Clinical trial NCT02086825: A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
Official title: A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hepatic Encephalopathy
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2014-03-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older
2. Cirrhosis of the liver based on biopsy or clinical and radiographic criteria
3. Ability to provide informed consent (Grade 0 to 1 HE)
4. Acute renal failure (increase in baseline creatinine of 0.5mg/dL to a value of \>2.0 mg/dL within 3 days).
5. 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:

1. Previous history of sensitivity/allergy to lactulose or rifaximin or rifampin
2. Pregnancy
3. Inability to obtain informed consent

Primary outcomes:
measure: Development of Progressive Hepatic Encephalopathy to Stage 3 or 4 in patients with progressive renal failure
timeFrame: 90 days (including follow-ups)
Secondary outcomes:
measure: In-hospital mortality
timeFrame: Patient's hospital stay up to 14 days
measure: Hospital Length of Stay
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
Study officials:
affiliation: NYU MEDICAL CENTER
name: Samuel Sigal
role: PRINCIPAL_INVESTIGATOR
References: