Condition category
Respiratory
Date applied
15/05/2015
Date assigned
02/07/2015
Last edited
02/07/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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?
Marie Curie Actions

Who is the main contact?
Dr Pauline van Oort

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 measures

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

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 South Manchester NHS Foundation Trust
United Kingdom

Trial participating centre

Central Manchester University Hospitals NHS Foundation Trust
Manchester
United Kingdom

Trial participating centre

Central Manchester University Hospitals NHS Foundation Trust
United Kingdom

Sponsor information

Organisation

R&D University Hospital South Manchester

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Marie Curie Actions

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes