Clinical trial NCT05715567: Re-EValuating the Inhibition of Stress Erosions (REVISE) - COVID-19 Cohort Study
Official title: Re-EValuating the Inhibition of Stress Erosions (REVISE) - COVID-19 Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
GastroIntestinal Bleeding
Keywords: COVID-19
pandemic
gastrointestinal bleeding
pneumonia
Clostridioides difficile
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: The Physicians' Services Incorporated Foundation
First posted: 2023-02-08
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients are eligible according to the inclusion and exclusion criteria of the REVISE trial, regardless of COVID status

Brief 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. 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:

1. Do critically ill patients projected to receive mechanical ventilation for \>48 hours with COVID-19 have different clinical outcomes without PPIs?
2. Are there prognostically relevant demographic, biomarker and clinical data to characterize critically ill patients with COVID-19?
3. 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)

Eligibility criteria: Inclusion Criteria:

Adults ≥18 years old projected to receive invasive mechanical ventilation for ≥48 hours according to the treating physician

Exclusion Criteria:

1. Already received invasive mechanical ventilation \>72 hours during this hospital admission
2. 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); \[dyspepsia or gastroesophageal reflux is not an exclusion criterion\]
3. Acid suppression in the intensive care unit for \>1 daily dose equivalent of a proton pump inhibitor or histamine-2-receptor antagonist
4. Dual antiplatelet therapy
5. Combined antiplatelet and therapeutic anticoagulation
6. Pantoprazole contraindication per local product information
7. Palliative care or anticipated withdrawal of advanced life support
8. Pregnancy
9. Previous enrolment in REVISE, or a related trial, or trial for which co-enrolment is prohibited
10. Patient, proxy or physician declines

Primary outcomes:
measure: Rate of clinically important gastro-intestinal bleeding
timeFrame: 90 days
measure: Primary Safety Outcome: 90 Day Mortality
timeFrame: 90 days after randomization
Secondary outcomes:
measure: Ventilator-associated pneumonia
timeFrame: 90 Days (while in ICU,censored at 90 days after randomization)
measure: C. difficile infection
timeFrame: 90 days (during the index hospital admission, censored at 90 days)
measure: Renal replacement therapy
timeFrame: While in ICU,censored at 90 days after randomization
measure: Hospital mortality
timeFrame: While in hospital, censored at 90 days after randomization
measure: Patient important GI bleeding
timeFrame: Censored at 90 days after randomization
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St Joseph's Healthcare Hamilton
state: Ontario
Study officials:
affiliation: McMaster University
name: Deborah Cook, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Brittany Dennis, MD
role: PRINCIPAL_INVESTIGATOR
References: