Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

Overview

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.

Full Title of Study: “Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2016

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

Interventions

  • Drug: Prednisone
    • Prednisone PO 40mg/day or IV equivalent dosage for 30 days. Patients not responding at 7 days (e.g. Lille Model ≥ 0.45) treatment with Prednisone will be suspended.
  • Drug: Rifaximin
    • Rifaximin PO 1200 mg/day for 90 days

Arms, Groups and Cohorts

  • Active Comparator: Prednisone
    • Prednisone PO 40mg/day for 30 days plus standard supportive care measurements
  • Experimental: Prednisone plus Rifaximin
    • Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements

Clinical Trial Outcome Measures

Primary Measures

  • Rate of bacterial infections
    • Time Frame: 90 days
    • Development of any bacterial infection.

Secondary Measures

  • Rate of Decompensations of Liver Cirrhosis
    • Time Frame: 90 days
    • Development of any liver cirrhosis decompensations Hepatic Encephalopathy Acute Kidney Injury (including Hepatorenal Syndrome) Acute variceal bleeding Ascites Death

Participating in This Clinical Trial

Inclusion Criteria

  • 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. Exclusion Criteria:

  • 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hospital Universitari Vall d’Hebron Research Institute
  • Collaborator
    • Germans Trias i Pujol Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Victor Vargas, MD, Principal Investigator, Internal Medicine Service. Vall d’Hebron Hospital

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