Clinical trial NCT02508623: Effect of Administration of Rifaximin on the Portal Pressure of Patients With Liver Cirrhosis and Esophageal Varices
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Liver Cirrhosis
Portal Hypertension
Keywords: Portal hypertension
liver cirrhosis
Rifaximin
Lead sponsor: University of Padova
Sponsor class: OTHER
First posted: 2015-07-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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

Primary outcomes:
measure: Change of Hepatic Venous Pressure Gradient
timeFrame: Time 0 and after 60 days
Secondary outcomes:
measure: Modification of fecal bacteria
timeFrame: Time 0 and after 60 days
measure: Change of systemic inflammatory response
timeFrame: Time 0 and after 60 days
measure: Change of cognitive function
timeFrame: Time 0 and after 60 days
Other outcomes:
Locations:
city: Padua
country: Italy
facility: Azienda Ospedaliera di Padova
Study officials:
affiliation: University of Padova
name: Piero Amodio
role: PRINCIPAL_INVESTIGATOR
References: