Back to resultsStress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU)
Primary Purpose
Gastrointestinal Bleeding, Stress Ulcers
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Pantoprazole
Saline (0.9%)
Sponsored by
About this trial
This is an interventional prevention trial for Gastrointestinal Bleeding focused on measuring Stress ulcer prophylaxis, Proton pump inhibitor, Pneumonia, Clostridium difficile infection
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
Sites / Locations
- Dept. of Intensive Care, Aalborg University Hospital
- Dept. of Intensive Care, Århus University Hospital Nørrebrogade
- Dept. of Intensive Care, Århus University Hospital Skejby
- Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
- Dept. of Neurointensive Care, Copenhagen University Hospital Rigshospitalet
- Dept. of Intensive Care, Bispebjerg Hospital
- Dept. of Intensive Care, Copenhagen University Hospital Herlev
- Dept. of Intensive Care, Herning Hospital
- Dept. of Intensive Care, Hillerød Hospital
- Dept. of Intensive Care, Hjørring Hospital
- Dept. of Intensive Care, Holbæk Hospital
- Dept. of Intensive Care, Holstebro Hospital
- Dept. of Intensive Care, Køge University Hospital
- Dept. of Intensive Care, Nykøbing Falster Sygehus
- Dept. of Intensive Care, Randers Hospital
- Dept. of Intensive Care, Roskilde Hospital
- Dept. of Intensive Care, Slagelse Hospital
- Dept. of Intensive Care, Vejle Hospital
- Dept. of Intensive Care, Viborg Hospital
- Dept. of Intensive Care, Helsinki University Hospital
- Dept. of Intensive Care, Kuopio University Hospital
- Dept. of Intensive Care, Oulu University Hospital
- Dept. of Intensive Care, Tampere University Hospital
- Dept. of Intensive Care, Turku University Hospital
- Dept. of Intensive Care, University Medical Center Groningen
- Dept. of Intensive Care, Heerlen Hospital
- Dept. of Intensive Care, Bergen University Hospital
- Dept. of Intensive Care, Akershus University Hospital
- Dept. of Intensive Care, Oslo University Hospital
- Dept. of Intensive Care, Stavanger University Hospital
- Dept. of Intensive Care, Basel University Hospital
- Dept. of Intensive Care, Bern University Hospital
- Dept. of Intensive Care, University Hospital of Wales
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Proton pump inhibitor (PPI)
Normal saline
Arm Description
Pantoprazole 40 mg
Saline (0.9%)
Outcomes
Primary Outcome Measures
Mortality
Landmark mortality 90-days after randomization
Secondary Outcome Measures
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
Number of Participants With Clinically Important GI Bleeding
Number of participants with one or more episodes of clinically important GI bleeding in the ICU
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
Mortality
Data for landmark mortality 1 year after randomization.
Percentage of Days Alive Without Organ Support
Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
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.
A Health Economic Analysis
This has not been completed yet.
Full Information
NCT ID
NCT02467621
First Posted
June 5, 2015
Last Updated
October 26, 2022
Sponsor
Dr. Morten Hylander Møller
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research
1. Study Identification
Unique Protocol Identification Number
NCT02467621
Brief Title
Stress Ulcer Prophylaxis in the Intensive Care Unit
Acronym
SUP-ICU
Official Title
Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
October 22, 2017 (Actual)
Study Completion Date
January 21, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Morten Hylander Møller
Collaborators
Rigshospitalet, Denmark, Copenhagen Trial Unit, Center for Clinical Intervention Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Bleeding, Stress Ulcers
Keywords
Stress ulcer prophylaxis, Proton pump inhibitor, Pneumonia, Clostridium difficile infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3350 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Proton pump inhibitor (PPI)
Arm Type
Experimental
Arm Description
Pantoprazole 40 mg
Arm Title
Normal saline
Arm Type
Placebo Comparator
Arm Description
Saline (0.9%)
Intervention Type
Drug
Intervention Name(s)
Pantoprazole
Other Intervention Name(s)
Pantoloc
Intervention Description
40 mg x 1 daily intravenously from ICU admission to ICU discharge
Intervention Type
Other
Intervention Name(s)
Saline (0.9%)
Intervention Description
10 ml of isotonic saline x 1 daily intravenously from ICU admission to ICU discharge
Primary Outcome Measure Information:
Title
Mortality
Description
Landmark mortality 90-days after randomization
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia
Description
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
Title
Number of Participants With Clinically Important GI Bleeding
Description
Number of participants with one or more episodes of clinically important GI bleeding in the ICU
Time Frame
Until ICU discharge, maximum 90 days
Title
Number of Participants With One or More Infectious Adverse Events
Description
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
Title
Mortality
Description
Data for landmark mortality 1 year after randomization.
Time Frame
1 year
Title
Percentage of Days Alive Without Organ Support
Description
Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
Time Frame
Within 90 days
Title
Number of Serious Adverse Reactions
Description
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
Title
A Health Economic Analysis
Description
This has not been completed yet.
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morten Hylander Møller, MD, PhD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anders Perner, MD, PhD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Study Chair
Facility Information:
Facility Name
Dept. of Intensive Care, Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Dept. of Intensive Care, Århus University Hospital Nørrebrogade
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Dept. of Intensive Care, Århus University Hospital Skejby
City
Arhus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Dept. of Neurointensive Care, Copenhagen University Hospital Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Dept. of Intensive Care, Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Facility Name
Dept. of Intensive Care, Copenhagen University Hospital Herlev
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Dept. of Intensive Care, Herning Hospital
City
Herning
ZIP/Postal Code
7400
Country
Denmark
Facility Name
Dept. of Intensive Care, Hillerød Hospital
City
Hillerød
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Dept. of Intensive Care, Hjørring Hospital
City
Hjørring
ZIP/Postal Code
9800
Country
Denmark
Facility Name
Dept. of Intensive Care, Holbæk Hospital
City
Holbæk
ZIP/Postal Code
4300
Country
Denmark
Facility Name
Dept. of Intensive Care, Holstebro Hospital
City
Holstebro
ZIP/Postal Code
7500
Country
Denmark
Facility Name
Dept. of Intensive Care, Køge University Hospital
City
Køge
ZIP/Postal Code
4600
Country
Denmark
Facility Name
Dept. of Intensive Care, Nykøbing Falster Sygehus
City
Nykøbing Falster
ZIP/Postal Code
4800
Country
Denmark
Facility Name
Dept. of Intensive Care, Randers Hospital
City
Randers
ZIP/Postal Code
8930
Country
Denmark
Facility Name
Dept. of Intensive Care, Roskilde Hospital
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Facility Name
Dept. of Intensive Care, Slagelse Hospital
City
Slagelse
ZIP/Postal Code
4200
Country
Denmark
Facility Name
Dept. of Intensive Care, Vejle Hospital
City
Vejle
ZIP/Postal Code
7100
Country
Denmark
Facility Name
Dept. of Intensive Care, Viborg Hospital
City
Viborg
ZIP/Postal Code
8800
Country
Denmark
Facility Name
Dept. of Intensive Care, Helsinki University Hospital
City
Helsinki
ZIP/Postal Code
00120
Country
Finland
Facility Name
Dept. of Intensive Care, Kuopio University Hospital
City
Kuopio
ZIP/Postal Code
70029
Country
Finland
Facility Name
Dept. of Intensive Care, Oulu University Hospital
City
Oulu
ZIP/Postal Code
90210
Country
Finland
Facility Name
Dept. of Intensive Care, Tampere University Hospital
City
Tampere
ZIP/Postal Code
33520
Country
Finland
Facility Name
Dept. of Intensive Care, Turku University Hospital
City
Turku
ZIP/Postal Code
20521
Country
Finland
Facility Name
Dept. of Intensive Care, University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713
Country
Netherlands
Facility Name
Dept. of Intensive Care, Heerlen Hospital
City
Heerlen
ZIP/Postal Code
6419
Country
Netherlands
Facility Name
Dept. of Intensive Care, Bergen University Hospital
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
Dept. of Intensive Care, Akershus University Hospital
City
Lørenskog
ZIP/Postal Code
1478
Country
Norway
Facility Name
Dept. of Intensive Care, Oslo University Hospital
City
Oslo
ZIP/Postal Code
0450
Country
Norway
Facility Name
Dept. of Intensive Care, Stavanger University Hospital
City
Stavanger
ZIP/Postal Code
4011
Country
Norway
Facility Name
Dept. of Intensive Care, Basel University Hospital
City
Basel
ZIP/Postal Code
4056
Country
Switzerland
Facility Name
Dept. of Intensive Care, Bern University Hospital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Dept. of Intensive Care, University Hospital of Wales
City
Cardiff
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
24141808
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.
Results Reference
background
PubMed Identifier
25860444
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.
Results Reference
background
PubMed Identifier
35122105
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.
Results Reference
derived
PubMed Identifier
31938829
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.
Results Reference
derived
PubMed Identifier
31441031
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.
Results Reference
derived
PubMed Identifier
31321771
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.
Results Reference
derived
PubMed Identifier
31282567
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.
Results Reference
derived
PubMed Identifier
30863936
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.
Results Reference
derived
PubMed Identifier
30354950
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.
Results Reference
derived
PubMed Identifier
27093939
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.
Results Reference
derived
Learn more about this trial
Stress Ulcer Prophylaxis in the Intensive Care Unit
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