Stop of proton-pump inhibitor treatment in patients with liver cirrhosis – a doubleblind, placebo-controlled trial (STOPPIT)
- Conditions
- Liver cirrhosis
- Registration Number
- 2023-509863-26-00
- Lead Sponsor
- University Medical Center Hamburg-Eppendorf
- Brief Summary
To determine the time to first unplanned re-hospitalization or death
(composite endpoint) in patients with liver cirrhosis who discontinue
long-term proton-pump inhibitor (PPI) therapy (intervention group) as
compared to patients who continue PPI therapy (control group) over a
period of 12 months (360 days).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 476
Male or female adult (18 years) patient.
Provided written informed consent.
Liver cirrhosis (diagnosed either histologically or by a combination of clinical, laboratory and/or radiological signs).
Hospitalized or recently hospitalized (0 to 42 days before baseline) with complicated liver cirrhosis.
PPI treatment for at least 28 days prior to screening
PPI treatment with a single standard dose/day or less for a minimum of 7 days prior to screening.
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.
Severe esophageal reflux disease (LA grade C or D) diagnosed by esophago-gastro-duodenoscopy (EGD) < 2 months prior to screening without PPI treatment for at least 8 weeks prior to screening.
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 or for up to 5 days after the last scheduled dose of IMP.
Peptic ulcers diagnosed by EGD < 28 days prior to screening.
Endoscopic therapy for varices < 14 days prior to screening.
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 < 1 year due to liver cirrhosis are not regarded as exclusion criteria.
Regular intake of non-steroidal anti-inflammatory drugs on a daily basis with the exemption of acetylsalicylic acid in a dosage of up to 100mg/day.
Patients with one or more of the following measurements at the time of screening or documented during 48 hours before screening: a. Body temperature > 38.5°C, or b. systolic blood pressure < 90 mmHg and tachycardia > 100 beats per minute, or c. ongoing catecholamine treatment higher than low dose norepinephrine ( 0.1 μg/kg/minute) (NB: terlipressin treatment for possible hepatorenal syndrome is not regarded as an exclusion criterion), or d. respiratory rate 22/minute.
Hypersensitivity or intolerance to esomeprazole, substituted benzimidazoles or other excipients of the investigational medicinal product (IMP; Nexium mups or Placebo).
Ongoing therapy with nelfinavir.
Participating 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 receive the first dose within this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time to first unplanned re-hospitalization* or death within 12 months after randomization (composite endpoint). *Exception: expected re-hospitalization for paracentesis in patients with a history of refractory ascites (without any other complication of cirrhosis) during a period of 30 days. Time to first unplanned re-hospitalization* or death within 12 months after randomization (composite endpoint). *Exception: expected re-hospitalization for paracentesis in patients with a history of refractory ascites (without any other complication of cirrhosis) during a period of 30 days.
- Secondary Outcome Measures
Name Time Method Death (all-cause and liver-related). Death (all-cause and liver-related).
Unplanned re-hospitalization. Unplanned re-hospitalization.
Any Infection and differentiated by site of infection (SBP, pneumonia, urinary tract infection, blood stream infection, Clostridium difficile-associated enterocolitis, Norovirus infection, Sars-CoV-2-infection). Any Infection and differentiated by site of infection (SBP, pneumonia, urinary tract infection, blood stream infection, Clostridium difficile-associated enterocolitis, Norovirus infection, Sars-CoV-2-infection).
Acute hepatic decompensation and ACLF. Acute hepatic decompensation and ACLF.
Upper and lower gastrointestinal bleeding event. Upper and lower gastrointestinal bleeding event.
Experimental Endpoint: Changes of intestinal microbiota between baseline and day 90. Experimental Endpoint: Changes of intestinal microbiota between baseline and day 90.
Trial Locations
- Locations (19)
Universitaetsklinikum Jena KöR
🇩🇪Jena, Germany
Universitaetsklinikum Tuebingen AöR
🇩🇪Tuebingen, Germany
Charite Universitaetsmedizin Berlin KöR
🇩🇪Berlin, Germany
Universitaetsklinikum Bonn AöR
🇩🇪Bonn, Germany
Zentrum Fuer Innere Medizin
🇩🇪Rostock, Germany
Universitaetsklinikum Frankfurt AöR
🇩🇪Frankfurt Am Main, Germany
Universitaetsklinikum Leipzig AöR
🇩🇪Leipzig, Germany
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Universitaetsklinikum Brandenburg an der Havel GmbH
🇩🇪Brandenburg An Der Havel, Germany
University Medical Center Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Scroll for more (9 remaining)Universitaetsklinikum Jena KöR🇩🇪Jena, GermanyPhilipp ReukenSite contact+4936419324402Philipp.reuken@med.uni-jena.de