Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
- Conditions
- Alcoholic Hepatitis
- Interventions
- Drug: PlaceboDrug: 10 mg Obeticholic Acid (OCA)
- Registration Number
- NCT02039219
- Lead Sponsor
- Naga P. Chalasani
- Brief Summary
The main purpose of this study is to test the effectiveness of Obeticholic Acid when used in patients with moderately severe alcoholic hepatitis. The researchers suspect that individuals with alcoholic hepatitis have certain abnormalities in how their body handles bile acids (a product made by the liver on a daily basis) produced by the liver. Obeticholic acid has been shown to affect bile acid abnormalities and thus it is possible that obeticholic acid may improve liver condition in individuals with alcoholic hepatitis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
- Individuals ≥ 21 years with a diagnosis of acute AH. The diagnosis of acute alcoholic hepatitis will be based on clinical features and testing including hepatomegaly, jaundice, fever, leukocytosis, compatible liver biochemistries in the context of heavy alcohol consumption. A liver biopsy is not mandatory, but will be required to confirm the diagnosis if a firm diagnosis of AH cannot be made on clinical and laboratory criteria
- Moderate severity defined as MELD score > 11 and < 20
- Heavy alcohol consumption (defined as > 40 grams per day on average in women and > 60 grams per day on average in men for a minimum of 6 months and within the 6 weeks prior to study enrollment)
- Written informed consent
- Negative urine pregnancy test where appropriate
- Women of child bearing potential should be willing to practice contraception throughout the treatment period
- Significant active infection (e.g., sepsis, or spontaneous bacterial peritonitis; SBP). Subjects can be reconsidered after the infection is under control.
- Serum creatinine > 2.5 mg/dL
- Must not be receiving systemic steroids > 1 week at the time of Screening or any experimental medicines for AH
- Presence of any other disease or condition that is interfering with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine. Patients who have undergone gastric bypass procedures will be excluded (gastric lap band is acceptable).
- Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo 10 mg Obeticholic Acid (OCA) 10 mg Obeticholic Acid (OCA) 10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks.
- Primary Outcome Measures
Name Time Method Incidence of Serious Adverse Events (SAEs) During the Treatment Phase Baseline to 6 weeks (Day 42) Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
MELD Score Mean(SD) Baseline to 6 weeks (Day 42) The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
MELD Score Change From Baseline Mean(SD) Baseline to 6 weeks (Day 42) The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
- Secondary Outcome Measures
Name Time Method Any SAEs During the Follow-up Phase Days 42 to 180 Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases Baseline to 180 days Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Change in MELD Score at 90 and 180 Days Days 90 and 180 The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
Adverse Events (AEs) During the Treatment and Follow-up Phases Baseline to 180 days Number of subjects with one or more AEs are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Percentage of Participants Deceased at Day 42, 90 and 180 Days 42, 90 and 180 Number of subjects deceased at day 42, 90, and 180.
Rates of Hospitalization Baseline to 180 days Number of subjects with one or more hospitalization are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Changes in Intestinal Inflammation Baseline to Day 180 Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
Changes in Serum Oxidative Stress. Baseline to 180 days Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
Length of Hospital Stays Baseline to 180 days Changes in Bacterial Translocation Baseline to 180 days Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
Changes in Cytokines Baseline to 180 days Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
Change in Child-Pugh Score at Day 42, 90 and 180 Days Days 42, 90 and 180 The Child-Pugh score is a system for assessing the prognosis - including the required strength of treatment and necessity of liver transplant - of chronic liver disease, primarily cirrhosis. It provides a forecast of the increasing severity of your liver disease and your expected survival rate. The Child-Pugh score is determined by scoring five clinical measures of liver disease. A score of 1, 2, or 3 is given to each measure, with 3 being the most severe. The total Child-Pugh range is 5-15, with 15 being the most severe.
Changes in Activation of Innate Immunity Baseline to 180 days Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
Discontinuation Rate During the Treatment and Follow-up Phases Baseline to 180 days
Trial Locations
- Locations (4)
Indiana University
🇺🇸Indianapolis, Indiana, United States
Virgina Commonwealth University
🇺🇸Richmond, Virginia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Einstein Healthcare Network
🇺🇸Philadelphia, Pennsylvania, United States