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Open Access 01-12-2022 | Hepatic Encephalopathy | Study protocol

Stop of proton-pump inhibitor treatment in patients with liver cirrhosis (STOPPIT): study protocol for a prospective, multicentre, controlled, randomized, double-blind trial

Authors: Malte H. Wehmeyer, Thomas Horvatits, Anika Buchholz, Linda Krause, Sarah Walter, Antonia Zapf, Ansgar W. Lohse, Johannes Kluwe, the STOPPIT-trial group

Published in: Trials | Issue 1/2022

Abstract

Background

Proton-pump inhibitors (PPI) are liberally prescribed in patients with liver cirrhosis. Observational studies link PPI therapy in cirrhotic patients with an increased risk for infectious complications, hepatic encephalopathy and an increased risk for hospitalization and mortality. However, patients with liver cirrhosis are also considered to be at risk for peptic ulcer bleeding. The STOPPIT trial evaluates if discontinuation of a pre-existing PPI treatment delays a composite endpoint of re-hospitalization and/or death in patients (recently) hospitalized with liver cirrhosis compared to patients on continued PPI medication.

Methods

The STOPPIT-trial is a prospective, multicentre, randomized, double-blinded, placebo-controlled, parallel-group trial. In total, 476 patients with complicated liver cirrhosis who already receive long-term PPI therapy without evidence-based indication are 1:1 randomized to receive either esomeprazole 20 mg (control group) or placebo (intervention group) for 360 days. Patients with an indication for PPI therapy (such as a recent diagnosis of peptic ulcers, severe reflux esophagitis, severe hemorrhagic gastritis, recent endoscopic therapy for oesophageal varices) are excluded. The primary composite endpoint is the time-to re-hospitalization and/or death. Secondary endpoints include rates of re-hospitalization, mortality, occurrence of infections, hepatic decompensation and acute-on-chronic liver failure. The safety endpoint is defined as manifestation of an evidence-based indication for PPI re-therapy. The impact of PPI continuation or discontinuation on the intestinal microbiota will be studied. The recruitment will take place at 18 study sites throughout Germany. Recruitment has started in April 2021.

Discussion

The STOPPIT trial is the first clinical trial to study the effects of PPI withdrawal on relevant outcome variables in patients with complicated liver cirrhosis. If the hypothesis that PPI withdrawal improves clinical outcomes of cirrhosis patients is confirmed, this would argue for a strong restriction of the currently liberal prescription practice of PPIs in this population. If, on the other hand, the trial demonstrates an increased risk of gastrointestinal bleeding events in patients after PPI withdrawal, this could create a rationale for a more liberal, prophylactic PPI treatment in patients with liver cirrhosis.

Trial registration

EU clinical trials register EudraCT 2019-005008-16 (registered December 27, 2019). ClinicalTrials.gov NCT04448028 (registered June 25, 2020). German Clinical Trials Register DRKS00021290 (registered March 10, 2021).

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Title: Stop of proton-pump inhibitor treatment in patients with liver cirrhosis (STOPPIT): study protocol for a prospective, multicentre, controlled, randomized, double-blind trial
Authors: Malte H. Wehmeyer
Thomas Horvatits
Anika Buchholz
Linda Krause
Sarah Walter
Antonia Zapf
Ansgar W. Lohse
Johannes Kluwe
the STOPPIT-trial group
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Hepatic Encephalopathy
Esomeprazole
Liver Cirrhosis
Hepatic Encephalopathy
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06232-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Stop of proton-pump inhibitor treatment in patients with liver cirrhosis (STOPPIT): study protocol for a prospective, multicentre, controlled, randomized, double-blind trial

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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