Effect of Administration of Rifaximin on the Portal Pressure of Patients With Liver Cirrhosis and Esophageal Varices (ERASE)

Effect of Administration "Add on" of Rifaximin on Portal Hypertension of Patients With Liver Cirrhosis and Esophageal Varices in Standard Therapy With Propranolol

The purpose of this study is to assess whether the add of Rifaximin in patients with liver cirrhosis and esophageal varices treated with a standard therapy with beta blockers, leads to a significant reduction of portal hypertension.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis; Portal Hypertension
• Intervention / Treatment: Drug: Rifaximin; Drug: Placebo

Detailed Description

It is well recognized that the gut flora may play an important role in the development of complications of liver cirrhosis, such as hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP) and variceal bleeding, which are are directly caused or aggravated by the translocation of enteric bacteria or their products into the blood of cirrhotic patients.Preliminary studies have shown that selective intestinal decontamination appears to ameliorate the hyperdynamic circulatory state of cirrhosis. The investigators hypothesize that a modulation of gut microbiota by administering a non-adsorbable antibiotic, in addition to beta-blockers, can be a safe strategy to reduce the portal pressure, influencing favorably hemodynamics of portal circulation. Thus, the purpose of this study is to evaluate if in patients with liver cirrhosis and esophageal varices at high risk of bleeding, Rifaximin, administered in addition to standard therapy with beta - blockers (propranolol), for a time of 60 days: leads to a significant reduction of Hepatic Venous Pressure Gradient (it will be assessed by hepatic vein catheterization), 2) modify the intestinal flora in favor of specific families of bacteria (it will be assessed by fecal microbiota analysis), 3) change systemic inflammatory responses (it will be assessed by serum pro-inflammatory cytokines) 4) change in cognitive functions (it will be assessed by neuropsychological and electroencephalogram evaluations).

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Francesca Campagna, MD; Phone Number: +39 0498218675; Email: francescacampagna3@gmail.com

Study Locations

• Italy
  • Padua, Italy, 35140
    • Recruiting
    • Azienda Ospedaliera di Padova
    • Contact: Claudio Dario; Phone Number: +39 0498212105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of liver cirrhosis (based on clinical, biochemical and radiological criteria with or without liver biopsy)
• Presence of esophageal varices at high risk of bleeding
• Hepatic Venous Pressure Gradient > 12 mmHg.
• 19≤ age ≤75
• Informed Consent

Exclusion Criteria:

• Patients already treated with beta blockers
• Treatment with systemic antibiotics and/or non-absorbable intestinal antibiotics in the previous two weeks
• Bacterial infection, spontaneous bacterial peritonitis
• overt hepatic encephalopathy in the last week
• active gastrointestinal bleeding, or in the last week
• active alcoholism or drug abuse in last 3 weeks
• Acute Alcoholic Hepatitis
• Hepatocellular carcinoma or other neoplasm
• significant coronary artery disease (angina NYHA III/IV), congestive heart failure (NYHA III/IV), relevant cardiomyopathy, history of myocardial infarct within the last 12 months
• Contraindications to the administration of beta blockers; allergy to Rifaximin
• Pregnancy or breastfeeding
• Refusal to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifaximin; Rifaximin 550 mg 1 tablet BID for 60 days	Drug: Rifaximin; Rifaximin 550 mg tablet BID for 60 days
Placebo Comparator: Placebo; Placebo 1 tablet BID for +60 days	Drug: Placebo; Placebo 1 tablet BID for 60 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Hepatic Venous Pressure Gradient	At Time 0 and after 60 days all patients will underwent hepatic vein catheterization to obtain the Hepatic Venous Pressure Gradient. Treatment response is defined as a decrease from baseline in the hepatic venous pressure gradient of at least 20% or less than 12 mmHg	Time 0 and after 60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modification of fecal bacteria	Both at time 0 and after 60 days, samples of 3 mL of faeces produced within 6 hours will be collected and frozen at -80° for the analysis of the gut microbiota (the samples will be stored at -80°C). Gut microbiota will be studied through sequencing of hyper-variable regions of the 16S Ribosomal Ribonucleic Acid gene.	Time 0 and after 60 days
Change of systemic inflammatory response	Both at time 0 and after 60 days, the storage of a serum sample at -80 ° for the assay of proinflammatory cytokines will be done.	Time 0 and after 60 days
Change of cognitive function	Cognitive function will be assessed at time 0 and after 60 days by neuropsychological and neurophysiological measures. Neuropsychological investigation will be performed using the Italian version of the Psychometric Hepatic Encephalopathy Score that and with the Animal Naming Test (number of animals named in 60 sec). Neurophysiological investigation will be done by Emotiv Electroencephalogram equipment. Spontaneous closed-eyes rest activity will be recorded by a 14 channels plus 2 references offering optimal positioning for accurate spatial resolution.	Time 0 and after 60 days

Collaborators and Investigators

• Sponsor: University of Padova
• Investigators: Principal Investigator: Piero Amodio, University of Padova

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): July 1, 2017

Study Registration Dates

• First Submitted: July 21, 2015
• First Submitted That Met QC Criteria: July 24, 2015
• First Posted (Estimate): July 27, 2015

Study Record Updates

• Last Update Posted (Estimate): July 28, 2015
• Last Update Submitted That Met QC Criteria: July 27, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Rifaximin; liver cirrhosis; Portal hypertension
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Fibrosis; Hypertension; Liver Cirrhosis; Esophageal and Gastric Varices; Hypertension, Portal; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin
• Other Study ID Numbers: 3250/AO/14; 2014-000102-35 (EudraCT Number)