Hepatic EncephalopathyPhase 4NCT01842581
The Safety/Efficacy of Rifaximin With/Without Lactulose in Participants With A History of Recurrent Hepatic Encephalopathy
A Phase 4 study testing Rifaximin and Lactulose in people with Hepatic Encephalopathy and Cirrhosis, run by Bausch Health Americas, Inc. at 43 sites in United States.
Trial summary
The purpose of the study is to evaluate if rifaximin alone or rifaximin plus lactulose delays the onset of hepatic encephalopathy (HE) in participants with cirrhosis who have had a previous episode of HE. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy, Cirrhosis
- What is being tested?
- Rifaximin and Lactulose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 43 sitesUnited States
- Study dates
- 8 Jan 2013to 17 Dec 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or non-pregnant, non-lactating females greater than or equal to (≥) 18 years old.
- In remission from demonstrated overt HE (Conn score 0 or 1).
- Have had one or more episodes of overt HE associated with cirrhosis within 6 months prior to screening visit (Day -7 to -1).
- Participant has a close family member or other personal contact who is familiar with the participant's HE and can provide continuing oversight to the participant and is willing to perform as caregiver for the participant during the conduct of the trial.
Who cannot join
- Participant has been diagnosed with human immunodeficiency virus (HIV) as determined by medical history.
- History of tuberculosis infection.
- Participant has been diagnosed with chronic respiratory insufficiency.
- Participant has been diagnosed with a current infection for which they are currently taking oral or parenteral antibiotics.
- Renal insufficiency requiring routine dialysis.
- Participant has an active spontaneous bacterial peritonitis(SBP) infection.
Show all 11Show fewer
- Intestinal obstruction or inflammatory bowel disease.
- Participant has active malignancy within the last 5 years prior to screening visit, except basal cell carcinoma of the skin, or if female, in situ cervical carcinoma that has been surgically excised.
- Current gastrointestinal (GI) bleeding or has a history of a GI hemorrhage of sufficient severity to require hospitalization and a transfusion of ≥2 units of blood within 3 months prior to screening visit.
- Participant is anemic, as defined by a hemoglobin of less than (<) 8 grams/deciliter (g/dL).
- Scheduled to receive a liver transplant within 1 month of screening.
Trial locations and contacts
43 sites in 1 country.
43 sites in 1 country
United States43 sites
Asheville Gastroenterology Associates, PA
Asheville, North Carolina, 28801
University of Colorado Denver
Aurora, Colorado, 80045
The Center for Liver and Biliary Disease
Baltimore, Maryland, 21202-2165
Brigham and Women's Hospital Division of Gastroenterology & Hepatology
Boston, Massachusetts, 02115
UNC School of Medicine/Division of Gastroenterology and Hepatology
Chapel Hill, North Carolina, 27599-7584
Carolina Medical Center
Charlotte, North Carolina, 28204
Salix Site
Chicago, Illinois, 60611
Southern California Liver Centers
Coronado, California, 92118
Central Iowa Hospital Corp
Des Moines, Iowa, 50309-1453
South Denver GI
Englewood, Colorado, 80113
UCSF/Fresno - CRMC
Fresno, California, 93721
University of Florida Hepatology
Gainesville, Florida, 32610-0277
Research Specialists of Texas
Houston, Texas, 77030
Amcare Research Inc
Houston, Texas, 77090
Indiana University
Indianapolis, Indiana, 46202
Salix Site
Jefferson, Louisiana, 70124
Kansas City Research Institute
Kansas City, Missouri, 64131
UCSD Clinical & Translational Research Institute
La Jolla, California, 92037
Salix Site
Long Beach, California, 90822
Gastroenterology Associates
Macon, Georgia, 31201
University of Wisconsin Hospital & Clinics
Madison, Wisconsin, 53792
Delta Research Partners, LLC
Monroe, Louisiana, 71201
Concorde Medical Group PLLC
New York, New York, 10016
New York University Medical Center
New York, New York, 10016
Salix Site
New York, New York, 10016
Columbia University Medical Ctr. Center for Liver Disease & Transplantation
New York, New York, 10032
Salix Site
Odessa, Texas, 79761
Integris Nazh Zuhdi Transplant Institute
Oklahoma City, Oklahoma, 73112
Univ. of Nebraska Medical Center
Omaha, Nebraska, 68198-3285
Albert Einstien Medical Center
Philadelphia, Pennsylvania, 19141
Banner Research
Phoenix, Arizona, 85016
Inland Empire Liver Foundation
Rialto, California, 92377
VCU/MCV Health Systems
Richmond, Virginia, 23298
Salix Site
Riverside, California, 92501
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester Strong Memorial Hospital
Rochester, New York, 14642
University of Utah Hospital
Salt Lake City, Utah, 84132
Alamo Medical Research
San Antonio, Texas, 78215
Methodist Hospital
San Antonio, Texas, 78229
Salix Site
San Diego, California, 92103
Salix Site
San Francisco, California, 94115
St. Louis University
St Louis, Missouri, 63104
Tampa General Medical Group
Tampa, Florida, 33605
About this study
Official title: A Multicenter, Randomized, Open-Label, Active-Controlled, Trial to Evaluate the Safety and Efficacy of Rifaximin 550 mg With and Without Lactulose in Subjects With a History of Recurrent Overt Hepatic Encephalopathy
The purpose of the study is to evaluate if rifaximin alone or rifaximin plus lactulose delays the onset of hepatic encephalopathy (HE) in participants with cirrhosis who have had a previous episode of HE.
- Conditions
- Hepatic Encephalopathy, Cirrhosis
- Being tested
- Rifaximin, Lactulose
- Keywords
- Liver Failure, Hepatic Insufficiency, Liver Diseases, Brain Diseases, Rifaximin, Cirrhosis
- Medical subject headings
- Hepatic Encephalopathy, Fibrosis, Liver Failure, Hepatic Insufficiency, Liver Diseases, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifaximinDrug
Also called Xifaxan®
Rifaximin will be administered per the dose and schedule specified in the arms.
LactuloseDrug
Laculose will be administered per the schedule specified in the respective arm.
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin 550 mg BID | Experimental | Participants will receive rifaximin 550 milligrams (mg) tablet orally twice daily (BID) for 24 weeks. Receives: Drug: Rifaximin |
| Rifaximin 550 mg BID + Lactulose | Experimental | Participants will receive rifaximin 550 mg tablet orally BID with lactulose solution for 24 weeks. Lactulose dose will be self-titrated by the participant to produce 2 to 3 soft stools per day. Receives: Drug: Rifaximin; Drug: Lactulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting a First Breakthrough HE Episode
A breakthrough HE episode was defined as an increase of the Conn score to Grade greater than or equal to (≥) 2 (ie, 0 or 1 to ≥ 2). Conn score is widely used as a measure of mental state in HE. The scale used in Conn scoring system include: Grade 0=No personality or behavioral abnormality; Grade 1=Trivial lack of awareness, euphoria, or anxiety; shortened attention span, impairment of addition or subtraction; Grade 2=Lethargy, disorientation for time, obvious personality change, inappropriate behaviour; Grade 3=Somnolence to semi-stupor, responsive to stimuli, confused, gross disorientation, bizarre behaviour; Grade 4=Coma, unable to test mental state. The time to the first breakthrough HE episode was defined as the duration between the date of first dose of study drug and the date of first breakthrough HE episode. Number of participants reporting a first breakthrough HE episode during randomization to Month 6 is presented.
Measured: From randomization (Day 1) up to Day 170
Secondary outcomes (2)
Number of Participants Who Were Hospitalized Due to HE Episode
An HE-related hospitalization was defined as a hospitalization directly resulting from HE, or when HE events occurred during hospitalization. The time to first HE-related hospitalization was defined as the duration between the date of first dose of study drug and the date of first HE-related hospitalization. Number of participants who were hospitalized due to HE episode during randomization to Month 6 is presented.
Measured: From randomization (Day 1) up to Day 170
Number of Participants Who Died Due to Any Reason
Measured: From randomization (Day 1) up to end of study (Day 186)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2013 (estimated)
- Study start8 Jan 2013
- Primary completion17 Dec 2014
- Study completion17 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Bausch Health Americas, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bausch Health Americas, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lindsey Mathew, Study director, Bausch Health Americas, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01842581
- Sponsor's protocol ID
- RFHE4044
- Status last verified
- Sep 2019
- First submitted
- 16 Apr 2013
- Last updated
- 9 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.
PubMed 37467180
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Open-Label, Active-Controlled, Trial to Evaluate the Safety and Efficacy of Rifaximin 550 mg With and Without Lactulose in Subjects With a History of Recurrent Overt Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT01842581
- Acronym / sponsor ID
- RFHE4044
- Conditions
- Hepatic Encephalopathy, Cirrhosis
- Keywords
- Liver Failure, Hepatic Insufficiency, Liver Diseases, Brain Diseases, Rifaximin, Cirrhosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- Bausch Health Americas, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Jan 2013 (actual)
- Primary completion
- 17 Dec 2014 (actual)
- Study completion
- 17 Dec 2014 (actual)
- First posted
- 29 Apr 2013 (estimated)
- Results
- Posted 9 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate if rifaximin alone or rifaximin plus lactulose delays the onset of hepatic encephalopathy (HE) in participants with cirrhosis who have had a previous episode of HE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin 550 mg BID | Experimental | Drug: RifaximinParticipants will receive rifaximin 550 milligrams (mg) tablet orally twice daily (BID) for 24 weeks. |
| Rifaximin 550 mg BID + Lactulose | Experimental | Drug: Rifaximin, Drug: LactuloseParticipants will receive rifaximin 550 mg tablet orally BID with lactulose solution for 24 weeks. Lactulose dose will be self-titrated by the participant to produce 2 to 3 soft stools per day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or non-pregnant, non-lactating females greater than or equal to (≥) 18 years old.
- In remission from demonstrated overt HE (Conn score 0 or 1).
- Have had one or more episodes of overt HE associated with cirrhosis within 6 months prior to screening visit (Day -7 to -1).
- Participant has a close family member or other personal contact who is familiar with the participant's HE and can provide continuing oversight to the participant and is willing to perform as caregiver for the participant during the conduct of the trial.
Key exclusion criteria (11 listed)
- Participant has been diagnosed with human immunodeficiency virus (HIV) as determined by medical history.
- History of tuberculosis infection.
- Participant has been diagnosed with chronic respiratory insufficiency.
- Participant has been diagnosed with a current infection for which they are currently taking oral or parenteral antibiotics.
- Renal insufficiency requiring routine dialysis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RifaximinAlso: Xifaxan®Rifaximin will be administered per the dose and schedule specified in the arms. | Drug | Rifaximin 550 mg BID, Rifaximin 550 mg BID + Lactulose |
| LactuloseLaculose will be administered per the schedule specified in the respective arm. | Drug | Rifaximin 550 mg BID + Lactulose |
Primary outcome
Number of Participants Reporting a First Breakthrough HE Episode
Time frame: From randomization (Day 1) up to Day 170
A breakthrough HE episode was defined as an increase of the Conn score to Grade greater than or equal to (≥) 2 (ie, 0 or 1 to ≥ 2). Conn score is widely used as a measure of mental state in HE. The scale used in Conn scoring system include: Grade 0=No personality or behavioral abnormality; Grade 1=Trivial lack of awareness, euphoria, or anxiety; shortened attention span, impairment of addition or subtraction; Grade 2=Lethargy, disorientation for time, obvious personality change, inappropriate behaviour; Grade 3=Somnolence to semi-stupor, responsive to stimuli, confused, gross disorientation, bizarre behaviour; Grade 4=Coma, unable to test mental state. The time to the first breakthrough HE episode was defined as the duration between the date of first dose of study drug and the date of first breakthrough HE episode. Number of participants reporting a first breakthrough HE episode during randomization to Month 6 is presented.
2 secondary outcomes
Number of Participants Who Were Hospitalized Due to HE Episode
Time frame: From randomization (Day 1) up to Day 170
Number of Participants Who Died Due to Any Reason
Time frame: From randomization (Day 1) up to end of study (Day 186)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37467180Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindsey Mathew study director
Bausch Health Americas, Inc.
43 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifaximin and Lactulose in people with Hepatic Encephalopathy and Cirrhosis, run by Bausch Health Americas, Inc. at 43 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting a First Breakthrough HE Episode (time frame: From randomization (Day 1) up to Day 170). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01842581, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2019.