Hepatic Encephalopathy
Conditions
Keywords
Minimal hepatic encephalopathy
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.
Interventions
DRUGRifaximin
550mg BID rifaximin for 8 weeks
DRUGplacebo
same as the experimental arm
Sponsors
Bausch Health Americas, Inc.
Hunter Holmes Mcguire Veteran Affairs Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Psychometric Test Performance | 8 weeks | Z score of combined cognitive tests at end of rifaximin/placebo; higher scores indicate better psychometric test performance |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Will be given placebo and follow the exact procedures as the experimental section
placebo: same as the experimental arm | 21 |
| Rifaximin Rifaximin: 550mg BID rifaximin for 8 weeks | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Placebo | Rifaximin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 21 Participants | 42 Participants |
| Region of Enrollment United States | 21 participants | 21 participants | 42 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
Driving Performance
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Driving Performance | 7.6 raw number of driving errors | Standard Deviation 3.9 |
| Rifaximin | Driving Performance | 5.5 raw number of driving errors | Standard Deviation 3.8 |
Secondary
Psychometric Test Performance
Z score of combined cognitive tests at end of rifaximin/placebo; higher scores indicate better psychometric test performance
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Psychometric Test Performance | 0.46 Z scores | Standard Deviation 0.17 |
| Rifaximin | Psychometric Test Performance | 1.19 Z scores | Standard Deviation 0.24 |
Secondary
Total Sickness Impact Profile Score
Total score ranging from 0 through \>100 at the end of drug/placebo. Higher score indicates worse QOL
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Sickness Impact Profile Score | 12 score on a scale | Standard Deviation 3 |
| Rifaximin | Total Sickness Impact Profile Score | 10 score on a scale | Standard Deviation 2 |