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


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov Identifier: NCT02467621 .
Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. mette.krag.01@regionh.dk.
Mette
M
Krag
Department of Intensive Care 4131 and Centre for Research in Intensive Care (CRIC), Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Anders
A
Perner
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Jørn
J
Wetterslev
Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK.
Matt P
MP
Wise
Pharmacy Department, Oxford University Hospitals NHS Trust, Oxford, UK.
Mark
M
Borthwick
Department of Intensive Care Medicine, Kuopio University Hospital, Kuopio, Finland.
Stepani
S
Bendel
Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino IST, University of Genoa, Genoa, Italy.
Paolo
P
Pelosi
University of Groningen, Department of Critical Care, University Medical Center Groningen, Groningen, The Netherlands.
Frederik
F
Keus
Department of Anaesthesia and Intensive Care, Haukeland University Hospital and Clinical Institute 1 UiB, Bergen, Norway.
Anne Berit
AB
Guttormsen
Department of Intensive Care Medicine, University Hospital Inselspital, Bern, Switzerland.
Joerg C
JC
Schefold
Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Morten Hylander
MH
Møller
D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D016638:Critical Illness; D003428:Cross Infection / Q000209:etiology; D004334:Drug Administration Schedule; D016527:Drug Costs; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology; D005060:Europe; D017721:Hospital Costs; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology; D010437:Peptic Ulcer / Q000191:economics / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D010438:Peptic Ulcer Hemorrhage / Q000191:economics / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011014:Pneumonia / Q000209:etiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors
Adverse event; Critically ill; Gastrointestinal bleeding; Intensive care unit; Placebo; Randomised clinical trial; Stress ulcer prophylaxis