- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02086825
A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Phase
- Phase 3
Contacts and Locations
Study Locations
-
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New York
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New York, New York, United States, 10010
- New York University Langone Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- Previous history of sensitivity/allergy to lactulose or rifaximin or rifampin
- Pregnancy
- Inability to obtain informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rifaximin
|
(Xifaxin®, Salix Pharmaceuticals) 550mg tablet twice daily.
Other Names:
|
Experimental: Lactulose
|
20g dose titrated
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
90 days (including follow-ups)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
In-hospital mortality
Time Frame: Patient's hospital stay up to 14 days
|
Patient's hospital stay up to 14 days
|
Hospital Length of Stay
Time Frame: Up to 14 days
|
Up to 14 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Samuel Sigal, NYU Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Liver Failure
- Hepatic Insufficiency
- Metabolic Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Kidney Diseases
- Urologic Diseases
- Liver Diseases
- Brain Diseases, Metabolic
- Renal Insufficiency
- Hepatic Encephalopathy
- Brain Diseases
- Anti-Infective Agents
- Gastrointestinal Agents
- Anti-Bacterial Agents
- Rifaximin
- Lactulose
Other Study ID Numbers
- 11-00665
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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