Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis (RIFA-AAH)

November 3, 2016 updated by: Hospital Universitari Vall d'Hebron Research Institute

Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain
        • Hospital Universitari Germans Trias I Pujol
      • Barcelona, Spain
        • Vall d'Hebron Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Prednisone
Prednisone PO 40mg/day for 30 days plus standard supportive care measurements
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.
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of bacterial infections
Time Frame: 90 days
Development of any bacterial infection.
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Decompensations of Liver Cirrhosis
Time Frame: 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
90 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endotoxemia serum levels
Time Frame: 90 days
Measurement of serum changes in endotoxemia levels during the rifaximin treatment.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitari Vall d'Hebron Research Institute

Collaborators

Germans Trias i Pujol Hospital
Hospital del Mar
Hospital de Sant Pau

Investigators

  • Principal Investigator: Victor Vargas, MD, Internal Medicine Service. Vall d'Hebron Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

April 15, 2014

First Submitted That Met QC Criteria

April 15, 2014

First Posted (Estimate)

April 17, 2014

Study Record Updates

Last Update Posted (Estimate)

November 4, 2016

Last Update Submitted That Met QC Criteria

November 3, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RIFA-AAH.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alcoholic Hepatitis

Clinical Trials on Prednisone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe