defined as an increase of the Conn score to Grade greater than or equal to (≥) 2 (ie, 0 or 1 to ≥ 2). Conn score is widely used as a measure of mental state in HE. The scale used in Conn scoring system include: Grade 0=No personality or behavioral abnormality; Grade 1=Trivial lack of awareness, euphoria, or anxiety; shortened attention span, impairment of addition or subtraction; Grade 2=Lethargy, disorientation for time, obvious personality change, inappropriate behaviour; Grade 3=Somnolence to semi-stupor, responsive to stimuli, confused, gross disorientation, bizarre behaviour; Grade 4=Coma, unable to test mental state. The time to the first breakthrough HE episode was defined as the duration between the date of first dose of study drug and the date of first breakthrough HE episode. Number of participants reporting a first breakthrough HE episode during randomization to Month 6 is presented.
From randomization (Day 1) up to Day 170
Secondary Outcomes (2)
Number of Participants Who Were Hospitalized Due to HE Episode
From randomization (Day 1) up to Day 170
Number of Participants Who Died Due to Any Reason
From randomization (Day 1) up to end of study (Day 186)
Other Outcomes (3)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
From randomization (Day 1) up to end of study (Day 186)
Change From Baseline in Total Chronic Liver Disease Questionnaire (CLDQ) Score at Day 170
Baseline, Day 170
Change From Baseline in Critical Flicker Frequency (CFF) at Day 170
Baseline, Day 170
Study Arms (2)
Rifaximin 550 mg BID
EXPERIMENTALParticipants will receive rifaximin 550 milligrams (mg) tablet orally twice daily (BID) for 24 weeks.
Rifaximin 550 mg BID + Lactulose
EXPERIMENTALParticipants will receive rifaximin 550 mg tablet orally BID with lactulose solution for 24 weeks. Lactulose dose will be self-titrated by the participant to produce 2 to 3 soft stools per day.
Interventions
Eligibility Criteria
You may qualify if:
- Male or non-pregnant, non-lactating females greater than or equal to (≥) 18 years old.
- In remission from demonstrated overt HE (Conn score 0 or 1).
- Have had one or more episodes of overt HE associated with cirrhosis within 6 months prior to screening visit (Day -7 to -1).
- Participant has a close family member or other personal contact who is familiar with the participant's HE and can provide continuing oversight to the participant and is willing to perform as caregiver for the participant during the conduct of the trial.
You may not qualify if:
- Participant has been diagnosed with human immunodeficiency virus (HIV) as determined by medical history.
- History of tuberculosis infection.
- Participant has been diagnosed with chronic respiratory insufficiency.
- Participant has been diagnosed with a current infection for which they are currently taking oral or parenteral antibiotics.
- Renal insufficiency requiring routine dialysis.
- Participant has an active spontaneous bacterial peritonitis(SBP) infection.
- Intestinal obstruction or inflammatory bowel disease.
- Participant has active malignancy within the last 5 years prior to screening visit, except basal cell carcinoma of the skin, or if female, in situ cervical carcinoma that has been surgically excised.
- Current gastrointestinal (GI) bleeding or has a history of a GI hemorrhage of sufficient severity to require hospitalization and a transfusion of ≥2 units of blood within 3 months prior to screening visit.
- Participant is anemic, as defined by a hemoglobin of less than (\<) 8 grams/deciliter (g/dL).
- Scheduled to receive a liver transplant within 1 month of screening.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (43)
Banner Research
Phoenix, Arizona, 85016, United States
Southern California Liver Centers
Coronado, California, 92118, United States
UCSF/Fresno - CRMC
Fresno, California, 93721, United States
UCSD Clinical & Translational Research Institute
La Jolla, California, 92037, United States
Salix Site
Long Beach, California, 90822, United States
Inland Empire Liver Foundation
Rialto, California, 92377, United States
Salix Site
Riverside, California, 92501, United States
Salix Site
San Diego, California, 92103, United States
Salix Site
San Francisco, California, 94115, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
South Denver GI
Englewood, Colorado, 80113, United States
University of Florida Hepatology
Gainesville, Florida, 32610-0277, United States
Tampa General Medical Group
Tampa, Florida, 33605, United States
Gastroenterology Associates
Macon, Georgia, 31201, United States
Salix Site
Chicago, Illinois, 60611, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Central Iowa Hospital Corp
Des Moines, Iowa, 50309-1453, United States
Salix Site
Jefferson, Louisiana, 70124, United States
Delta Research Partners, LLC
Monroe, Louisiana, 71201, United States
The Center for Liver and Biliary Disease
Baltimore, Maryland, 21202-2165, United States
Brigham and Women's Hospital Division of Gastroenterology & Hepatology
Boston, Massachusetts, 02115, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Kansas City Research Institute
Kansas City, Missouri, 64131, United States
St. Louis University
St Louis, Missouri, 63104, United States
Univ. of Nebraska Medical Center
Omaha, Nebraska, 68198-3285, United States
Concorde Medical Group PLLC
New York, New York, 10016, United States
New York University Medical Center
New York, New York, 10016, United States
Salix Site
New York, New York, 10016, United States
Columbia University Medical Ctr. Center for Liver Disease & Transplantation
New York, New York, 10032, United States
University of Rochester Strong Memorial Hospital
Rochester, New York, 14642, United States
Asheville Gastroenterology Associates, PA
Asheville, North Carolina, 28801, United States
UNC School of Medicine/Division of Gastroenterology and Hepatology
Chapel Hill, North Carolina, 27599-7584, United States
Carolina Medical Center
Charlotte, North Carolina, 28204, United States
Integris Nazh Zuhdi Transplant Institute
Oklahoma City, Oklahoma, 73112, United States
Albert Einstien Medical Center
Philadelphia, Pennsylvania, 19141, United States
Research Specialists of Texas
Houston, Texas, 77030, United States
Amcare Research Inc
Houston, Texas, 77090, United States
Salix Site
Odessa, Texas, 79761, United States
Alamo Medical Research
San Antonio, Texas, 78215, United States
Methodist Hospital
San Antonio, Texas, 78229, United States
University of Utah Hospital
Salt Lake City, Utah, 84132, United States
VCU/MCV Health Systems
Richmond, Virginia, 23298, United States
University of Wisconsin Hospital & Clinics
Madison, Wisconsin, 53792, United States
Related Publications (1)
Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.
PMID: 37467180DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The rifaximin monotherapy arm included a subset of rifaximin/lactulose dependent participants for whom lactulose was withdrawn upon randomization (88.5% of participants in that group), which led to earlier HE breakthrough in this subset.
Results Point of Contact
- Title
- Director of Clinical Operations
- Organization
- Bausch Health Americas, Inc.
Study Officials
- STUDY DIRECTOR
Lindsey Mathew
Bausch Health Americas, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 16, 2013
First Posted
April 29, 2013
Study Start
January 8, 2013
Primary Completion
December 17, 2014
Study Completion
December 17, 2014
Last Updated
September 9, 2019
Results First Posted
September 9, 2019
Record last verified: 2019-09