Stress Ulcer Prophylaxis in the Intensive Care Unit

Study Overview
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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.

Official Title
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Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU)

Conditions
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Gastrointestinal Bleeding, Stress Ulcers

Intervention / Treatment
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* Drug: Pantoprazole
* Other: Saline (0.9%)


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proton pump inhibitor (PPI)<br>Pantoprazole 40 mg | Drug: Pantoprazole<br>* 40 mg x 1 daily intravenously from ICU admission to ICU discharge<br>* Other names: Pantoloc;|
| Placebo Comparator: Normal saline<br>Saline (0.9%) | Other: Saline (0.9%)<br>* 10 ml of isotonic saline x 1 daily intravenously from ICU admission to ICU discharge<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Landmark mortality 90-days after randomization | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia | Composite outcome of the number of participants with one or more of the mentioned conditions in the ICU | Until ICU discharge, maximum 90 days | 
| Number of Participants With Clinically Important GI Bleeding | Number of participants with one or more episodes of clinically important GI bleeding in the ICU | Until ICU discharge, maximum 90 days | 
| Number of Participants With One or More Infectious Adverse Events | Number of participants with one or more episodes of pneumonia or clostridium difficile infection in the ICU | Until ICU discharge, maximum 90 days | 
| Mortality | Data for landmark mortality 1 year after randomization. | 1 year | 
| Percentage of Days Alive Without Organ Support | Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy | Within 90 days | 
| Number of Serious Adverse Reactions | Serious adverse reactions are: anaphylactic reactions, agranulocytosis, pancytopenia, acute hepatic failure, Steven Johnsons Syndrome and toxic epidermal necrolysis, interstitial nephritis and angioedema. | Until ICU discharge, maximum 90 days | 
| A Health Economic Analysis | This has not been completed yet. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stress ulcer prophylaxis, Proton pump inhibitor, Pneumonia, Clostridium difficile infection