Condition category
Respiratory
Date applied
22/08/2013
Date assigned
22/08/2013
Last edited
18/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Critically ill patients whose lungs are supported by breathing machines (ventilators) commonly develop a new lung infection, called ventilator-associated pneumonia (VAP). Because VAP is often fatal, antibiotics are administered whenever it is suspected. However, VAP is hard to distinguish from several non-infective lung conditions and most patients with suspected VAP do not have pneumonia. Therefore, many patients receive unnecessary antibiotics for several days, promoting the emergence of 'superbugs'. Laboratory test results for diagnosing VAP typically only reach the doctors after 3 days. A simple test rapidly and confidently excluding VAP should improve patient care, reduce unnecessary antibiotic use and decrease costs. We recently showed that low levels of specific proteins in fluid from the lungs of patients with suspected VAP effectively excluded VAP, using a test that may yield results within 6 hours. The test used is an extension of existing technology produced by our commercial partner Becton Dickinson (BD) Biosciences. Our previous findings were derived from a single hospital's intensive care unit. We have recently confirmed this finding across many intensive care units, which will help show that the test can be used in 'real life'. The aim of this study is to take the new test to the next step and determine whether it can improve the care of patients by reducing the amount of unnecessary antibiotics prescribed.

Who can participate?
Patients with suspected VAP, aged 18 or over.

What does the study involve?
All participants will have a lung sample taken. They will then be randomly allocated to receive either 'usual care' for suspected VAP, or to have the new test performed on their lung fluid. If the new test suggests no lung infection, the doctors will be asked to consider not giving antibiotics. We shall test how much antibiotic is given to each group. Patients are followed up for a maximum of 56 days.

What are the possible benefits and risks of participating?
There are no direct benefits to patients. However, being part of the study probably gives us a better chance of making an accurate diagnosis of infection - we believe that the bronchoscopy test is by far the best way of diagnosing infection. The bronchoscopy is a common procedure on the intensive care unit and is safe.

Where is the study run from?
The study is run from the University of Newcastle Upon Tyne, and patients will be recruited from 23 hospitals in the UK.

When is the study starting and how long is it expected to run for?
November 2013 to December 2015

Who is funding the study?
Wellcome Trust (UK)

Who is the main contact?
Jennie Parker
jennie.parker@ncl.ac.uk

Trial website

http://www.ncl.ac.uk/icm/research/project/5004

Contact information

Type

Scientific

Primary contact

Ms Jennie Parker

ORCID ID

Contact details

4th Floor William Leech Building
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom
-
jennie.parker@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01972425

Protocol/serial number

14666

Study information

Scientific title

A randomised controlled trial of biomarker-based exclusion of ventilator-associated pneumonia to improve antibiotic stewardship

Acronym

Study hypothesis

Critically ill patients whose lungs are supported by breathing machines (ventilators) commonly develop a new lung infection, called ventilator-associated pneumonia (VAP). Because VAP is often fatal, antibiotics are administered whenever it is suspected. However VAP is hard to distinguish from several non-infective lung conditions and most patients with suspected VAP do not have pneumonia. Therefore many patients receive unnecessary antibiotics for several days, promoting emergence of 'superbugs'. Laboratory test results for diagnosing VAP typically only reach the doctors after 3 days.

A simple test rapidly and confidently excluding VAP should improve patient care, reduce unnecessary antibiotics and decrease costs. We recently showed that low levels of specific proteins in fluid from the lungs of patients with suspected VAP effectively excluded VAP, using a test that may yield results within 6 hours. The test used is an extension of existing technology produced by our commercial partner Becton Dickinson (BD) Biosciences.

Our previous findings were derived from a single hospital's intensive care unit. We are carrying out a study to see if we can show this finding across many intensive care units, which will help show that the test can be used in 'real life'. The aim of this study is to take the new test to the next step and determine whether it can improve the care of patients by reducing the amount of unnecessary antibiotics prescribed.

Ethics approval

13/LO/0651; First MREC approval date 28/06/2013

Study design

Randomised; Interventional; Design type: Prevention

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Respiratory, Generic Health Relevance and Cross Cutting Themes; Subtopic: Respiratory (all Subtopics), Generic Health Relevance (all Subtopics); Disease: Respiratory, Critical Care

Intervention

We shall identify patients with suspected VAP, all of whom will have a lung sample - half of the patients will receive 'usual care' for suspected VAP, the other half will have the new biomarker-based diagnostic test performed on their lung fluid. If the new test suggests no lung infection, the doctors will be asked to consider not giving antibiotics. We shall test how much antibiotic is given to each group.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Antibiotic-free days (AFD); Timepoint(s): The frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL

Secondary outcome measures

Current secondary outcome measures as of 27/11/2013:
1. Antibiotic associated infections; Timepoint(s): upto day 56 post-BAL follow up
2. Antibiotic days in the 28 days following BAL; Timepoint(s): number of days on antibiotics compared with both interventions on both randomised groups
3. Antibiotic resistant pathogens; Timepoint(s): collected up to day 56 post-BAL follow up
4. Antibiotics days in 28 days following BAL; Timepoint(s): Comparison of AFD in 28 days between both randomised arms
5. Duration of ICU and hospital stay; Timepoint(s): up to 56 day post-BAL follow up
6. Length of ICU sty and level 3 or level 2 patient; Timepoint(s): up to day 56 post-BAL follow up
7. Mortality; Timepoint(s): 28 day mortality and ICU mortality
8. Sequential organ failure (SOFA) score; Timepoint(s): SOFA score at day 3, day 7, day 14 after enrollment on the study
9. Ventilator Free days; Timepoint(s): Total number of ventilator free days up to day 28 post-BAL follow-up

Previous secondary outcome measures:
1. Antibiotic associated infections; Timepoint(s): upto day 56 post-BAL follow up
2. Antibiotic days in the 28 days following BAL; Timepoint(s): number of days on antibiotics compared with both interventions on both randomised groups
3. Antibiotic resistant pathogens; Timepoint(s): collected up to day 56 post-BAL follow up
4. Antibiotics days in 28 days following BAL; Timepoint(s): Comparison of AFD in 28 days between both randomised arms
5. Duration of ICU and hospital stay; Timepoint(s): up to 56 day post-BAL follow up
6. Length of ICU sty and level 3 or level 2 patient; Timepoint(s): up to day 56 post-BAL follow up
7. Mortality; Timepoint(s): 28 day mortality and ICU mortality
8. Sequential organ failure (SOFA) score; Timepoint(s): SOFA score at day 3, day 7, day 28 after enrollment on the study
9. Ventilator Free days; Timepoint(s): Total number of ventilator free days up to day 56 post-BAL follow-up

Overall trial start date

01/09/2013

Overall trial end date

25/11/2016

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 27/11/2013:
1. Age 18 years or over
2. Mechanically ventilated for 48hrs
3. New or worsening changes on chest x-ray or CT scan of the lungs
4. Two or more from:
4.1. Temperature <35ºC or >38ºC
4.2. Blood white cell count <4x10*9/L or >11x10*9/L
4.3. Purulent tracheal secretions
5. The patient is considered suitable for early discontinuation of antibiotics
Target Gender: Male & Female ; Lower Age Limit 18 years

Previous inclusion criteria:
1. Age 18 years or over
2. Intubated and mechanically ventilated for 48 hrs
3. New or worsening changes on chest x-ray or CT scan of the lungs
4. Two or more from:
4.1. Temperature <35ºC or >38ºC
4.2. Blood white cell count <4x10*9/L or >11x10*9/L
4.3. Purulent tracheal secretions
Target Gender: Male & Female ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 210; UK Sample Size: 210

Participant exclusion criteria

1. PaO2 <8kPa on FiO2 >0.7
2. Positive end-expiratory pressure >15 cmH2O
3. Peak airway pressure >35 cmH2O
4. Heart rate >140 bpm
5. Mean arterial pressure <65 mmHg
6. Bleeding diathesis (including platelet count <20x10*9 per litre of blood or international normalised ratio (INR) >3)
7. Poorly controlled intracranial pressure (>20 mmHg)
8. ICU consultant deems procedure not to be safe
9. Previous BAL as part of this study
10. Consent declined

* Patients who are enrolled in observational studies will be eligible for co-enrolment. Co-enrolment with interventional studies will be possible following consideration of any scientific or statistical interaction, in accordance with current UK Critical Care Research Forum (UKCCRF) recommendations (see appendix). Until coenrolment
is considered appropriate for a particular study, patients enrolled in an interventional trial will not be included.

Recruitment start date

01/09/2013

Recruitment end date

30/09/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Newcastle University
Newcastle Upon Tyne
NE2 4HH
United Kingdom

Trial participating centre

23 hospitals
-
United Kingdom

Sponsor information

Organisation

Newcastle Upon Tyne Hospitals NHS Trust and University of Newcastle Upon Tyne (UK)

Sponsor details

School of Medical SciencesMedical School
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Wellcome Trust; Grant Codes: WT094949

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27422026

Publication citations

Additional files

Editorial Notes

18/07/2016: Publication reference added. 11/04/2016: the following changes were made to the trial record: 1. The recruitment end date was changed from 01/01/2016 to 30/09/2016. 2. The overall trial end date was changed from 26/02/2016 to 25/11/2016. 23/07/2015: the overall trial end date was changed from 01/12/2014 to 26/02/2016. 27/11/2013: the target number of participants was changed from 192 to 210.