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

Toulouse University Hospital

Status and phase: Completed; Phase 3

Conditions: Cirrhosis

Treatments: Drug: Rifaximin; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02016196

RC31/12/0551

Details and patient eligibility

About

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 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.

Enrollment: 211 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

211 participants in 2 patient groups, including a placebo group

rifaximin

Experimental group

Description:

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

Treatment:

Drug: Rifaximin

placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo