A Randomized Comparison of Rifaximin Versus Lactulose in Hospitalized Cirrhotic Patients With Renal Failure
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.
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.
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