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

• ClinicalTrials.gov Identifier: NCT02508623
• Recruitment Status: Unknown
• First Posted: July 27, 2015
• Last Update Posted: July 28, 2015
• Sponsor: University of Padova
• Information provided by (Responsible Party): Piero Amodio, University of Padova

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Liver Cirrhosis; Portal Hypertension	Drug: Rifaximin; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Administration "Add on" of Rifaximin on Portal Hypertension of Patients With Liver Cirrhosis and Esophageal Varices in Standard Therapy With Propranolol
• Study Start Date: July 2015
• Estimated Primary Completion Date: January 2017
• Estimated Study Completion Date: July 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change of Hepatic Venous Pressure Gradient [ Time Frame: Time 0 and after 60 days ]
   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

Secondary Outcome Measures :

1. Modification of fecal bacteria [ Time Frame: Time 0 and after 60 days ]
   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.
2. Change of systemic inflammatory response [ Time Frame: Time 0 and after 60 days ]
   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.
3. Change of cognitive function [ Time Frame: Time 0 and after 60 days ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Francesca Campagna, MD; +39 0498218675; francescacampagna3@gmail.com

Locations

Italy

Azienda Ospedaliera di Padova; Recruiting

Padua, Italy, 35140

Contact: Claudio Dario +39 0498212105

Sponsors and Collaborators

University of Padova

Investigators

• Principal Investigator: Piero Amodio; University of Padova

More Information

• Responsible Party: Piero Amodio, Professor, University of Padova
• ClinicalTrials.gov Identifier: NCT02508623
• Other Study ID Numbers: 3250/AO/14; 2014-000102-35 ( EudraCT Number )
• First Posted: July 27, 2015
• Last Update Posted: July 28, 2015
• Last Verified: July 2015

Keywords provided by Piero Amodio, University of Padova:

Portal hypertension; liver cirrhosis; Rifaximin

Additional relevant MeSH terms:

Liver Cirrhosis; Hypertension, Portal; Esophageal and Gastric Varices; Hypertension; Fibrosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Liver Diseases; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Rifaximin; Anti-Bacterial Agents; Anti-Infective Agents; Gastrointestinal Agents