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

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.

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.

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.

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.

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.