NCT04073290

Prevention of Post-TIPS Hepatic Encephalopathy by Administration of 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.

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 238 (estimated)
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Rationale: Hepatic encephalopathy (HE) is a major and common complication in patients with liver cirrhosis. HE can be classified in the extensive range of neurocognitive deterioration as minimal HE (MHE), covert HE (grade I), or overt HE (OHE, grade II-IV). Liver cirrhosis is the most common cause of portal hypertension (PH). Patients who develop complications of PH, like variceal bleeding or refractory ascites, can benefit from a Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. Unfortunately, post-TIPS HE is a common and often severe complication. Incidence of new onset or worsening of HE after TIPS is approximately 20-45%. Currently there is no strategy to prevent post-TIPS HE.

Detailed description

Objective: To assess the incidence of post-TIPS OHE within the first three months after prophylactic administration of lactulose and rifaximin versus placebo in patients who undergo Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. Study design: A multicentre, randomized, placebo-controlled, double blind study. Study population: Adult consecutive patients undergoing elective TIPS placement (for refractory ascites or secondary prophylaxis in variceal bleeding) in all Dutch academic centres where TIPS procedures are performed: Amsterdam UMC, location Academic Medical Centre (AMC), Erasmus MC, Leiden University Medical Centre (LUMC), Maastricht University Medical Centre+ (MUMC+), Radboud University Medical Centre (Radboudumc), University Medical Centre Groningen (UMCG), and University Hospitals Leuven (UZ Leuven) in Belgium. Intervention: Rifaximin 550 milligram (mg) b.i.d. will be prescribed, in combination with a starting dose of 25 milliliter (mL) lactulose b.i.d. and further dependent on the amount of daily bowel movements, with the objective not to exceed more than two soft stools per day. Intervention will start 72 hours before TIPS placement, and will last till three months after TIPS placement. The control group will receive placebo in combination with lactulose (as described above). Main study parameters/endpoints: Primary endpoint is the development of OHE within three months after TIPS placement determined by the West Haven criteria. Secondary endpoints are 90 day mortality; development of a second episode of OHE within the first three months; development of OHE in the period between three and twelve months after TIPS placement; development of MHE between TIPS placement and twelve months after placement; the increase of the psychometric hepatic encephalopathy score (PHES) and simplified one minute animal naming test (S-ANT1) compared to baseline. Differences in molecular composition of peripheral / portal blood samples at TIPS placement. Furthermore, quality of life will be assessed.

Conditions

• Hepatic Encephalopathy
• Cirrhosis, Liver
• Portal Hypertension
• Liver Diseases
• Pathological Processes

Interventions

Type	Name	Description
DRUG	Rifaximin 550 milligram Oral Tablet [XIFAXAN]	Rifaximin 550 milligram b.i.d. 72 hours before TIPS placement till 3 months post-TIPS
DRUG	Placebo oral tablet	Placebo b.i.d. 72 hours before TIPS placement till 3 months post-TIPS
DRUG	Lactulose 667 milligram/milliliter Oral Solution	Lactulose based on soft stool frequency, 72 hours before TIPS placement till 3 months post-TIPS

Timeline

• Start date: 2020-01-21
• Primary completion: 2026-09-30
• Completion: 2026-12-31
• First posted: 2019-08-29
• Last updated: 2025-01-28

Locations

6 sites across 2 countries: Belgium, Netherlands