Plain English Summary
Background and study aims
Intensive Care Units (ICUs) treat and monitor critically ill or unstable patients who may be unable to breathe on their own and whose organs may not be working properly. Medical equipment supports organ function until the patient recovers. Mechanical ventilators (‘life support machines’) support breathing. While this technology works well, patients on mechanical ventilators can develop life-threatening lung infections (pneumonia) as a complication. Pneumonia is treated quickly and effectively with antibiotic drugs. However, because patients on ventilators are already ill, it is not possible to diagnose pneumonia quickly and accurately. Therefore many mechanically ventilated patients will also receive antibiotic treatments ‘just in case’ which means that antibiotics will be used unnecessarily. A consequence of antibiotic overuse is that infecting bugs (microorganisms) become resistant so that it will be difficult to treat life- threatening pneumonia in the future. We need to develop new technologies to help decide quickly who has developed pneumonia during their time on mechanical ventilation. Recently, we have discovered that it is possible and safe to capture and measure breath chemicals of patients who are mechanically ventilated. The chemical profiles appear to distinguish patients acquiring dangerous lung microorganisms. This exciting finding implies that we could use these chemical patterns to determine quickly who is likely to require antibiotics and who does not. To progress this idea, we now wish to use our breath capture system in ICU ventilated patients suspected of developing pneumonia and, using analysis already developed in our laboratories, we will seek proof that these chemicals can distinguish between the presence and absence of pneumonia. At project completion we will be able to decide whether our innovation is ready for clinical testing across NHS ICUs.
Who can participate?
Adults (aged at least 18), incubated and mechanically ventilated for at least 48 hours and suspected of having ventilator associated pneumonia (VAP).
What does the study involve?
Exhaled air samples are taken from participants within 24 hours of them having been suspected of developing VAP. Broncho-alveolar lavage fluid is collected to diagnose VAP. Blood samples are also taken .
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
NHS hospitals run by University Hospital South Manchester NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust and the Central Manchester University Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
September 2014 to March 2017.
Who is funding the study?
NIHR i4i
Who is the main contact?
Dr Pauline van Oort, pouline.vanoort@gmail.com
Trial website
Contact information
Type
Public
Primary contact
Dr Pouline van Oort
ORCID ID
http://orcid.org/0000-0002-2719-8817
Contact details
Education and Research Centre
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
BReath Analysis in intensive care: proof of concept for non-invasive diagnosis of Ventilator associated pneumonia
Acronym
BRAVo
Study hypothesis
In ICU mechanical ventilation can be associated with the development of ventilator associated pneumonia (VAP) as a complication. As per current practice it is not possible to diagnose VAP quickly and accurately and many patients are treated with antibiotics unnecessarily. Volatile organic compounds (VOCs) arise from various metabolic pathways. Capturing these VOC breath biomarkers through an ICU-compatible breath sampling device could help to determine quickly who requires antibiotics and who does not. To progress this idea, we now wish to use our breath capture system in ICU ventilated patients suspected of developing pneumonia and, using analysis already developed in our laboratories, we will seek proof that these chemicals can distinguish between the presence and absence of pneumonia. At project completion we will be able to decide whether our innovation is ready for clinical testing across NHS ICUs.
Ethics approval
RES Committee North West - Greater Manchester South, ref: 15/NW/0393
Study design
Multicentre cross-sectional observational proof of concept study
Primary study design
Observational
Secondary study design
Cross sectional study
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
Ventilator-associated pneumonia (VAP)
Intervention
Included patients will have been intubated and mechanically ventilated for at least 48 hours (based on the definition of VAP) and clinically suspected of having VAP. Exhaled air samples will be taken within 24 hours after the patient is suspected of VAP. Broncho-alveolar lavage fluid will be collected to determine clinically the presence of VAP. In addition two blood samples will be taken.
Intervention type
Device
Phase
Drug names
Primary outcome measure
Providing proof of concept supporting the use of a novel minimally-invasive breath sampler to enhance the diagnosis of ventilator-associated pneumonia (VAP) in patients in intensive care.
Secondary outcome measures
1. The development of a bespoke minimally-invasive breath sampling methodology for critically ill ventilated patients on a mechanical ventilator
2. Precise identification of the breath biomarkers / VOCs responsible for discriminating VAP in critical ill patients
Overall trial start date
01/09/2014
Overall trial end date
01/03/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Inclusion criteria
1. 18 years and older
2. Intubated and mechanically ventilated for >48 hours
3. Suspected for ventilator associated pneumonia (VAP)
Definition of suspected VAP
Criteria for clinically suspected VAP are fulfilled if a patient has been intubated and mechanically ventilated for at least 48 hours and has new or worsening alveolar infiltrates on chest X-ray and has two or more from
1. Temperature >38°C or <35ºC
2. White cell count >11x109 or <4x109 per litre of blood
3. Purulent tracheal secretions
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
120
Participant exclusion criteria
1. Patients receiving end of life care
2. Patients where there is clinical suspicion of highly infectious disease (patients in strict isolation such as Middle East Respiratory Syndrome, Ebola or resistant tuberculosis)
3. Patients showing features considered to predict poor tolerance of BAL:
3.1. PaO2 <8 kPa on FiO2 >0.7
3.2. Positive end-expiratory pressure >15 cmH2O
3.3. Peak airway pressure >35 cmH2O
3.4. Heart rate >140 bpm
3.5. Mean arterial pressure <65 mmHg
3.6. Bleeding diathesis (including platelet count <20 x 109 p/L of blood or international normalised ratio (INR) >3)
3.7. Poorly controlled intracranial pressure (>20mmHg)
Recruitment start date
01/07/2015
Recruitment end date
01/12/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Hospital of South Manchester NHS Foundation Trust
Southmoor Rd
Wythenshawe
Manchester
M23 9LT
United Kingdom
Trial participating centre
Central Manchester University Hospitals NHS Foundation Trust
Cobbett House
Oxford Road
Manchester
M13 9WL
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The results of the study will be disseminated by presentations to national bodies and in the form of peer reviewed publications in the scientific/clinical literature. The Salford Citizen Scientist group (http://www.citizenscientist.org.uk) whose remit is to encourage and facilitate participation of the local community in research and who have been consulted about the design and conduct of this project will be involved in review of the project findings.
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list