Clinical trial NCT02016196: Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS
Official title: Double Blind Randomized Study, Comparing Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cirrhosis
Keywords: TIPS
portal pressure
rifaximin
overt hepatic encephalopathy
microbiota
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2013-12-19
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 %.

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.

Eligibility 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

Primary outcomes:
measure: First episode of overt encephalopathy in patients treated by TIPS
timeFrame: 6 months
Secondary outcomes:
measure: number of hospitalisation days
timeFrame: 6 months
measure: Frequency of kidney insufficiency
timeFrame: 6 months
measure: transplants, deaths
timeFrame: 6 months
measure: intestinal microbiota
timeFrame: 6 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Lille
country: France
facility: CHRU Lille
city: Marseille
country: France
facility: CHU Marseille
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: CHU Beaujon Clichy
city: Paris
country: France
facility: CHU Saint-Antoine
city: Paris
country: France
facility: Pitié Salpêtrière
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Toulouse
country: France
facility: UHToulouse
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: University Hospital, Toulouse
name: Christophe Bureau, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bureau C, Thabut D, Jezequel C, Archambeaud I, D'Alteroche L, Dharancy S, Borentain P, Oberti F, Plessier A, De Ledinghen V, Ganne-Carrie N, Carbonell N, Rousseau V, Sommet A, Peron JM, Vinel JP. The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial. Ann Intern Med. 2021 May;174(5):633-640. doi: 10.7326/M20-0202. Epub 2021 Feb 2.