Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

NCT02116556 | Unknown Phase 2 DMC

• 1 other identifier: RIFA-AAH.
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

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.

Conditions

Alcoholic Hepatitis

Keywords

Alcoholic Hepatitis; Bacterial Infections; Acute-on-Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• Rate of bacterial infections

  Development of any bacterial infection.

  90 days

Secondary Outcomes (1)

• Rate of Decompensations of Liver Cirrhosis

  90 days

Other Outcomes (1)

• Endotoxemia serum levels

  90 days

Study Arms (2)

Prednisone

ACTIVE COMPARATOR

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

Drug: Prednisone

Prednisone plus Rifaximin

EXPERIMENTAL

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

Drug: Prednisone; Drug: Rifaximin

Interventions

Prednisone DRUG

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.

Prednisone; Prednisone plus Rifaximin

Rifaximin DRUG

Rifaximin PO 1200 mg/day for 90 days

Prednisone plus Rifaximin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead
• Germans Trias i Pujol Hospital: collaborator
• Hospital del Mar: collaborator
• Hospital de Sant Pau: collaborator

Study Sites (4)

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, Spain

Location

Vall d'Hebron Hospital

Barcelona, Spain

Location

MeSH Terms

Conditions

Hepatitis, Alcoholic; Bacterial Infections; Acute-On-Chronic Liver Failure

Interventions

Prednisone; Rifaximin

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Bacterial Infections and Mycoses; Infections; Liver Failure, Acute; Liver Failure; Hepatic Insufficiency

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds

Study Officials

• Victor Vargas, MD

  Internal Medicine Service. Vall d'Hebron Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 17, 2014
• Study Start: April 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 4, 2016

Record last verified: 2016-11

Locations

ES (4)