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

Overview

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 %.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: July 2017

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.

Interventions

  • Drug: Rifaximin
    • 6 rifaximin caps of 200 mg 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

Arms, Groups and Cohorts

  • Experimental: rifaximin
    • 6 rifaximin caps of 200 mg per day morning and night, during 15 days before TIPS, and after TIPS during 6 months.
  • Placebo Comparator: placebo
    • 6 caps placebo morning and night, 15 days before and 6 months after TIPS

Clinical Trial Outcome Measures

Primary Measures

  • First episode of overt encephalopathy in patients treated by TIPS
    • Time Frame: 6 months
    • First episode of overt encephalopathy in patients treated by TIPS

Secondary Measures

  • number of hospitalisation days
    • Time Frame: 6 months
    • Number and days of hospitalisations for encephalopathy
  • 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
  • transplants, deaths
    • Time Frame: 6 months
    • – number of transplants and deaths
  • intestinal microbiota
    • Time Frame: 6 months
    • Composition of intestinal microbiota in 30 patients (only UHToulouse)

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Toulouse
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Christophe Bureau, MD PhD, Principal Investigator, University Hospital, Toulouse

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