Preventing liver complications after TIPS placement with rifaximin and lactulose

Prevention of Hepatic Encephalopathy by Administration of Rifaximin and Lactulose in Patients With Liver Cirrhosis Undergoing TIPS Placement: a Multi-centre Randomized, Double Blind, Placebo Controlled Trial.

This study is testing if taking rifaximin and lactulose can help prevent brain problems in adults with liver cirrhosis after they have a procedure called TIPS.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 238 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (other)
• Locations: 6 sites (Leuven and 5 other locations)
• Trial ID: NCT04073290 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of rifaximin and lactulose in preventing post-TIPS hepatic encephalopathy (HE) in patients undergoing Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. It is a multicenter, randomized, placebo-controlled, double-blind study involving adult patients with liver cirrhosis who are at risk of developing HE. Participants will receive either the active treatment or a placebo starting 72 hours before the procedure and continuing for three months post-TIPS. The primary outcome will be the incidence of overt HE within three months, assessed using the West Haven criteria.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed liver cirrhosis who are undergoing elective TIPS placement for refractory ascites or recurrent variceal bleeding.

Not a fit: Patients who do not have liver cirrhosis or those who are not undergoing TIPS placement will likely not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of severe hepatic encephalopathy in patients undergoing TIPS, improving their quality of life and clinical outcomes.

How similar studies have performed: While the approach of using rifaximin and lactulose for this specific indication is novel, similar studies have shown promise in managing hepatic encephalopathy in other contexts.

Eligibility criteria

Inclusion Criteria:

1. Elective TIPS placement for refractory ascites or recurrent variceal bleeding:

   Recurrent tense ascites and one or more of the following criteria:

   i. Not responding to the maximal dose of diuretics (400 milligram spironolactone and 160 milligram furosemide).

   ii. Kidney insufficiency (Creatinine \> 135 umol/L) induced by diuretics. iii. Electrolyte disturbances (Sodium \< 125 mmol/L, Potassium \> 5.5 mmol/L) induced by diuretics.

   iv. Not tolerating higher dose of diuretics (e.g. because of subjective side effects like muscle cramps).

   Recurrent variceal bleeding, not responsive to treatment with endoscopic band ligation and beta-blockers, with a high risk of failure of endoscopic treatment:

   i. Patients with a variceal bleeding and Child-Pugh C (10-13 points) cirrhosis or ii. Patients with a variceal bleeding, Child-Pugh B and an active bleeding during endoscopy
2. Age ≥18 years
3. Confirmed liver cirrhosis as documented by liver biopsy, elastography (e.g. Fibroscan) or combination of usual radiological and biochemical criteria.
4. Signed informed consent

Exclusion Criteria:

1. Any absolute contraindications for TIPS placement
2. Use of ciclosporin
3. Life-threatening variceal bleeding with emergency TIPS placement which can not be delayed 72 hours
4. Age \> 80 years
5. Non-cirrhotic portal hypertension
6. Portal vein thrombosis (main trunk)
7. HIV
8. Current or recent (\<3 months) use of rifaximin
9. Overt neurologic diseases such as Alzheimer's disease, Parkinson's disease
10. Pregnant or breastfeeding women
11. Patients refusing or unable to sign informed consent

Where this trial is running

Leuven and 5 other locations

• Universitaire Ziekenhuizen Leuven — Leuven, Belgium (RECRUITING)
• Academic Medical Centre — Amsterdam, Netherlands (RECRUITING)
• University Medical Center Groningen — Groningen, Netherlands (RECRUITING)
• Leiden University Medical Center — Leiden, Netherlands (RECRUITING)
• Radboud University — Nijmegen, Netherlands (RECRUITING)
• Erasmus Medical Center — Rotterdam, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Bart Takkenberg, MD, PhD — Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Study coordinator: Koos de Wit, MD

Conditions: Hepatic Encephalopathy, Cirrhosis, Liver, Portal Hypertension, Liver Diseases, Pathological Processes, Rifaximin, Lactulose, post-TIPS HE