Stopping proton-pump inhibitors in patients with liver cirrhosis

Stop of Proton-pump Inhibitor Treatment in Patients With Liver Cirrhosis - a Double-blind, Placebo-controlled Trial

This study is testing whether stopping proton-pump inhibitors can reduce infection rates and brain issues in people with liver cirrhosis who have been hospitalized.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 476 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Universitätsklinikum Hamburg-Eppendorf (other)
• Locations: 1 site (Hamburg, Free and Hanseatic City of Hamburg)
• Trial ID: NCT04448028 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of discontinuing proton-pump inhibitors (PPIs) in patients with liver cirrhosis who have been hospitalized for related complications. It is a double-blind, placebo-controlled trial where participants will receive either a placebo or Esomeprazole, a common PPI, to assess the impact on infection rates and hepatic encephalopathy. The study aims to clarify the ambiguous evidence surrounding PPI use in cirrhotic patients and its potential risks. By evaluating these outcomes, the trial seeks to provide clearer guidelines for PPI use in this vulnerable population.

Who should consider this trial

Good fit: Ideal candidates are patients diagnosed with liver cirrhosis who have been hospitalized for complications and have been on PPI treatment for at least 28 days.

Not a fit: Patients with severe reflux esophagitis or those not meeting the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management of liver cirrhosis by reducing the risk of infections and other complications associated with unnecessary PPI use.

How similar studies have performed: Other studies have shown mixed results regarding the safety and efficacy of PPI use in cirrhotic patients, making this trial a valuable investigation into an area of ongoing debate.

Eligibility criteria

Inclusion Criteria:

* Patients with liver cirrhosis. The diagnosis of liver cirrhosis may be based on histology or a combination of clinical, laboratory and radiological criteria.
* Hospitalization or recent hospitalization (0 to 42 days prior to the baseline visit) with complications of liver cirrhosis.
* Treatment with proton pump inhibitors (PPI) for at least 28 days prior to the screening visit.
* PPI treatment with a single standard dose/day or less for at least 7 days prior to the screening visit.
* Females/males who agree to comply with the applicable contraceptive requirements of the protocol.
* Non-pregnant, non-lactating females.
* Ability to understand the patient information and to personally sign and date the informed consent to participate in the study, before completing any study related procedures.
* The patient is co-operative and available for the entire study.
* Provided written informed consent.

Exclusion Criteria:

* Diagnosis of severe reflux esophagitis (LA grade C or D) by EGD \< 2 months prior to the screening visit without PPI-therapy for at least 8 weeks prior to the screening visit.
* Peptic ulcers diagnosed by EGD \< 28 days prior to the screening visit.
* History of endoscopic therapy for esophageal varices \< 14 days prior to the screening visit.
* Life-expectancy \< 1 year (at the discretion of the investigator) due to extrahepatic malignancies, metastasized hepatocellular carcinoma (HCC) or other severe extrahepatic diseases. Importantly, HCC without extrahepatic metastases or a reduced life-expectancy of \< 1 year due to liver cirrhosis are not regarded as exclusion criteria.
* Regular intake of non-steroidal anti-inflammatory drugs (NSAID) on a daily basis with the exemption of acetylsalicylic acid (ASS) 100mg/day orally.
* Hypersensitivity or intolerance to esomeprazole, substituted benzimidazoles or other excipients of the IMP.
* Ongoing therapy with nelfinavir.
* Participation in a clinical trial or use of an IMP within 30 days or five times the half-life of the IMP - whichever is longer - prior to receiving the first dose within this study.
* Positive urine pregnancy test at screening or positive serum pregnancy test before the first treatment or is breast feeding.
* Patient is not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of IMP.

Where this trial is running

Hamburg, Free and Hanseatic City of Hamburg

• University Medical Center Hamburg-Eppendorf — Hamburg, Free and Hanseatic City of Hamburg, Germany (RECRUITING)

Study contacts

• Principal investigator: Johannes Kluwe, MD — I. Department of Medicine, University Medical Center Hamburg-Eppendorf
• Study coordinator: STOPPIT Project Team

Conditions: Liver Cirrhosis, liver cirrhosis, cirrhosis, fibrosis, complications, drugs, safety, side effects