A 6-month Efficacy, Safety, and Tolerability Study of Rifaximin In Preventing Hepatic Encephalopathy

Time to a breakthrough overt HE episode was the duration (number of days) from time of first dose of study drug to the first breakthrough overt HE episode. A breakthrough overt HE episode was defined as an increase of Conn score from Grade 0 or 1 to ≥2, or an increase in Conn and asterixis score of 1 grade each for those participants who entered the study with a Conn score of 0. Participants who completed the study and did not experience a breakthrough overt HE episode were censored at the time of their 6-month visit. Participants who terminated early for reasons other than a breakthrough overt HE episode were contacted at 6 months from randomization to determine if they had experienced a breakthrough overt HE event or other outcome. Participants without breakthrough overt HE were censored at the time of last contact or death, whichever was earlier. The number of events of a first breakthrough overt HE episode during the treatment interval is presented.

Time frame: Baseline up to 6 Months (168 days)

Population: Randomized participants who received at least 1 dose of study drug (ITT population). Assuming censored cases were at risk for half of the interval for onset of breakthrough HE episode, the censored cases only counted for half in figuring number at risk. Numbers at risk were rounded up to whole integers.

The 29-item Chronic Liver Disease Questionnaire (CLDQ) questionnaire consists of the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. Participants ranked their level of fatigue by using a 7-point scale from the worst response (1, high degree of fatigue) to the best response (7, minimal fatigue).

Time frame: Baseline, 6 months (End Of Treatment)

Population: Randomized participants who received at least 1 dose of study drug (ITT population) and able to complete the questionnaire at the applicable time point.

Venous blood samples (10 mL) were collected at Baseline/Randomization (Day 0) and Days 28, 84, and 168. Baseline value was the last available value prior to first dose of study drug, and end of treatment value was the last available post-baseline value during the treatment period.

Time frame: Baseline, Month 6 (End Of Treatment)

Population: Randomized participants who received at least 1 dose of study drug (ITT population) with evaluable venous ammonia data.

Time to any increase in asterixis grade was computed as the number of days from the first dose of study drug to the initial occurrence of an increase from baseline in asterixis grade. Asterixis (flapping tremor) was determined with the participant holding both arms and forearms extended with wrists dorsiflexed and fingers open for ≥30 seconds per standard practice. Asterixis grade range: Grade 0 (no abnormal movement) to Grade 4 (almost continuous flapping motions). Participants who discontinued prior to experiencing an increase in asterixis grade and prior to completion of the 6-month treatment period were censored at the time of discontinuation. The number of events of the initial occurrence of an increase from baseline in asterixis grade during the treatment interval is presented.

Time frame: Baseline up to 6 months

Population: Randomized participants who received at least 1 dose of study drug (ITT population). Assuming censored cases were at risk for half of the interval for onset of breakthrough HE episode, the censored cases only counted for half in figuring number at risk. Numbers at risk were rounded up to whole integers.

Time to any increase in Conn score (mental state grade) was computed as the number of days from the first dose of study drug to the initial occurrence of an increase from baseline in Conn score. Conn score range: Grade 0 (no behavioral abnormality) to Grade 4 (coma; unable to test mental state). Participants who discontinued prior to experiencing an increase in Conn score and prior to completion of the 6-month treatment period were censored at the time of discontinuation. The number of events of the initial occurrence of an increase from baseline in Conn score during the treatment interval is presented.

Time frame: Baseline up to 6 months

Population: Randomized participants who received at least 1 dose of study drug (ITT population). Assuming censored cases were at risk for half of the interval for onset of breakthrough HE episode, the censored cases only counted for half in figuring number at risk. Numbers at risk were rounded up to whole integers.

Time to first HE-related hospitalization is defined as the duration (number of days) between the first dose of study drug and the date of first HE-related hospitalization. Participants who discontinued prior to hospitalization due to HE and prior to completion of the 6-month treatment period were censored at the time of discontinuation. The number of participants with their first HE-related hospitalization per interval is presented. The number of events of the first HE-related hospitalization during the treatment interval is presented.

Time frame: Baseline up to 6 months

Population: Randomized participants who received at least 1 dose of study drug (ITT population). Assuming censored cases were at risk for half of the interval for onset of breakthrough HE episode, the censored cases only counted for half in figuring number at risk. Numbers at risk were rounded up to whole integers.