Trial record 8 of 37 for:    "Hepatitis, Alcoholic"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Hospital Universitari Vall d'Hebron Research Institute
Sponsor:
Collaborators:
Germans Trias i Pujol Hospital
Hospital del Mar
Hospital Clinic of Barcelona
Hospital de Sant Pau
Information provided by (Responsible Party):
Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier:
NCT02116556
First received: April 15, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Alcoholic Hepatitis
Drug: Prednisone
Drug: Rifaximin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Rifaximin Treatment in Patients With Acute Alcoholic Hepatitis: A Comparative Pilot Study

Resource links provided by NLM:


Further study details as provided by Hospital Universitari Vall d'Hebron Research Institute:

Primary Outcome Measures:
  • Rate of bacterial infections [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Development of any bacterial infection.


Secondary Outcome Measures:
  • Rate of Decompensations of Liver Cirrhosis [ Time Frame: 90 days ] [ Designated as safety issue: No ]

    Development of any liver cirrhosis decompensations

    1. Hepatic Encephalopathy
    2. Acute Kidney Injury (including Hepatorenal Syndrome)
    3. Acute variceal bleeding
    4. Ascites
    5. Death


Other Outcome Measures:
  • Endotoxemia serum levels [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Measurement of serum changes in endotoxemia levels during the rifaximin treatment.


Estimated Enrollment: 66
Study Start Date: April 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Prednisone
Prednisone PO 40mg/day for 30 days plus standard supportive care measurements
Drug: 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.
Experimental: Prednisone plus Rifaximin
Prednisone PO 40mg/day for 30 days plus Rifaximin PO 1200 mg/day for 90 days plus standard supportive care measurements
Drug: 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.
Drug: Rifaximin
Rifaximin PO 1200 mg/day for 90 days

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02116556

Contacts
Contact: Victor Vargas, MD vvargas@vhebron.net
Contact: Joan Genescà, MD jgenesca@vhebron.net

Locations
Spain
Vall d'Hebron Hospital Recruiting
Barcelona, Spain
Hospital del Mar Recruiting
Barcelona, Spain
Hospital Clinic Active, not recruiting
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Hospital Universitari Germans Trias i Pujol Recruiting
Barcelona, Spain
Sponsors and Collaborators
Hospital Universitari Vall d'Hebron Research Institute
Germans Trias i Pujol Hospital
Hospital del Mar
Hospital Clinic of Barcelona
Hospital de Sant Pau
Investigators
Principal Investigator: Victor Vargas, MD Internal Medicine Service. Vall d'Hebron Hospital
  More Information

No publications provided

Responsible Party: Hospital Universitari Vall d'Hebron Research Institute
ClinicalTrials.gov Identifier: NCT02116556     History of Changes
Other Study ID Numbers: RIFA-AAH.
Study First Received: April 15, 2014
Last Updated: April 15, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Universitari Vall d'Hebron Research Institute:
Alcoholic Hepatitis
Bacterial Infections
Acute-on-Chronic Liver Failure

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Prednisone
Rifaximin
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Anti-Infective Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 20, 2014