Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis
- Registration Number
- NCT02116556
- Brief Summary
Acute alcoholic hepatitis (AAH) is a serious condition and one of the most frequent causes of Acute-on-Chronic Liver Failure. The current standard therapy (corticosteroids) is theme of debate and unsatisfactory in many patients (year mortality: 30%). One of the main causes of death is bacterial infections, which affect 40-50% of patients at 90 days. Intestinal decontamination with rifaximin (a nonabsorbable antibiotic) reduces endotoxemia, improves liver function and reduces the complications of decompensated alcoholic cirrhosis.
The Hypothesis/Objective: To assess whether oral decontamination with rifaximin prevents the development of infections associated with AAH and analyze its consequences.
- Detailed Description
Design: Open multicenter comparative study. A cohort (n = 66) will receive rifaximin (1200 mg / d) for 90 days. Results will be compared with those of a cohort of AAH prospectively included in an observational study. Both groups with a uniform treatment protocol (which includes the administration of corticosteroids and standardized treatment for complications of liver failure). Patients will be monitorized until hospital discharge and a follow-up visit at 7, 30, 45, 60 and 90 days will be performed.
Endpoints:
1. Primary endpoint: Bacterial infections after 90 days.
2. Secondary endpoints: :
2.1. Liver function tests 2.2. Levels of endotoxemia 2.3. Complications of liver cirrhosis. 2.4. Survival
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 29
- Patients ≥18 and <70 years of age.
- Active alcohol abuse and excessive alcohol consumption prior to admission defined as > 50 g per day for men and> 40 g per day for women.
- Jaundice (Bilirubin >2 mg/dl) for no more than 3 months.
- Clinical suspicion of Alcoholic Hepatitis with a modified Maddrey's Discriminant Function > 32 points.
- Hypersensitivity to Rifaximin
- Advanced Chronic or Terminal illness. Advanced Chronic illness will be defined as: all conditions evolved into a clinical stage to limit the patient's functional status (eg, heart failure NYHA> II, COPD PCO2> 50 mmHg or PO2 <60 mmHg, stroke or other disabling neurological disease, disabling or uncontrolled oncological conditions, etc ...).
Terminal illness will be defined as any clinical conditions with a survival expectancy less than 3 months
- Hepatocellular carcinoma (previously diagnosed) beyond Milan's criteria.
- Complete portal vein thrombosis (previously diagnosed).
- Autoimmune liver disease.
- Hepatitis B and C and HIV infection (anti-HCV, surface HBV antigen and anti-HIV positive).
- Pregnancy or nursing.
- Use of Rifaximin during the previous 2 months.
- Treatment with Pentoxifylline.
- Lack of informed consent.
Removal criteria:
- Lack of histological confirmation of Alcoholic Hepatitis during the first 7 days after inclusion.
Because there are no non-diagnostic tools to diagnose alcoholic hepatitis, histological confirmation is required in all patients (preferably through a transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histologic features:
Hepatocellular damage (eg, hepatocyte ballooning and presence of Mallory-Denk bodies).
Inflammatory infiltrate (predominantly polymorphonuclear cells). Pericellular or sinusoidal fibrosis.
- Hepatocellular carcinoma beyond Milan's criteria diagnosed during the first 7 days after inclusion.
- Complete portal vein thrombosis diagnosed during the first 7 days after inclusion.
- Protocol violation.
- Severe adverse event directly related with Rifaximin.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Prednisone Prednisone Prednisone PO 40mg/day for 30 days plus standard supportive care measurements Prednisone plus Rifaximin Prednisone Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements Prednisone plus Rifaximin Rifaximin Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements
- Primary Outcome Measures
Name Time Method Rate of bacterial infections 90 days Development of any bacterial infection.
- Secondary Outcome Measures
Name Time Method Rate of Decompensations of Liver Cirrhosis 90 days Development of any liver cirrhosis decompensations
1. Hepatic Encephalopathy
2. Acute Kidney Injury (including Hepatorenal Syndrome)
3. Acute variceal bleeding
4. Ascites
5. Death
Trial Locations
- Locations (4)
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Vall d'Hebron Hospital
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸Barcelona, Spain