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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cirrhosis

Intervention / Treatment
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* Drug: Rifaximin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rifaximin<br>6 rifaximin caps of 200 mg per day morning and night, during 15 days before TIPS, and after TIPS during 6 months. | Drug: Rifaximin<br>* 6 rifaximin caps of 200 mg morning and night, 15 days before and 6 months after TIPS --------------------------------------------------------------------------------<br>* Other names: NORMIX;|
| Placebo Comparator: placebo<br>6 caps placebo morning and night, 15 days before and 6 months after TIPS | Drug: placebo<br>* 6 placebo caps per day morning and night, during 15 days before TIPS and 6 months after TIPS<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIPS, portal pressure, rifaximin, overt hepatic encephalopathy, microbiota