Stress Ulcer Prophylaxis in the Intensive Care Unit

NCT02467621 | Completed Phase 4 Results DMC

• 1 other identifier: RH-ITA-006
• Study Type: interventional
• Target: 3,350
• Locations: 6 countries
• Sites: 33

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.

Conditions

Gastrointestinal Bleeding; Stress Ulcers

Keywords

Stress ulcer prophylaxis; Proton pump inhibitor; Pneumonia; Clostridium difficile infection

Outcome Measures

Primary Outcomes (1)

• Mortality

  Landmark mortality 90-days after randomization

  90 days

Secondary Outcomes (7)

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

  Until ICU discharge, maximum 90 days

• Number of Participants With Clinically Important GI Bleeding

  Until ICU discharge, maximum 90 days

• Number of Participants With One or More Infectious Adverse Events

  Until ICU discharge, maximum 90 days

• Mortality

  1 year

• Percentage of Days Alive Without Organ Support

  Within 90 days

Study Arms (2)

Proton pump inhibitor (PPI)

EXPERIMENTAL

Pantoprazole 40 mg

Drug: Pantoprazole

Normal saline

PLACEBO COMPARATOR

Saline (0.9%)

Other: Saline (0.9%)

Interventions

Pantoprazole DRUG

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

Also known as: Pantoloc

Proton pump inhibitor (PPI)

Saline (0.9%) OTHER

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

Normal saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr. Morten Hylander Møller: lead
• Rigshospitalet, Denmark: collaborator
• Copenhagen Trial Unit, Center for Clinical Intervention Research: collaborator

Study Sites (33)

Dept. of Intensive Care, Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Dept. of Intensive Care, Århus University Hospital Nørrebrogade

Aarhus, 8000, Denmark

Location

Dept. of Intensive Care, Århus University Hospital Skejby

Aarhus, 8000, Denmark

Location

Dept. of Intensive Care 4131, Copenhagen University Hospital Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept. of Neurointensive Care, Copenhagen University Hospital Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept. of Intensive Care, Bispebjerg Hospital

Copenhagen, 2400, Denmark

Location

Dept. of Intensive Care, Copenhagen University Hospital Herlev

Herlev, 2730, Denmark

Location

Dept. of Intensive Care, Herning Hospital

Herning, 7400, Denmark

Location

Dept. of Intensive Care, Hillerød Hospital

Hillerød, 3400, Denmark

Location

Dept. of Intensive Care, Hjørring Hospital

Hjørring, 9800, Denmark

Location

Dept. of Intensive Care, Holbæk Hospital

Holbæk, 4300, Denmark

Location

Dept. of Intensive Care, Holstebro Hospital

Holstebro, 7500, Denmark

Location

Dept. of Intensive Care, Køge University Hospital

Køge, 4600, Denmark

Location

Dept. of Intensive Care, Nykøbing Falster Sygehus

Nykøbing Falster, 4800, Denmark

Location

Dept. of Intensive Care, Randers Hospital

Randers, 8930, Denmark

Location

Dept. of Intensive Care, Roskilde Hospital

Roskilde, 4000, Denmark

Location

Dept. of Intensive Care, Slagelse Hospital

Slagelse, 4200, Denmark

Location

Dept. of Intensive Care, Vejle Hospital

Vejle, 7100, Denmark

Location

Dept. of Intensive Care, Viborg Hospital

Viborg, 8800, Denmark

Location

Dept. of Intensive Care, Helsinki University Hospital

Helsinki, 00120, Finland

Location

Dept. of Intensive Care, Kuopio University Hospital

Kuopio, 70029, Finland

Location

Dept. of Intensive Care, Oulu University Hospital

Oulu, 90210, Finland

Location

Dept. of Intensive Care, Tampere University Hospital

Tampere, 33520, Finland

Location

Dept. of Intensive Care, Turku University Hospital

Turku, 20521, Finland

Location

Dept. of Intensive Care, University Medical Center Groningen

Groningen, 9713, Netherlands

Location

Dept. of Intensive Care, Heerlen Hospital

Heerlen, 6419, Netherlands

Location

Dept. of Intensive Care, Bergen University Hospital

Bergen, 5021, Norway

Location

Dept. of Intensive Care, Akershus University Hospital

Lørenskog, 1478, Norway

Location

Dept. of Intensive Care, Oslo University Hospital

Oslo, 0450, Norway

Location

Dept. of Intensive Care, Stavanger University Hospital

Stavanger, 4011, Norway

Location

Dept. of Intensive Care, Basel University Hospital

Basel, 4056, Switzerland

Location

Dept. of Intensive Care, Bern University Hospital

Bern, 3010, Switzerland

Location

Dept. of Intensive Care, University Hospital of Wales

Cardiff, United Kingdom

Location

Related Publications (10)

• 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.

  PMID: 24141808 BACKGROUND

• 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.

  PMID: 25860444 BACKGROUND

• 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.

  PMID: 35122105 DERIVED

• 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.

  PMID: 31938829 DERIVED

• 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.

  PMID: 31441031 DERIVED

• 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.

  PMID: 31321771 DERIVED

• 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.

  PMID: 31282567 DERIVED

• 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.

  PMID: 30863936 DERIVED

• 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.

  PMID: 30354950 DERIVED

• 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.

  PMID: 27093939 DERIVED

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Duodenal Ulcer; Pneumonia; Clostridium Infections

Interventions

Pantoprazole; Sodium Chloride

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Morten Hylander Møller
• Organization: Copenhagen University Hospital Rigshospitalet, Dept. of Intensive Care 4131

mortenhylander@gmail.com

22555343

Study Officials

• Morten Hylander Møller, MD, PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Anders Perner, MD, PhD

  Rigshospitalet, Denmark

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: June 5, 2015
• First Posted: June 10, 2015
• Study Start: January 1, 2016
• Primary Completion: October 22, 2017
• Study Completion: January 21, 2018
• Last Updated: November 15, 2022
• Results First Posted: June 7, 2019

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

FI (5); NO (4); NL (2); GB (1); DK (19); CH (2)