The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Prevention of hepatic encephalopathy by administration of rifaximin and lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS): a multicentre randomised, double blind, placebo controlled trial (PEARL trial)
BMJ Open Gastroenterol. 2020 Dec;7(1):e000531. doi: 10.1136/bmjgast-2020-000531.
K de Wit1, J J Schaapman2, F Nevens3, J Verbeek3, S Coenen4, F J C Cuperus5, M Kramer6, E T T L Tjwa7, N Mostafavi8, M G W Dijkgraaf9, O M van Delden10, U H W Beuers1, M J Coenraad2, R B Takkenberg11
Author information
1Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
2Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
3Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
4Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
5Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
7Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
8Biostatistics Unit, Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands.
9Epidemiology and Data Science, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
10Interventional Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
11Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands r.b.takkenberg@amsterdamumc.nl.
Abstract
Introduction: Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%-54%) and often severe complication. A prophylactic strategy is lacking.
Methods and analysis: The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium.
Ethics and dissemination: This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal.
Trial registration numbers: ClinicalTrials.gov (NCT04073290) and EudraCT database (2018-004323-37).