Glucocorticoids in adults with acute respiratory distress syndrome (GuARDS Trial)
| ISRCTN | ISRCTN15076735 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15076735 |
| IRAS number | 1007694 |
| Secondary identifying numbers | AC23038, IRAS 1007694, CPMS 58497 |
- Submission date
- 15/06/2023
- Registration date
- 26/09/2023
- Last edited
- 07/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English Summary
Background and study aims
Every year about 120,000 adults who are admitted to Intensive Care Units (ICUs) require a machine, called a ventilator, to help them breathe. In patients who need ventilation, about 1 in 4 have a life-threatening condition with severe breathing difficulties called acute respiratory distress syndrome (ARDS) where there is a large amount of inflammation in the lung. Unfortunately, around 40% of patients with ARDS die within 60 days of developing this condition. At present, there are no drugs that cure ARDS. However, in 2020, a small research study (the DEXA-ARDS trial) looked at dexamethasone as a treatment for ARDS. Dexamethasone is a well-known steroid, which is a cheap anti-inflammatory drug, that is already widely used to treat other illnesses. The result of the DEXA-ARDS trial showed that it may help patients survive ARDS but to help us know how effective it is, dexamethasone needs to be tested in a much bigger group of patients who come into the NHS with ARDS. A large clinical trial is planned to be conducted across the UK to answer if dexamethasone treatment in patients with ARDS can save lives, reduce the need for extended ICU care, improve longer-term patient quality of life and find the best value for the public and health services. The study design is called a randomised controlled trial (RCT).
Who can participate?
Patients aged 16 years old and over with ARDS
What does the study involve?
The study plans to recruit up to patients with ARDS, in approximately 60 ICUs throughout the UK. Patients, or their Legal Representatives (relatives) if patients cannot make decisions about their care will be asked to agree (consent) to participating in the study. They will also be asked if they can be followed up for 6 months after their treatment, as this will give us important information about the clinical effectiveness and cost-effectiveness of the treatment.
What are the possible benefits and risks of participating?
Participants may or may not see an improvement in their long-term health from taking part in GuARDS but their taking part will give us information to help us treat others in the future.
There may be some discomfort and bruising from blood sampling. The sampling is done by an experienced person to minimise discomfort. The amount of blood taken is minimal and poses no risk.
Dexamethasone has routinely been used in clinical practice for over 60 years for a number of conditions where it is well tolerated. However, for the patients in Group A getting the dexamethasone treatment, some side effects are possible such as a higher risk of infection and high blood sugar - but the DEXA-ARDS study mentioned above did not see an increased risk of these. More likely side effects are indigestion or heartburn, difficulty sleeping, and changes in mood and behaviour - such as feeling irritable or anxious. These should pass when this short course of treatment of up to 10 days stops.
Although all patients need to take part in the study follow-ups, they will be given a reasonable time to complete the follow-up questionnaire by a phone call with a member of the research team and/or by email.
Where is the study run from?
The Queen's Medical Research Institute (UK)
When is the study starting and how long is it expected to run for?
June 2023 to June 2028
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
Study team, guards@ed.ac.uk
Contact information
Scientific
Level 2, IRR South
Edinburgh BioQuarter
4-5 Little France Drive
Edinburgh
EH16 4UU
United Kingdom
| Phone | +44 (0)131 651 8167 |
|---|---|
| guards@ed.ac.uk |
Principal Investigator
Level 2, IRR South
Edinburgh BioQuarter
4-5 Little France Drive
Edinburgh
EH16 4UU
United Kingdom
| Phone | +44 (0)131 651 8167 |
|---|---|
| guards@ed.ac.uk |
Study information
| Study design | Randomized parallel-group allocation-concealed open-label pragmatic group-sequential-design clinical and cost-effectiveness study with internal pilot |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital, Medical and other records, Telephone |
| Study type | Treatment, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Glucocorticoids in adults with acute respiratory distress syndrome: A randomised, parallel-group, allocation-concealed, open-label, pragmatic, group-sequential design, clinical and cost-effectiveness trial with internal pilot |
| Study acronym | GuARDS |
| Study hypothesis | To determine the clinical effectiveness of dexamethasone in patients with ARDS with moderate to severe hypoxaemia (referred to as patients with moderate to severe ARDS) on the primary outcome of 60-day mortality. To determine the clinical effectiveness of dexamethasone in moderate to severe ARDS on a range of clinically relevant secondary outcomes included within the CoVENT core outcome set (COS) for ventilation trials. To assess the cost-efficiency of dexamethasone plus usual care versus usual care alone in the treatment of ARDS, as per NICE reference case specifications modelled over 1, 3, and 5 year, and lifetime time horizons. |
| Ethics approval(s) |
Approved 26/09/2023, Scotland A Research Ethics Committee (Ethics Department, 2nd Floor Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, United Kingdom; +44 (0)7814609032; Manx.Neill@nhslothian.scot.nhs.uk), ref: 23/SS/0077 |
| Condition | Acute respiratory distress syndrome (ARDS) |
| Intervention | In GUARDS, Usual Care + Dexamethasone will be compared to Usual Care. An online tool will be used to randomise patients. On days 1-5, 20mg/day of intravenous (iv) dexamethasone will be administered to patients in the Usual Care + Dexamethasone arm. On days 6-10, the iv dexamethasone will drop to 10mg/day. The intervention is a 10-day treatment regime whilst patients are in ICU. All other care will be usual practice. The intervention will stop early if patients are well enough to be discharged from ICU before the 10-day intervention is completed. Patients in both arms of the trial will be followed up for 6 months after their randomisation. Mortality data will be collected 60, 90 and 180 days post-randomisation. Patients will also be asked to complete a health-related quality of life questionnaire at 60 and 180 days. Patients will be asked about their use of the health service at 90 and 180 days. Information will also be collected via data linkage health economics at these time points. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacoeconomic |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Dexamethasone |
| Primary outcome measure | All-cause mortality measured using medical records at 60 days from randomisation |
| Secondary outcome measures | Our proposed secondary outcomes (endpoints) are from the CoVENT core outcome set (COS) for ventilation trials and are measured using medical records as and when they occur: 1. First successful extubation, defined as the time from randomization until the first successful extubation or the patient’s death occurs, measured using a record of the date/time of all periods of ventilation up to day 60. Successful extubation is being free from all tubes, endotracheal tube, and tracheostomy with success being defined as remaining free from tubes at 48 hours. If discharged from the hospital before the 48-hour success period, successful extubation is assumed. 2. Duration of mechanical ventilation - Unassisted breathing, defined as no inspiratory support (includes time receiving invasive mechanical ventilation and non-invasive ventilation) or extracorporeal lung support. Success is defined as remaining to breathe unassisted at 48 hours. Defined as the time from randomization until the first successful unassisted breathing or the patient’s death occurs. Death prior to the end of mechanical ventilation or within the 48-hour period after the end of mechanical ventilation is considered censored. 3. Reintubation - All reintubation events with date/time to report the total number of reintubations after planned extubation in each group and the average number of reintubation events/participants in each group. The COS recommends reintubation rates at 60 days. To capture the risk of delayed reintubation we will collect this outcome for up to 180 days from randomization, censored at hospital discharge. 4. Duration of ICU and hospital stay at the time from randomisation until participant first leaves the relevant facility or death 5. Health-related quality of life (HRQoL) measured using the EQ-5D (www.euroqol.org) and is participant reported at 60 and 180 days post-randomisation 6. Mortality - will record the event date/time of the event, as well as the date/time of randomization to enable a survival analysis at 90 and 180 days post-randomisation. 7. Health service use since hospital discharge – will be a telephone questionnaire completed with a research nurse at 90 and 180 days. It will include questions on rehospitalisations and Health service usage. Data will also be collected via data linkage. |
| Overall study start date | 13/06/2023 |
| Overall study end date | 01/06/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 1708 |
| Participant inclusion criteria | 1. Provision of informed consent 2. Aged 16 years or older 3. Admitted to intensive care unit or high dependency unit (ICU) 4. Receiving respiratory support via invasive mechanical ventilation or non-invasive ventilatory support (non-invasive ventilatory support includes mask or helmet) or high flow nasal cannula (HFNC) >30L/min 5. Within 72 hours of diagnosis of ARDS with moderate to severe hypoxaemia defined as 6. Known acute clinical insult or new or worsening respiratory dysfunction (Note: this includes new deterioration at any time-point during the ICU stay), and 6.1. Opacities on chest imaging not fully explained by effusions, lobar/lung collapse/atelectasis, or nodules, and 6.2. Respiratory failure not fully explained by cardiac failure or fluid overload, and 6.3. Assessment of hypoxaemia done with either PaO2/FiO2 ratio <26.7 kPa from arterial blood gases, or SpO2/FiO2 <235 with SaO2<97% |
| Participant exclusion criteria | 1. ARDS due to microbiologically confirmed SARS-Co-V2 infection (COVID-19 ARDS) 2. Major upper gastrointestinal bleeding during current hospital admission, defined as requiring endoscopy and transfusion for two or more units of packed red blood cells. This exclusion criterion will exclude patients with contraindications to glucocorticoids on safety grounds. 3. High-dose glucocorticoids are required for a separate proven clinical indication at the time of randomisation as withholding treatments that have been deemed clinically effective, would be unethical. Note: Low-dose glucocorticoid treatments for clinical indications (defined as maximum daily dose of 200mg hydrocortisone or equivalent other steroids) is not an exclusion criterion. 4. Known hypersensitivity to dexamethasone 5. Infections that are not being effectively treated as determined by the treating medical team. Note: Once infections are considered as effectively treated by the treating medical team, they are eligible for the trial. 6. Planned intensive care treatment withdrawal within next 24 hours as determined by the treating medical team 7. Patients who are known to be pregnant 8. Previous enrolment in the GuARDS trial |
| Recruitment start date | 08/03/2024 |
| Recruitment end date | 10/10/2028 |
Locations
Countries of recruitment
- England
- Northern Ireland
- United Kingdom
Study participating centres
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Stott Lane
Salford
M6 8HD
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Liverpool
L9 7AL
United Kingdom
Barnsley
S75 2PS
United Kingdom
Basildon
SS16 5NL
United Kingdom
Belfast
BT9 7AB
United Kingdom
Bristol
BS2 8HW
United Kingdom
Craigavon
BT63 5QQ
United Kingdom
Haslingden Road
Blackburn
BB2 3HH
United Kingdom
Old Dalkeith Road
Edinburgh
Lothian
EH16 4SA
United Kingdom
Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom
Leicester
LE3 9QP
United Kingdom
Harefield
Uxbridge
UB9 6JH
United Kingdom
London
E9 6SR
United Kingdom
Hull
HU3 2JZ
United Kingdom
Rothwell Road
Kettering
NN16 8UZ
United Kingdom
London
SE5 9RS
United Kingdom
Kingston upon Thames
KT2 7QB
United Kingdom
Victoria Road
Macclesfield
SK10 3BL
United Kingdom
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
Gillingham
ME7 5NY
United Kingdom
TA1 5DA
United Kingdom
Dundee
DD1 9SY
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Rake Lane
North Shields
NE29 8NH
United Kingdom
Northampton
NN1 5BD
United Kingdom
Pinderfields General Hospital
Aberford Road
Wakefield
WF1 4EE
United Kingdom
Poole
BH15 2JB
United Kingdom
Sherriff Hill
Gateshead
NE9 6SX
United Kingdom
Rotherham
S60 2UD
United Kingdom
Minerva Road
Farnworth
Bolton
BL4 0JR
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
London
SW3 6HP
United Kingdom
TR1 3LI
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Rochdale Road
Oldham
OL1 2JH
United Kingdom
Stoke-on-trent
ST4 6QG
United Kingdom
Bath
BA1 3NG
United Kingdom
Belfast
BT12 6BA
United Kingdom
M6 8HD
United Kingdom
Mansfield Road
Sutton-in-ashfield
NG17 4JL
United Kingdom
Southampton
SO16 6YD
United Kingdom
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Leeds
LS9 7TF
United Kingdom
London
SW17 0QT
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Tonbridge Road
Pembury
Tunbridge Wells
TN2 4QJ
United Kingdom
London
NW1 2PG
United Kingdom
East Kilbride
G75 8RG
United Kingdom
London
SE13 6LH
United Kingdom
Watford
WD18 0HB
United Kingdom
Isleworth
TW7 6AF
United Kingdom
Sponsor information
University/education
Queen's Medical Research Institute (QMRI)
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 242 3353 |
|---|---|
| tiago.santos@ed.ac.uk | |
| Website | http://www.ed.ac.uk/home |
"ROR" |
https://ror.org/01nrxwf90 |
Funders
Funder type
Government
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 | 01/06/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Conference presentation 3. Publication on the website 4. Submission to regulatory authorities |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from the study team, guards@ed.ac.uk. Any decision to share study data will be discussed and agreed between the study team (grant co-applicants). If sharing of data is deemed appropriate, we will share only anonymised data. The participant information leaflet (PIS) explains to patients that we would like to retain trial data after the trial has ended so that it can be used in future research studies. Participants have to explicitly agree to this on the consent form (Yes/No) option. If participants do not agree to us retaining their data this will be recorded within the database thereby ensuring their data is removed from any future exports to external research groups. |
Editorial Notes
07/04/2025: Study website added. Addenbrookes, Aintree Hospital, Barnsley Hospitals, Basildon University Hospital, Belfast City Hospital, Bristol Royal Infirmary, Craigavon Area Hospital, East Lancashire Hospitals NHS Trust, Royal Infirmary of Edinburgh at Little France, Glan Clwd Hospital, Glenfield Hospital NHS Trust, Harefield Hospital, Homerton Hospital, Hull Royal Infirmary, Kettering General Hospital, Kings College Hospital, Kingston Hospital, Macclesfield District General Hospital, Maidstone Hospital, Medway Maritime Hospital, Musgrove Park Hospital, Ninewells Hospital, Norfolk and Norwich University Hospital, Northumbria Healthcare NHS Foundation Trust, Northampton General Hospital, Pinderfields Hospitals NHS Trust, Poole Hospital, Gateshead - Queen Elizabeth Hospital, Rotherham District General Hospital, The Royal Bolton Hospital Laboratory, Royal Bournemouth General Hospital, Royal Brompton Hospital, Royal Cornwall Hospital, Royal Devon and Exeter Hospital NHS Trust, Royal Liverpool University Hospital, Royal Oldham Hospital, Royal Stoke University Hospital, Royal United Hospitals Bath, Royal Victoria Hospital, Belfast, Salford Care Organisation, Sherwood Forest Hospitals NHS Foundation Trust, Southampton General Hospital, Southmead Hospital, St James's University Hospital (Leeds), St George's University Hospital, Sunderland Royal Hospital, Tunbridge Wells Hospital, University College London Hospitals NHS Foundation Trust, University Hospital Hairmyres, University Hospital Lewisham, Watford General Hospital, West Middlesex University Hospital were added to the study participating centres.
13/03/2024: The recruitment start date was changed from 15/04/2024 to 08/03/2024
12/01/2024: The recruitment start date was changed from 15/01/2024 to 15/04/2024.
09/11/2023: The recruitment start date was changed from 13/11/2023 to 15/01/2024.
04/10/2023: Internal review.
26/09/2023: ISRCTN received notification of combined HRA/MHRA approval for this trial on 26/09/2023
15/06/2023: Trial's existence confirmed by Health Research Authority (HRA) (UK).
