RECOVERY Respiratory Support: Respiratory Strategies in patients with coronavirus COVID-19 – CPAP, high-flow nasal oxygen, and standard care

Plain English Summary

Current plain English summary as of 04/05/2021:
Background and study aims:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 as a novel coronavirus. It has been declared as a global pandemic. Some people develop no symptoms, whilst others develop worsening breathing problems and may die. Throughout the world, a huge burden has been placed on intensive care units due to the number of people with worsening breathing problems that need to be placed on a ventilator (breathing machine). It is essential that we avoid ventilator use wherever possible to allow as many individuals as possible to benefit.

In this trial, we will test whether two treatments are better than standard treatment at preventing people from dying or needing to go on a ventilator.

Who can participate?
Adult hospital inpatients with suspected or proven COVID-19

What does the study involve?
Individuals that have or are believed to have COVID-19 that are requiring a certain amount of oxygen will be randomly allocated to receive one of three interventions. In the first group, participants will be placed on a tight-fitting mask (CPAP). In the second group, participants will receive oxygen blown quickly up their nose by a machine (HFNO). In the third arm, participants will receive standard treatment (a normal oxygen mask). Both CPAP and HFNO are already used routinely in the NHS for other conditions.

Where possible, we will seek informed consent from participants prior to trial enrolment. In some cases, the urgency of treatment may require that participants are enrolled and their consent sought later. This is because some participants are likely to be confused and, due to COVID-19, visiting is restricted. In addition, for treatments to be effective, they will need to be started as quickly as possible to have the best possible outcomes.

We will record the need for people to be placed on a ventilator and death over a 30-day period. We will also see how long people spend on intensive care units and in hospital.

What are the possible benefits and risks of participating?
The planned interventions are already in routine use across NHS Hospitals. The interventions (HFNO and CPAP) may help to reduce the need for patients to go on a ventilator. However, they have some side-effects such as nausea, dryness to the mouth and nose, and pressure sores to the face.

Where is the study run from?
The trial is led by the University of Warwick Clinical Trials Unit

When is the study starting and how long is it expected to run for?
From March 2020 to June 2021

Who is funding the study?
The National Institute for Health Research (UK)

Who is the main contact?
Unfortunately, this study is not recruiting public volunteers at this time. This is because the research isn’t ready for volunteers yet or the researchers are directly identifying volunteers in certain areas or hospitals. Please do not contact the research team as they will not be able to respond. For more information about COVID-19 research, visit the Be Part of Research homepage.


Previous plain English summary:
Background and study aims:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 as a novel coronavirus. It has been declared as a global pandemic. Some people develop no symptoms, whilst others develop worsening breathing problems and may die. Throughout the world, a huge burden has been placed on intensive care units due to the number of people with worsening breathing problems that need to be placed on a ventilator (breathing machine). It is essential that we avoid ventilator use wherever possible to allow as many individuals as possible to benefit.

In this trial, we will test whether two treatments are better than standard treatment at preventing people from dying or needing to go on a ventilator.

Who can participate?
Adult patients with suspected or proven COVID-19 admitted to hospital

What does the study involve?
Individuals that have or are believed to have COVID-19 that are requiring a certain amount of oxygen will be randomly allocated to receive one of three interventions. In the first group, participants will be placed on a tight-fitting mask (CPAP). In the second group, participants will receive oxygen blown quickly up their nose by a machine (HFNO). In the third arm, participants will receive standard treatment (a normal oxygen mask). Both CPAP and HFNO are already used routinely in the NHS for other conditions.

Due to the urgency of treatment, we plan to enrol potential participants immediately and seek their consent later. This is because many participants are likely to be confused and due to COVID-19 visiting will be restricted. In addition, for the treatments to be effective, they will need to be started as quickly as possible to have the best outcomes.

We will record the need for people to be placed on a ventilator and death over a 30-day period. We will also see how long people spend on intensive care units and in hospital.

What are the possible benefits and risks of participating?
The planned interventions are already in routine use across NHS Hospitals. The interventions (HFNO and CPAP) may help to reduce the need for patients to go on a ventilator. However, they have some side-effects such as nausea, dryness to the mouth and nose, and pressure sores to the face.

Where is the study run from?
The trial is led by the University of Warwick Clinical Trials Unit

When is the study starting and how long is it expected to run for?
From March 2020 to May 2021

Who is funding the study?
The National Institute for Health Research (UK)

Who is the main contact?
Unfortunately, this study is not recruiting public volunteers at this time. This is because the research isn’t ready for volunteers yet or the researchers are directly identifying volunteers in certain areas or hospitals. Please do not contact the research team as they will not be able to respond. For more information about COVID-19 research, visit the Be Part of Research homepage.

Study website

https://warwick.ac.uk/fac/sci/med/research/ctu/trials/recovery-rs/

Type

Public

Contact name

Dr Keith Couper

ORCID ID

http://orcid.org/0000-0003-2123-2022

Contact details

Clinical Trials Unit
Warwick Medical School
University of Warwick
Coventry
CV4 7AL
United Kingdom
+442476151179
k.couper@warwick.ac.uk

EudraCT/CTIS number

Nil known

IRAS number

282338

ClinicalTrials.gov number

Nil known

Protocol/serial number

Sponsor: 26/19-20, IRAS 282338

Scientific title

In adult patients with known or suspected COVID-19, does the use of Continuous Positive Airway Pressure (CPAP) or high-flow nasal oxygen (HFNO), compared with standard care reduce mortality or need for tracheal intubation?

Acronym

Recovery-RS

Study hypothesis

CPAP is superior to standard care in reducing mortality or need for tracheal intubation in COVID-19 patients
HFNO is superior to standard care in reducing mortality or need for tracheal intubation in COVID-19 patients
CPAP is superior to HFNO in reducing mortality or need for tracheal intubation in COVID-19 patients

Ethics approval(s)

Approved 03/04/2020, the London - Brighton & Sussex Research Ethics Committee
(Health Research Authority, Ground Floor, Skipton House, 80 London Road, London SE1 6LH; +44 0207 104 8241; brightonandsussex.rec@hra.nhs.uk), ref: 20/HRA/1696

Study design

Adaptive (group-sequential), pragmatic, randomised controlled, open-label, multi-centre, effectiveness trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Respiratory failure in patients with known or suspected COVID-19 (SARS-CoV-2 infection)

Intervention

Patients will be randomised in a 1:1:1 ratio to:
Arm 1: Continuous positive airway pressure (CPAP), administered according to local protocol/guidelines. Administration will be left to clinical discretion.
Arm 2: High flow nasal oxygen (HFNO) will be administered according to local protocol/guidelines. Administration will be left to clinical discretion.
Arm 3: Standard care. Standard oxygen therapy according to local protocol/guidelines.

Intervention type

Procedure/Surgery

Primary outcome measure

Composite outcome comprising tracheal intubation or mortality within 30 days. Mortality will be reported from hospital records up until discharge and tracked after discharge. Intubation will be obtained from hospital data.

Secondary outcome measures

Current secondary outcome measures as of 04/05/2021:
All outcome measures are assessed at up to 30-days or hospital discharge, whichever is later, and obtained from hospital records unless otherwise specified.
1. Intubation rate
2. Time to intubation
3. Time to death (mortality), obtained from hospital record or other source
4. Mortality in critical care (level 2/3)
5. Mortality during hospital stay
6. Mortality at 30 days, obtained from hospital record or other source
7. Length of stay in critical care (level 2/3)
8. Length of stay in hospital
9. Duration of invasive ventilation
10. Admission to ICU



Previous secondary outcome measures:
All outcome measures are assessed at up to 30-days or hospital discharge, whichever is later, and obtained from hospital records unless otherwise specified.
1. Intubation rate
2. Time to intubation
3. Time to death (mortality), obtained from hospital record or other source
4. Mortality in critical care (level 2/3)
5. Mortality during hospital stay
6. Mortality at 30 days, obtained from hospital record or other source
7. Length of stay in critical care (level 2/3)
8. Length of stay in hospital

Overall study start date

30/03/2020

Overall study end date

02/06/2021

Reason abandoned (if study stopped)

Participant inclusion criteria

Current participant inclusion criteria as of 04/05/2021:
1. Adults ≥18 years
2. Hospital inpatient with suspected or proven COVID-19
3. FiO2 ≥0.4 and SpO2 ≤94%
4. Plan for escalation to intubation if needed


Previous participant inclusion criteria:
1. Adults ≥ 18 years
2. Admitted to hospital with suspected or proven COVID-19
3. On 40% oxygen (or greater) with SpO2 <94%
4. Plan for escalation to intubation if needed

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

4002

Participant exclusion criteria

Current participant exclusion criteria as of 04/05/2021:
1. Planned intubation and mechanical ventilation imminent within 1 hour
2. Known or clinically apparent pregnancy
3. Any absolute contraindication to CPAP or HFNO
4. Decision not to intubate due to ceiling of treatment or withdrawal of treatment anticipated
5. Equipment for both CPAP and HFNO not available


Previous participant exclusion criteria:
1. Planned intubation and mechanical ventilation imminent within 1 hour
2. Known or clinically apparent pregnancy
3. Any absolute contraindication to CPAP or HFNO
4. Decision not to intubate due to ceiling of treatment or withdrawal of care anticipated
5. Equipment for both CPAP and HFNO not available

Recruitment start date

06/04/2020

Recruitment end date

03/05/2021

Countries of recruitment

England, Northern Ireland, Scotland, United Kingdom, Wales

Study participating centre

Warwick Clinical Trials Unit
Warwick Medical School
University of Warwick
Coventry
CV4 7AL
United Kingdom

Study participating centre

Aintree Hospital
Lower Lane
Liverpool
L9 7AL
United Kingdom

Study participating centre

Altnagelvin Hospital
Glenshane Road
Londonderry
BT47 6SB
United Kingdom

Study participating centre

Barnet Hospital
Wellhouse Lane
Barnet
EN5 3DJ
United Kingdom

Study participating centre

Bedford Hospital
Kempston Road
Bedford
MK42 9DJ
United Kingdom

Study participating centre

Belfast City Hospital
51 Lisburn Road
Belfast
BT9 7AB
United Kingdom

Study participating centre

Castle Hill Hospital
Castle Road
Cottingham
HU16 5JQ
United Kingdom

Study participating centre

Charing Cross Hospital (Lead Centre)
Fulham Palace Road
London
W6 8RF
United Kingdom

Study participating centre

Colchester General Hospital
Turner Road
Colchester
CO4 5JL
United Kingdom

Study participating centre

Conquest Hospital, Hastings
The Ridge
St. Leonards-On-Sea
TN37 7RD
United Kingdom

Study participating centre

Croydon University Hospital
London Road
Croydon
CR7 7YE
United Kingdom

Study participating centre

Derriford Hospital
Derriford Road
Crownhill
Plymouth
PL6 8DH
United Kingdom

Study participating centre

Diana, Princess Of Wales Hospital
Scartho Road
Grimsby
DN33 2BA
United Kingdom

Study participating centre

Eastbourne District General
Kings Drive
Eastbourne
BN21 2UD
United Kingdom

Study participating centre

Fairfield General Hospital
Rochdale Old Road
Bury
BL9 7TD
United Kingdom

Study participating centre

Freeman Hospital
Freeman Road
High Heaton
Newcastle Upon Tyne
NE7 7DN
United Kingdom

Study participating centre

Glenfield Hospital
Groby Road
Leicester
LE3 9QP
United Kingdom

Study participating centre

Good Hope Hospital
Rectory Road
Sutton Coldfield
B75 7RR
United Kingdom

Study participating centre

Harefield Hospital
Hill End Road
Harefield
UB9 6JH
United Kingdom

Study participating centre

Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Study participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Study participating centre

Inverclyde Royal Hospital
Larkfield Road
Greenock
PA16 0XN
United Kingdom

Study participating centre

Ipswich Hospital
Heath Road
Ipswich
IP4 5PD
United Kingdom

Study participating centre

James Paget University Hospital
Lowestoft Road
Gorleston
Great Yarmouth
NR31 6LA
United Kingdom

Study participating centre

Jersey General Hospital
The Parade
Jersey
JE1 3UH
United Kingdom

Study participating centre

Kent & Canterbury
Ethelbert Road
Canterbury
CT1 3NG
United Kingdom

Study participating centre

King's College (Denmark Hill)
Denmark Hill
London
SE5 9RS
United Kingdom

Study participating centre

Leighton Hospital
Leighton
Crewe
CW1 4QJ
United Kingdom

Study participating centre

Lister Hospital
Coreys Mill Lane
Stevenage
SG1 4AB
United Kingdom

Study participating centre

Macclesfield District General Hospital
Victoria Road
Macclesfield
SK10 3BL
United Kingdom

Study participating centre

Manor Hospital
Moat Road
Walsall
WS2 9PS
United Kingdom

Study participating centre

Medway Maritime Hospital
Windmill Road
Gillingham
ME7 5NY
United Kingdom

Study participating centre

Musgrove Park Hospital
Musgrove Park
Taunton
TA1 5DA
United Kingdom

Study participating centre

New Cross Hospital
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom

Study participating centre

Norfolk And Norwich University Hospital
Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom

Study participating centre

North Manchester
Delaunays Road
Manchester
M8 5RB
United Kingdom

Study participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Study participating centre

Princess Of Wales Hospital (Wales)
Coity Road
Bridgend
CF31 1RQ
United Kingdom

Study participating centre

Princess Royal Hospital, Telford
Apley Castle
Grainger Drive
Telford
TF1 6TF
United Kingdom

Study participating centre

Princess Royal University Hospital
Farnborough Common
Orpington
BR6 8ND
United Kingdom

Study participating centre

Queen Alexandra Hospital
Southwick Hill Road
Cosham
Portsmouth
PO6 3LY
United Kingdom

Study participating centre

Queen Elizabeth Hospital – Gateshead
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom

Study participating centre

Queen Elizabeth Hospital (Birmingham)
Queen Elizabeth Medical Centre
Edgbaston
Birmingham
B15 2TH
United Kingdom

Study participating centre

Queen Elizabeth University Hospital, Glasgow
1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Study participating centre

Queens Medical Centre
Nottingham University Hospital
Derby Road
Nottingham
NG7 2UH
United Kingdom

Study participating centre

Raigmore Hospital
Old Perth Rd
Inverness
IV2 3UJ
United Kingdom

Study participating centre

Royal Alexandra Hospital, Paisley
Corsebar Road
Paisley
PA2 9PN
United Kingdom

Study participating centre

Royal Brompton
Sydney Street
London
SW3 6NP
United Kingdom

Study participating centre

Royal Gwent Hospital
Cardiff Road
Newport
Gwent
NP20 2UB
United Kingdom

Study participating centre

Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Study participating centre

Royal Marsden (London)
Fulham Road
London
SW3 6JJ
United Kingdom

Study participating centre

Royal Marsden (Surrey)
Downs Road
Sutton
SM2 5PT
United Kingdom

Study participating centre

Royal Oldham Hospital
Rochdale Road
Oldham
OL1 2JH
United Kingdom

Study participating centre

Russell's Hall
Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Study participating centre

Salford Royal Hospital
Stott Lane
Salford
M6 8HD
United Kingdom

Study participating centre

Scunthorpe General Hospital
Cliff Gardens
Scunthorpe
DN15 7BH
United Kingdom

Study participating centre

South Tyneside District Hospital
Harton Ln
South Shields
NE34 0PL
United Kingdom

Study participating centre

Southmead Hospital
Southmead Road
Westbury-On-Trym
Bristol
BS10 5NB
United Kingdom

Study participating centre

St George's Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom

Study participating centre

St Mary's Hospital
Praed Street
London
W2 1NY
United Kingdom

Study participating centre

St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom

Study participating centre

Stepping Hill Hospital
Poplar Grove
Stockport
SK2 7JE
United Kingdom

Study participating centre

Sunderland Royal Hospital
Kayll Road
Sunderland
SR4 7TP
United Kingdom

Study participating centre

The Christie NHS Foundation Trust
550 Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom

Study participating centre

The Grange University Hospital
Caerleon Road
Cwmbran
NP44 8YN
United Kingdom

Study participating centre

The Royal Victoria Infirmary
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Study participating centre

Torbay Hospital
Newton Road
Torquay
TQ2 7AA
United Kingdom

Study participating centre

University Hospital Southampton
Tremona Road
Southampton
SO16 6YD
United Kingdom

Study participating centre

Victoria Hospital
Hayfield Road
Kirkcaldy
KY2 5AH
United Kingdom

Study participating centre

Warwick Hospital
Lakin Road
Warwick
CV34 5BW
United Kingdom

Study participating centre

Watford General Hospital
Vicarage Road
Watford
WD18 0HB
United Kingdom

Study participating centre

West Suffolk Hospital
Hardwick Lane
Bury St. Edmunds
IP33 2QZ
United Kingdom

Study participating centre

William Harvey Hospital, Ashford
Kennington Road
Willesborough
Ashford
TN24 0LZ
United Kingdom

Study participating centre

Wishaw General Hospital
50 Netherton Street
Wishaw
ML2 0DP
United Kingdom

Study participating centre

Wrexham Maelor Hospital
Croesnewydd Road
Wrexham Technology Park
Wrexham
LL13 7TD
United Kingdom

Study participating centre

Wythenshawe Hospital
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom

Organisation

University of Warwick

Sponsor details

Gibbet Hill Road
Coventry
Coventry
CV4 7AL
England
United Kingdom
+44 247 652 2746
wmssponsorship@warwick.ac.uk

Sponsor type

University/education

Website

http://www2.warwick.ac.uk/

ROR

https://ror.org/01a77tt86

Funder type

Government

Funder name

National Institute for Health Research

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

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Publication and dissemination plan

Trial results will be published as soon as data are analysed. Dissemination will include development of lay summaries and publication in a peer-reviewed journal.

Intention to publish date

03/10/2021

Individual participant data (IPD) sharing plan

The data sharing plans for the current study are unknown and will be made available at a later date

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs