Hepatic EncephalopathyPhase 3NCT02086825
A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
A Phase 3 study testing Rifaximin and Lactulose in people with Hepatic Encephalopathy, run by NYU Langone Health at 1 site in United States.
Trial summary
The aim of the current study is to determine whether rifaximin or lactulose is more effective in preventing the development of severe hepatic encephalopathy in hospitalized patients with cirrhosis and new onset kidney failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy
- 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
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Dec 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Age 18 years or older
- Cirrhosis of the liver based on biopsy or clinical and radiographic criteria
- Ability to provide informed consent (Grade 0 to 1 HE)
- Acute renal failure (increase in baseline creatinine of 0.5mg/dL to a value of >2.0 mg/dL within 3 days).
- Absence of improvement in renal function after adequate fluid resuscitation using either normal saline or blood products (25% salt poor albumin, fresh frozen plasma, or packed red blood cells)
Who cannot join
- Previous history of sensitivity/allergy to lactulose or rifaximin or rifampin
- Pregnancy
- Inability to obtain informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University Langone Medical Center
New York, New York, 10010
About this study
The aim of the current study is to determine whether rifaximin or lactulose is more effective in preventing the development of severe hepatic encephalopathy in hospitalized patients with cirrhosis and new onset kidney failure.
Subjects will be randomly assigned to one of two treatment groups:
Group A: Lactulose 20g dose titrated to 2-3 soft-formed bowel movements per day Group B: Rifaximin 550mg tablet twice daily.
Subjects will be followed daily for two weeks or until hospital discharge. Treatment success is defined as prevention of grade 3 or 4 HE during hospitalization.
Read the detailed description
Hepatic Encephalopathy (HE) is a reversible neuropsychiatric syndrome that develops in patients with cirrhosis due to the accumulation of a variety of toxic substances that are produced from bacteria in the gastrointestinal tract. It is characterized by slowing of function of the brain function and ranges in severity from mild cognitive impairment (grade 1), presence of a shaking tremor called asterixis (grade 2), lethargy but arousable state (grade 3), and coma (grade 4). Decreased kidney function exacerbates the condition, and hospitalized patients with cirrhosis with new onset kidney failure are at risk for the development of severe HE.
Possible treatments for HE include lactulose and antibiotics. Lactulose reduces the production of many of the toxins by the bacteria, and antibiotics work by reducing the number of bacteria in the gastrointestinal tract. Rifaximin is an antibiotic that is an antibiotic that is not absorbed, possesses a wide antibacterial spectrum, and was approved by the Food and Drug Administration in 3/2010 for prevention of relapse for patients with recurrent severe hepatic encephalopathy. The aim of the current study is to determine whether rifaximin or lactulose is more effective in preventing the development of severe hepatic encephalopathy in hospitalized patients with cirrhosis and new onset kidney failure.
To determine whether rifaximin or lactulose is more effective in preventing severe HE, seventy consecutive hospitalized patients with cirrhosis and new onset kidney failure will be recruited. New onset kidney failure will defined as a progressive and sustained increase in serum creatinine >0.5mg/dl from baseline to a value of 2.0mg/dl or greater within 3 days. Subjects will be randomly assigned to one of two treatment groups:
Group A: Lactulose 20g dose titrated to 2-3 soft-formed bowel movements per day Group B: Rifaximin 550mg tablet twice daily. Subjects will be followed daily for two weeks or until hospital discharge. Severity of hepatic encephalopathy will be graded by physical examination, review of hospital chart, and performance of standard paper and pencil tests that evaluates the ability to concentrate. In addition, approximately one tablespoon will be drawn twice a week at every 3 to 4 day for ammonia level and other toxins. A sample of breath will also be collected by having the subjects breathe into a collection bag to measure substances that determine whether there are bacteria present in the small intestine. Treatment success is defined as prevention of grade 3 or 4 HE during hospitalization.
- Conditions
- Hepatic Encephalopathy
- Being tested
- Rifaximin, Lactulose
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifaximinDrug
Also called Xifaxin
(Xifaxin®, Salix Pharmaceuticals) 550mg tablet twice daily.
LactuloseDrug
20g dose titrated
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin | Experimental | Not described Receives: Drug: Rifaximin |
| Lactulose | Experimental | Not described Receives: Drug: Lactulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of Progressive Hepatic Encephalopathy to Stage 3 or 4 in patients with progressive renal failure
The primary outcome for this study is the development of progressive hepatic encephalopathy to stage 3 or 4 in patients with progressive renal failure. For the purpose of this study, acute renal failure is defined as a progressive and sustained increase in serum creatinine >0.5mg/dl from baseline to a value of 2.0mg/dl, irrespective of etiology in 3 days. Renal failure is progressive and sustained if there is no improvement after volume resuscitation with 1.5 L of normal saline or equivalent colloid infusion (serum albumin or blood product transfusion).
Measured: 90 days (including follow-ups)
Secondary outcomes (2)
In-hospital mortality
Measured: Patient's hospital stay up to 14 days
Hospital Length of Stay
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2014 (estimated)
- Study startOct 2015
- Primary completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Sigal, Principal investigator, NYU MEDICAL CENTER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02086825
- Sponsor's protocol ID
- 11-00665
- Status last verified
- Mar 2016
- First submitted
- 11 Feb 2014
- Last updated
- 2 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
- ClinicalTrials.gov ID
- NCT02086825
- Acronym / sponsor ID
- 11-00665
- Conditions
- Hepatic Encephalopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Dec 2016 (estimated)
- First posted
- 13 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the current study is to determine whether rifaximin or lactulose is more effective in preventing the development of severe hepatic encephalopathy in hospitalized patients with cirrhosis and new onset kidney failure.
Subjects will be randomly assigned to one of two treatment groups:
Group A: Lactulose 20g dose titrated to 2-3 soft-formed bowel movements per day Group B: Rifaximin 550mg tablet twice daily.
Subjects will be followed daily for two weeks or until hospital discharge. Treatment success is defined as prevention of grade 3 or 4 HE during hospitalization.
Detailed description
Hepatic Encephalopathy (HE) is a reversible neuropsychiatric syndrome that develops in patients with cirrhosis due to the accumulation of a variety of toxic substances that are produced from bacteria in the gastrointestinal tract. It is characterized by slowing of function of the brain function and ranges in severity from mild cognitive impairment (grade 1), presence of a shaking tremor called asterixis (grade 2), lethargy but arousable state (grade 3), and coma (grade 4). Decreased kidney function exacerbates the condition, and hospitalized patients with cirrhosis with new onset kidney failure are at risk for the development of severe HE.
Possible treatments for HE include lactulose and antibiotics. Lactulose reduces the production of many of the toxins by the bacteria, and antibiotics work by reducing the number of bacteria in the gastrointestinal tract. Rifaximin is an antibiotic that is an antibiotic that is not absorbed, possesses a wide antibacterial spectrum, and was approved by the Food and Drug Administration in 3/2010 for prevention of relapse for patients with recurrent severe hepatic encephalopathy. The aim of the current study is to determine whether rifaximin or lactulose is more effective in preventing the development of severe hepatic encephalopathy in hospitalized patients with cirrhosis and new onset kidney failure.
To determine whether rifaximin or lactulose is more effective in preventing severe HE, seventy consecutive hospitalized patients with cirrhosis and new onset kidney failure will be recruited. New onset kidney failure will defined as a progressive and sustained increase in serum creatinine >0.5mg/dl from baseline to a value of 2.0mg/dl or greater within 3 days. Subjects will be randomly assigned to one of two treatment groups:
Group A: Lactulose 20g dose titrated to 2-3 soft-formed bowel movements per day Group B: Rifaximin 550mg tablet twice daily. Subjects will be followed daily for two weeks or until hospital discharge. Severity of hepatic encephalopathy will be graded by physical examination, review of hospital chart, and performance of standard paper and pencil tests that evaluates the ability to concentrate. In addition, approximately one tablespoon will be drawn twice a week at every 3 to 4 day for ammonia level and other toxins. A sample of breath will also be collected by having the subjects breathe into a collection bag to measure substances that determine whether there are bacteria present in the small intestine. Treatment success is defined as prevention of grade 3 or 4 HE during hospitalization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin | Experimental | Drug: Rifaximin |
| Lactulose | Experimental | Drug: Lactulose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 years or older
- Cirrhosis of the liver based on biopsy or clinical and radiographic criteria
- Ability to provide informed consent (Grade 0 to 1 HE)
- Acute renal failure (increase in baseline creatinine of 0.5mg/dL to a value of >2.0 mg/dL within 3 days).
- Absence of improvement in renal function after adequate fluid resuscitation using either normal saline or blood products (25% salt poor albumin, fresh frozen plasma, or packed red blood cells)
Key exclusion criteria (3 listed)
- Previous history of sensitivity/allergy to lactulose or rifaximin or rifampin
- Pregnancy
- Inability to obtain informed consent
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: Xifaxin(Xifaxin®, Salix Pharmaceuticals) 550mg tablet twice daily. | Drug | Rifaximin |
| Lactulose20g dose titrated | Drug | Lactulose |
Primary outcome
Development of Progressive Hepatic Encephalopathy to Stage 3 or 4 in patients with progressive renal failure
Time frame: 90 days (including follow-ups)
The primary outcome for this study is the development of progressive hepatic encephalopathy to stage 3 or 4 in patients with progressive renal failure. For the purpose of this study, acute renal failure is defined as a progressive and sustained increase in serum creatinine >0.5mg/dl from baseline to a value of 2.0mg/dl, irrespective of etiology in 3 days. Renal failure is progressive and sustained if there is no improvement after volume resuscitation with 1.5 L of normal saline or equivalent colloid infusion (serum albumin or blood product transfusion).
2 secondary outcomes
In-hospital mortality
Time frame: Patient's hospital stay up to 14 days
Hospital Length of Stay
Time frame: Up to 14 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2016.
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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.
Samuel Sigal principal investigator
NYU MEDICAL CENTER
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rifaximin and Lactulose in people with Hepatic Encephalopathy, run by NYU Langone Health at 1 site 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 5 inclusion and 3 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: withdrawn, as of the sponsor's last update on 2 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Development of Progressive Hepatic Encephalopathy to Stage 3 or 4 in patients with progressive renal failure (time frame: 90 days (including follow-ups)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Mar 2016.