Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis

NCT ID: NCT02116556

Last Updated: 2016-11-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2016-12-31

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

Conditions

Alcoholic Hepatitis

Keywords

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prednisone

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

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: 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 plus Rifaximin

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

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: 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.

Rifaximin

Intervention Type: DRUG

Rifaximin PO 1200 mg/day for 90 days

Interventions

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.

Intervention Type: DRUG

Rifaximin

Rifaximin PO 1200 mg/day for 90 days

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Germans Trias i Pujol Hospital

OTHER

Sponsor Role: collaborator

Hospital del Mar

OTHER

Sponsor Role: collaborator

Hospital de Sant Pau

OTHER

Sponsor Role: collaborator

Hospital Universitari Vall d'Hebron Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victor Vargas, MD

Role: PRINCIPAL_INVESTIGATOR

Internal Medicine Service. Vall d'Hebron Hospital

Locations

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

Vall d'Hebron Hospital

Barcelona, , Spain

Countries

Spain

Other Identifiers

RIFA-AAH.

Identifier Type: -

Identifier Source: org_study_id