ISRCTN ISRCTN44583186
DOI https://doi.org/10.1186/ISRCTN44583186
Secondary identifying numbers N/A
Submission date
15/05/2015
Registration date
02/07/2015
Last edited
23/04/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

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

Contact information

Dr Pouline van Oort
Public

Education and Research Centre
Wythenshawe Hospital, Southmoor Road
Manchester
M23 9LT
United Kingdom

ORCiD logoORCID ID 0000-0002-2719-8817

Study information

Study designMulticentre cross-sectional observational proof of concept study
Primary study designObservational
Secondary study designCross sectional study
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet.
Scientific titleBReath Analysis in intensive care: proof of concept for non-invasive diagnosis of Ventilator associated pneumonia
Study acronymBRAVo
Study objectivesIn 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(s)RES Committee North West - Greater Manchester South, ref: 15/NW/0393
Health condition(s) or problem(s) studiedVentilator-associated pneumonia (VAP)
InterventionIncluded 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 typeDevice
Pharmaceutical study type(s)
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measureProviding 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 measures1. 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 study start date01/09/2014
Completion date01/03/2017

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants120
Key inclusion criteriaInclusion 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
Key exclusion criteria1. 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)
Date of first enrolment01/07/2015
Date of final enrolment01/12/2016

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

University Hospital of South Manchester NHS Foundation Trust
Southmoor Rd
Wythenshawe
Manchester
M23 9LT
United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
Cobbett House
Oxford Road
Manchester
M13 9WL
United Kingdom

Sponsor information

R&D University Hospital South Manchester
Hospital/treatment centre

R&D Directorate
1st Floor NIHR building Wythenshawe Hospital
Southmoor Road
Manchester
M23 9QZ
England
United Kingdom

ROR logo "ROR" https://ror.org/00he80998

Funders

Funder type

Government

National Institute for Health Research
Government organisation / National government
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planThe 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.
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Thesis results 23/04/2021 No No
HRA research summary 28/06/2023 No No

Editorial Notes

23/04/2021: Publication reference added.
21/03/2019: The funder has been changed from Marie Curie Actions to NIHR i4i