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

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT02016196

Collaborator

(none)

211

Enrollment

Locations

Arms

Actual Duration (Months)

16.2

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 Design

Study Type:

Interventional

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 :

Sep 1, 2013

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Jul 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

First episode of overt encephalopathy in patients treated by TIPS [6 months]
First episode of overt encephalopathy in patients treated by TIPS

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Angers	Angers	France
2	Hôpital Jean Verdier	Bondy	France
3	CHU Bordeaux	Bordeaux	France
4	CHRU Lille	Lille	France
5	CHU Marseille	Marseille	France
6	CHU Nantes	Nantes	France
7	CHU Beaujon Clichy	Paris	France
8	CHU Saint-Antoine	Paris	France
9	Pitié Salpêtrière	Paris	France
10	CHU Poitiers	Poitiers	France
11	CHU Rennes	Rennes	France
12	UHToulouse	Toulouse	France	31059
13	CHU Tours	Tours	France