Does setting the breathing machine (ventilator) to deliver breaths using a method called airway pressure release ventilation help patients with diseased lungs to heal faster and spend less time on a ventilator?
| ISRCTN | ISRCTN17158033 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17158033 |
| IRAS number | 335630 |
| Secondary identifying numbers | IRAS 335630, NIHR154501, CPMS 62929 |
- Submission date
- 12/06/2024
- Registration date
- 21/06/2024
- Last edited
- 14/03/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Around half of all patients in critical care need help from a breathing machine (ventilator) to maintain oxygen levels. Although they may be life-saving, breathing machines can cause damage to diseased lungs and make chest infections more likely.
The usual way a breathing machine is used aims to protect the lungs from damage until they are healed. However, damage can still occur, and the lungs take time to recover. Airway pressure release ventilation (APRV) is a way of using the breathing machine that we think causes less damage. It moves gas into the lungs gently over a longer time. This helps to reduce lung damage, helping faster healing. APRV may reduce time on the breathing machine and in the hospital which may save costs. APRV may also reduce the risk of death.
The aim of this study is to find out if setting the breathing machine to deliver breaths using APRV helps patients with diseased lungs to heal faster and spend less time on a ventilator compared to the usual way breathing support is given in critical care. The researchers also want to know if APRV saves more lives, improves quality of life, and saves the NHS money by helping people leave CCU sooner.
Who can participate?
Patients admitted to a CCU in the UK who are:
1. Aged 18 years or more
2. Receiving support from a breathing machine
3. Have moderate to severely low oxygen levels
4. Are expected by the critical care team to stay on a breathing machine for more than 2 days
What does the study involve?
Participants will be assigned by chance (randomised) to one of two groups.
1. APRV: The breathing machine will be set to the APRV mode. APRV moves gas into the lungs gently over a longer time. APRV is available on all ventilators that are used within the NHS.
2. Usual care: The breathing machine will be set as usual by the critical care team.
There will be no other changes to care delivered by the critical care team for patients in both the APRV and usual care group.
Participants, the research team, or the critical care team will not be able to choose which group your relative/friend is in. This is decided by a computer at random, just like tossing a coin or drawing lots.
The research team will collect information about the care the participants receive while in critical care including how the breathing machine is used, how long they need the machine, and how long they stay in critical care. The research team will collect the participants’ personal information such as age, ethnicity, sex and past medical conditions before coming to critical care as this helps them to understand the effect of APRV on different groups of people.
After leaving the hospital, participants will be sent a questionnaire 2 and 6 months after hospital discharge asking about their overall wellbeing and quality of life. Each questionnaire will take about 5 to 10 minutes to complete. If needed, someone can complete them on the participant's behalf. The researchers will share the participant’s name, email address, and phone number with a third-party company in order to send them the questionnaires by text message or email. They may also get in touch with participants by text message or email if we have any queries about their questionnaire or if we have any updates related to the study.
What are the possible benefits and risks of participating?
As this is a study, participants may or may not benefit from taking part. However, the findings of the research will help to improve the treatments and care provided to patients with a similar condition now and in the future.
There is no payment for taking part in this study. However, to thank participants for their time in completing the follow-up questionnaires at 2 and 6 months, they will be given a small monetary gift voucher alongside each questionnaire.
The University of Warwick is currently leading several studies looking at how we treat patients with respiratory failure. This group of studies is called the ‘Confederation of Respiratory Critical Care Trials’ or ‘CoReCCT’. If participants are taking part in other studies within CoReCCT, they will not need to complete questionnaires for each study. Participants will only be asked to complete the questionnaires once and will receive one voucher with each questionnaire.
At this time, there are no important disadvantages or risks to taking part.
Where is the study run from?
Warwick University in partnership with NHS hospitals across the UK
When is the study starting and how long is it expected to run for?
January 2024 to August 2027
Who is funding the study?
National Institute for Health Research, Health Technology Assessment (NIHR154501) (UK)
Who is the main contact?
RELEASE trial manager, RELEASE@warwick.ac.uk
Contact information
Scientific, Principal Investigator
Department of Critical Care
Guy’s & St Thomas’ NHS Foundation Trust
Westminster Bridge
London
SE1 7EH
United Kingdom
 ORCID ID |
0000-0001-5600-1676 |
|---|---|
| release@warwick.ac.uk |
Scientific, Principal Investigator
Wellcome-Wolfson Institute for Experimental Medicine
The Queen's University of Belfast
Belfast
BT9 7BL
United Kingdom
| ORCID ID |
0000-0002-3283-1947 |
|---|---|
| release@warwick.ac.uk |
Public, Scientific
Warwick Clinical Trials Unit
Warwick Medical School
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
United Kingdom
| Phone | +44 (0)2476 575 194 |
|---|---|
| release@warwick.ac.uk |
Study information
| Study design | Multi-centre randomized allocation-concealed controlled open-label pragmatic parallel-group clinical and cost-effectiveness trial with an internal pilot |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Airway Pressure Release Ventilation (APRV) vs conventional ventilation for patients with moderate to severe acute hypoxemic respiratory failure: the RELEASE trial |
| Study acronym | RELEASE |
| Study hypothesis | What is the clinical and cost-effectiveness of airway pressure release ventilation (APRV) for adults requiring invasive mechanical ventilation (IMV) for moderate-severe acute hypoxaemic respiratory failure (AHRF)? |
| Ethics approval(s) |
Approved 08/07/2024, Wales REC 2 (The Cardiff North Inn by Accor, Circle Way East, Llanaderyn, Cardiff, CF23 9XF, United Kingdom; +44 (0)2922941119; Wales.REC2@wales.nhs.uk), ref: 24/WA/0128 |
| Condition | Moderate to severe acute hypoxaemic respiratory failure (AHRF) |
| Intervention | Participants are randomised to either: 1. Early airway pressure release ventilation (APRV) 2. Standard conventional lung protective invasive mechanical ventilation (no APRV) Participants will be randomised via randomly permuted blocks using an automated web-based system on a one-to-one basis, stratified by site and prior enrolment into the Awake Prone Positioning and Protect Airways trials, using a computer-generated randomisation schedule managed by the Warwick CTU. The researchers have selected a parallel group RCT design to minimise selection bias and ensure against accidental bias. The intervention (APRV or control) will continue until one of the following criteria is met: 1. 60 days after randomisation 2. Successful unassisted breathing (at 48 hours with no further requirement for inspiratory support or extracorporeal lung support. See section 2.4.3 for the full definition) 3. Trial intervention-related serious adverse event 4. Death or discontinuation of active treatment 5. Withdrawal of consent |
| Intervention type | Other |
| Primary outcome measure | Duration of invasive mechanical ventilation (defined as the time from randomisation to first successful unassisted breathing or death) measured using data collected from site staff at the time of first successful unassisted breathing or death |
| Secondary outcome measures | 1. All-cause mortality measured using data collected from site staff at 2 and 6 months 2. Time to first extubation measured using data collected from site staff at time of extubation 3. Reintubation measured using data collected from site staff at time of reintubation 4. Use of non-invasive ventilation following extubation measured using data collected from site staff at time of extubation 5. CCU and hospital length of stay measured using data collected from site staff at time of CCU and hospital discharge 6. Serious adverse events measured using data collected from site staff up to time of hospital discharge 7. Health-related quality of life measured using the 5-level EQ-5D version (EQ-5D-5L) at 2 and 6 months 8. Acute health care use measured using participant-completed resource use questionnaires and, if available, enriched using data obtained from site staff or linkage at 2 and 6 months 9. Within-trial cost-utility analysis from an NHS hospital care perspective using data collected from site staff and data obtained through linkage to routine datasets at 2 and 6 months |
| Overall study start date | 01/01/2024 |
| Overall study end date | 31/08/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 710 |
| Participant inclusion criteria | 1. Age ≥18 years 2. Receiving invasive mechanical ventilation 3. Moderate to severe AHRF (PaO2/FiO2 <20 kPa with Positive End Expiratory Pressure (PEEP) ≥5 cmH2O) assessed at the time of screening (or as documented in the medical record in the preceding 2 hours) 4. Expected to stay on invasive mechanical ventilation for >48 hours |
| Participant exclusion criteria | 1. Receiving IMV ≥60 hours at the time of screening as will be unable to deliver early APRV 2. Primary reason for invasive mechanical ventilation is one of the following: 2.1. Asthma 2.2. Severe COPD 2.3. Pulmonary embolism (massive or sub-massive) (as cause of hypoxaemia is not primarily due to collapse of lung tissue) 2.4. Existing neuromuscular disease such as motor neurone disease, Guillain Barre or myasthenia gravis (as the cause of respiratory failure is not primarily lung-related) 3. Refractory shock (systolic blood pressure < 90 mmHg, despite fluid administration and vasoactive drugs)* 4. Severe hypercapnic respiratory acidosis (pH <7.20 on the arterial blood gas assessed for trial inclusion)* 5. Ongoing air leak (e.g. unresolved pneumothorax at time of screening)* 6. Traumatic brain injury with uncontrolled intracranial hypertension* 7. Likely death or treatment withdrawal in the next 24 hours 8. Home ventilation or home oxygen therapy prior to admission *(patients can be recruited if this resolves and remain eligible) |
| Recruitment start date | 03/02/2025 |
| Recruitment end date | 31/05/2027 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Arrowe Park Road
Wirral
CH49 5PE
United Kingdom
Kempston Road
Bedford
MK42 9DJ
United Kingdom
Marlborough Street
Bristol
BS2 8HW
United Kingdom
St. Leonards-on-sea
TN37 7RD
United Kingdom
Cosham
Portsmouth
PO6 3LY
United Kingdom
Ashton-under-lyne
OL6 9RW
United Kingdom
Sponsor information
University/education
Research and Impact Services
University House
Gibbet Hill Road
Coventry
CV4 8UW
England
United Kingdom
| Phone | +44 (0)2476 575 733 |
|---|---|
| sponsorship@warwick.ac.uk | |
| Website | https://warwick.ac.uk/fac/sci/med/research/ctu/ |
"ROR" |
https://ror.org/01a77tt86 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal. The researchers will use a multi-modal dissemination strategy: open access publication in high-impact factor journals; presentation at relevant national/international scientific conferences; and communication with participant and family networks including social media and lay press with a lay results summary to participants. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.0 | 13/06/2024 | 16/07/2024 | No | No |
Additional files
Editorial Notes
14/03/2025: The study participating centres Arrow Park Hospital, Bedford Hospital, University Hospital Bristol, Conquest Hospital, Queen Alexandras Hospital, Tameside General Hospital were added.
17/01/2025: The following changes were made to the study record:
1. The recruitment start date was changed from 01/10/2024 to 03/02/2025.
2. The recruitment end date was changed from 31/03/2027 to 31/05/2027.
16/07/2024: The following changes were made to the study record:
1. Protocol uploaded.
2. Ethics approval details added.
3. The recruitment start date was changed from 01/08/2024 to 01/10/2024.
12/06/2024: Study's existence confirmed by the NIHR.
