Rifaximin in Minimal Hepatic Encephalopathy

• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00533910
• Collaborator: Bausch Health Americas, Inc. (Industry)
• Enrollment: 42
• Location: 1
• Arms: 2
• Duration (Months): 31
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether alteration of gut flora with rifaximin can lead to improvement in driving performance, psychometric test performance, and quality of life in patients with minimal hepatic encephalopathy (MHE) and cirrhosis in a randomized, blinded, placebo-controlled trial.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Drug: Rifaximin; Drug: placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Rifaximin on Driving Performance, Psychometric Test Performance and Quality of Life in Cirrhotic Patients With Minimal Hepatic Encephalopathy: Randomized, Double-blind, Placebo-controlled Trial.
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Will be given placebo and follow the exact procedures as the experimental section	Drug: placebo; same as the experimental arm
Experimental: Drug	Drug: Rifaximin; 550mg BID rifaximin for 8 weeks

Outcome Measures

Primary Outcome Measures

1. Driving Performance [8 weeks]

   Total driving errors at the end of drug/placebo. Minimum is zero, maximum is not defined. Higher number indicates greater errors.

Secondary Outcome Measures

1. Psychometric Test Performance [8 weeks]

   Z score of combined cognitive tests at end of rifaximin/placebo; higher scores indicate better psychometric test performance

2. Total Sickness Impact Profile Score [8 weeks]

   Total score ranging from 0 through >100 at the end of drug/placebo. Higher score indicates worse QOL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-65 years

• Cirrhosis diagnosed on clinical grounds

• MHE diagnosed by abnormalities in a psychometric battery (NCT-A, NCT-B, ICT BDT and DST impaired beyond 2 standard deviations of known control values on any of the above 3 tests will be considered to have MHE)

• Current drivers (valid driving license and driving at least 20 miles/week)

• All women of child-bearing potential will be required to use effective contraception

Exclusion Criteria:

• Current or recent (< 6 month) use of alcohol (AUDIT questionnaire will be used; any cirrhotic with a value of > 0 will be excluded) and a positive blood alcohol level

• Use of antibiotics within last 6 weeks

• Allergy to rifaximin, rifabutin, rifampin, or rifapentine

• Infection or gastrointestinal hemorrhage within the last 6 weeks

• Renal insufficiency

• Hepatocellular carcinoma

• Psychoactive drug use, including interferon concurrently

• Non-drivers and those who drive less than 20 miles/week

• Pregnancy and breastfeeding

• Excluding patients with OHE:

• Detailed neurological examination to check for dysarthria, asterixis, ataxia and disorientation

• Detailed history-taking from friends/relatives only after taking the patient's permission

• Mini-mental status examination > 25

• Episode of overt (clinical hepatic encephalopathy) within 6 months

• Current treatment with lactulose, rifaximin, zinc, or metronidazole

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia	United States	23249

Sponsors and Collaborators

• Hunter Holmes Mcguire Veteran Affairs Medical Center
• Bausch Health Americas, Inc.

Investigators

• Principal Investigator: Jasmohan S Bajaj, MBBS, MD, MS, Medical College of Wisconsin

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center
• ClinicalTrials.gov Identifier: NCT00533910
• Other Study ID Numbers: PRO00006863
• First Posted: Sep 24, 2007
• Last Update Posted: Dec 17, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by Jasmohan Bajaj, Associate Professor of Medicine, Hunter Holmes Mcguire Veteran Affairs Medical Center: Minimal hepatic encephalopathy
• Additional relevant MeSH terms: Hepatic Encephalopathy; Brain Diseases; Rifaximin

Study Results

Participant Flow

Arm/Group Title	Placebo	Rifaximin
Arm/Group Description	Will be given placebo and follow the exact procedures as the experimental section placebo: same as the experimental arm	Rifaximin: 550mg BID rifaximin for 8 weeks
Period Title: Overall Study
STARTED	21	21
COMPLETED	21	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Rifaximin	Total
Arm/Group Description	Will be given placebo and follow the exact procedures as the experimental section placebo: same as the experimental arm	Rifaximin: 550mg BID rifaximin for 8 weeks	Total of all reporting groups
Overall Participants	21	21	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 100%	21 100%	42 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 23.8%	5 23.8%	10 23.8%
Male	16 76.2%	16 76.2%	32 76.2%
Region of Enrollment (participants) [Number]
United States	21 100%	21 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Driving Performance
Description	Total driving errors at the end of drug/placebo. Minimum is zero, maximum is not defined. Higher number indicates greater errors.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rifaximin
Arm/Group Description	Will be given placebo and follow the exact procedures as the experimental section placebo: same as the experimental arm	Rifaximin: 550mg BID rifaximin for 8 weeks
Measure Participants	21	21
Mean (Standard Deviation) [raw number of driving errors]	7.6 (3.9)	5.5 (3.8)

2. Secondary Outcome

Title	Psychometric Test Performance
Description	Z score of combined cognitive tests at end of rifaximin/placebo; higher scores indicate better psychometric test performance
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rifaximin
Arm/Group Description	Will be given placebo and follow the exact procedures as the experimental section placebo: same as the experimental arm	Rifaximin: 550mg BID rifaximin for 8 weeks
Measure Participants	21	21
Mean (Standard Deviation) [Z scores]	0.46 (0.17)	1.19 (0.24)

3. Secondary Outcome

Title	Total Sickness Impact Profile Score
Description	Total score ranging from 0 through >100 at the end of drug/placebo. Higher score indicates worse QOL
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rifaximin
Arm/Group Description	Will be given placebo and follow the exact procedures as the experimental section placebo: same as the experimental arm	Rifaximin: 550mg BID rifaximin for 8 weeks
Measure Participants	21	21
Mean (Standard Deviation) [score on a scale]	12 (3)	10 (2)

Adverse Events

Time Frame	8 weels
Adverse Event Reporting Description	Same as the ones in www.clinicaltrials.gov definitions
Arm/Group Title	Placebo		Rifaximin
Arm/Group Description	Will be given placebo and follow the exact procedures as the experimental section placebo: same as the experimental arm		Rifaximin: 550mg BID rifaximin for 8 weeks
All Cause Mortality
	Placebo		Rifaximin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Serious Adverse Events
	Placebo		Rifaximin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Rifaximin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.