ANZCTR - Registration

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

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

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Gastrointestinal Bleeding

Critical Illness

Ventilator-associated Pneumonia

Clostridium difficile infection

Condition category

Condition code

Metabolic and Endocrine

Other metabolic disorders

Infection

Other infectious diseases

Oral and Gastrointestinal

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]

Treatment: Drugs

Intervention code [2]

Prevention

Comparator / control treatment

Placebo = normal saline

Control group

Placebo

Outcomes

Primary outcome [1]

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]

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]

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]

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]

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]

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]

Overt gastrointestinal bleeding: documented haematemesis, bloody gastric aspirate, melaena or haematochezia

Timepoint [1]

Data will be collected for a maximum of 21 days

Secondary outcome [2]

Survival (ICU and hospital)

Timepoint [2]

Data will be collected for a maximum of 21 days

Secondary outcome [3]

Length of Stay (ICU and Hospital)

Timepoint [3]

Data will be collected for a maximum of 21 days

Secondary outcome [4]

Ventilator-free days at Day 28

Timepoint [4]

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

Sex

Both males and females

Can healthy volunteers participate?

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

5/08/2013

Actual

28/01/2014

Date of last participant enrolment

Anticipated

28/01/2015

Actual

27/01/2015

Date of last data collection

Anticipated

Actual

Sample size

Target

500

Accrual to date

Final

216

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council Grant

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Ethics Committee

Ethics committee address [1]

North Terrace
Adelaide
SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

28/06/2013

Ethics approval number [1]

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

Dr Adam Deane

Address

ICU Research
Royal Adelaide Hospital
North Terrace
SA 5000

Country

Australia

Phone

+61 8 8222 4624

Fax

[email protected]

Contact person for public queries

Name

Adam Deane

Address

ICU Research
Royal Adelaide Hospital
North Terrace
SA 5000

Country

Australia

Phone

+61 8 8222 4624

Fax

[email protected]

Contact person for scientific queries

Name

Adam Deane

Address

ICU Research
Royal Adelaide Hospital
North Terrace
SA 5000

Country

Australia

Phone

+61 8 8222 4624

Fax

[email protected]

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study.	2016	https://dx.doi.org/10.1097/CCM.0000000000001819

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically