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

• Sponsor: Bausch Health Americas, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00298038
• Collaborator: (none)
• Enrollment: 299
• Arms: 2
• Actual Duration (Months): 31.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if the study drug is safe and effective in preventing hepatic encephalopathy (HE).

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Drug: Rifaximin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 299 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy, Safety and Tolerability of Rifaximin 550 mg BID For 6 Months In Preventing Hepatic Encephalopathy
• Actual Study Start Date: Dec 19, 2005
• Actual Primary Completion Date: Aug 15, 2008
• Actual Study Completion Date: Aug 15, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rifaximin Participants were administered a single rifaximin 550 milligram (mg) tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Drug: Rifaximin; Oral; Other Names: Xifaxan®
Placebo Comparator: Placebo Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Drug: Placebo; Oral

Outcome Measures

Primary Outcome Measures

1. Time To The First Breakthrough Overt HE Episode [Baseline up to 6 Months (168 days)]

   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.

Secondary Outcome Measures

1. Time To First HE-related Hospitalization [Baseline up to 6 months]

   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.

2. Time To Any Increase From Baseline In Conn Score [Baseline up to 6 months]

   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.

3. Time To Any Increase From Baseline In Asterixis Grade [Baseline up to 6 months]

   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.

4. Mean Change From Baseline In Fatigue Domain Score On The CLDQ At End Of Treatment [Baseline, 6 months (End Of Treatment)]

   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).

5. Mean Change From Baseline In Venous Ammonia Concentration At End Of Treatment [Baseline, Month 6 (End Of Treatment)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must sign an Informed Consent Form

• In remission from past HE

• Uses appropriate birth control measures

• More than or equal to 18 years of age

• Must have potential to benefit from treatment

• Recent prior HE episodes

• Capable and willing to comply with all study procedures

• Participant has personal support available

• Has a certain Model End Stage Liver Disease (MELD) score

• Recent transjugular intrahepatic portosystemic shunt (TIPS) placement or revision

Exclusion Criteria:

• Significant medical conditions, medical conditions that may impact study participation, or Investigator decision not to include

• Allergies to the study drug or similar drugs

• Laboratory abnormalities

• Recent participation in another clinical trial

• History of non-compliance

• Pregnant or at risk of pregnancy, or is lactating

• Recent alcohol consumption

• Active bacterial or viral Infections

• Bowel issues

• Active malignancy

• On a prohibited medication

• Liver transplant expected in near term

• Lactulose intolerance

• Participant shows presence of intestinal obstruction or has inflammatory bowel disease

• Ongoing or recent GI bleed

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Bausch Health Americas, Inc.

Investigators

• Study Director: Lindsey Mathew, Bausch Health Companies

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bausch Health Americas, Inc.
• ClinicalTrials.gov Identifier: NCT00298038
• Other Study ID Numbers: RFHE3001
• First Posted: Mar 1, 2006
• Last Update Posted: Sep 18, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Hepatic Encephalopathy; Brain Diseases; Rifaximin

Study Results

Participant Flow

Pre-assignment Detail	Participants were to be withdrawn from the study after experiencing a breakthrough overt hepatic encephalopathy (HE) episode.

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 milligrams (mg) tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Period Title: Overall Study
STARTED	140	159
Received At Least 1 Dose Of Study Drug	140	159
COMPLETED	88	66
NOT COMPLETED	52	93

Baseline Characteristics

Arm/Group Title	Rifaximin	Placebo	Total
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Total of all reporting groups
Overall Participants	140	159	299
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (9.57)	56.8 (9.18)	56.2 (56.0)
Sex: Female, Male (Count of Participants)
Female	65 46.4%	52 32.7%	117 39.1%
Male	75 53.6%	107 67.3%	182 60.9%

Outcome Measures

1. Primary Outcome

Title	Time To The First Breakthrough Overt HE Episode
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Measure Participants	140	159
0 to <28 Days	13	20
28 to <56 Days	4	23
56 to <84 Days	6	14
84 to <140 Days	7	10
140 to <168 Days	1	6
≥168 Days	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rifaximin, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Analysis based on the overall comparison of time to the first breakthrough overt HE episode between rifaximin and placebo groups adjusting for analysis region, using the Cox proportional hazards model (Score test, [that is, Log rank test stratified by analysis region]) with a 2-sided test at a significance level of 0.05 under the proportional hazards assumption.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.421
	Confidence Interval	(2-Sided) 95%; 0.276 to 0.641
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time To First HE-related Hospitalization
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Measure Participants	140	159
0 to <28 Days	4	11
28 to <56 Days	4	12
56 to <84 Days	4	7
84 to 140 Days	5	4
140 to <168 Days	2	2
≥168 Days	0	0

3. Secondary Outcome

Title	Time To Any Increase From Baseline In Conn Score
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Measure Participants	140	159
0 to <28 Days	17	26
28 to <56 Days	5	21
56 to <84 Days	9	15
84 to <140 Days	5	10
140 to <168 Days	0	5
≥168 Days	1	0

4. Secondary Outcome

Title	Time To Any Increase From Baseline In Asterixis Grade
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Measure Participants	140	159
0 to <28 Days	13	20
28 to <56 Days	7	15
56 to <84 Days	7	4
84 to <140 Days	3	6
140 to <168 Days	1	4
≥168 Days	1	1

5. Secondary Outcome

Title	Mean Change From Baseline In Fatigue Domain Score On The CLDQ At End Of Treatment
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Measure Participants	140	159
Baseline	3.28 (1.326)	3.34 (1.406)
Change from Baseline	0.30 (1.262)	0.11 (1.319)

6. Secondary Outcome

Title	Mean Change From Baseline In Venous Ammonia Concentration At End Of Treatment
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Rifaximin	Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.	Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
Measure Participants	140	159
Baseline	87.9 (47.76)	92.1 (55.24)
Change from Baseline	-5.7 (46.77)	-1.2 (60.98)

Adverse Events

Time Frame	Baseline up to 6.5 months
Adverse Event Reporting Description	Randomized participants who received at least 1 dose of study drug (ITT population).
Arm/Group Title	Rifaximin		Placebo
Arm/Group Description	Participants were administered a single rifaximin 550 mg tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.		Participants were administered a single matching placebo tablet 2 times per day (approximately every 12 hours) for 6 months or until a breakthrough episode of hepatic encephalopathy or another reason for discontinuation.
All Cause Mortality
	Rifaximin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Rifaximin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/140 (36.4%)		63/159 (39.6%)
Blood and lymphatic system disorders
Anaemia	4/140 (2.9%)		0/159 (0%)
Disseminated intravascular coagulation	1/140 (0.7%)		0/159 (0%)
Cardiac disorders
Acute myocardial infarction	1/140 (0.7%)		0/159 (0%)
Atrial fibrillation	1/140 (0.7%)		2/159 (1.3%)
Cardiac arrest	1/140 (0.7%)		0/159 (0%)
Cardiac failure congestive	2/140 (1.4%)		2/159 (1.3%)
Coronary artery disease	0/140 (0%)		1/159 (0.6%)
Myocardial infarction	0/140 (0%)		1/159 (0.6%)
Ear and labyrinth disorders
Vertigo	0/140 (0%)		1/159 (0.6%)
Eye disorders
Endophthalmitis	1/140 (0.7%)		0/159 (0%)
Gastrointestinal disorders
Ascites	4/140 (2.9%)		4/159 (2.5%)
Abdominal hernia	1/140 (0.7%)		0/159 (0%)
Abdominal pain	2/140 (1.4%)		1/159 (0.6%)
Constipation	0/140 (0%)		1/159 (0.6%)
Diarrhoea	1/140 (0.7%)		1/159 (0.6%)
Gastritis	1/140 (0.7%)		0/159 (0%)
Gastrointestinal haemorrhage	1/140 (0.7%)		3/159 (1.9%)
Lower gastrointestinal haemorrhage	1/140 (0.7%)		0/159 (0%)
Nausea	1/140 (0.7%)		0/159 (0%)
Oesophageal varices haemorrhage	4/140 (2.9%)		2/159 (1.3%)
Peritonitis	1/140 (0.7%)		1/159 (0.6%)
Rectal haemorrhage	0/140 (0%)		1/159 (0.6%)
Upper gastrointestinal haemorrhage	0/140 (0%)		2/159 (1.3%)
Vomiting	3/140 (2.1%)		0/159 (0%)
Abdominal distension	1/140 (0.7%)		1/159 (0.6%)
General disorders
Asthenia	0/140 (0%)		1/159 (0.6%)
Chest pain	1/140 (0.7%)		0/159 (0%)
Generalised oedema	3/140 (2.1%)		2/159 (1.3%)
Multi-organ failure	1/140 (0.7%)		1/159 (0.6%)
Pyrexia	1/140 (0.7%)		0/159 (0%)
Hepatobiliary disorders
Biliary cirrhosis primary	1/140 (0.7%)		0/159 (0%)
Cholecystitis acute	0/140 (0%)		1/159 (0.6%)
Cholecystitis chronic	0/140 (0%)		1/159 (0.6%)
Cholestasis	0/140 (0%)		1/159 (0.6%)
Cirrhosis alcoholic	1/140 (0.7%)		0/159 (0%)
Hepatic cirrhosis	3/140 (2.1%)		6/159 (3.8%)
Hepatic failure	1/140 (0.7%)		1/159 (0.6%)
Portal hypertension	0/140 (0%)		1/159 (0.6%)
Portal vein thrombosis	1/140 (0.7%)		0/159 (0%)
Immune system disorders
Liver transplant rejection	1/140 (0.7%)		0/159 (0%)
Infections and infestations
Arthritis bacterial	0/140 (0%)		1/159 (0.6%)
Bacteraemia	1/140 (0.7%)		1/159 (0.6%)
Bronchitis	0/140 (0%)		1/159 (0.6%)
Cellulitis	3/140 (2.1%)		2/159 (1.3%)
Clostridium colitis	2/140 (1.4%)		0/159 (0%)
Gastroenteritis	1/140 (0.7%)		0/159 (0%)
Oesophageal candidiasis	0/140 (0%)		1/159 (0.6%)
Peritonitis bacterial	1/140 (0.7%)		3/159 (1.9%)
Pneumonia	4/140 (2.9%)		1/159 (0.6%)
Sepsis	0/140 (0%)		2/159 (1.3%)
Urinary tract infection	2/140 (1.4%)		1/159 (0.6%)
Urosepsis	1/140 (0.7%)		1/159 (0.6%)
Injury, poisoning and procedural complications
Injury	0/140 (0%)		1/159 (0.6%)
Patella fracture	0/140 (0%)		1/159 (0.6%)
Post procedural haematoma	0/140 (0%)		1/159 (0.6%)
Investigations
Troponin increased	0/140 (0%)		1/159 (0.6%)
Metabolism and nutrition disorders
Decreased appetite	1/140 (0.7%)		0/159 (0%)
Dehydration	1/140 (0.7%)		1/159 (0.6%)
Fluid overload	1/140 (0.7%)		0/159 (0%)
Hyperglycaemia	1/140 (0.7%)		1/159 (0.6%)
Hyperkalaemia	2/140 (1.4%)		0/159 (0%)
Hypoglycaemia	0/140 (0%)		1/159 (0.6%)
Hyponatraemia	1/140 (0.7%)		1/159 (0.6%)
Musculoskeletal and connective tissue disorders
Tendonitis	0/140 (0%)		1/159 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic myeloid leukaemia	0/140 (0%)		1/159 (0.6%)
Hepatic neoplasm malignant	2/140 (1.4%)		2/159 (1.3%)
Hepatic neoplasm malignant resectable	0/140 (0%)		1/159 (0.6%)
Nervous system disorders
Dizziness	0/140 (0%)		1/159 (0.6%)
Hepatic encephalopathy	16/140 (11.4%)		34/159 (21.4%)
Syncope	2/140 (1.4%)		1/159 (0.6%)
Psychiatric disorders
Alcohol withdrawal syndrome	0/140 (0%)		1/159 (0.6%)
Suicidal ideation	1/140 (0.7%)		0/159 (0%)
Renal and urinary disorders
Renal failure	0/140 (0%)		2/159 (1.3%)
Renal failure acute	2/140 (1.4%)		4/159 (2.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/140 (0.7%)		0/159 (0%)
Epistaxis	0/140 (0%)		1/159 (0.6%)
Haemoptysis	0/140 (0%)		1/159 (0.6%)
Hepatopulmonary syndrome	0/140 (0%)		1/159 (0.6%)
Hydrothorax	1/140 (0.7%)		0/159 (0%)
Pleural effusion	2/140 (1.4%)		0/159 (0%)
Respiratory failure	0/140 (0%)		1/159 (0.6%)
Tachypnoea	0/140 (0%)		1/159 (0.6%)
Social circumstances
Respite care	1/140 (0.7%)		0/159 (0%)
Vascular disorders
Hypotension	1/140 (0.7%)		2/159 (1.3%)
Other (Not Including Serious) Adverse Events
	Rifaximin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/140 (65%)		101/159 (63.5%)
Blood and lymphatic system disorders
Anaemia	7/140 (5%)		6/159 (3.8%)
Gastrointestinal disorders
Nausea	19/140 (13.6%)		21/159 (13.2%)
Diarrhoea	15/140 (10.7%)		21/159 (13.2%)
Ascites	15/140 (10.7%)		13/159 (8.2%)
Abdominal pain	11/140 (7.9%)		13/159 (8.2%)
Vomiting	8/140 (5.7%)		14/159 (8.8%)
Abdominal distension	10/140 (7.1%)		11/159 (6.9%)
Constipation	9/140 (6.4%)		9/159 (5.7%)
Abdominal pain upper	9/140 (6.4%)		8/159 (5%)
General disorders
Pyrexia	8/140 (5.7%)		5/159 (3.1%)
Fatigue	17/140 (12.1%)		18/159 (11.3%)
Oedema peripheral	21/140 (15%)		13/159 (8.2%)
Asthenia	4/140 (2.9%)		11/159 (6.9%)
Infections and infestations
Nasopharyngitis	10/140 (7.1%)		10/159 (6.3%)
Urinary tract infection	6/140 (4.3%)		14/159 (8.8%)
Musculoskeletal and connective tissue disorders
Muscle spasms	13/140 (9.3%)		11/159 (6.9%)
Back pain	9/140 (6.4%)		10/159 (6.3%)
Arthralgia	9/140 (6.4%)		4/159 (2.5%)
Nervous system disorders
Headache	14/140 (10%)		17/159 (10.7%)
Dizziness	18/140 (12.9%)		12/159 (7.5%)
Hepatic encephalopathy	8/140 (5.7%)		16/159 (10.1%)
Psychiatric disorders
Insomnia	10/140 (7.1%)		11/159 (6.9%)
Depression	10/140 (7.1%)		8/159 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	10/140 (7.1%)		11/159 (6.9%)
Dyspnoea	9/140 (6.4%)		7/159 (4.4%)
Skin and subcutaneous tissue disorders
Pruritus	13/140 (9.3%)		10/159 (6.3%)
Rash	7/140 (5%)		6/159 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Please contact Sponsor directly for additional information.