Condition category
Respiratory
Date applied
28/11/2012
Date assigned
29/11/2012
Last edited
11/11/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 from our team 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 will be assessed daily for their readiness to commence weaning using a system we have previously developed and tested. Those ready for weaning will be 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 will measure 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 will also measure 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?
The study will run for 4 years from January 2013.

Who is funding the study?
National Institute for Health Research (NIHR), UK.

Who is the main contact?
Mrs Beverley Hoddell
b.hoddell@warwick.ac.uk

Trial website

http://www.warwick.ac.uk/breathe

Contact information

Type

Scientific

Primary contact

Mrs Beverley Hoddell

ORCID ID

Contact details

Clinical Trials Unit
Warwick Medical School
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
b.hoddell@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: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13347

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 below 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: EuroQol, EQ-5D, SF12 at baseline (estimated), 3 and 6 months

Overall trial start date

01/01/2013

Overall trial end date

01/06/2016

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

Planned Sample Size: 920; UK Sample Size: 920

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

01/06/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Trials Unit
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

http://www.heartofengland.nhs.uk/

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment - HTA (UK) Grant Codes: 10/134/06

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes