Stop of Proton-pump Inhibitor Treatment in Patients With Liver Cirrhosis - a Double-blind, Placebo-controlled Trial
Status:
Recruiting
Trial end date:
2025-03-01
Target enrollment:
Participant gender:
Summary
Proton-pump inhibitors (PPI) are commonly prescribed in an uncritical manner to patients with
liver cirrhosis without a clear evidence-based indication. Observational studies suggests
that PPI use in cirrhotic patients may be a risk factor for the development of infections,
especially spontaneous bacterial peritonitis (SBP). A possible explanation are PPI-associated
microbiotic shifts leading to small intestinal bacterial overgrowth with subsequently
increased bacterial translocation. Furthermore, PPI therapy in cirrhotic patients may lead to
an increased risk for pneumonia and Clostridium difficile-infections.
However, the evidence is ambiguous, as other published studies found no evidence for an
association of PPI use with an increased risk for SBP or pneumonia.
Moreover, an association between episodes of hepatic encephalopathy and PPI use has been
reported.
Infections and hepatic encephalopathy may often lead to a hospitalization of cirrhotic
patients and PPI use at discharge has also been associated to early re-hospitalization.
While some studies found an association of PPI and increased mortality in cirrhotic patients,
other studies could not observe this association.
Thus, some of the current evidence suggests an unfavourable risk profile of PPIs in patients
with liver cirrhosis. However, this patient population is considered to be at a high risk of
gastrointestinal haemorrhage from peptic ulcers. Importantly, patients with liver cirrhosis
have an increased mortality after peptic ulcer bleeding as compared to patients without
cirrhosis. Therefore, generous PPI use may also have a yet unproven preventive effect against
upper gastrointestinal bleeding.
The STOPPIT trial is the first prospective, randomized, controlled, double-blind trial
investigating the effect of discontinuation of long-term PPI therapy on hospitalized patients
with complicated liver cirrhosis with a pre-existing long-term PPI therapy. Importantly,
patients with an evidence-based indication for PPI therapy are excluded from the trial. All
study participants (n=476) stop their previous PPI treatment and are then randomized (1:1) to
receive either placebo (intervention group) or esomeprazole 20mg/day (control group) for 360
days.
The primary hypothesis anticipates a delay of re-hospitalisation and/or death (composite
endpoint) in patients who discontinue PPI treatment as compared to patients who continue PPI
therapy. Secondary objectives include the assessment of mortality, re-hospitalisation rates,
infection rates, rate of acute hepatic decompensation and ACLF, as well as rates of upper and
lower gastrointestinal bleeding events in both groups. Impact of prolonged or discontinued
PPI therapy on the intestinal microbiota and pharmacoeconomics will be studied as a secondary
assessment.
Phase:
Phase 4
Details
Lead Sponsor:
Universitätsklinikum Hamburg-Eppendorf
Collaborators:
German Federal Ministry of Education and Research University Hospital Heidelberg