Krag 2016.

Trial name or title	Stress ulcer prophylaxis with a proton pump inhibitor vs placebo in critically ill patients (SUP‐ICU trial): study protocol for a randomised controlled trial
Methods	Investigator‐initiated pragmatic international multi‐centre randomised blinded parallel‐group study
Participants	Inclusion criteria All adults (≥ 18 years) Acutely admitted to the ICU with 1 or more risk factors for GI bleeding: Shock (continuous infusion with vasopressors or inotropes, systolic blood pressure < 90 mmHg, mean arterial blood pressure < 70 mmHg, or plasma lactate level ≥ 4 mmol/L) Acute or chronic intermittent or continuous renal replacement therapy (RRT) Invasive mechanical ventilation that is expected to last more than 24 hours Coagulopathy (platelets < 50 × 10⁹/L or international normalised ratio (INR) > 1.5, or prothrombin time (PT) > 20 s) documented within the last 24 hours Ongoing treatment with anticoagulant drugs (prophylactic doses excluded) History of coagulopathy (platelets < 50 × 10⁹/L or INR > 1.5 or PT > 20 s within the 6 months before hospital admission) History of chronic liver disease (portal hypertension; cirrhosis proven by biopsy, computed tomography (CT) scan, or ultrasound; or history of variceal bleeding or hepatic encephalopathy) Exclusion criteria Contraindications to PPIs (including intolerance of PPIs and treatment with atazanavir (anti‐human immunodeficiency virus (HIV) medication)) Current daily treatment with a PPI and/or a H2RA GI bleeding of any origin during current hospital admission Diagnosis of peptic ulcer during current hospital admission Organ transplant during current hospital admission Withdrawal from active therapy or brain death Fertile woman with positive test for urinary or plasma human chorionic gonadotropin (hCG) Consent according to national regulations not obtainable
Interventions	Intervention: pantoprazole 40 mg IV (pantoprazole; Actavis, Gentofte, Denmark) Control: placebo, given once daily IV, from randomisation until ICU discharge or death for a maximum of 90 days
Outcomes	Primary outcomes All‐cause mortality 90 days after randomisation Secondary outcomes Adverse events during ICU stay: clinically important GI bleeding, pneumonia, CDI, or acute myocardial ischaemia Clinically important GI bleeding during ICU stay Infectious adverse events (pneumonia or CDI) during ICU stay Days alive without use of mechanical ventilation, RRT, or circulatory support in the 90‐day trial period Number of serious adverse reactions (SARs) during ICU stay Mortality 1 year after randomisation A health economic analysis will be performed. Analytical details will be based on results of the study and will be specified at that time (cost‐benefit vs cost‐minimisation analyses)
Starting date	January 2016
Contact information	Mette Krag, Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet; mette.krag.01@regionh.dk
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