Stress Ulcer Prophylaxis in the Intensive Care Unit

NCT ID: NCT02467621

Last Updated: 2022-11-15

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

3350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2018-01-21

Brief Summary

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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

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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.

Conditions

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Gastrointestinal Bleeding Stress Ulcers

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Proton pump inhibitor (PPI)

Pantoprazole 40 mg

Group Type EXPERIMENTAL

Pantoprazole

Intervention Type DRUG

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

Normal saline

Saline (0.9%)

Group Type PLACEBO_COMPARATOR

Saline (0.9%)

Intervention Type OTHER

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

Interventions

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Pantoprazole

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

Intervention Type DRUG

Saline (0.9%)

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

Intervention Type OTHER

Other Intervention Names

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Pantoloc

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

Copenhagen Trial Unit, Center for Clinical Intervention Research

OTHER

Sponsor Role collaborator

Dr. Morten Hylander Møller

OTHER

Sponsor Role lead

Responsible Party

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Dr. Morten Hylander Møller

Principal investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Morten Hylander Møller, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Anders Perner, MD, PhD

Role: STUDY_CHAIR

Rigshospitalet, Denmark

Locations

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Dept. of Intensive Care, Aalborg University Hospital

Aalborg, , Denmark

Site Status

Dept. of Intensive Care, Århus University Hospital Nørrebrogade

Aarhus, , Denmark

Site Status

Dept. of Intensive Care, Århus University Hospital Skejby

Aarhus, , Denmark

Site Status

Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet

Copenhagen, , Denmark

Site Status

Dept. of Neurointensive Care, Copenhagen University Hospital Rigshospitalet

Copenhagen, , Denmark

Site Status

Dept. of Intensive Care, Bispebjerg Hospital

Copenhagen, , Denmark

Site Status

Dept. of Intensive Care, Copenhagen University Hospital Herlev

Herlev, , Denmark

Site Status

Dept. of Intensive Care, Herning Hospital

Herning, , Denmark

Site Status

Dept. of Intensive Care, Hillerød Hospital

Hillerød, , Denmark

Site Status

Dept. of Intensive Care, Hjørring Hospital

Hjørring, , Denmark

Site Status

Dept. of Intensive Care, Holbæk Hospital

Holbæk, , Denmark

Site Status

Dept. of Intensive Care, Holstebro Hospital

Holstebro, , Denmark

Site Status

Dept. of Intensive Care, Køge University Hospital

Køge, , Denmark

Site Status

Dept. of Intensive Care, Nykøbing Falster Sygehus

Nykøbing Falster, , Denmark

Site Status

Dept. of Intensive Care, Randers Hospital

Randers, , Denmark

Site Status

Dept. of Intensive Care, Roskilde Hospital

Roskilde, , Denmark

Site Status

Dept. of Intensive Care, Slagelse Hospital

Slagelse, , Denmark

Site Status

Dept. of Intensive Care, Vejle Hospital

Vejle, , Denmark

Site Status

Dept. of Intensive Care, Viborg Hospital

Viborg, , Denmark

Site Status

Dept. of Intensive Care, Helsinki University Hospital

Helsinki, , Finland

Site Status

Dept. of Intensive Care, Kuopio University Hospital

Kuopio, , Finland

Site Status

Dept. of Intensive Care, Oulu University Hospital

Oulu, , Finland

Site Status

Dept. of Intensive Care, Tampere University Hospital

Tampere, , Finland

Site Status

Dept. of Intensive Care, Turku University Hospital

Turku, , Finland

Site Status

Dept. of Intensive Care, University Medical Center Groningen

Groningen, , Netherlands

Site Status

Dept. of Intensive Care, Heerlen Hospital

Heerlen, , Netherlands

Site Status

Dept. of Intensive Care, Bergen University Hospital

Bergen, , Norway

Site Status

Dept. of Intensive Care, Akershus University Hospital

Lørenskog, , Norway

Site Status

Dept. of Intensive Care, Oslo University Hospital

Oslo, , Norway

Site Status

Dept. of Intensive Care, Stavanger University Hospital

Stavanger, , Norway

Site Status

Dept. of Intensive Care, Basel University Hospital

Basel, , Switzerland

Site Status

Dept. of Intensive Care, Bern University Hospital

Bern, , Switzerland

Site Status

Dept. of Intensive Care, University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Countries

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Denmark Finland Netherlands Norway Switzerland United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 24141808 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25860444 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35122105 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31938829 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31441031 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31321771 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31282567 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30863936 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30354950 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27093939 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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RH-ITA-006

Identifier Type: -

Identifier Source: org_study_id

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