Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS (PRPET)

April 29, 2026 updated by: University Hospital, Toulouse

Double Blind Randomized Study, Comparing Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS

TIPS has been used for 20 years, as a means of reducing portal pressure in patients with cirrhosis and portal hypertension related complications. TIPS proved more effective than alternative treatments in controlling or preventing variceal bleeding and refractory ascites. The main drawback of the TIPS procedure is progressive overt hepatic encephalopathy (OHE). Three risk factors for post-TIPS OHE have been identified: age over 65 years, history of previous episodes of OHE, and Child-Pugh score equal to or over 10. However, the incidence of post-TIPS OHE in patients fulfilling these criteria remains close to 35 %.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

TIPS has been used for 20 years, as a means of reducing portal pressure in patients with cirrhosis and portal hypertension related complications. TIPS proved more effective than alternative treatments in controlling or preventing variceal bleeding and refractory ascites. The main drawback of the TIPS procedure is progressive overt hepatic encephalopathy (OHE). Three risk factors for post-TIPS OHE have been identified: age over 65 years, history of previous episodes of OHE, and Child-Pugh score equal to or over 10. However, the incidence of post-TIPS OHE in patients fulfilling these criteria remains close to 35 %. Furthermore, the pathogenesis of HE in general but also in patients treated by TIPS is still not well understood. Therefore, there is a real challenge in discovering new molecular mechanisms involved in pathogenesis of OHE as well as new treatment to better prevent the risk of OHE in patients treated by TIPS. Observational and experimental studies suggest a microbiota's role in the mechanism of OHE and recently a non absorbable antibiotic has proven to reduce the risk of recurrence of OHE. However, the effect of this drug for the prevention of a first episode of OHE in patients treated by TIPS is not known. In addition, the mechanisms of the beneficial effect of rifaximin remain poorly understood.

Study Type

Interventional

Enrollment (Actual)

211

Phase

  • 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
      • Angers, France
        • CHU Angers
      • Bondy, France
        • Hôpital Jean Verdier
      • Bordeaux, France
        • CHU Bordeaux
      • Lille, France
        • CHRU LILLE
      • Marseille, France
        • CHU Marseille
      • Nantes, France
        • CHU Nantes
      • Paris, France
        • CHU Saint-Antoine
      • Paris, France
        • CHU Beaujon Clichy
      • Paris, France
        • Pitié Salpêtrière
      • Poitiers, France
        • CHU Poitiers
      • Rennes, France
        • CHU Rennes
      • Tours, France
        • CHU Tours
    • France
      • Toulouse, France, France, 31059
        • UHToulouse

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

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • cirrhosis with TIPS for ascit treatment or hydrothorax
  • prevention digestive bleeding follow up portal hypertension -
  • signed consent

Exclusion Criteria:

  • hepatocellular carcinoma out of Milan criteria or palliative phase cancer
  • Child Pugh score > 12
  • TIPS indicated for other indication than bellow
  • encephalopathy signs : asterixis or confusion
  • Hypersensibility to rifaximin, or derivated of rifamycin
  • Patients treated by same class antibacterial
  • pregnant woman
  • Patient with hepatic transplant

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: rifaximin
6 rifaximin caps of 200 mg per day morning and night, during 15 days before TIPS, and after TIPS during 6 months.
Drug: Rifaximin

6 rifaximin caps of 200 mg morning and night, 15 days before and 6 months after TIPS

--------------------------------------------------------------------------------

Other Names:
  • NORMIX
Placebo Comparator: placebo
6 caps placebo morning and night, 15 days before and 6 months after TIPS
Drug: placebo
6 placebo caps per day morning and night, during 15 days before TIPS and 6 months after TIPS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
First episode of overt encephalopathy in patients treated by TIPS
Time Frame: 6 months
First episode of overt encephalopathy in patients treated by TIPS
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of hospitalisation days
Time Frame: 6 months
Number and days of hospitalisations for encephalopathy
6 months
Frequency of kidney insufficiency
Time Frame: 6 months
number of digestive bleeding follow up to portal hypertension, number of ascit punctions, frequency kidney insufficiency and hepatocellular carcinoma
6 months
transplants, deaths
Time Frame: 6 months
- number of transplants and deaths
6 months
intestinal microbiota
Time Frame: 6 months
Composition of intestinal microbiota in 30 patients (only UHToulouse)
6 months

Collaborators and Investigators

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

Sponsor

University Hospital, Toulouse

Investigators

  • Principal Investigator: Christophe Bureau, MD PhD, University Hospital, Toulouse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 1, 2013

Primary Completion (Actual)

July 1, 2017

Study Completion (Actual)

July 1, 2017

Study Registration Dates

First Submitted

December 13, 2013

First Submitted That Met QC Criteria

December 18, 2013

First Posted (Estimated)

December 19, 2013

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

April 29, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/12/0551

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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