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

Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01842581
• Other study ID #: RFHE4044
• Status: Completed
• Phase: Phase 4
• Start date: January 8, 2013
• Est. completion date: December 17, 2014

Study information

• Verified date: September 2019
• Source: Bausch Health Americas, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: December 17, 2014
• Est. primary completion date: December 17, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Cirrhosis
• Fibrosis
• Hepatic Encephalopathy

Intervention

Drug:
• Rifaximin
Rifaximin will be administered per the dose and schedule specified in the arms.
• Lactulose
Laculose will be administered per the schedule specified in the respective arm.

Locations

Country	Name	City	State
United States	Asheville Gastroenterology Associates, PA	Asheville	North Carolina
United States	University of Colorado Denver	Aurora	Colorado
United States	The Center for Liver and Biliary Disease	Baltimore	Maryland
United States	Brigham and Women's Hospital Division of Gastroenterology & Hepatology	Boston	Massachusetts
United States	UNC School of Medicine/Division of Gastroenterology and Hepatology	Chapel Hill	North Carolina
United States	Carolina Medical Center	Charlotte	North Carolina
United States	Salix Site	Chicago	Illinois
United States	Southern California Liver Centers	Coronado	California
United States	Central Iowa Hospital Corp	Des Moines	Iowa
United States	South Denver GI	Englewood	Colorado
United States	UCSF/Fresno - CRMC	Fresno	California
United States	University of Florida Hepatology	Gainesville	Florida
United States	Amcare Research Inc	Houston	Texas
United States	Research Specialists of Texas	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Salix Site	Jefferson	Louisiana
United States	Kansas City Research Institute	Kansas City	Missouri
United States	UCSD Clinical & Translational Research Institute	La Jolla	California
United States	Salix Site	Long Beach	California
United States	Gastroenterology Associates	Macon	Georgia
United States	University of Wisconsin Hospital & Clinics	Madison	Wisconsin
United States	Delta Research Partners, LLC	Monroe	Louisiana
United States	Columbia University Medical Ctr. Center for Liver Disease & Transplantation	New York	New York
United States	Concorde Medical Group PLLC	New York	New York
United States	New York University Medical Center	New York	New York
United States	Salix Site	New York	New York
United States	Salix Site	Odessa	Texas
United States	Integris Nazh Zuhdi Transplant Institute	Oklahoma City	Oklahoma
United States	Univ. of Nebraska Medical Center	Omaha	Nebraska
United States	Albert Einstien Medical Center	Philadelphia	Pennsylvania
United States	Banner Research	Phoenix	Arizona
United States	Inland Empire Liver Foundation	Rialto	California
United States	VCU/MCV Health Systems	Richmond	Virginia
United States	Salix Site	Riverside	California
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Strong Memorial Hospital	Rochester	New York
United States	St. Louis University	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Alamo Medical Research	San Antonio	Texas
United States	Methodist Hospital	San Antonio	Texas
United States	Salix Site	San Diego	California
United States	Salix Site	San Francisco	California
United States	Tampa General Medical Group	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bausch Health Americas, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAE was defined as an AE that occurred from first dose of study drug until last dose of study drug plus 5 days (for non-fatal AEs) or plus 30 days (for fatal AEs).A summary of non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.	From randomization (Day 1) up to end of study (Day 186)
Other	Change From Baseline in Total Chronic Liver Disease Questionnaire (CLDQ) Score at Day 170	CLDQ was used to measure health-related quality of life. CLDQ includes 29 items in the following 6 domains: abdominal symptoms (3 items), fatigue (5 items), systemic symptoms (5 items), activity (3 items), emotional function (8 items), and worry (5 items). All items were measured on a 7-point Likert scale, ranging from 0 to 6 with higher values indicating better quality of life. Each domain score of CLDQ was calculated as the mean of the responses of items in that domain. Overall CLDQ score was obtained by adding scores for each item and dividing by the total number of items. Overall CLDQ score ranged from 0 (most impairment) to 6 (least impairment) with higher scores indicating better quality of life. If at least half of the items were non-missing for a domain, mean values of the non-missing items for that domain were used as imputed values for missing values. If more than half of the items in a domain were missing, no values were imputed and domain score was considered as missing.	Baseline, Day 170
Other	Change From Baseline in Critical Flicker Frequency (CFF) at Day 170	The critical flicker frequency (CFF), a validated assessment of neurological function was assessed using a specialized CFF instrument. The CFF is the frequency at which the participant observes a constant light transition to a flickering light and was measured in Hertz. The CFF was measured on a continuous scale and was the mean of 8 separate fusion-to-flicker transition tests performed in rapid succession. Increases in CFF results represent improvement in neurological function in participants with HE.	Baseline, Day 170
Primary	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	Number of Participants Who Were Hospitalized Due to HE Episode	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.	From randomization (Day 1) up to Day 170
Secondary	Number of Participants Who Died Due to Any Reason		From randomization (Day 1) up to end of study (Day 186)