The PEARL trial: 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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

1 Mar 2026 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512040-28-01

EudraCT number

2018-004323-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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.

Conditions and MedDRA coding

Confirmed diagnosis of Alcoholic liver cirrhosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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 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 10

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 NL 68205.018.18 / The PEARL trial Version number: 1.9.1, 23 January 2024 21 of 58 f. Unrelieved bile duct obstruction g. Technically not feasible h. Poor liver function (MELD score > 20)
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. Current or recent (<3 months) use of rifaximin
8. Overt neurologic diseases such as Alzheimer’s disease, Parkinson’s disease
9. Pregnant or breastfeeding women
10. Patients refusing or unable to sign informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint is the development of OHE within three months after TIPS placement determined by the West Haven criteria.

Secondary endpoints 1

1. Secondary endpoints include 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 post-placement; time to development of OHE or MHE episodes; the increase in PHES, S-ANT1 score and LFI compared to baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

DJ van Doorn

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

DJ van Doorn

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications