Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

doi:10.1186/s13063-016-1331-3

Randomized Controlled Trial

. 2016 Apr 19;17(1):205.

doi: 10.1186/s13063-016-1331-3.

Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

Affiliations

¹ Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. mette.krag.01@regionh.dk.
² Department of Intensive Care 4131 and Centre for Research in Intensive Care (CRIC), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
³ Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK.
⁵ Pharmacy Department, Oxford University Hospitals NHS Trust, Oxford, UK.
⁶ Department of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland.
⁷ Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino IST, University of Genoa, Genoa, Italy.
⁸ University of Groningen, Department of Critical Care, University Medical Center Groningen, Groningen, The Netherlands.
⁹ Department of Anaesthesia and Intensive Care, Haukeland University Hospital and Clinical Institute 1 UiB, Bergen, Norway.
¹⁰ Department of Intensive Care Medicine, University Hospital Inselspital, Bern, Switzerland.
¹¹ Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.

PMID: 27093939
PMCID: PMC4837508
DOI: 10.1186/s13063-016-1331-3

Randomized Controlled Trial

Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

Mette Krag et al. Trials. 2016.

. 2016 Apr 19;17(1):205.

doi: 10.1186/s13063-016-1331-3.

Authors

Affiliations

¹ Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. mette.krag.01@regionh.dk.
² Department of Intensive Care 4131 and Centre for Research in Intensive Care (CRIC), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
³ Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK.
⁵ Pharmacy Department, Oxford University Hospitals NHS Trust, Oxford, UK.
⁶ Department of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland.
⁷ Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino IST, University of Genoa, Genoa, Italy.
⁸ University of Groningen, Department of Critical Care, University Medical Center Groningen, Groningen, The Netherlands.
⁹ Department of Anaesthesia and Intensive Care, Haukeland University Hospital and Clinical Institute 1 UiB, Bergen, Norway.
¹⁰ Department of Intensive Care Medicine, University Hospital Inselspital, Bern, Switzerland.
¹¹ Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.

PMID: 27093939
PMCID: PMC4837508
DOI: 10.1186/s13063-016-1331-3

Abstract

Background: Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable.

Methods/design: The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses. The sample size will enable us to detect a 20 % relative risk difference (5 % absolute risk difference) in 90-day mortality assuming a 25 % event rate with a risk of type I error of 5 % and power of 90 %. The trial will be externally monitored according to Good Clinical Practice standards. Interim analyses will be performed after 1650 and 2500 patients.

Conclusion: The SUP-ICU trial will provide high-quality data on the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in critically ill adult patients admitted in the ICU.

Trial registration: ClinicalTrials.gov Identifier: NCT02467621 .

Keywords: Adverse event; Critically ill; Gastrointestinal bleeding; Intensive care unit; Placebo; Randomised clinical trial; Stress ulcer prophylaxis.

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Figures

**Fig. 2**
Trial sequential analysis of all-cause mortality (16 trials)

See this image and copyright information in PMC

Cited by

Heterogeneity of treatment effect of prophylactic pantoprazole in adult ICU patients: a post hoc analysis of the SUP-ICU trial.
Granholm A, Marker S, Krag M, Zampieri FG, Thorsen-Meyer HC, Kaas-Hansen BS, van der Horst ICC, Lange T, Wetterslev J, Perner A, Møller MH. Granholm A, et al. Intensive Care Med. 2020 Apr;46(4):717-726. doi: 10.1007/s00134-019-05903-8. Epub 2020 Jan 14. Intensive Care Med. 2020. PMID: 31938829
What's new with stress ulcer prophylaxis in the ICU?
Marker S, Krag M, Møller MH. Marker S, et al. Intensive Care Med. 2017 Aug;43(8):1132-1134. doi: 10.1007/s00134-017-4733-0. Epub 2017 Feb 25. Intensive Care Med. 2017. PMID: 28238056 Review. No abstract available.
Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial.
Marker S, Perner A, Wetterslev J, Krag M, Lange T, Wise MP, Borthwick M, Bendel S, Keus F, Guttormsen AB, Schefold JC, Møller MH; SUP-ICU investigators. Marker S, et al. Intensive Care Med. 2019 May;45(5):609-618. doi: 10.1007/s00134-019-05589-y. Epub 2019 Mar 12. Intensive Care Med. 2019. PMID: 30863936
Stress Ulcer Prophylaxis in Neurocritical Care.
Barletta JF, Mangram AJ, Sucher JF, Zach V. Barletta JF, et al. Neurocrit Care. 2018 Dec;29(3):344-357. doi: 10.1007/s12028-017-0447-y. Neurocrit Care. 2018. PMID: 28929324 Review.
Is research from databases reliable? No.
Perner A, Bellomo R, Møller MH. Perner A, et al. Intensive Care Med. 2019 Jan;45(1):115-117. doi: 10.1007/s00134-018-5073-4. Epub 2019 Jan 16. Intensive Care Med. 2019. PMID: 30649588 No abstract available.

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References

1. Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5:368–75. doi: 10.1186/cc1071. - DOI - PMC - PubMed
1. Eddleston JM, Pearson RC, Holland J, Tooth JA, Vohra A, Doran BH. Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Crit Care Med. 1994;22:1949–54. doi: 10.1097/00003246-199422120-00010. - DOI - PubMed
1. Martin LF. Stress ulcers are common after aortic surgery. Endoscopic evaluation of prophylactic therapy. Am Surg. 1994;60:169–74. - PubMed
1. Fennerty MB. Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. Crit Care Med. 2002;30:351–5. doi: 10.1097/00003246-200206001-00002. - DOI - PubMed
1. Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015;41:833–45. doi: 10.1007/s00134-015-3725-1. - DOI - PubMed

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[1] Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5:368–75. doi: 10.1186/cc1071. - DOI - PMC - PubMed

[2] Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5:368–75. doi: 10.1186/cc1071. - DOI - PMC - PubMed

[3] Eddleston JM, Pearson RC, Holland J, Tooth JA, Vohra A, Doran BH. Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Crit Care Med. 1994;22:1949–54. doi: 10.1097/00003246-199422120-00010. - DOI - PubMed

[4] Eddleston JM, Pearson RC, Holland J, Tooth JA, Vohra A, Doran BH. Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Crit Care Med. 1994;22:1949–54. doi: 10.1097/00003246-199422120-00010. - DOI - PubMed

[5] Martin LF. Stress ulcers are common after aortic surgery. Endoscopic evaluation of prophylactic therapy. Am Surg. 1994;60:169–74. - PubMed

[6] Martin LF. Stress ulcers are common after aortic surgery. Endoscopic evaluation of prophylactic therapy. Am Surg. 1994;60:169–74. - PubMed

[7] Fennerty MB. Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. Crit Care Med. 2002;30:351–5. doi: 10.1097/00003246-200206001-00002. - DOI - PubMed

[8] Fennerty MB. Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. Crit Care Med. 2002;30:351–5. doi: 10.1097/00003246-200206001-00002. - DOI - PubMed

[9] Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015;41:833–45. doi: 10.1007/s00134-015-3725-1. - DOI - PubMed

[10] Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015;41:833–45. doi: 10.1007/s00134-015-3725-1. - DOI - PubMed

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Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

Affiliations

Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial

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