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CompletedNCT02467621SUP-ICUUpdated May 19, 2026Results posted

Stress Ulcer Prophylaxis in the Intensive Care Unit

A Phase 4 interventional study of Pantoprazole and Saline (0.9%) in Gastrointestinal Bleeding and Stress Ulcers, sponsored by Dr. Morten Hylander Møller. Completed at 33 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-19.

Sponsored by Dr. Morten Hylander Møller · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
3,350
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Gastrointestinal Bleeding
  • Stress Ulcers

Keywords

  • Stress ulcer prophylaxis
  • Proton pump inhibitor
  • Pneumonia
  • Clostridium difficile infection
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
3,350 participants (actual)

Study arms

  • Experimental
    Proton pump inhibitor (PPI)

    Pantoprazole 40 mg

    Drug: Pantoprazole

  • Placebo comparator
    Normal saline

    Saline (0.9%)

    Other: Saline (0.9%)

Interventions

  • DrugPantoprazole

    40 mg x 1 daily intravenously from ICU admission to ICU discharge

    Also known as: Pantoloc

  • OtherSaline (0.9%)

    10 ml of isotonic saline x 1 daily intravenously from ICU admission to ICU discharge

05

What researchers measure

Primary outcomes

  1. Mortality

    Landmark mortality 90-days after randomization

    Time frame: 90 days

Secondary outcomes

  1. Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia

    Composite outcome of the number of participants with one or more of the mentioned conditions in the ICU

    Time frame: Until ICU discharge, maximum 90 days

  2. Number of Participants With Clinically Important GI Bleeding

    Number of participants with one or more episodes of clinically important GI bleeding in the ICU

    Time frame: Until ICU discharge, maximum 90 days

  3. Number of Participants With One or More Infectious Adverse Events

    Number of participants with one or more episodes of pneumonia or clostridium difficile infection in the ICU

    Time frame: Until ICU discharge, maximum 90 days

  4. Mortality

    Data for landmark mortality 1 year after randomization.

    Time frame: 1 year

  5. Percentage of Days Alive Without Organ Support

    Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy

    Time frame: Within 90 days

  6. Number of Serious Adverse Reactions

    Serious adverse reactions are: anaphylactic reactions, agranulocytosis, pancytopenia, acute hepatic failure, Steven Johnsons Syndrome and toxic epidermal necrolysis, interstitial nephritis and angioedema.

    Time frame: Until ICU discharge, maximum 90 days

  7. A Health Economic Analysis

    This has not been completed yet.

    Time frame: 90 days

06

Results

Posted Jun 7, 2019

Participant flow

Participant flow — Overall Study
MilestoneProton Pump Inhibitor (PPI)Normal Saline
Started16451653
Completed16441647
Not completed16

Outcome measures

PrimaryMortality

Landmark mortality 90-days after randomization

Time frame:
90 days
Reported as:
Count of participants · Participants
Mortality
ParticipantsProton Pump Inhibitor (PPI)Normal Saline
Mortality510499
SecondaryNumber of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia

Composite outcome of the number of participants with one or more of the mentioned conditions in the ICU

Time frame:
Until ICU discharge, maximum 90 days
Reported as:
Count of participants · Participants
Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia
ParticipantsProton Pump Inhibitor (PPI)Normal Saline
Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia360372
SecondaryNumber of Participants With Clinically Important GI Bleeding

Number of participants with one or more episodes of clinically important GI bleeding in the ICU

Time frame:
Until ICU discharge, maximum 90 days
Reported as:
Count of participants · Participants
Number of Participants With Clinically Important GI Bleeding
ParticipantsProton Pump Inhibitor (PPI)Normal Saline
Number of Participants With Clinically Important GI Bleeding4169
SecondaryNumber of Participants With One or More Infectious Adverse Events

Number of participants with one or more episodes of pneumonia or clostridium difficile infection in the ICU

Time frame:
Until ICU discharge, maximum 90 days
Reported as:
Count of participants · Participants
Number of Participants With One or More Infectious Adverse Events
ParticipantsProton Pump Inhibitor (PPI)Normal Saline
Number of Participants With One or More Infectious Adverse Events276279
SecondaryMortality

Data for landmark mortality 1 year after randomization.

Time frame:
1 year
Reported as:
Count of participants · Participants
Mortality
ParticipantsProton Pump Inhibitor (PPI)Normal Saline
Mortality610601
SecondaryPercentage of Days Alive Without Organ Support

Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy

Time frame:
Within 90 days
Reported as:
Number · percentage of days
Percentage of Days Alive Without Organ Support
percentage of daysProton Pump Inhibitor (PPI)Normal Saline
Percentage of Days Alive Without Organ Support9292
SecondaryNumber of Serious Adverse Reactions

Serious adverse reactions are: anaphylactic reactions, agranulocytosis, pancytopenia, acute hepatic failure, Steven Johnsons Syndrome and toxic epidermal necrolysis, interstitial nephritis and angioedema.

Time frame:
Until ICU discharge, maximum 90 days
Reported as:
Count of participants · Participants
Number of Serious Adverse Reactions
ParticipantsProton Pump Inhibitor (PPI)Normal Saline
Number of Serious Adverse Reactions00
SecondaryA Health Economic Analysis

This has not been completed yet.

Time frame:
90 days

Results for this outcome have not been posted.

Adverse events

Collected over 90 days (for mortality 1 year). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Proton Pump Inhibitor (PPI)610/1,635 (37.3%)0/1,644 (0%)360/1,644 (21.9%)
Normal Saline601/1,626 (37%)0/1,647 (0%)372/1,647 (22.6%)
Most frequent other events
Most frequent other events
EventProton Pump Inhibitor (PPI)Normal Saline
Clinically important eventsGeneral disorders360/1644372/1647

Baseline characteristics

Age, Continuous
Age, Continuous(years)Proton Pump Inhibitor (PPI)Normal SalineTotal
Median67 (56 to 75)67 (55 to 75)67 (55 to 75)
Sex: Female, Male
Sex: Female, Male(Participants)Proton Pump Inhibitor (PPI)Normal SalineTotal
Female6055801185
Male103910672106
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Proton Pump Inhibitor (PPI)Normal SalineTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported164416473291
Region of Enrollment
Region of Enrollment(participants)Proton Pump Inhibitor (PPI)Normal SalineTotal
Netherlands8884172
Norway96101197
Finland128130258
Denmark106110642125
United Kingdom343367
Switzerland237235472
07

Study locations

33 sites
  • Dept. of Intensive Care, Aalborg University Hospital
    Aalborg, 9000, Denmark
  • Dept. of Intensive Care, Århus University Hospital Nørrebrogade
    Aarhus, 8000, Denmark
  • Dept. of Intensive Care, Århus University Hospital Skejby
    Aarhus, 8000, Denmark
  • Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
    Copenhagen, 2100, Denmark
  • Dept. of Neurointensive Care, Copenhagen University Hospital Rigshospitalet
    Copenhagen, 2100, Denmark
  • Dept. of Intensive Care, Bispebjerg Hospital
    Copenhagen, 2400, Denmark
  • Dept. of Intensive Care, Copenhagen University Hospital Herlev
    Herlev, 2730, Denmark
  • Dept. of Intensive Care, Herning Hospital
    Herning, 7400, Denmark
  • Dept. of Intensive Care, Hillerød Hospital
    Hillerød, 3400, Denmark
  • Dept. of Intensive Care, Hjørring Hospital
    Hjørring, 9800, Denmark
  • Dept. of Intensive Care, Holbæk Hospital
    Holbæk, 4300, Denmark
  • Dept. of Intensive Care, Holstebro Hospital
    Holstebro, 7500, Denmark
  • Dept. of Intensive Care, Køge University Hospital
    Køge, 4600, Denmark
  • Dept. of Intensive Care, Nykøbing Falster Sygehus
    Nykøbing Falster, 4800, Denmark
  • Dept. of Intensive Care, Randers Hospital
    Randers, 8930, Denmark
  • Dept. of Intensive Care, Roskilde Hospital
    Roskilde, 4000, Denmark
  • Dept. of Intensive Care, Slagelse Hospital
    Slagelse, 4200, Denmark
  • Dept. of Intensive Care, Vejle Hospital
    Vejle, 7100, Denmark
  • Dept. of Intensive Care, Viborg Hospital
    Viborg, 8800, Denmark
  • Dept. of Intensive Care, Helsinki University Hospital
    Helsinki, 00120, Finland
  • Dept. of Intensive Care, Kuopio University Hospital
    Kuopio, 70029, Finland
  • Dept. of Intensive Care, Oulu University Hospital
    Oulu, 90210, Finland
  • Dept. of Intensive Care, Tampere University Hospital
    Tampere, 33520, Finland
  • Dept. of Intensive Care, Turku University Hospital
    Turku, 20521, Finland
  • Dept. of Intensive Care, University Medical Center Groningen
    Groningen, 9713, Netherlands
  • Dept. of Intensive Care, Heerlen Hospital
    Heerlen, 6419, Netherlands
  • Dept. of Intensive Care, Bergen University Hospital
    Bergen, 5021, Norway
  • Dept. of Intensive Care, Akershus University Hospital
    Lørenskog, 1478, Norway
  • Dept. of Intensive Care, Oslo University Hospital
    Oslo, 0450, Norway
  • Dept. of Intensive Care, Stavanger University Hospital
    Stavanger, 4011, Norway
  • Dept. of Intensive Care, Basel University Hospital
    Basel, 4056, Switzerland
  • Dept. of Intensive Care, Bern University Hospital
    Bern, 3010, Switzerland
  • Dept. of Intensive Care, University Hospital of Wales
    Cardiff, United Kingdom
08

References and documents

Publications

  • 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. PubMed 24141808 ↗
  • 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. PubMed 25860444 ↗
  • 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. PubMed 35122105 ↗
  • 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. PubMed 31938829 ↗
  • 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. PubMed 31441031 ↗
  • 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. PubMed 31321771 ↗
  • 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. PubMed 31282567 ↗
  • 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. PubMed 30863936 ↗
  • 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. PubMed 30354950 ↗
  • 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. PubMed 27093939 ↗

Study documents

  • Protocol and statistical analysis plan · Aug 1, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes

09

Registry details

Key details

Study ID
NCT02467621
Lead sponsor
Dr. Morten Hylander Møller
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research
Responsible party
Dr. Morten Hylander Møller (Principal investigator, Scandinavian Critical Care Trials Group) — Sponsor-investigator
First posted
Jun 10, 2015
Start date
Jan 2016
Primary completion
Oct 22, 2017
Completion
Jan 21, 2018
Results posted
Jun 7, 2019
Last update
May 19, 2026

Study contacts

Morten Hylander Møller, MD, PhD
principal investigator · Rigshospitalet, Denmark
Anders Perner, MD, PhD
study chair · Rigshospitalet, Denmark

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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