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Trial registered on ANZCTR


Registration number
ACTRN12613000807752
Ethics application status
Approved
Date submitted
15/07/2013
Date registered
22/07/2013
Date last updated
7/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of routine pantoprazole administration when compared to placebo on gastrointestinal bleeding, ventilator-associated pneumonia and Clostridium difficile infection in enterally-fed mechanically ventilated critically ill patients: A prospective randomised study
Scientific title
The effect of routine pantoprazole administration when compared to placebo on gastrointestinal bleeding, ventilator-associated pneumonia and Clostridium difficile infection in enterally-fed mechanically ventilated critically ill patients: A prospective randomised study
Secondary ID [1] 282821 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal Bleeding 289604 0
Critical Illness 289639 0
Ventilator-associated Pneumonia 289640 0
Clostridium difficile infection 289641 0
Condition category
Condition code
Metabolic and Endocrine 289941 289941 0 0
Other metabolic disorders
Infection 289959 289959 0 0
Other infectious diseases
Oral and Gastrointestinal 289960 289960 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a randomised double-blind parallel study comparing 40mg IV pantoprazole daily to placebo in mechanically-ventilated critically ill patients receiving enteral nutrition for up to a maximum of 14 days
Intervention code [1] 287506 0
Treatment: Drugs
Intervention code [2] 287526 0
Prevention
Comparator / control treatment
Placebo = normal saline
Control group
Placebo

Outcomes
Primary outcome [1] 289994 0
Clinically important gastrointestinal bleeding is defined as a case of overt bleeding (haematemesis, bloody gastric aspirate, melaena or haematochezia) plus any of the following 1. In the absence of another cause (e.g. drug induced, new sepsis) a reduction in mean arterial pressure of 20 mmHg within 24 hours of bleeding;
2. A reduction in haemoglobin of 20 g/L (regardless of the need for blood transfusion), within 24 hours of bleeding;
3. A need for surgery to control gastrointestinal bleeding
Timepoint [1] 289994 0
The drug will be administered for a maximum of 14 days and data will be collected for a maximum of 21 days
Primary outcome [2] 290011 0
Ventilator-associated pneumonia (defined as):

Ventilator-associated condition - greater than or equal to 2 calender days of stable or decreasing daily minimum positive end-expiratory pressure or daily minimum fraction of inspired oxygen, followed by a rise in the daily minimum positive end-expiratory pressure of greater than or equal to 3cm of water or a rise in the daily minimum percentage of inspired oxygen by >20 points sustained for greater than or equal to 2 calender days

Infection-related Ventilator-associated Complication (iVAC) - VAC plus a temp <36 degrees Celsius or >38 degrees Celsius or a leukocyte count of less than or equal to 4000 or greater than or equal to 12,000 per cubic millimeter, plus one or more new antibiotics continued for at least 4 days within 2 calender days before or after onset of a VAC (excluding the first 2 days of ventilation)

Possible Pneumonia - iVAC plus Gram's staining of endotracheal aspirated or bronchoalveolar lavage showing greater than or equal to 25 neutrophils and less than or equal to 10 epithelial cells per lower-power field, or a positive culture for a potentially pathogenic organism, within 2 calender before or after onset of a VAC (excluding the first 2 days of ventilation)

Probable Pneumonia - iVAC plus Gram's staining of endotracheal aspirated or bronchoalveolar lavage showing greater than or equal to 25 neutrophils and less than or equal to 10 epithelial cells per lower-power field, plus endotracheal aspirate with greater than or equal to 10x5 colony-forming units per millilitre or broncho-alveolar-lavage culture with greater than or equal to 10x4 colony-forming units per millilitre, or endotraeal-aspirate or bronchoalveolar-lavage semiquantitative equivalent, within 2 calender days before or after onset of a VAC (excluding the first 2 days of ventilation)










Timepoint [2] 290011 0
The drug will be administered for a maximum of 14 days and data will be collected for a maximum of 21 days
Primary outcome [3] 290012 0
Clostridium difficile infection: All ‘symptomatic’ patients, defined as patients with greater than or equal to 3 bowel movements in a 24 hour period or patients with a temperature greater than or equal to 38.6 AND white cell count greater than or equal to 20, will have a single sample sent for testing, which is part of current standard medical care.
Timepoint [3] 290012 0
The drug will be administered for a maximum of 14 days and data will be collected for a maximum of 21 days
Secondary outcome [1] 303739 0
Overt gastrointestinal bleeding: documented haematemesis, bloody gastric aspirate, melaena or haematochezia
Timepoint [1] 303739 0
Data will be collected for a maximum of 21 days
Secondary outcome [2] 303773 0
Survival (ICU and hospital)
Timepoint [2] 303773 0
Data will be collected for a maximum of 21 days
Secondary outcome [3] 303774 0
Length of Stay (ICU and Hospital)
Timepoint [3] 303774 0
Data will be collected for a maximum of 21 days
Secondary outcome [4] 303775 0
Ventilator-free days at Day 28
Timepoint [4] 303775 0
This will be assessed at Day 28 following post ICU admission

Eligibility
Key inclusion criteria
Consecutive patients admitted to the ICU at the RAH who are anticipated to remain mechanically ventilated for > 24 hours AND receive enteral nutrition within 48 hours of admission
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Current (prior to hospital admission) use of proton pump inhibitor or histamine-2 receptor blocker drugs
2. Pregnancy
3. Patients admitted with suspected or proven gastrointestinal bleeding
4. Patients with a history of proven peptic ulcer disease
5. Patients receiving > 400 mg/day of hydrocortisone (or equivalent of prednisolone (100mg) or dexamethasone (15mg))
6. History of surgery on the oesophagus, stomach or duodenum during the current hospital admission
7. Patients where the treating consultant intensive care physician believes that stress ulcer prophylaxis is either clearly indicated or contraindicated
8. Patients who are Jehovah’s Witnesses
9. Patients who do not receive their first dose of study medication within 36 hours of initiation of mechanical ventilation (this criterion is required to avoid contamination of cohorts as if stress ulcer prophylaxis is beneficial it is likely to be of benefit when commenced as early as possible and patients who have been ventilated at another hospital for > 24 hours may have received stress ulcer prophylaxis).
10. Patients admitted for palliative care.
11. Patients readmitted to the Intensive Care Unit

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be enrolled using an enrollment number and then randomised into their specific treatment by the clinical trials pharmacy department (this will be blinded).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be completed by the clinical trials pharmacy department using a randomisation table created by computer software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
. It is acknowledged that the study may be underpowered to determine a difference between any of the three primary outcomes. Indeed, because of insufficient observational data we are unable to accurate estimate a cohort number required using a power calculation. However, a 12-month period will be sufficient to identify whether the current protocol at the Royal Adelaide Hospital (i.e. to not administer stress ulcer prophylaxis) is overtly harmful and provides us with far more data to base our decision on than we currently have.

Data will be presented and analysed using parametric and/or non-parametric approaches as appropriate based on distribution of data. As the primary outcomes are disparate the null hypothesis will be rejected at the 0.05 significance

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1277 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 7161 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 287603 0
Government body
Name [1] 287603 0
National Health and Medical Research Council Grant
Address [1] 287603 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 287603 0
Australia
Primary sponsor type
Individual
Name
Dr Adam Deane
Address
ICU Research
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 286351 0
None
Name [1] 286351 0
Address [1] 286351 0
Country [1] 286351 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289578 0
Royal Adelaide Hospital Ethics Committee
Ethics committee address [1] 289578 0
North Terrace
Adelaide
SA 5000
Ethics committee country [1] 289578 0
Australia
Date submitted for ethics approval [1] 289578 0
Approval date [1] 289578 0
28/06/2013
Ethics approval number [1] 289578 0
130517

Summary
Brief summary
To evaluate whether routine administration of proton pump inhibitor (intravenous pantoprazole) to mechanically-ventilated critically ill patients:

(1) Reduces the incidence and severity of gastrointestinal bleeding; and

(2) Increases the incidence of ventilator-associated pneumonia and/or Clostridium difficile infection
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41398 0
Dr Adam Deane
Address 41398 0
ICU Research
Royal Adelaide Hospital
North Terrace
SA 5000
Country 41398 0
Australia
Phone 41398 0
+61 8 8222 4624
Fax 41398 0
Email 41398 0
adam.m.deane@gmail.com
Contact person for public queries
Name 41399 0
Dr Adam Deane
Address 41399 0
ICU Research
Royal Adelaide Hospital
North Terrace
SA 5000
Country 41399 0
Australia
Phone 41399 0
+61 8 8222 4624
Fax 41399 0
Email 41399 0
adam.deane@adelaide.edu.au
Contact person for scientific queries
Name 41400 0
Dr Adam Deane
Address 41400 0
ICU Research
Royal Adelaide Hospital
North Terrace
SA 5000
Country 41400 0
Australia
Phone 41400 0
+61 8 8222 4624
Fax 41400 0
Email 41400 0
adam.deane@adelaide.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary