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
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 measure
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 (if study stopped)
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
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United Kingdom
Funders
Funder type
Charity
Funder name
Wellcome Trust; Grant Codes: WT094949
Alternative name(s)
Wellcome
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
Basic results (scientific)
Publication list
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27422026