Proton Pump Inhibitors vs. Histamine-2 REceptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit

• Register: ANZCTR
• Last refreshed on: 16 November 2020
• Main ID: ACTRN12616000481471
• Date of registration: 13/04/2016
• Prospective Registration: Yes
• Primary sponsor: Medical Research Institute of New Zealand
• Public title: Proton Pump Inhibitors vs. Histamine-2 REceptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit
• Scientific title: A multi-centre, cluster randomised, crossover, registry trial comparing the safety and efficacy of proton pump inhibitors with histamine-2 receptor blockers for ulcer prophylaxis in intensive care patients requiring invasive mechanical intervention.
• Date of first enrolment: 01/08/2016
• Target sample size: 26797
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12616000481471.aspx
• Study type: Interventional
• Study design: Purpose: Prevention; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Crossover;Type of endpoint: Safety/efficacy;
• Phase: Phase 3 / Phase 4

Countries of recruitment

Australia, Canada, Ireland, New Zealand, United Kingdom

Contacts

• Name: Dr Paul Young

• Name: Dr Paul Young

Key inclusion & exclusion criteria

Inclusion criteria: All patients aged 18 years or older who are mechanically ventilated within 24 hours of ICU admission.
Exclusion criteria: Patients who are admitted to ICU with upper GI bleeding (APACHE III admission diagnostic codes 303, 305, and 1403)

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Critical illness;Mechanical ventilation;Ulcer prophylaxis;
Critical illness
Mechanical ventilation
Ulcer prophylaxis

Oral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention(s)

Study treatment is open label Proton Pump Inhibitors (PPIs) vs. Histamine-2 Receptor Blockers (H2RBs) as the default routine therapy for ulcer prophylaxis. Each study ICU will use PPIs or H2RBs as routine therapy for a period of six months. At the end of this six month period, the ICU will then swap to the opposite routine ulcer prophylaxis strategy which will then be used for the next six months. The specific PPI or H2RB, dose, mode of administration and duration of study treatment will be the individual ICU clinician’s decision or until the patient is discharged from ICU (whichever is shorter). The PPI and H2RBs will be given as per routine medication (usually by the ICU nurse). Study treatment will only be administered in situations where the treating clinician believes ulcer prophylaxis is in the patient’s best interests and, irrespective of the treatment assigned to the ICU, either a PPI or an H2RB can be used for an individual patient, if the treating clinician believes that a particular treatment is indicated. Intervention adherence will not be checked for individual patients; however once a month, at a set time, stress ulcer prophylaxis use will be recorded for all mechanically ventilated patients.

Primary Outcome(s)

In-hospital mortality[Censoring of all study end points will apply at the time of hospital discharge following the index ICU admission or at 90 days (whichever is earlier).]

Secondary Outcome(s)

ICU length of stay, which will be obtained from the ANZICS APD.[Index ICU admission]

Clostridium difficile infection rates.
Clostridium difficile infections are defined as toxin-positive or culture-positive stool samples collected during an ICU admission (excluding any patients who had positive tests from specimens collected prior to ICU admission).[Censored at 90 days]

Hospital length of stay, which will be obtained from the ANZICS APD.[Hospital length of stay for index ICU admission]

Hours of mechanical ventilation (where available)[Index ICU admission]

Upper gastrointestinal bleeding (new clinically significant upper GI bleeding developing as a complication in ICU).
Clinically significant upper GI bleeding is defined as: overt GI bleeding (eg. haematemesis, malaena or frank blood in the nasogastric tube or upper GI endoscopy)
AND 1 or more of the following features within 24 hours of GI bleeding: 1) spontaneous drop of systolic, mean arterial pressure or diastolic blood pressure of 20 mmHg or more, 2) start of vasopressor or a 20% increase in vasopressor dose 3) decrease in haemoglobin of at least 20 g/L or 4) transfusion of 2 units of packed red blood cells or more).
[Censored at 90 days]

Secondary ID(s)

None

Source(s) of Monetary Support

Canadian Institutes of Health Research

Intensive Care Foundation

National Institute of Health Research

Health Research Council of NZ

Irish Health Research Board

Secondary Sponsor(s)

Austin Hospital

Alberta Health

Intensive Care National Audit & Research Centre (ICNARC)

Ethics review

Status: Approved
Approval date: 23/03/2015
Contact:

St Vincent's Healthcare Group Research Ethics Committee

Status: Approved
Approval date: 14/04/2015
Contact:

Northern B Health and Disability Ethics Committee

Status: Approved
Approval date: 19/11/2015
Contact:

Austin Health Human Research Ethics Committee

Status: Approved
Approval date: 10/08/2017
Contact:

The University of Alberta Health Research Ethics Board

Status: Approved
Approval date: 11/10/2017
Contact:

London-Bromley Research Ethics Committee

Results

• Results available: Yes
• Date Posted: 30/08/2019
• Date Completed: 01/05/2019