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The Safety/Efficacy of Rifaximin With/Without Lactulose in Participants With A History of Recurrent Hepatic Encephalopathy

Phase 4
Completed
Conditions
Hepatic Encephalopathy
Cirrhosis
Interventions
Registration Number
NCT01842581
Lead Sponsor
Bausch Health Americas, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
222
Inclusion Criteria
  • 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.
Exclusion Criteria
  • 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Rifaximin 550 mg BIDRifaximinParticipants will receive rifaximin 550 milligrams (mg) tablet orally twice daily (BID) for 24 weeks.
Rifaximin 550 mg BID + LactuloseRifaximinParticipants 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.
Rifaximin 550 mg BID + LactuloseLactuloseParticipants 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.
Primary Outcome Measures
NameTimeMethod
Number of Participants Reporting a First Breakthrough HE EpisodeFrom randomization (Day 1) up to Day 170

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.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Who Died Due to Any ReasonFrom randomization (Day 1) up to end of study (Day 186)
Number of Participants Who Were Hospitalized Due to HE EpisodeFrom randomization (Day 1) up to Day 170

An HE-related hospitalization was defined as a hospitalization directly resulting from HE, or when HE events occurred during hospitalization. The time to first HE-related hospitalization was defined as the duration between the date of first dose of study drug and the date of first HE-related hospitalization. Number of participants who were hospitalized due to HE episode during randomization to Month 6 is presented.

Trial Locations

Locations (36)

The Center for Liver and Biliary Disease

🇺🇸

Baltimore, Maryland, United States

Inland Empire Liver Foundation

🇺🇸

Rialto, California, United States

Asheville Gastroenterology Associates, PA

🇺🇸

Asheville, North Carolina, United States

Albert Einstien Medical Center

🇺🇸

Philadelphia, Pennsylvania, United States

VCU/MCV Health Systems

🇺🇸

Richmond, Virginia, United States

UCSD Clinical & Translational Research Institute

🇺🇸

La Jolla, California, United States

University of Florida Hepatology

🇺🇸

Gainesville, Florida, United States

University of Rochester Strong Memorial Hospital

🇺🇸

Rochester, New York, United States

New York University Medical Center

🇺🇸

New York, New York, United States

Carolina Medical Center

🇺🇸

Charlotte, North Carolina, United States

Southern California Liver Centers

🇺🇸

Coronado, California, United States

Concorde Medical Group PLLC

🇺🇸

New York, New York, United States

Salix Site

🇺🇸

Odessa, Texas, United States

University of Wisconsin Hospital & Clinics

🇺🇸

Madison, Wisconsin, United States

Columbia University Medical Ctr. Center for Liver Disease & Transplantation

🇺🇸

New York, New York, United States

Research Specialists of Texas

🇺🇸

Houston, Texas, United States

Amcare Research Inc

🇺🇸

Houston, Texas, United States

Alamo Medical Research

🇺🇸

San Antonio, Texas, United States

Methodist Hospital

🇺🇸

San Antonio, Texas, United States

University of Utah Hospital

🇺🇸

Salt Lake City, Utah, United States

Integris Nazh Zuhdi Transplant Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Univ. of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Banner Research

🇺🇸

Phoenix, Arizona, United States

UCSF/Fresno - CRMC

🇺🇸

Fresno, California, United States

Gastroenterology Associates

🇺🇸

Macon, Georgia, United States

South Denver GI

🇺🇸

Englewood, Colorado, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Delta Research Partners, LLC

🇺🇸

Monroe, Louisiana, United States

Brigham and Women's Hospital Division of Gastroenterology & Hepatology

🇺🇸

Boston, Massachusetts, United States

St. Louis University

🇺🇸

Saint Louis, Missouri, United States

Central Iowa Hospital Corp

🇺🇸

Des Moines, Iowa, United States

University of Colorado Denver

🇺🇸

Aurora, Colorado, United States

Tampa General Medical Group

🇺🇸

Tampa, Florida, United States

Kansas City Research Institute

🇺🇸

Kansas City, Missouri, United States

UNC School of Medicine/Division of Gastroenterology and Hepatology

🇺🇸

Chapel Hill, North Carolina, United States

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