Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt: a multi-centre randomized, double blind, placebo controlled trial. The PEARL trial

Phase 1

• Conditions: post-TIPS Hepatic Encephalopathy (HE); MedDRA version: 21.1Level: PTClassification code 10019660Term: Hepatic encephalopathySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.1Level: PTClassification code 10066599Term: Hepatic encephalopathy prophylaxisSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 21.1Level: LLTClassification code 10068826Term: Transjugular intrahepatic portosystemic shuntSystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 20.0Level: PTClassification code 10076204Term: Minimal hepatic encephalopathySystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

• Registration Number: EUCTR2018-004323-37-NL
• Lead Sponsor: Academic Medical Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-01-07
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 238

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 (400mg spironolactone and 160mg 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/or 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
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 226
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

1.Any absolute contraindications for TIPS placement:
a.History of hepatic encephalopathy grade II-IV without precipitating factor
b.Heart failure NYHA = grade 3
c.Hepatocellular carcinoma (multifocal or large or centrally located)
d.Systemic infection / sepsis
e.Severe pulmonary hypertension
f.Unrelieved bile duct obstruction
g.Technically not feasible
h.Poor liver function (MELD score > 20)
2.Use of ciclosporin
3.Life-threating variceal bleeding with emergency TIPS placement
4.Age > 80 years
5.Non-cirrhotic portal hypertension
6.Portal vein thrombosis
7.Current or recent (<3 months) use of rifaximin
8.Overt neurologic diseases such as Alzheimer’s disease, Parkinson’s disease
9.HIV
10. Pregnant or breastfeeding women
11.Patients refusing or unable to sign informed consent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified