Clinical trial NCT02116556: Effects of Rifaximin in Patients With Acute Alcoholic Hepatitis
Official title: Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Alcoholic Hepatitis
Keywords: Alcoholic Hepatitis
Bacterial Infections
Acute-on-Chronic Liver Failure
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: Germans Trias i Pujol Hospital
name: Hospital del Mar
name: Hospital de Sant Pau
First posted: 2014-04-17
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Rate of bacterial infections
timeFrame: 90 days
Secondary outcomes:
measure: Rate of Decompensations of Liver Cirrhosis
timeFrame: 90 days
Other outcomes:
measure: Endotoxemia serum levels
timeFrame: 90 days
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Vall d'Hebron Hospital
Study officials:
affiliation: Internal Medicine Service. Vall d'Hebron Hospital
name: Victor Vargas, MD
role: PRINCIPAL_INVESTIGATOR
References: