Gastrointestinal Bleeding, Stress Ulcers
Conditions
Keywords
Stress ulcer prophylaxis, Proton pump inhibitor, Pneumonia, Clostridium difficile infection
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.
Detailed description
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.
Interventions
DRUGPantoprazole
40 mg x 1 daily intravenously from ICU admission to ICU discharge
OTHERSaline (0.9%)
10 ml of isotonic saline x 1 daily intravenously from ICU admission to ICU discharge
Sponsors
Dr. Morten Hylander Møller
Rigshospitalet, Denmark
Copenhagen Trial Unit, Center for Clinical Intervention Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 90 days | Landmark mortality 90-days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia | Until ICU discharge, maximum 90 days | Composite outcome of the number of participants with one or more of the mentioned conditions in the ICU |
| Number of Participants With Clinically Important GI Bleeding | Until ICU discharge, maximum 90 days | Number of participants with one or more episodes of clinically important GI bleeding in the ICU |
| Number of Participants With One or More Infectious Adverse Events | Until ICU discharge, maximum 90 days | Number of participants with one or more episodes of pneumonia or clostridium difficile infection in the ICU |
| Mortality | 1 year | Data for landmark mortality 1 year after randomization. |
| Percentage of Days Alive Without Organ Support | Within 90 days | Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy |
| Number of Serious Adverse Reactions | Until ICU discharge, maximum 90 days | Serious adverse reactions are: anaphylactic reactions, agranulocytosis, pancytopenia, acute hepatic failure, Steven Johnsons Syndrome and toxic epidermal necrolysis, interstitial nephritis and angioedema. |
| A Health Economic Analysis | 90 days | This has not been completed yet. |
Countries
Denmark, Finland, Netherlands, Norway, Switzerland, United Kingdom
Contacts
PRINCIPAL_INVESTIGATORMorten Hylander Møller, MD, PhD
Rigshospitalet, Denmark
STUDY_CHAIRAnders Perner, MD, PhD
Rigshospitalet, Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Pump Inhibitor (PPI) Pantoprazole 40 mg
Pantoprazole: 40 mg x 1 daily intravenously from ICU admission to ICU discharge | 1,644 |
| Normal Saline Saline (0.9%)
Saline (0.9%): 10 ml of isotonic saline x 1 daily intravenously from ICU admission to ICU discharge | 1,647 |
| Total | 3,291 |
Baseline characteristics
| Characteristic | Proton Pump Inhibitor (PPI) | Normal Saline | Total |
|---|---|---|---|
| Age, Continuous | 67 years | 67 years | 67 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1644 Participants | 1647 Participants | 3291 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Denmark | 1061 participants | 1064 participants | 2125 participants |
| Region of Enrollment Finland | 128 participants | 130 participants | 258 participants |
| Region of Enrollment Netherlands | 88 participants | 84 participants | 172 participants |
| Region of Enrollment Norway | 96 participants | 101 participants | 197 participants |
| Region of Enrollment Switzerland | 237 participants | 235 participants | 472 participants |
| Region of Enrollment United Kingdom | 34 participants | 33 participants | 67 participants |
| Sex: Female, Male Female | 605 Participants | 580 Participants | 1185 Participants |
| Sex: Female, Male Male | 1039 Participants | 1067 Participants | 2106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 610 / 1,635 | 601 / 1,626 |
| other Total, other adverse events | 360 / 1,644 | 372 / 1,647 |
| serious Total, serious adverse events | 0 / 1,644 | 0 / 1,647 |
Outcome results
Primary
Mortality
Landmark mortality 90-days after randomization
Time frame: 90 days
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Mortality | 510 Participants |
| Normal Saline | Mortality | 499 Participants |
Secondary
A Health Economic Analysis
This has not been completed yet.
Time frame: 90 days
Secondary
Mortality
Data for landmark mortality 1 year after randomization.
Time frame: 1 year
Population: Twenty-one patients were lost to follow-up, as compared to the primary outcome (90-day mortality): 7 patients in the PPI arm and 14 patients in the placebo arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Mortality | 610 Participants |
| Normal Saline | Mortality | 601 Participants |
Secondary
Number of Participants With Clinically Important GI Bleeding
Number of participants with one or more episodes of clinically important GI bleeding in the ICU
Time frame: Until ICU discharge, maximum 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Number of Participants With Clinically Important GI Bleeding | 41 Participants |
| Normal Saline | Number of Participants With Clinically Important GI Bleeding | 69 Participants |
Secondary
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
Time frame: Until ICU discharge, maximum 90 days
Population: Intention-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia | 360 Participants |
| Normal Saline | Number of Participants With Clinically Important GI Bleeding, Pneumonia, Clostridium Difficile Infection or Acute Myocardial Ischemia | 372 Participants |
Secondary
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
Time frame: Until ICU discharge, maximum 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Number of Participants With One or More Infectious Adverse Events | 276 Participants |
| Normal Saline | Number of Participants With One or More Infectious Adverse Events | 279 Participants |
Secondary
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.
Time frame: Until ICU discharge, maximum 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Number of Serious Adverse Reactions | 0 Participants |
| Normal Saline | Number of Serious Adverse Reactions | 0 Participants |
Secondary
Percentage of Days Alive Without Organ Support
Percentage of days alive and free from mechanical ventilation, circulatory support and renal replacement therapy
Time frame: Within 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Proton Pump Inhibitor (PPI) | Percentage of Days Alive Without Organ Support | 92 percentage of days |
| Normal Saline | Percentage of Days Alive Without Organ Support | 92 percentage of days |