Condition category
Respiratory
Date applied
20/01/2016
Date assigned
14/04/2016
Last edited
15/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
The researchers running this study want to test a new way of treating respiratory failure. When people are very ill their lungs often stop working. This is called respiratory failure. As a result, breathing becomes difficult and they need to be treated in an intensive care unit (ICU) where they will be connected to a machine to help their breathing. This is called mechanical ventilation. Respiratory failure is common in the UK; about 100,000 people each year need treatment with mechanical ventilation. Almost half of these patients die. Although there is evidence that mechanical ventilation does save lives, it can be linked with damage to the lungs. A mechanical ventilator acts like bellows as air is forced into the lungs under pressure. If the pressure needed to help the patient breathe is too high this can cause lung damage. New devices are now available to help patients breathe. These devices help remove carbon dioxide from the patient’s blood, which is one of the main functions of the lungs. This may allow more gentle mechanical ventilation. This more gentle ventilation may cause less harm to the lungs and improve the outcome of patients with respiratory failure. These new devices involve a tube called a catheter being placed in a large blood vessel called a vein. Blood passes from the patient through the device where it is “washed” to remove carbon dioxide before it is returned to the patient. This is called extracorporeal carbon dioxide removal. Kidney dialysis uses very similar equipment. Kidney dialysis is common for patients admitted to intensive care units and doctors are used to putting this type of catheter into patients on the ICU. These new devices may help doctors and nurses care for patients with respiratory failure, but there is not enough information about the devices to help them decide whether they are helpful or not. This study investigates whether they work or not.

Who can participate?
Patients aged at least 16 with respiratory failure and have been admitted to an intensive care unit (ICU).

What does the study involve?
Patients are randomly allocated to one of two groups. Those in group 1 are given the best level of care that is advised by current NHS guidelines. Those in group 2 also receive the best level of care but are, in addition, also treated with the device to remove carbon dioxide from their blood to allow the pressure in their lungs to be reduced. The treatment a patient receives is decided at random by a computer programme and at the end of the study researchers will know whether this new device reduces death from respiratory failure and look at the long-term survival and quality of life of the patients in the study. The cost of using the new device compared to usual care is also investigated.

What are the possible benefits and risks of participating?
Taking part in this study may have contributed to improved treatment of patients with acute respiratory failure in the future. ECCO2R is a procedure that is used in the UK in patients who have respiratory failure. A previous study found ECCO2R was well tolerated and associated with few side effects (about one in every 40 patients); however all procedures have potential side effects. Side effects of ECCO2R include complications with catheter placement such as blood vessel damage, dislodgement, infection and an increased risk of bleeding. Catheter insertion is similar to other tubes that are placed in the neck or groin veins during any ICU admission with respiratory failure and carry the same level of risk. To minimise such risks, the catheter is inserted with the help of ultrasound. Ultrasound is a medical test that uses soundwaves to capture live images from the inside of the body; this helped the doctor to directly see the blood vessel and ensure a more accurate insertion of the catheter. The potential complications whilst ECCO2R is running are uncommon and include clot formation within the device or the blood vessel (reduced by anticoagulation) or air entrainment into the device (reduced by safety mechanisms within the device). Bleeding can also occur in any patient placed on blood thinning agents (anticoagulation) and although uncommon (less than one in every 50 patients) can be significant, requiring blood transfusion and can potentially lead to serious bleeding. To minimise this risk of bleeding we regularly measured the effect of blood thinning agents on the ability of the blood to clot. All participants in the trial are monitored to ensure that any side effects are promptly picked up. ECCO2R would be stopped if they occur.

Where is the study run from?
The study is run in at least 40 ICUs in NHS hospitals in the UK.

When is the study starting and how long is it expected to run for?
December 2015 to April 2021

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

Who is the main contact?
Miss Colette Jackson
REST@nictu.hscni.net

Trial website

Contact information

Type

Public

Primary contact

Miss Colette Jackson

ORCID ID

http://orcid.org/0000-0001-7814-0749

Contact details

NICTU
1st Floor Elliott Dynes Building
Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
00 44 (0) 28 90635794
REST@nictu.hscni.net

Additional identifiers

EudraCT number

2015-005280-17

ClinicalTrials.gov number

NCT02654327

Protocol/serial number

15084DMcA-AS

Study information

Scientific title

PRotective vEntilation with veno-venouS lung assisT in respiratory failure

Acronym

The REST Trial

Study hypothesis

In adult patients who require invasive mechanical ventilation for acute hypoxaemic respiratory failure, VV-ECCO2R and lower tidal volume ventilation results in reduced mortality.

Ethics approval

Office of Research Ethics Committees Northern Ireland, 14/03/2016 (England and Wales),

Study design

Randomised, allocation concealed, controlled, open, pragmatic clinical and cost effectiveness trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

See additional files

Condition

Acute hypoxaemic respiratory failure

Intervention

Intervention treatment will last for up to 7 days, patient follow up will be for 12 months.

INTERVENTION ARM: A dual lumen catheter will be inserted into a central vein and veno-venous extracorpoeal carbon dioxide removal (vv-ECCO2R) initiated as soon as possible and no later than 8 hours after randomisation. The pump blood flow rate and gas flow through the vv-ECCO2R device will be set up according to study manual. Thereafter tidal volumes on mechanical will be gradually decreased to less than or equal to 3ml/kg predicted body weight maintaining arterial pH of greater than 7.2 and plateau pressure less than or equal to 25cm H2O. A heparin infusion is used as anticoagulation to prevent circuit clotting. vv-ECCO2R will be considered for weaning after a minimum of 48 hours when weaning criteria are achieved.

CONTROL ARM: Standard management of acute hypoxamic respiratory failure with mechanical ventilation set according to the ARDSNetwork trial aiming for tidal volumes less than 6ml/kg predicted body weight and plateau pressure less than or equal to 30cm H2O.

Intervention type

Device

Phase

Drug names

Primary outcome measures

Mortality at 90 days after randomisation

Secondary outcome measures

1. Tidal volume (ml/kg PBW) at day 1 and day 3 after randomisation
2. Ventilator free days at 28 days after randomisation
3. Duration of ventilation in survivors after randomisation at 28 days
4. Need for ECMO up to Day 7
5. Mortality rate at 28 days, 6 months and 1 year after randomisation
6. Health Related Quality of Life (HRQoL) at 6 months and 1 year after randomisation
7. Adverse event rate
8. Health and Social Care Service costs at 6 months and 1 year
9. Saint George’s Respiratory Questionnaire (SGRQ) at 1 year and need for home oxygen at 6 months and 1 year after randomisation

Overall trial start date

01/12/2015

Overall trial end date

01/04/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Invasive mechanical ventilation using PEEP ≥ 5cmH2O*
2. Acute and potentially reversible cause of acute respiratory failure as determined by the treating physician
3. Within 48 hours of the onset of hypoxaemia as defined by PaO2/FiO2 ≤ 20kPa**

*Recommended on low tidal volume ventilation ≤ 6 ml/kg PBW
**Requires two ABG with a PaO2/FiO2 ≤ 20kPa separated by at least 6 hours. 48 hour duration begins at the time of 2nd ABG demonstrating PaO2/FiO2 ratio ≤ 20kPa

(ABGs with PaO2/FiO2 ≥ 20kPa are permitted between the two trial inclusion ABGs).

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1120

Participant exclusion criteria

1. Age <16 years old
2. Intubated and mechanically ventilated via an endotracheal or tracheostomy tube ≥ 7 days (168 hours) up to the time of randomisation
3. Ability to maintain Vt to ≤ 3ml/kg PBW while maintaining pH ≥ 7.2 as determined by the treating physician
4. Receiving, or decision to commence, ECMO in the next 24 hours.
5. Mechanical ventilation using HFOV or APRV
6. Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure.
7. Acute respiratory failure fully explained by left ventricular failure or fluid overload (May be determined by clinical assessment or echocardiography/cardiac output monitoring).
8. Left ventricular failure requiring mechanical support
9. Contra-indication to limited systemic anticoagulation with heparin
10. Unable to obtain vascular access to a central vein (internal jugular or femoral vein)
11. Inferior vena cava filter (if using femoral vein catheter)
12. Consent declined
13. Treatment withdrawal imminent within 24 hours
14. Patients not expected to survive 6 months on basis of premorbid health status
15. DNAR (Do Not Attempt Resuscitation) order in place
16. Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)
17. Severe chronic liver disease (Child Pugh >11)
18. Platelet count < 40,000 mm3
19. Previously enrolled in the REST trial

Recruitment start date

23/04/2016

Recruitment end date

01/12/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Trial participating centre

St Thomas' Hospital
London
SE1 7EH
United Kingdom

Trial participating centre

Kings College Hospital
London
SE5 9RS
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Manchester
M13 9WL
United Kingdom

Trial participating centre

Leeds Teaching Hospital
Great George Street
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Hammersmith Hospital
London
W12 0HS
United Kingdom

Trial participating centre

Charing Cross Hospital
London
W6 8RF
United Kingdom

Trial participating centre

Royal Infirmary of Edinburgh
Edinburgh
EH16 4SB
United Kingdom

Trial participating centre

Birmingham Heartlands Hospital & Good Hope
Birmingham
B9 5SS
United Kingdom

Trial participating centre

Wythenshawe Hospital
Manchester
M23 9LT
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Royal Liverpool University Hospital
Liverpool
L7 8XP
United Kingdom

Trial participating centre

Royal Free Hospital
London
NW3 2QG
United Kingdom

Trial participating centre

University Hospital of Wales
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Newcastle
NE1 4LP
United Kingdom

Trial participating centre

Freemans Hospital
Newcastle
NE7 7DN
United Kingdom

Trial participating centre

Papworth Hospital
Cambrideshire
CB23 3BE
United Kingdom

Trial participating centre

Bristol Royal Infirmary
Bristol
BS2 8HW
United Kingdom

Trial participating centre

Glenfield Hospital
Leicester
LE3 9QP
United Kingdom

Trial participating centre

Royal Blackburn Hospital
Blackburn
BB2 3HH
United Kingdom

Trial participating centre

John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Trial participating centre

Great Western Hospital
Swindon
SN3 6BB
United Kingdom

Trial participating centre

Royal Berkshire Hospital
Reading
RG1 5AN
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Sandwell General Hospital
West Bromwich
B71 4HJ
United Kingdom

Trial participating centre

Southmead Hospital
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Whiston Hospital
Liverpool
L35 5DR
United Kingdom

Trial participating centre

Poole Hospital
Poole
BH15 2JB
United Kingdom

Trial participating centre

Royal Derby Hospital
Derby
DE22 3NE
United Kingdom

Trial participating centre

Royal Cornwall Hospital
Cornwall
TR1 3LJ
United Kingdom

Trial participating centre

Kettering General Hospital
Kettering
NN16 8UZ
United Kingdom

Trial participating centre

Worcester Royal Hospital
Worcester
WR5 1DD
United Kingdom

Trial participating centre

New Cross Hospital
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

St Georges Hospital
Tooting
SW17 0QT
United Kingdom

Trial participating centre

Altnagelvin Hospital
Derry
BT47 6SB
United Kingdom

Trial participating centre

Victoria Hosptial
Kircaldy
KY2 5AH
United Kingdom

Trial participating centre

Royal Stoke Hospitals
Stoke
ST4 6QG
United Kingdom

Trial participating centre

James Cook University Hospital
Middlesborough
TS4 3BW
United Kingdom

Trial participating centre

Royal Infirmary
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Norfolk & Norwich University Hospital
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Pinderfields Hospital
Wakefield
WF1 4DG
United Kingdom

Trial participating centre

Medway Maritime Hospital
Gillingham, Kent
ME7 5NY
United Kingdom

Trial participating centre

Aintree University Hospital
Liverpool
L9 7AL
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Royal Brompton Hospital
London
SW3 6NP
United Kingdom

Trial participating centre

Antrim Area Hospital
Antrim
BT41 2RL
United Kingdom

Trial participating centre

Royal London Hospital
London
E1 1BB
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Glasgow
G51 4TF
United Kingdom

Trial participating centre

West Suffolk Hospital
Suffolk
IP33 2QZ
United Kingdom

Trial participating centre

Chelsea & Westminster Hospital
London
SW10 9NH
United Kingdom

Sponsor information

Organisation

Belfast Health & Social Care Trust

Sponsor details

Research Office
2nd Floor King Edward Building
Royal Hospitals
Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

We plan to publish our trial protocol and statistical analysis plan to ensure transparency in our methodology. The study findings will be presented at national and international meetings with abstracts on-line. Presentation at these meetings will ensure that results and any implications quickly reach all of the UK intensive care community. This will be facilitated by our investigator group which includes individuals in executive positions in the UK Intensive Care Society. In accordance with the open access policies proposed by the NIHR we aim to publish the clinical findings of the trial as well as a paper describing the cost-effectiveness in the NHS setting in high quality peer-reviewed open access (via Pubmed) journals. This will secure a searchable compendium of these publications and make the results readily accessible to the public, health care professionals and scientists. A final report will also be published in the NIHR HTA journal.

We will actively promote the findings of the study to journal editors and critical care opinion leaders to ensure the findings are widely disseminated (e.g. through editorials and conference presentations) and are included in future guidelines

Intention to publish date

31/12/2021

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

15/04/2016: Added participant information sheet