Clinical trial NCT02467621: Stress Ulcer Prophylaxis in the Intensive Care Unit
Official title: Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gastrointestinal Bleeding
Stress Ulcers
Keywords: Stress ulcer prophylaxis
Proton pump inhibitor
Pneumonia
Clostridium difficile infection
Lead sponsor: Scandinavian Critical Care Trials Group
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Copenhagen Trial Unit, Center for Clinical Intervention Research
First posted: 2015-06-10
Enrollment: 3350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Stress ulcer prophylaxis (SUP) is standard of care in the intensive care unit (ICU), however the quantity and quality of evidence is low and potential harm has been reported.

The aim of the SUP-ICU trial is to asses the overall benefits and harms of SUP with proton pump inhibitor in adult critically ill patients in the ICU.

Detailed description: Critically ill patients in the ICU are at risk of stress related gastrointestinal (GI) bleeding, and SUP is recommended. However, the quantity and quality of evidence supporting SUP is low and has been questioned. Furthermore studies have shown that proton pump inhibitors (PPIs) may increase the risk of pneumonia, clostridium difficile infection and acute myocardial ischemia. The aim of the SUP-ICU trial is to assess the benefits and harms of SUP with PPI in adult critically ill patients in the ICU.

Eligibility criteria: INCLUSION CRITERIA:

* Acute admission to the ICU
* Age ≥ 18 years
* One or more of the following risk factors:

  * Shock (continuous infusion with vasopressors or inotropes, systolic blood pressure \< 90 mmHg, mean arterial blood pressure \< 70 mmHg or lactate \> 4 mmol/l)
  * Acute or chronic intermittent or continuous renal replacement therapy
  * Invasive mechanical ventilation which is expected to last \> 24 hours
  * Coagulopathy (platelets \< 50 x 109/l or international normalized ratio (INR) \> 1.5 or prothrombin time (PT) \> 20 seconds) documented within the last 24 hours
  * Ongoing treatment with anticoagulant drugs (prophylaxis doses excluded)
  * History of coagulopathy (platelets \< 50 x 109/l or INR \> 1.5 or PT \> 20 seconds) within 6 months prior to hospital admission
  * History of chronic liver disease (portal hypertension, cirrhosis proven by biopsy, computed tomography (CT) scan or ultrasound, history of variceal bleeding or hepatic encephalopathy in the past medical history)

EXCLUSION CRITERIA:

* Contraindications to PPI
* Ongoing treatment with PPI and/or H2RA on a daily basis
* GI bleeding of any origin during current hospital admission
* Diagnosed with peptic ulcer during current hospital admission
* Organ transplant during current hospital admission
* Withdrawal from active therapy or brain death
* Fertile woman with positive urine human chorionic gonadotropin (hCG) or plasma-hCG
* Consent according to national regulations not obtainable

Primary outcomes:
measure: Mortality
timeFrame: 90 days
Secondary outcomes:
measure: Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia
timeFrame: Until ICU discharge, maximum 90 days
measure: Number of Participants With Clinically Important GI Bleeding
timeFrame: Until ICU discharge, maximum 90 days
measure: Number of Participants With One or More Infectious Adverse Events
timeFrame: Until ICU discharge, maximum 90 days
measure: Mortality
timeFrame: 1 year
measure: Percentage of Days Alive Without Organ Support
timeFrame: Within 90 days
measure: Number of Serious Adverse Reactions
timeFrame: Until ICU discharge, maximum 90 days
measure: A Health Economic Analysis
timeFrame: 90 days
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Dept. of Intensive Care, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Dept. of Intensive Care, Århus University Hospital Nørrebrogade
city: Arhus
country: Denmark
facility: Dept. of Intensive Care, Århus University Hospital Skejby
city: Copenhagen
country: Denmark
facility: Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
city: Copenhagen
country: Denmark
facility: Dept. of Neurointensive Care, Copenhagen University Hospital Rigshospitalet
city: Copenhagen
country: Denmark
facility: Dept. of Intensive Care, Bispebjerg Hospital
city: Herlev
country: Denmark
facility: Dept. of Intensive Care, Copenhagen University Hospital Herlev
city: Herning
country: Denmark
facility: Dept. of Intensive Care, Herning Hospital
city: Hillerød
country: Denmark
facility: Dept. of Intensive Care, Hillerød Hospital
city: Hjørring
country: Denmark
facility: Dept. of Intensive Care, Hjørring Hospital
city: Holbæk
country: Denmark
facility: Dept. of Intensive Care, Holbæk Hospital
city: Holstebro
country: Denmark
facility: Dept. of Intensive Care, Holstebro Hospital
city: Køge
country: Denmark
facility: Dept. of Intensive Care, Køge University Hospital
city: Nykøbing Falster
country: Denmark
facility: Dept. of Intensive Care, Nykøbing Falster Sygehus
city: Randers
country: Denmark
facility: Dept. of Intensive Care, Randers Hospital
city: Roskilde
country: Denmark
facility: Dept. of Intensive Care, Roskilde Hospital
city: Slagelse
country: Denmark
facility: Dept. of Intensive Care, Slagelse Hospital
city: Vejle
country: Denmark
facility: Dept. of Intensive Care, Vejle Hospital
city: Viborg
country: Denmark
facility: Dept. of Intensive Care, Viborg Hospital
city: Helsinki
country: Finland
facility: Dept. of Intensive Care, Helsinki University Hospital
city: Kuopio
country: Finland
facility: Dept. of Intensive Care, Kuopio University Hospital
city: Oulu
country: Finland
facility: Dept. of Intensive Care, Oulu University Hospital
city: Tampere
country: Finland
facility: Dept. of Intensive Care, Tampere University Hospital
city: Turku
country: Finland
facility: Dept. of Intensive Care, Turku University Hospital
city: Groningen
country: Netherlands
facility: Dept. of Intensive Care, University Medical Center Groningen
city: Heerlen
country: Netherlands
facility: Dept. of Intensive Care, Heerlen Hospital
city: Bergen
country: Norway
facility: Dept. of Intensive Care, Bergen University Hospital
city: Lørenskog
country: Norway
facility: Dept. of Intensive Care, Akershus University Hospital
city: Oslo
country: Norway
facility: Dept. of Intensive Care, Oslo University Hospital
city: Stavanger
country: Norway
facility: Dept. of Intensive Care, Stavanger University Hospital
city: Basel
country: Switzerland
facility: Dept. of Intensive Care, Basel University Hospital
city: Bern
country: Switzerland
facility: Dept. of Intensive Care, Bern University Hospital
city: Cardiff
country: United Kingdom
facility: Dept. of Intensive Care, University Hospital of Wales
Study officials:
affiliation: Rigshospitalet, Denmark
name: Morten Hylander Møller, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Anders Perner, MD, PhD
role: STUDY_CHAIR
References:
citation: Krag M, Perner A, Wetterslev J, Wise MP, Hylander Moller M. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2014 Jan;40(1):11-22. doi: 10.1007/s00134-013-3125-3. Epub 2013 Oct 19.
citation: Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, McArthur C, Cook D, Nielsen N, Pelosi P, Keus F, Guttormsen AB, Moller AD, Moller MH; SUP-ICU co-authors. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015 May;41(5):833-45. doi: 10.1007/s00134-015-3725-1. Epub 2015 Apr 10.
citation: Halling CMB, Moller MH, Marker S, Krag M, Kjellberg J, Perner A, Gyrd-Hansen D. The effects of pantoprazole vs. placebo on 1-year outcomes, resource use and employment status in ICU patients at risk for gastrointestinal bleeding: a secondary analysis of the SUP-ICU trial. Intensive Care Med. 2022 Apr;48(4):426-434. doi: 10.1007/s00134-022-06631-2. Epub 2022 Feb 5.
citation: Granholm A, Marker S, Krag M, Zampieri FG, Thorsen-Meyer HC, Kaas-Hansen BS, van der Horst ICC, Lange T, Wetterslev J, Perner A, Moller MH. Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial. Intensive Care Med. 2020 Apr;46(4):717-726. doi: 10.1007/s00134-019-05903-8. Epub 2020 Jan 14.
citation: Granholm A, Lange T, Anthon CT, Marker S, Krag M, Meyhoff TS, Wise MP, Borthwick M, Bendel S, Keus F, Guttormsen AB, Schefold JC, Wetterslev J, Perner A, Moller MH. Time to onset of gastrointestinal bleeding in the SUP-ICU trial: A pre-planned substudy. Acta Anaesthesiol Scand. 2019 Nov;63(10):1346-1356. doi: 10.1111/aas.13459. Epub 2019 Sep 11.
citation: Granholm A, Marker S, Krag M, Zampieri FG, Thorsen-Meyer HC, Kaas-Hansen BS, van der Horst ICC, Lange T, Wetterslev J, Perner A, Moller MH. Heterogeneity of treatment effect of stress ulcer prophylaxis in ICU patients: A secondary analysis protocol. Acta Anaesthesiol Scand. 2019 Oct;63(9):1251-1256. doi: 10.1111/aas.13432. Epub 2019 Jul 18.
citation: Marker S, Krag M, Perner A, Wetterslev J, Lange T, Wise MP, Borthwick M, Bendel S, Keus F, Guttormsen AB, Schefold JC, Rasmussen BS, Elkmann T, Bestle M, Arenkiel B, Laake JH, Kamper MK, Lang M, Pawlowicz-Dworzanska MB, Karlsson S, Liisanantti J, Dey N, Knudsen H, Granholm A, Moller MH; SUP-ICU trial investigators. Pantoprazole in ICU patients at risk for gastrointestinal bleeding-1-year mortality in the SUP-ICU trial. Acta Anaesthesiol Scand. 2019 Oct;63(9):1184-1190. doi: 10.1111/aas.13436. Epub 2019 Jul 19.
citation: Marker S, Perner A, Wetterslev J, Krag M, Lange T, Wise MP, Borthwick M, Bendel S, Keus F, Guttormsen AB, Schefold JC, Moller MH; SUP-ICU investigators. Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial. Intensive Care Med. 2019 May;45(5):609-618. doi: 10.1007/s00134-019-05589-y. Epub 2019 Mar 12.
citation: Krag M, Marker S, Perner A, Wetterslev J, Wise MP, Schefold JC, Keus F, Guttormsen AB, Bendel S, Borthwick M, Lange T, Rasmussen BS, Siegemund M, Bundgaard H, Elkmann T, Jensen JV, Nielsen RD, Liboriussen L, Bestle MH, Elkjaer JM, Palmqvist DF, Backlund M, Laake JH, Badstolokken PM, Gronlund J, Breum O, Walli A, Winding R, Iversen S, Jarnvig IL, White JO, Brand B, Madsen MB, Quist L, Thornberg KJ, Moller A, Wiis J, Granholm A, Anthon CT, Meyhoff TS, Hjortrup PB, Aagaard SR, Andreasen JB, Sorensen CA, Haure P, Hauge J, Hollinger A, Scheuzger J, Tuchscherer D, Vuilliomenet T, Takala J, Jakob SM, Vang ML, Paelestik KB, Andersen KLD, van der Horst ICC, Dieperink W, Fjolner J, Kjer CKW, Solling C, Solling CG, Karttunen J, Morgan MPG, Sjobo B, Engstrom J, Agerholm-Larsen B, Moller MH; SUP-ICU trial group. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. N Engl J Med. 2018 Dec 6;379(23):2199-2208. doi: 10.1056/NEJMoa1714919. Epub 2018 Oct 24.
citation: Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, Pelosi P, Keus F, Guttormsen AB, Schefold JC, Moller MH; SUP-ICU investigators. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial. Trials. 2016 Apr 19;17(1):205. doi: 10.1186/s13063-016-1331-3.