Plain English Summary
Background and study aims
About 60,000 people each year in the UK become critically ill and require sedation and treatment with invasive mechanical ventilation given via a tube placed in the windpipe. Although initially lifesaving, invasive mechanical ventilation is associated with a number of complications including ventilator-associated pneumonia and prolonged requirements for sedatives with weakening of the leg, arm and breathing muscles. The longer a person requires invasive ventilation the poorer their chances of surviving. The process of liberating patients from invasive ventilation is referred to as weaning. Previous research has shown that implementing protocols for weaning can reduce the amount of time on a ventilator machine. There is also evidence that switching from invasive to non-invasive ventilation (also called mask ventilation) as an intermediate step in the weaning process may reduce the amount of time spent on the ventilator and complications. This study will compare protocolised invasive (tube) and non-invasive (mask) weaning strategies.
Who can participate?
Adult patients (male and female, age over 16 years) with respiratory failure who have received invasive ventilation for more than 48 hours (from the time of intubation) and fail a spontaneous breathing trial.
What does the study involve?
Patients are assessed daily for their readiness to commence weaning. Those ready for weaning are randomly allocated to either a protocolised weaning pathway that includes a period of mask ventilation or a protocolised pathway that does not include mask ventilation. The study measures the cost effectiveness and health benefits (time spent on a ventilator; survival, time spent in hospital including intensive care, complication rates) of each approach. The study also measures the impact of each approach on health-related quality of life using questionnaires.
What are the possible benefits and risks of participating?
Not provided.
Where is the study run from?
Warwick Clinical Trials Unit (UK).
When is the study starting and how long is it expected to run for?
January 2013 to July 2017
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Mr Adam de Paeztron
a.de-paeztron@warwick.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Mr Adam de Paeztron
ORCID ID
Contact details
Warwick Clinical Trials Unit
Warwick Medical School
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
+44 2476 150 955
a.de-paeztron@warwick.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HTA 10/134/06, 13347
Study information
Scientific title
Protocolised trial of invasive and non-invasive weaning off ventilation (The 'Breathe' Study): a pragmatic randomised controlled open multi-centre effectiveness trial
Acronym
BREATHE
Study hypothesis
The BREATHE trial will be a pragmatic, randomised, controlled, open, multi-centre, effectiveness trial to determine if the use of Non Invasive Ventilation (NIV) as an intermediate step in the protocolised weaning of patients off invasive ventilation is clinically and cost effective.
Patients with respiratory failure who have received invasive ventilation for more than 48 hours (from the time of intubation) and fail a spontaneous breathing test (SBT) will be randomised in a 1:1 ratio to invasive or non-invasive weaning strategies.
More details can be found at: https://www.journalslibrary.nihr.ac.uk/programmes/hta/1013406/#/
Ethics approval
NRES Committee South Central Oxford C, First MREC approval date 05/10/2012, ref: 12/SC/0515
Study design
Pragmatic randomised controlled open multi-centre effectiveness trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: Generic Health Relevance and Cross Cutting Themes; Subtopic: Generic Health Relevance (all Subtopics); Disease: Critical Care
Intervention
The health technology being assessed is the use of NIV as an adjunct to protocolised weaning compared to protocolised weaning that does not include NIV following a failed spontaneous breathing trial.
Protocolised invasive weaning arm
The participant will be restarted on pressure supported ventilation at the previous settings. The level of pressure support (Psupp) will be titrated to achieve patient comfort and respiratory rate <30 breaths min-1. Causes for distress / fatigue / weaning failure will be sought and corrective treatments initiated as appropriate. The patient will be reassessed every 2 hours. If there are no signs of distress / fatigue then the level of Psupp will be reduced by 2 cmH2O. This cycle will be repeated every two hours as tolerated. If at any stage the patient develops signs of distress / fatigue then they be will increased by 2 cmH2O. FiO2 will be titrated to maintain SaO2 > 90%. A further SBT will take place each morning. This cycle will continue until the patient has either been extubated (due to passing the SBT or tolerating Psupp 5 cmH2O) or a tracheostomy is performed.
This active weaning protocol will occur between 8am-10pm. Unless the participant develops signs of fatigue or distress, ventilator settings will not be changed overnight.
Protocolised non-invasive arm
Participants allocated to the NIV arm will be extubated and immediately provided with NIV with an equivalent level of pressure support and PEEP to the ventilator settings prior to extubation. After 2 hours, if no signs of distress / fatigue occur then the NIV interface will be removed and the participant will undergo a self-ventilation trial with supplemental oxygen (equivalent to the previous FiO2) being provided via a standard oxygen mask.
If no signs of distress or fatigue develop during the self-ventilation trial the patient will continue receiving unsupported ventilation with inhaled oxygen being provided as required. If the participant subsequently develops signs of distress or fatigue, NIV will be re-started (as below). Otherwise the participant will continue with unsupported self-ventilation. FiO2 will be titrated to maintain SaO2 > 90%.
If signs of distress or fatigue develop NIV will be re-instated at the previous settings. The level of pressure support (Psupp) will be titrated to achieve participant comfort and a respiratory rate < 30 breaths min-1. Causes for distress / fatigue / weaning failure will be sought and corrective treatments initiated as appropriate. The participant will be reassessed every 2 hours. If there are no signs of distress / fatigue then a further trial of self-ventilation will be commenced as described above.
This active weaning protocol will occur between 8am-10pm. Unless the participant develops signs of fatigue or distress, ventilator settings will not be changed overnight.
NIV will be withdrawn when the participant tolerates 12 hours unsupported spontaneous ventilation.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
Time from randomisation to liberation from ventilation
Secondary outcome measures
Efficacy:
1. Mortality at 30, 90 and 180 days
2. Duration of IMV and total ventilator days (invasive and non-invasive ventilation)
3. Time to meeting ICU discharge criteria (defined as no further requirement for level 2/3 care)
4. Proportion of patients receiving antibiotics for presumed respiratory infection and total antibiotic days
5. Re-intubation rates (protocolised end-point and actual event)
6. Tracheostomy
Safety:
1. Adverse events
2. Serious adverse events
Patient focused outcomes:
Health-related quality of life, measured using EuroQol, EQ-5D, SF12 at baseline (estimated), 3 and 6 months
Overall trial start date
01/01/2013
Overall trial end date
31/07/2017
Reason abandoned
Eligibility
Participant inclusion criteria
1. Male and female, age > 16 years
2. Patients with respiratory failure who have received invasive ventilation for more than 48 hours (from the time of intubation)
3. Fail a spontaneous breathing trial (SBT)
4. Provision of written informed consent
The trial inclusion criteria will be adult patients with respiratory failure who have received invasive ventilation for more than 48 hours (from the time of intubation) and fail a SBT. We will not include patients who require shorter periods of invasive ventilation or those who pass the SBT as this group are typically rapidly weaned and have good clinical outcomes.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Revised sample size 364; UK sample size 364
Participant exclusion criteria
1. Presence of tracheostomy
2. Profound neurological deficit
3. Any absolute contraindication to NIV
4. Home ventilation prior to ICU admission
5. Decision not to re-intubate or withdrawal of care anticipated
6. Further surgery / procedure requiring sedation planned in next 48 hours
7. Previous participation in the trial
Recruitment start date
01/01/2013
Recruitment end date
04/10/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Warwick Medical School
Coventry
CV4 7AL
United Kingdom
Sponsor information
Organisation
Heart of England NHS Foundation Trust (UK)
Sponsor details
3 Bordesley Green East
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal one year after overall trail end date.
IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary