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

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ClinicalTrials.gov Identifier: NCT03374800
Recruitment Status : Not yet recruiting
First Posted : December 15, 2017
Last Update Posted : May 18, 2018
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Canadian Critical Care Trials Group
Australian and New Zealand Intensive Care Society Clinical Trials Group
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
McMaster University

Brief 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.

Condition or disease Intervention/treatment Phase
Gastrointestinal Hemorrhage (Clinically Important, Upper) Drug: Placebo (0.9% saline) Drug: Pantoprazole Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4800 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized stratified, parallel group blinded non-Inferiority trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: blinded study drug and placebo
Primary Purpose: Prevention
Official Title: Re-EValuating the Inhibition of Stress Erosions: Prophylaxis Against Gastrointestinal Bleeding in the Critically Ill (The REVISE) Trial
Estimated Study Start Date : June 1, 2018
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo (0.9% saline)
Withholding Stress ulcer prophylaxis (intravenous 0.9% saline as placebo)
Drug: Placebo (0.9% saline)
normal saline
Other Name: normal saline; NaCl 0.9%

Active Comparator: Stress Ulcer Prophylaxis (Pantoprazole)
pantoprazole 40mg powder for injection reconstituted with 0.9% saline
Drug: Pantoprazole
40 mg powder for injection reconstituted with 0.9% saline




Primary Outcome Measures :
  1. Clinically important GastroIntestinal bleeding [ Time Frame: 60 days (In ICU or resulting in ICU readmission, censored at 60 days after randomization) ]

    Clinically important GI bleeding requires the presence of overt GI bleeding which is defined as one of the following;

    • Hematemesis
    • Overt nasogastric bleeding
    • Melena
    • Hematochezia

    PLUS (in the absence of another cause), at least one of the following in the 24 hours following overt GI bleeding:

    • Haemodynamic change defined as a spontaneous decrease in invasively monitored mean arterial pressure or non-invasive systolic or diastolic blood pressure of 20 mmHg or more 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
    • A decrease in haemoglobin of ≥ 20 g/l in a 24-hour period or less,
    • Transfusion of ≥2 units of packed red blood cells within 24 hours of bleeding to maintain stable haemoglobin or haemodynamics, or
    • Need for therapeutic intervention (e.g. angiography, surgery or endoscopic treatment of bleeding).


Secondary Outcome Measures :
  1. Ventilator associated pneumonia (VAP) in ICU [ Time Frame: 60 Days (while in ICU,censored at 60 days after randomization) ]

    Diagnostic criteria for VAP include: previous mechanical ventilation for at least 48 hours, a new, progressive or persistent radiographic infiltrate on chest X-ray (without other obvious cause) plus at least 2 of the following 4 features:

    • fever or hypothermia (temperature >38 °C or <36 °C)
    • relative leukopenia or leukocytosis (WBC<4.0 or >12 x 10^9/L)
    • purulent sputum
    • gas exchange deterioration

  2. Clostridium difficile associated infection [ Time Frame: 60 days (during the index hospital admission, censored at 60 days) ]
    We will use clinical features (diarrhea, ileus, toxic megacolon) and either microbiological evidence of toxin producing Clostridium difficile or Pseudomembranous colitis on colonoscopy.

  3. Acute renal failure in the ICU [ Time Frame: 60 Days (In the ICU, censored at 60 days) ]
    Peak serum creatinine or initiation of treatment with renal replacement therapy in ICU

  4. Duration of mechanical ventilation [ Time Frame: 60 Days (In the ICU, censored at 60 days) ]
    Duration of mechanical ventilation

  5. Mortality in ICU [ Time Frame: 60 Days (In the ICU, censored at 60 days) ]
    All-cause mortality in ICU

  6. Duration of ICU stay [ Time Frame: 60 Days (duration of index hospital admission) ]
    Number of days in ICU

  7. Duration of hospital stay [ Time Frame: 60 Days (duration of index hospital admission) ]
    Number of days in hospital

  8. Hospital mortality [ Time Frame: 60 Days (duration of index hospital admission) ]
    All-cause in-hospital mortality



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374800


Contacts
Contact: Deborah J Cook, MD 905-979-9805 debcook@mcmaster.ca
Contact: Nicole Zytaruk, RN 905-522-1155 ext 35325 zytaruk@mcmaster.ca

Locations
Canada, Alberta
Foothills Hospital Not yet recruiting
Calgary, Alberta, Canada
Contact: Tom Stelfox, MD         
Contact: Joshua Booth         
Principal Investigator: Tom Stelfox, MD         
Peter Lougheed Hospital Not yet recruiting
Calgary, Alberta, Canada
Contact: Daniel Nivan, MD         
Contact: Joshua Booth         
Principal Investigator: Daniel Nivan, MD         
Canada, British Columbia
Royal Columbia Hospital Not yet recruiting
New Westminster, British Columbia, Canada
Contact: Steve Reynolds, MD         
Contact: Suzette Williams, RN         
Principal Investigator: Steve Reynolds, MD         
Vancouver Island Health Authority Not yet recruiting
Victoria, British Columbia, Canada
Contact: Gordon Wood, MD         
Contact: Fiona Auld, RN         
Principal Investigator: Gordon Wood, MD         
Canada, Ontario
Brantford General Hospital Not yet recruiting
Brantford, Ontario, Canada
Contact: Brenda Reeve, MD         
Contact: William Dechert         
Principal Investigator: Brenda Reeve, MD         
St. Joseph's Healthcare Hamilton Not yet recruiting
Hamilton, Ontario, Canada, L9N 4A6
Contact: Deborah Cook, MD    905-979-9805    debcook@mcmaster.ca   
Contact: France Clarke, RT    905-522-1155 ext 35325    clarkef@mcmaster.ca   
Principal Investigator: Deborah Cook, MD         
Hamilton Health Science Center - General Hospital Not yet recruiting
Hamilton, Ontario, Canada
Contact: Andreas Freitag, MD         
Principal Investigator: Andreas Freitag, MD         
Hamilton Health Science Center - Juravinski Hospital Not yet recruiting
Hamilton, Ontario, Canada
Contact: Bram Rochwerg, MD         
Contact: Tina Millen, RT         
Principal Investigator: Bram Rochwerh, MD         
Kingston General Hospital Not yet recruiting
Kingston, Ontario, Canada
Contact: John Muscedere, MD         
Contact: Miranda Hunt         
Principal Investigator: John Muscedere, MD         
London Health Science Center (LHSC) - University Hospital Not yet recruiting
London, Ontario, Canada
Contact: Tina Mele, MD         
Contact: Tracy Bental         
Principal Investigator: Tina Mele, MD         
London Health Science Center (LHSC) - Victoria Hospital Not yet recruiting
London, Ontario, Canada
Contact: Ian Ball, MD         
Contact: Eileen Campbell, RN         
Principal Investigator: Ian Ball, MD         
Ottawa Health Research Institute - OHRI (General and Civic Hospital) Not yet recruiting
Ottawa, Ontario, Canada
Contact: Shane English, MD         
Contact: Irene Watpool         
Principal Investigator: Shane English, MD         
Niagara Health Services - St. Catharine's Hospital Not yet recruiting
St. Catharines, Ontario, Canada
Contact: Erick Duan, MD         
Contact: Beverley Hoekstra, RN         
Principal Investigator: Erick Duan, MD         
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada
Contact: John Marshall, MD         
Principal Investigator: John Marshall, MD         
Canada, Quebec
Centre de recherche de l'Hôtel-Dieu de Lévis Not yet recruiting
Lévis, Quebec, Canada
Contact: Patrick Archambalt, MD         
Contact: Maude Dionne         
Principal Investigator: Patrick Archambalt, MD         
Centre Universitaire de Santé McGill / McGill University Health Centre Not yet recruiting
Montréal, Quebec, Canada
Contact: Arnold Kristof, MD         
Contact: Josie Campisi, RN         
Principal Investigator: Arnold Kristof, MD         
CIUSS du Nord de l'île de Montréal - Hôpital du Sacré-Cœur de Montréal Not yet recruiting
Montréal, Quebec, Canada
Contact: Emmanuel Charbonney, MD         
Contact: Virginie Williams, PhD         
Principal Investigator: Emmanuel Charbonney, MD         
McGill University Health Centre - Montreal General Hospital Not yet recruiting
Montréal, Quebec, Canada
Contact: Kosar Khwaja, MD         
Contact: Norine Alam         
Principal Investigator: Kosar Khwaja, MD         
CHU de Québec-Université Laval - Hôpital Enfant-Jésus Not yet recruiting
Quebec City, Quebec, Canada
Contact: Francois Lauzier, MD         
Contact: Marie-Claude Trembley, BSc         
Principal Investigator: Francois Lauzier, MD         
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Canadian Critical Care Trials Group
Australian and New Zealand Intensive Care Society Clinical Trials Group
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Deborah Cook, MD McMaster University

Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03374800     History of Changes
Other Study ID Numbers: CCT38473
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Hemorrhage
Gastrointestinal Hemorrhage
Pathologic Processes
Gastrointestinal Diseases
Digestive System Diseases
Pantoprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action