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

Primary Purpose

Alcoholic Hepatitis

Status
Unknown status
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Prednisone
Rifaximin
Sponsored by
Hospital Universitari Vall d'Hebron Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis focused on measuring Alcoholic Hepatitis, Bacterial Infections, Acute-on-Chronic Liver Failure

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Prednisone

Prednisone plus Rifaximin

Arm Description

Prednisone PO 40mg/day for 30 days plus standard supportive care measurements

Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements

Outcomes

Primary Outcome Measures

Rate of bacterial infections
Development of any bacterial infection.

Secondary Outcome Measures

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

Full Information

First Posted
April 15, 2014
Last Updated
November 3, 2016
Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Collaborators
Germans Trias i Pujol Hospital, Hospital del Mar, Hospital de Sant Pau
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1. Study Identification

Unique Protocol Identification Number
NCT02116556
Brief Title
Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis
Acronym
RIFA-AAH
Official Title
Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Unknown status
Study Start Date
April 2013 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitari Vall d'Hebron Research Institute
Collaborators
Germans Trias i Pujol Hospital, Hospital del Mar, Hospital de Sant Pau

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: Primary endpoint: Bacterial infections after 90 days. Secondary endpoints: : 2.1. Liver function tests 2.2. Levels of endotoxemia 2.3. Complications of liver cirrhosis. 2.4. Survival

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis
Keywords
Alcoholic Hepatitis, Bacterial Infections, Acute-on-Chronic Liver Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prednisone
Arm Type
Active Comparator
Arm Description
Prednisone PO 40mg/day for 30 days plus standard supportive care measurements
Arm Title
Prednisone plus Rifaximin
Arm Type
Experimental
Arm Description
Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rifaximin
Intervention Description
Rifaximin PO 1200 mg/day for 90 days
Primary Outcome Measure Information:
Title
Rate of bacterial infections
Description
Development of any bacterial infection.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Rate of Decompensations of Liver Cirrhosis
Description
Development of any liver cirrhosis decompensations Hepatic Encephalopathy Acute Kidney Injury (including Hepatorenal Syndrome) Acute variceal bleeding Ascites Death
Time Frame
90 days
Other Pre-specified Outcome Measures:
Title
Endotoxemia serum levels
Description
Measurement of serum changes in endotoxemia levels during the rifaximin treatment.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Victor Vargas, MD
Organizational Affiliation
Internal Medicine Service. Vall d'Hebron Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Barcelona
Country
Spain
Facility Name
Vall d'Hebron Hospital
City
Barcelona
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

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