Liver CirrhosisPhase 3ERASENCT02508623
Effect of Administration of Rifaximin on the Portal Pressure of Patients With Liver Cirrhosis and Esophageal Varices
A Phase 3 study testing Rifaximin in people with Liver Cirrhosis and Portal Hypertension, run by University of Padova at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis, Portal Hypertension
- What is being tested?
- Rifaximin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2015to Jul 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliera di Padova
Padua, Italy, 35140
Claudio Dario, +39 0498212105
About this study
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
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.
Read the 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).
- Conditions
- Liver Cirrhosis, Portal Hypertension
- Being tested
- Rifaximin, Placebo
- Keywords
- Portal hypertension, liver cirrhosis, Rifaximin
- Medical subject headings
- Liver Cirrhosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifaximinDrug
Rifaximin 550 mg tablet BID for 60 days
PlaceboDrug
Placebo 1 tablet BID for 60 days
| Study group | Role | What they receive |
|---|---|---|
| Rifaximin | Experimental | Rifaximin 550 mg 1 tablet BID for 60 days Receives: Drug: Rifaximin |
| Placebo | Placebo comparator | Placebo 1 tablet BID for +60 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Time 0 and after 60 days
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Time 0 and after 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionJan 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Piero Amodio, University of Padova
- Investigators
- Piero Amodio, Principal investigator, University of Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02508623
- Sponsor's protocol ID
- 3250/AO/14
- Other IDs
- 2014-000102-35, 2014
- Acronym
- ERASE
- Status last verified
- Jul 2015
- First submitted
- 21 Jul 2015
- Last updated
- 28 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02508623
- Acronym / sponsor ID
- ERASE / 3250/AO/14
- Conditions
- Liver Cirrhosis, Portal Hypertension
- Keywords
- Portal hypertension, liver cirrhosis, Rifaximin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 27 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rifaximin | Experimental | Drug: RifaximinRifaximin 550 mg 1 tablet BID for 60 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 1 tablet BID for +60 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RifaximinRifaximin 550 mg tablet BID for 60 days | Drug | Rifaximin |
| PlaceboPlacebo 1 tablet BID for 60 days | Drug | Placebo |
Primary outcome
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
3 secondary outcomes
Modification of fecal bacteria
Time frame: Time 0 and after 60 days
Change of systemic inflammatory response
Time frame: Time 0 and after 60 days
Change of cognitive function
Time frame: Time 0 and after 60 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Piero Amodio principal investigator
University of Padova
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rifaximin in people with Liver Cirrhosis and Portal Hypertension, run by University of Padova at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesca Campagna, MD (+39 0498218675, francescacampagna3@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Hepatic Venous Pressure Gradient (time frame: Time 0 and after 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2015.