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

NCT ID: NCT02016196

Last Updated: 2020-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-07-31

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.

Conditions

Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

rifaximin

6 rifaximin caps of 200 mg per day morning and night, during 15 days before TIPS, and after TIPS during 6 months.

Group Type: EXPERIMENTAL

Rifaximin

Intervention Type: DRUG

6 rifaximin caps of 200 mg morning and night, 15 days before and 6 months after TIPS

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placebo

6 caps placebo morning and night, 15 days before and 6 months after TIPS

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

6 placebo caps per day morning and night, during 15 days before TIPS and 6 months after TIPS

Interventions

Rifaximin

6 rifaximin caps of 200 mg morning and night, 15 days before and 6 months after TIPS

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Intervention Type: DRUG

placebo

6 placebo caps per day morning and night, during 15 days before TIPS and 6 months after TIPS

Intervention Type: DRUG

Other Intervention Names

NORMIX

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe Bureau, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

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

CHU Tours

Tours, , France

Countries

France

References

Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.

Reference Type: DERIVED

PMID: 37467180 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33524293 (View on PubMed)

Other Identifiers

RC31/12/0551

Identifier Type: -

Identifier Source: org_study_id