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

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ClinicalTrials.gov Identifier: NCT02016196
Recruitment Status : Completed
First Posted : December 19, 2013
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

Brief Summary:
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 %.

Condition or disease Intervention/treatment Phase
Cirrhosis Drug: Rifaximin Drug: placebo Phase 3

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  (Clinical Trial)
Actual Enrollment : 211 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind Randomized Study, Comparing Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS
Actual Study Start Date : September 2013
Actual Primary Completion Date : July 2017
Actual Study Completion Date : July 2017


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 Name: 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




Primary Outcome Measures :
  1. first episode of covert encephalopathy in patients treated by TIPS [ Time Frame: 6 months ]
    First episode of covert encephalopathy in patients treated by TIPS


Secondary Outcome Measures :
  1. number of hospitalisation days [ Time Frame: 6 months ]
    Number and days of hospitalisations for encephalopathy

  2. 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

  3. transplants, deaths [ Time Frame: 6 months ]
    - number of transplants and deaths

  4. intestinal microbiota [ Time Frame: 6 months ]
    Composition of intestinal microbiota in 30 patients (only UHToulouse)



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02016196


Locations
France
CHU Angers
Angers, France
Hôpital Jean Verdier
Bondy, France
CHU Bordeaux
Bordeaux, France
CHRU Lille
Lille, France
CHU Marseille
Marseille, France
CHU Nantes
Nantes, France
CHU Beaujon Clichy
Paris, France
CHU Saint-Antoine
Paris, France
Pitié Salpêtrière
Paris, France
CHU Poitiers
Poitiers, France
CHU Rennes
Rennes, France
UHToulouse
Toulouse, France, 31059
CHU Tours
Tours, France
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Christophe Bureau, MD PhD University Hospital, Toulouse

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02016196     History of Changes
Other Study ID Numbers: RC31/12/0551
First Posted: December 19, 2013    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University Hospital, Toulouse:
TIPS
portal pressure
rifaximin
overt hepatic encephalopathy
microbiota

Additional relevant MeSH terms:
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Rifaximin
Rifamycins
Anti-Infective Agents
Gastrointestinal Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents