Clinical trial NCT00558038: Safety and Efficacy of AST-120 Compared to Lactulose in Patients With Hepatic Encephalopathy
Official title: Comparison of Different Treatment Regimens in Patients With Stage 1-2 Type C Hepatic Encephalopathy: AST-120 vs Lactulose
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatic Encephalopathy
Keywords: Hepatic
Encephalopathy
Liver
Liver Disease
Liver Failure
Lactulose
AST-120
Lead sponsor: Ocera Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-11-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of the experimental drug AST-120 compared to lactulose in patients with mild hepatic encephalopathy.

Detailed description: This is a multi-center, open-label, four week trial comparing AST-120 to lactulose in patients with mild (Stage 1-2) hepatic encephalopathy.

Patients will be randomized into two groups:

* Lactulose
* AST-120

Patients meeting the inclusion criteria will take either AST-120 or lactulose for 4 weeks (28 days). AST-120 will be distributed in 2 gram sachets to be taken four times daily. Lactulose will be taken in the same formulation, at the same dose and frequency as previously prescribed for the individual patient.

Lactulose naïve patients who are randomized to lactulose will receive an initial dose of 30cc twice a day. The dose should be titrated at the discretion of the investigator until the patient is experiencing 2-3 soft stools per day.

Patients randomized to AST-120 will receive 2 grams four times a day for the duration of the study. Titration of AST-120 will NOT be allowed.

Patients will be evaluated throughout the study for efficacy and safety. A follow-up visit will be scheduled 1 week after the end of the 4 week treatment period.

Eligibility criteria: Inclusion Criteria:

* Patients with End Stage Liver Disease secondary to any cause (patients who have undergone portosystemic shunting (TIPS) procedure \> 3 months prior to randomization can be included)
* Lactulose naïve patients or patients currently on an established dose of lactulose
* MELD score ≤ 15 (MELD score up to 20 is allowable if it has remained stable for at least 3 months)
* Meet the criteria for Stage 1-2 hepatic encephalopathy according to the Westhaven Scale
* Patients must have discontinued rifaximin or other oral antibiotics for at least 48 hours prior to randomization
* Able and willing to comply with all protocol procedures for the planned duration of the study
* Able and willing to understand, sign and date an informed consent document, and authorize access to protected health information
* Have a person (spouse, relative, or friend) willing to accompany the patient to the study visits (patients in this condition are not recommended to drive a vehicle)
* Females must be postmenopausal, surgically incapable of bearing children, or practicing a reliable method of birth control (intrauterine devices, spermicide and barrier). Partner/spouse sterility may also qualify at the investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline.

Note: Patients already on lactulose and randomized to AST-120 will stop taking lactulose on the day they begin taking AST-120.

Exclusion Criteria:

* Patients whose condition necessitates continuous administration of antibiotics (e.g. rifaximin, neomycin, metronidazole)
* Patients undergoing chemotherapy for treatment of cancer (patients with hepatocellular carcinoma being treated by methods other than chemotherapy may be enrolled)
* Patients who require continued treatment with narcotics or sedatives
* Patients who have active GI bleeding
* Patients who have an active infection
* Patients who have signs and symptoms of severe dehydration
* Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling
* Unable to attend all visits required by the protocol
* Female patients must be EXCLUDED if they are pregnant, breast feeding, planning to become pregnant during the study or using hormonal contraception as their only method of birth control

Primary outcomes:
measure: Change in Westhaven Scale
timeFrame: 4 weeks
Secondary outcomes:
measure: Efficacy: Change in Hepatic Encephalopathy Scoring Algorithm (HESA)
timeFrame: 4 weeks
measure: Efficacy: Reduction of venous ammonia levels
timeFrame: 4 weeks
measure: Efficacy: Serum bile acids and amino acid profile
timeFrame: 4 weeks
measure: Efficacy: Reduction in itching (visual analog scale)
timeFrame: 4 weeks
measure: Efficacy: Presence or absence of asterixis
timeFrame: 4 weeks
measure: Safety: Clinical laboratory tests
timeFrame: 4 weeks
measure: Safety: Physical examination, vital signs (blood pressure, heart rate, respiration rate, body temperature)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Scripps Clinic
state: California
city: San Diego
country: United States
facility: Veterans Medical Center San Diego
state: California
city: Washington
country: United States
facility: Washington Hospital Center - MedStar Research Institute
state: District of Columbia
city: Atlanta
country: United States
facility: Digestive Healthcare of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Worchester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: New York
country: United States
facility: Weill Medical College of Cornell
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: St. Luke's Advanced Liver Therapies / St. Luke's Texas Liver Coalition - Baylor College of Medicine
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
Study officials:
affiliation: Scripps Clinic
name: Paul Pockros, MD
role: PRINCIPAL_INVESTIGATOR
References: