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

Phase 3

• Conditions: Liver Cirrhosis; Portal Hypertension
• Interventions: Drug: Placebo; Drug: Rifaximin

• Registration Number: NCT02508623
• Lead Sponsor: University of Padova

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.

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 Timeline

• Status Verified: 2015-07
• Study Start: 2015-07
• Study First Submitted: 2015-07-21
• Study First Submitted QC: 2015-07-24
• Study First Posted: 2015-07-27
• Last Update Submitted: 2015-07-27
• Last Update Posted: 2015-07-28
• Primary Completion: 2017-01
• Study Completion: 2017-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 1 tablet BID for +60 days
Rifaximin	Rifaximin	Rifaximin 550 mg 1 tablet BID for 60 days

Primary Outcome Measures

Name	Time	Method
Change of Hepatic Venous Pressure Gradient	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

Name	Time	Method
Change of cognitive function	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.
Modification of fecal bacteria	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.
Change of systemic inflammatory response	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.

Trial Locations

Locations (1)

Azienda Ospedaliera di Padova; 🇮🇹 Padua, Italy