Two Strategies of Primary Prophylaxis of Spontaneous Bacterial Peritonitis in Severe Cirrhotic Patients With Ascites (ProPILARifax)

April 8, 2025 updated by: Centre Hospitalier Universitaire de Besancon

A Multicenter, Double-blind, Placebo-controlled Randomized Clinical Trial Comparing Two Strategies of Primary Prophylaxis of Spontaneous Bacterial Peritonitis in Severe Cirrhotic Patients With Ascites : Using or Not Using Rifaximin

We wish to perform a multicenter, double-blind RCT with two parallel-group stratified on the center, comparing rifaximin to no rifaximin (placebo) for the primary prophylaxis of SBP in 'severe' cirrhotic patients with large ascites. The primary outcome will be the 12-month survival.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
160

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
        • CHU Amiens
      • Angers, France
        • CHU d'Angers
      • Besançon, France
        • CHU de BESANCON
      • Bondy, France
        • Hôpital Jean Verdier
      • Caen, France, 14033
        • CHU Caen
      • Clichy, France
        • Hôpital Beaujon
      • Créteil, France
        • CHIC de Créteil
      • La Tronche, France, 38700
        • CHU Grenoble
      • Lille, France
        • CHRU de Lille
      • Lyon, France, 69004
        • Hopital de la Croix-Rousse
      • Montpellier, France, 34295
        • CHU Montpellier
      • Nice, France
        • CHU de Nice
      • Paris, France
        • Hopital Pitie Salpetriere
      • Reims, France
        • CHU de reims
      • Rennes, France
        • CHU de Rennes
      • Rouen, France, 76031
        • Chu Rouen
      • Toulouse, France
        • CHU de Toulouse
      • Tours, France, 37044
        • CHU Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Cirrhosis diagnosed on clinical, radiological and/or histological findings
  • Patients with large ascites (i.e., grade 3 ascites requiring paracentesis). Patients with grade 2 ascites are also authorized.

  • Ascites with a low protein level in ascitic fluid (< 15 g/L) with one of the following three conditions:

    1. impaired renal function defined by serum creatinine ≥ 106 mmol/L, uremia ≥ 9 mmol/L or serum sodium ≤ 130 mmol/L), or
    2. severe liver impairment defined by Child-Pugh score ≥ 9 with serum total bilirubin levels ≥ 51 mmol/L.
    3. severe liver impairment defined by Child-Pugh C
  • Patient who signed an informed consent form
  • Patient with a social security system
  • Woman must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the study if childbearing potential.
  • Patients who needs a TIPS if the procedure is performed 3 months or more following the randomization
  • Patients with severe alcoholic hepatitis can be considered for inclusion if the MELD score < 30 and the Maddrey Discriminant Function < 60 providing that the patient is not infected (and consequently, will not receive antibiotics) and has not yet received corticosteroid (if necessary). Patients not responding to corticosteroid at day 7 (according to the Lille score) could be include after a wash-out of steroids for a period of 7 days.

Exclusion Criteria:

  • Pregnant woman or breastfeeding
  • Vulnerable person regarding french law
  • Individual under legal protection measure
  • Individual unable to exprim his/her consent
  • Person under 18 years of age and over 80 years of age
  • Transplanted patients, HIV infection (or patients who deny HIV serology) or immunosuppressive therapy (including patients under corticosteroids for severe alcoholic hepatitis if the patients respond to steroids with improvement of liver function)
  • Patients with a liver transplant project and an estimated waiting time for liver transplantation of 3 months or less
  • Past SBP or any present bacterial infection
  • Patient who have received a TIPS procedure before rhe randomization
  • Patients with an alfapump
  • Patient receiving antibiotics (including rifaximin) in the 7 days preceding the inclusion in this study exept for patients participating to the microbiota study (15 days).
  • Hypersensitivity to rifaximin, derivatives of rifamycin or one of the constituents of the preparation
  • Hepatocellular carcinoma outside the Milan criteria, other cancer at a palliative stage
  • Any clinical situation with a very low short-terme prognosis (other than cirrhosis), i.e. a survival estimated lower than one month
  • Gastrointestinal bleeding within 7 days
  • Intestinal obstruction
  • Grade 3 hepatic encephalopathy (HE) during the previous 6 months before randomization
  • Chronic heart failure (stage III or IV of the New York Heart Association [NYHA] Functional Classification
  • Patient judged as noncompliant
  • Patients who cannot receive a clear information and who have no trusted relatives
  • Patient who refuses the participation agreement by signing the information form and consent as defined in the protocol.
  • Exclusion period from another biomedical study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active rifaximin
Drug: Rifaximin
twice daily administration of 1 tablet containing 550 mg of active rifaximin
Placebo Comparator: Rifaximin placebo
Other: Placebo
twice daily administration of 1 rifaximin placebo tablet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
death
Time Frame: 12 months
record of death whatever the cause
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospital mortality rate and mortality rate at 3 months
Time Frame: 3 months
survival during hospitalization and at 3 months
3 months
Hospital mortality rate and mortality rate at 6 months
Time Frame: 6 months
survival during hospitalization and at 6 months
6 months
Patient hospitalizations during follow-up
Time Frame: 12 months
number of days of hospitalization during 12 months of follow-up
12 months
Quantitative variations of IL-6 in serum between day 1 and day 30
Time Frame: 1 month
Dosage of IL-6 in serum at D1 and D30
1 month
Quantitative variations of lipopolysaccharides (LPS) in serum between day 1 and day 30
Time Frame: 1 month
Dosage of LPS in serum at D1 and D30
1 month
Quantitative variations of copeptin in serum between day 1 and day 30
Time Frame: 1 month
Dosage of copeptin in serum at D1 and D30
1 month
Quantitative variations of CRP in serum between day 1 and day 30
Time Frame: 1 month
Dosage of CRP in serum at D1 and D30
1 month
Quantitative variations of von Willebrand Factor antigen in serum between day 1 and day 30
Time Frame: 1 month
Dosage of von Willebrand Factor antigen in serum at D1 and D30
1 month
Composition of the intestinal microbiota
Time Frame: up to 18 months
analyzis of microbiota (quantity and quality of main bacterial strains) in 25 patients from arms A and B at day 1, and at months 3, 6, 12 and 18
up to 18 months
Safety analysis of the study drug
Time Frame: 12 months
Record of adverse events and serious adverse events in each arm
12 months
Incidence of spontaneous bacterial peritonitis (SBP) during follow-up
Time Frame: 12 months
Bacterial analysis of ascites
12 months
Incidence of the other complications of liver cirrhosis during follow-up
Time Frame: 12 months
complications of liver cirrhosis : SBP, HE, gastrointestinal bleeding and hepatorenal syndrome
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire de Besancon

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Alfasigma S.p.A.
LC2 PHARMA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rodolphe ANTY, MD, Centre Hospitalier Universitaire de Nice
  • Principal Investigator: Eric Nguyen-Khac, MD, PhD, CHU Amiens
  • Principal Investigator: Edouard Bardou-Jacquet, MD, Rennes University Hospital
  • Principal Investigator: Christophe Bureau, MD, PhD, University Hospital, Toulouse
  • Principal Investigator: Vincent Di Martino, MD, PhD, CHRU De Besancon
  • Principal Investigator: Claire Francoz, MD, Hopital Beaujon, Clichy
  • Principal Investigator: Alexandra Heurgue-Berlot, MD, CHU de reims
  • Principal Investigator: Marianne Latournerie, MD, Centre Hospitalier Universitaire Dijon
  • Principal Investigator: Alexandre Louvet, MD, PhD, CHRU de Lille
  • Principal Investigator: Pierre Nahon, MD, PhD, HOPITAL JEAN VERDIER, BONDY
  • Principal Investigator: Frédéric Oberti, MD, University Hospital, Angers
  • Principal Investigator: Isabelle Rosa-Hezode, MD, CHIC de Créteil
  • Principal Investigator: Marika Rudler, MD, Hôpital Pitié-Salpêtrière, APHP
  • Principal Investigator: Matthieu Schnee, MD, Hôpital La Roche-sur-Yon
  • Principal Investigator: Ghassan Riachi, MD, Chu Rouen
  • Principal Investigator: Isabelle Ollivier, MD, CHU Caen
  • Principal Investigator: Laure Elkrief, MD, CHU Tours
  • Principal Investigator: Lucy Meunier, MD, University Hospital, Montpellier
  • Principal Investigator: Fanny Lebosse, MD, Hopital de la Croix-Rousse
  • Principal Investigator: Marie Noelle Hilleret, MD, University Hospital, Grenoble

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 5, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 3, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 20, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 3, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 10, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ProPILA-Rifax

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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