Rifaximin in Minimal Hepatic Encephalopathy

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.

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: placebo; Drug: Rifaximin

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychometric Test Performance	Z score of combined cognitive tests at end of rifaximin/placebo; higher scores indicate better psychometric test performance	8 weeks
Total Sickness Impact Profile Score	Total score ranging from 0 through >100 at the end of drug/placebo. Higher score indicates worse QOL	8 weeks

Collaborators and Investigators

• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
• Collaborators: Bausch Health Americas, Inc.
• Investigators: Principal Investigator: Jasmohan S Bajaj, MBBS, MD, MS, Medical College of Wisconsin

Publications and helpful links

General Publications

• Bajaj JS, Heuman DM, Wade JB, Gibson DP, Saeian K, Wegelin JA, Hafeezullah M, Bell DE, Sterling RK, Stravitz RT, Fuchs M, Luketic V, Sanyal AJ. Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology. 2011 Feb;140(2):478-487.e1. doi: 10.1053/j.gastro.2010.08.061. Epub 2010 Sep 21.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: September 20, 2007
• First Submitted That Met QC Criteria: September 21, 2007
• First Posted (Estimate): September 24, 2007

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Minimal hepatic encephalopathy
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: PRO00006863