COVID-19NCT05715567
Re-EValuating the Inhibition of Stress Erosions (REVISE) - COVID-19 Cohort Study
An observational study of COVID-19 and GastroIntestinal Bleeding, run by McMaster University at 1 site in Canada.
Trial summary
Commonly employed medications used in critically ill patients requiring life support include proton pump inhibitors (PPIs). These medications are thought to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, GastroIntestinal Bleeding
- What is being tested?
- Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800)
- How many people
- 600 participants
- Where
- 1 siteCanada
- Study dates
- 1 Dec 2021to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients are eligible according to the inclusion and exclusion criteria of the REVISE trial, regardless of COVID status
Who may be able to join
- Adults ≥18 years old projected to receive invasive mechanical ventilation for ≥48 hours according to the treating physician
Who cannot join
- Already received invasive mechanical ventilation >72 hours during this hospital admission
- Acid suppression for active gastrointestinal bleeding or high risk of bleeding (e.g., current bleeding, peptic ulcer bleeding within 8 weeks, recent severe esophagitis, Barrett's esophagus, Zollinger-Ellison syndrome); [dyspepsia or gastroesophageal reflux is not an exclusion criterion]
- Acid suppression in the intensive care unit for >1 daily dose equivalent of a proton pump inhibitor or histamine-2-receptor antagonist
- Dual antiplatelet therapy
- Combined antiplatelet and therapeutic anticoagulation
- Pantoprazole contraindication per local product information
Show all 10Show fewer
- Palliative care or anticipated withdrawal of advanced life support
- Pregnancy
- Previous enrolment in REVISE, or a related trial, or trial for which co-enrolment is prohibited
- Patient, proxy or physician declines
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
St Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Deborah Cook, MD, 905-522-1155 ext. 35325, debcook@mcmaster.ca
Nicole Zytaruk, Reg. N, 905-522-1155 ext. 35325, zytaruk@mcmaster.ca
About this study
Commonly employed medications used in critically ill patients requiring life support include proton pump inhibitors (PPIs). These medications are thought to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite their widespread use, they do hold some risks which include infection in the form of pneumonia and diarrheal illnesses such as Clostridioides difficile infection (C. difficile). Emerging high-quality studies suggest PPI usage does not influence susceptibility to COVID-19 infection, however some studies suggest PPI use leads to poor outcomes in this population, including prolonged time on life-support and death. While we can appreciate the negative effects of PPI may be magnified in the sickest of patients, namely hospitalized patients with COVID-19, the beneficial or potentially harmful role they play in this population remains unclear.
We aim to build a clinical profile to further describe critically ill patients with COVID-19 in Ontario using the infrastructure of an ongoing multicenter clinical trial of acid suppression. We will identify characteristics that predict poor outcomes among sick COVID patients, examining the impact of PPIs on this population.
Read the detailed description
The overall aims are to further characterize the high-risk population of COVID-19 patients nested within the multicenter REVISE trial. Specifically, we plan 1) to explore the impact of PPIs on mechanically ventilated critically ill COVID-19 patients, 2) describe the clinical course for patients with COVID-19 and identify characteristics that predict poor prognosis, and 3) compare outcomes to patients without COVID-19. The overall research questions are as follows:
- Do critically ill patients projected to receive mechanical ventilation for >48 hours with COVID-19 have different clinical outcomes without PPIs?
- Are there prognostically relevant demographic, biomarker and clinical data to characterize critically ill patients with COVID-19?
- Do critically ill patients with COVID-19 have significant higher rates of clinically important GI bleeding, 90-day mortality, and rates of infection when compared to a propensity-matched non-COVID REVISE cohort?
To accomplish this, the investigators propose to gather information in patients' medical charts including biomarkers drawn by the ICU team, venous thromboembolism (VTE) and tracheostomy timing, to link with extensive baseline characteristics and outcomes already collected in the REVISE trial (NCT03374800)
- Conditions
- COVID-19, GastroIntestinal Bleeding
- Being tested
- Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800)
- Keywords
- COVID-19, pandemic, gastrointestinal bleeding, pneumonia, Clostridioides difficile
- Medical subject headings
- COVID-19, Gastrointestinal Hemorrhage, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800)Other
Following the intervention of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800)
| Study group | Role | What they receive |
|---|---|---|
| Patients with COVID-19 | Not described Receives: Other: Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800) | |
| Patients without COVID-19 | Not described Receives: Other: Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of clinically important gastro-intestinal bleeding
The primary efficacy outcome is clinically important GI bleeding occurring in the ICU or resulting in ICU readmission during the index hospital stay.
The definition of clinically important GI bleeding is overt GI bleeding (i.e., hematemesis, frank blood or coffee ground nasogastric aspirate, melena or hematochezia) plus 1 of the following in the absence of other causes:
- Hemodynamic change defined as a spontaneous decrease in invasively monitored mean arterial pressure or non-invasive systolic or diastolic blood pressure of >20 mmHg, or an orthostatic increase in pulse rate of >20 beats/minute and a decrease in systolic blood pressure of >10 mmHg, with or without vasopressor initiation or increase;
- vasopressor initiation;
- hemoglobin decrease of >2 g/dl (20 g/L) within 24 h of bleeding;
- transfusion of >2 units red blood cells within 24 h of bleeding; or
- therapeutic intervention (e.g., therapeutic endoscopy, angiography, surgery).
Measured: 90 days
Primary Safety Outcome: 90 Day Mortality
Mortality status at day 90 post randomization
Measured: 90 days after randomization
Secondary outcomes (5)
Ventilator-associated pneumonia
VAP is diagnosed in patients who received invasive mechanical ventilation for >48 hours when there is a new, progressive or persistent radiographic infiltrate plus at least 2 of the following without other obvious cause: 1) fever (temperature>38 °C) or hypothermia (temperature <36 °C); 2) leukopenia (<4.0x106/L) or leukocytosis (>12x106/L); 3) purulent sputum; or 4) gas exchange deterioration.
Measured: 90 Days (while in ICU,censored at 90 days after randomization)
C. difficile infection
Defined as clinical features (diarrhea [>3 episodes of unformed stools or Bristol type 6 or 7), ileus, or toxic megacolon) and either microbiological evidence of toxin-producing C. difficile or pseudomembranous colitis on colonoscopy in hospital.
Measured: 90 days (during the index hospital admission, censored at 90 days)
Renal replacement therapy
Defined as initiation of new renal replacement therapy in the ICU.
Measured: While in ICU,censored at 90 days after randomization
Hospital mortality
Defined as all-cause mortality in hospital.
Measured: While in hospital, censored at 90 days after randomization
Patient important GI bleeding
Defined as overt GI bleeding, plus an invasive intervention (e.g., therapeutic endoscopy, angiography, surgery), acknowledging how some clinically important GI bleeds in prior studies did not actually require any tests or treatments, and thus may not be important to patients. This outcome will be refined by an ongoing mixed methods study with an overarching instrument-building aim.
Measured: Censored at 90 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2023
- Study start1 Dec 2021
- Primary completion31 Oct 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), The Physicians' Services Incorporated Foundation
- Responsible party
- Sponsor
- Investigators
- Deborah Cook, MD, Principal investigator, McMaster UniversityBrittany Dennis, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05715567
- Sponsor's protocol ID
- COVID-19 REVISE_Cohort_22
- Status last verified
- Feb 2023
- First submitted
- 3 Feb 2023
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dennis B, Heels-Ansdell D, Ibrahim Q, Basmaji J, Thabane L, Guyatt G, Saunders L, Hand L, Loy O, Zytaruk N, Hardie M, Deane AM, Marshall JC, Arabi Y, Lauzier F, Dionne JC, Burns KE, Alhazzani W, Vazquez-Grande G, Geagea A, Myburgh J, Muscedere J, English S, Binnie A, Tsang JL, Hunt M, Ostermann M, Al-Fares AA, Knowles S, Ahmed A, Cook DJ; REVISE Investigators and the Canadian Critical Care Trials Group. Proton pump inhibitors in invasively ventilated patients with SARS-CoV-2: a substudy of the re-evaluating the inhibition of stress erosions trial. BMJ Open. 2026 Aug 31;16(8):e119937. doi: 10.1136/bmjopen-2026-119937.
PubMed 42674788Dennis BB, Thabane L, Heels-Ansdell D, Dionne JC, Binnie A, Tsang J, Guyatt G, Ahmed A, Lauzier F, Deane A, Arabi Y, Marshall J, Zytaruk N, Saunders L, Finfer S, Myburgh J, Muscedere J, English S, Ostermann M, Hardie M, Knowles S, Cook D; REVISE Investigators the Canadian Critical Care Trials Group. Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial. Trials. 2023 Aug 30;24(1):561. doi: 10.1186/s13063-023-07589-2.
PubMed 37644556
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Re-EValuating the Inhibition of Stress Erosions (REVISE) - COVID-19 Cohort Study
- ClinicalTrials.gov ID
- NCT05715567
- Acronym / sponsor ID
- COVID-19 REVISE_Cohort_22
- Conditions
- COVID-19, GastroIntestinal Bleeding
- Keywords
- COVID-19, pandemic, gastrointestinal bleeding, pneumonia, Clostridioides difficile
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), The Physicians' Services Incorporated Foundation
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 31 Oct 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 8 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Commonly employed medications used in critically ill patients requiring life support include proton pump inhibitors (PPIs). These medications are thought to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite their widespread use, they do hold some risks which include infection in the form of pneumonia and diarrheal illnesses such as Clostridioides difficile infection (C. difficile). Emerging high-quality studies suggest PPI usage does not influence susceptibility to COVID-19 infection, however some studies suggest PPI use leads to poor outcomes in this population, including prolonged time on life-support and death. While we can appreciate the negative effects of PPI may be magnified in the sickest of patients, namely hospitalized patients with COVID-19, the beneficial or potentially harmful role they play in this population remains unclear.
We aim to build a clinical profile to further describe critically ill patients with COVID-19 in Ontario using the infrastructure of an ongoing multicenter clinical trial of acid suppression. We will identify characteristics that predict poor outcomes among sick COVID patients, examining the impact of PPIs on this population.
Detailed description
The overall aims are to further characterize the high-risk population of COVID-19 patients nested within the multicenter REVISE trial. Specifically, we plan 1) to explore the impact of PPIs on mechanically ventilated critically ill COVID-19 patients, 2) describe the clinical course for patients with COVID-19 and identify characteristics that predict poor prognosis, and 3) compare outcomes to patients without COVID-19. The overall research questions are as follows:
- Do critically ill patients projected to receive mechanical ventilation for >48 hours with COVID-19 have different clinical outcomes without PPIs?
- Are there prognostically relevant demographic, biomarker and clinical data to characterize critically ill patients with COVID-19?
- Do critically ill patients with COVID-19 have significant higher rates of clinically important GI bleeding, 90-day mortality, and rates of infection when compared to a propensity-matched non-COVID REVISE cohort?
To accomplish this, the investigators propose to gather information in patients' medical charts including biomarkers drawn by the ICU team, venous thromboembolism (VTE) and tracheostomy timing, to link with extensive baseline characteristics and outcomes already collected in the REVISE trial (NCT03374800)
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with COVID-19 | – | Other: Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800) |
| Patients without COVID-19 | – | Other: Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients are eligible according to the inclusion and exclusion criteria of the REVISE trial, regardless of COVID status
Key inclusion criteria (1 listed)
- Adults ≥18 years old projected to receive invasive mechanical ventilation for ≥48 hours according to the treating physician
Key exclusion criteria (10 listed)
- Already received invasive mechanical ventilation >72 hours during this hospital admission
- Acid suppression for active gastrointestinal bleeding or high risk of bleeding (e.g., current bleeding, peptic ulcer bleeding within 8 weeks, recent severe esophagitis, Barrett's esophagus, Zollinger-Ellison syndrome); [dyspepsia or gastroesophageal reflux is not an exclusion criterion]
- Acid suppression in the intensive care unit for >1 daily dose equivalent of a proton pump inhibitor or histamine-2-receptor antagonist
- Dual antiplatelet therapy
- Combined antiplatelet and therapeutic anticoagulation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800)Following the intervention of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial (NCT03374800) | Other | Patients with COVID-19, Patients without COVID-19 |
Primary outcome
Rate of clinically important gastro-intestinal bleeding
Time frame: 90 days
The primary efficacy outcome is clinically important GI bleeding occurring in the ICU or resulting in ICU readmission during the index hospital stay. The definition of clinically important GI bleeding is overt GI bleeding (i.e., hematemesis, frank blood or coffee ground nasogastric aspirate, melena or hematochezia) plus 1 of the following in the absence of other causes: 1. Hemodynamic change defined as a spontaneous decrease in invasively monitored mean arterial pressure or non-invasive systolic or diastolic blood pressure of >20 mmHg, or an orthostatic increase in pulse rate of >20 beats/minute and a decrease in systolic blood pressure of >10 mmHg, with or without vasopressor initiation or increase; 2. vasopressor initiation; 3. hemoglobin decrease of >2 g/dl (20 g/L) within 24 h of bleeding; 4. transfusion of >2 units red blood cells within 24 h of bleeding; or 5. therapeutic intervention (e.g., therapeutic endoscopy, angiography, surgery).
Primary Safety Outcome: 90 Day Mortality
Time frame: 90 days after randomization
Mortality status at day 90 post randomization
5 secondary outcomes
Ventilator-associated pneumonia
Time frame: 90 Days (while in ICU,censored at 90 days after randomization)
C. difficile infection
Time frame: 90 days (during the index hospital admission, censored at 90 days)
Renal replacement therapy
Time frame: While in ICU,censored at 90 days after randomization
Hospital mortality
Time frame: While in hospital, censored at 90 days after randomization
Patient important GI bleeding
Time frame: Censored at 90 days after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Derived from this study: PubMed 42674788Dennis B, Heels-Ansdell D, Ibrahim Q, Basmaji J, Thabane L, Guyatt G, Saunders L, Hand L, Loy O, Zytaruk N, Hardie M, Deane AM, Marshall JC, Arabi Y, Lauzier F, Dionne JC, Burns KE, Alhazzani W, Vazquez-Grande G, Geagea A, Myburgh J, Muscedere J, English S, Binnie A, Tsang JL, Hunt M, Ostermann M, Al-Fares AA, Knowles S, Ahmed A, Cook DJ; REVISE Investigators and the Canadian Critical Care Trials Group. Proton pump inhibitors in invasively ventilated patients with SARS-CoV-2: a substudy of the re-evaluating the inhibition of stress erosions trial. BMJ Open. 2026 Aug 31;16(8):e119937. doi: 10.1136/bmjopen-2026-119937.
- Derived from this study: PubMed 37644556Dennis BB, Thabane L, Heels-Ansdell D, Dionne JC, Binnie A, Tsang J, Guyatt G, Ahmed A, Lauzier F, Deane A, Arabi Y, Marshall J, Zytaruk N, Saunders L, Finfer S, Myburgh J, Muscedere J, English S, Ostermann M, Hardie M, Knowles S, Cook D; REVISE Investigators the Canadian Critical Care Trials Group. Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial. Trials. 2023 Aug 30;24(1):561. doi: 10.1186/s13063-023-07589-2.
- Individual participant dataSharing planned: No
Related trials for COVID-19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah Cook, MD principal investigator
McMaster University
Brittany Dennis, MD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19 and GastroIntestinal Bleeding, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Deborah J Cook, MD (9055221155 ext. 35325, debcook@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of clinically important gastro-intestinal bleeding (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05715567, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.