Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Patients who are critically ill in the in the Intensive Care Unit (ICU), especially those who need a breathing machine, can develop ulcers in the stomach that bleed. To prevent bleeding, many such patients around the world receive a drug called pantoprazole that decreases acid production. However, today, compared to decades ago, critically ill patients rarely develop gastrointestinal bleeding. This decrease is likely due to modern medicine, better resuscitation and earlier feeding. There may also be harms associated with pantoprazole and other drugs that reduce acid levels in the stomach including lung infections (pneumonia) and bowel infections (clostridium difficile). Studies in this area are old and of modest quality. Therefore, it is difficult to know whether pantoprazole does decrease stomach bleeding these days, or whether the possible harms of lung and bowel infections are actually more common and more serious problems. The goal of this international study is to determine if, in critically ill patients using breathing machines, the use of pantoprazole is effective in preventing bleeding from stomach ulcers or whether it causes more problems such as lung infection (pneumonia) and bowel infection (Clostridium difficile), or whether pantoprazole has no effect at all. Whether the harms are worth the benefits, and whether the benefits are worth the costs, will be determined by an economic analysis to inform patients, families, clinicians, and healthcare systems globally.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: McMaster University
• Collaborators: Australian and New Zealand Intensive Care Society Clinical Trials Group; Canadian Critical Care Trials Group; Canadian Institutes of Health Research (CIHR); National Health and Medical Research Council, Australia
• Treatments: Pantoprazole

Criteria

Inclusion Criteria:

1. Age 18 years or more.

2. Receiving invasive mechanical ventilation in an ICU and in the opinion of the treating ICU physician mechanical ventilation will not be discontinued before the end of the day after tomorrow.

Exclusion Criteria:

1. The treating clinician considers either Pantoprazole or placebo are indicated or contraindicated for this patient.

2. Pantoprazole contraindicated for patient due to local product information;

Australia/New Zealand;

• being treated with HIV protease inhibitors atazanavir or nelfinavir

• being treated with high dose methotrexate (i.e., greater than 300 mg as part of a chemotherapy regimen).

• documented cirrhosis or severe liver disease (for example as indicated by an INR greater than 5.0 due to underlying liver disease).

Canada;

• being treated with rilpivirine or atazanavir

3. Patients in whom a PPI or histamine 2 receptor antagonist (H2RA) is indicated due to active bleeding or increased bleeding risk, defined as patients with acute GI bleeding, severe oesophagitis or peptic ulcer disease within the previous 8 weeks, Zollinger Ellison syndrome, Barrett's oesophagus or any previous admission to hospital because of upper GI bleeding (patients receiving PPIs for mild dyspepsia or mild gastroesophageal reflux disease or an uncertain indication are not excluded).

4. Received invasive mechanical ventilation during this ICU admission for 72 hours or more.

5. Patients who have received more than 24 hours treatment (i.e., more than one daily dose equivalent) with a PPI or H2RA during this ICU admission.

6. Being treated with or need for dual anti-platelet therapy.

7. Admitted for palliative care or the ICU physician is not committed to continuing life-sustaining therapies at the time of enrolment.

8. Known or suspected pregnancy.

9. Physician, patient, or substitute decision maker (SDM) declines.

10. Previously enrolled in the REVISE trial

11. Enrolled in another trial for which co-enrolment is not approved.