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

Vall d'Hebron University Hospital (HUVH)

Status and phase: Unknown; Phase 2

Conditions: Alcoholic Hepatitis

Treatments: Drug: Prednisone; Drug: Rifaximin

Study type: Interventional

Funder types: Other

Identifiers

NCT02116556

RIFA-AAH.

Details and patient eligibility

About

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 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

Enrollment: 29 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 2 patient groups

Prednisone

Active Comparator group

Description:

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

Treatment:

Drug: Prednisone

Prednisone plus Rifaximin

Experimental group

Description:

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

Treatment:

Drug: Prednisone

Drug: Rifaximin