A new way of treating patients with respiratory failure
| ISRCTN | ISRCTN31262122 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN31262122 |
| EudraCT/CTIS number | 2015-005280-17 |
| ClinicalTrials.gov number | NCT02654327 |
| Secondary identifying numbers | 15084DMcA-AS |
- Submission date
- 20/01/2016
- Registration date
- 14/04/2016
- Last edited
- 17/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
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 many ICUs in NHS hospitals in the UK.
When is the study starting and how long is it expected to run for?
June 2016 to April 2022
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Miss Colette Jackson
REST@nictu.hscni.net
Contact information
Public
NICTU, 1st Floor Elliott Dynes Building
Royal Hospitals, Grosvenor Road
Belfast
BT12 6BA
United Kingdom
 ORCID ID |
0000-0001-7814-0749 |
|---|---|
| Phone | 00 44 (0) 28 90635794 |
| REST@nictu.hscni.net |
Study information
| Study design | Randomised, allocation concealed, controlled, open, pragmatic clinical and cost effectiveness trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | ISRCTN31262122_PIS.pdf |
| Scientific title | PRotective vEntilation with veno-venouS lung assisT in respiratory failure |
| Study acronym | The REST Trial |
| Study objectives | 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(s) | Current ethics approval as of 23/05/2017: 1. South Berkshire REC England, Wales and Northern Ireland, 14/03/2016, ref: 16/SC/0089 2. Scotland A REC, Scotland, 23/03/2016, ref:16/SS/0048 Previous ethics approval: Office of Research Ethics Committees Northern Ireland, 14/03/2016 (England and Wales) |
| Health condition(s) or problem(s) studied | Acute hypoxaemic respiratory failure |
| Intervention | Current interventions as of 05/03/2019: 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 within 8-24 hours of consent. 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 approximately 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. Previous interventions: 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Not provided at time of registration |
| Primary outcome measure | Mortality at 90 days after randomisation |
| Secondary outcome measures | Current secondary outcome measures as of 23/05/2017: 1. Tidal volume (ml/kg PBW) at day 1 and day 3 after randomisation (updated 05/03/2019: at day 2 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 10. Post Traumatic Stress Syndrome Questionnaire (PTSS-14) at 1 year after randomisation 11. Montreal Cognitive Assessment (MoCA-BLIND) or AD8 Dementia Screening Interview (AD8) at 1 year after randomisation Previous 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 Added 05/03/2019: Exploratory outcomes: Right heart function as determined by echocardiography during 6ml/kg PBW and ≤3ml/kg PBW tidal volume ventilation (ECHO data will only be collected at a selected number of sites) |
| Overall study start date | 01/03/2016 |
| Completion date | 30/04/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 1120 |
| Total final enrolment | 412 |
| Key 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. Added 05/03/2019: Site will then have a further 8 – 24 hours to randomise and administer the intervention. Added 23/05/2017: The onset of hypoxaemia is from time of intubation and invasive ventilation. (ABGs with PaO2/FiO2 ≥ 20kPa are permitted between the two trial inclusion ABGs). |
| Key exclusion criteria | Current exclusion criteria as of 23/05/2017: 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 90 days on basis of premorbid health status 15. DNAR (Do Not Attempt Resuscitation) order in place (added 05/03/2019: excluding advance directives) 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 (added 05/03/2019: prior to catheter insertion) 19. Previously enrolled in the REST trial 20. Prisoners Previous 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 |
| Date of first enrolment | 01/06/2016 |
| Date of final enrolment | 11/02/2020 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Belfast
BT12 6BA
United Kingdom
SE1 7EH
United Kingdom
SE5 9RS
United Kingdom
M13 9WL
United Kingdom
Leeds
LS1 3EX
United Kingdom
W12 0HS
United Kingdom
W6 8RF
United Kingdom
EH16 4SB
United Kingdom
B9 5SS
United Kingdom
M23 9LT
United Kingdom
Birmingham
B15 2TH
United Kingdom
L7 8XP
United Kingdom
NW3 2QG
United Kingdom
CF14 4XW
United Kingdom
CB2 0QQ
United Kingdom
NE1 4LP
United Kingdom
CB23 3BE
United Kingdom
BB2 3HH
United Kingdom
OX3 9DU
United Kingdom
RG1 5AN
United Kingdom
B71 4HJ
United Kingdom
BH15 2JB
United Kingdom
TR1 3LJ
United Kingdom
WR5 1DD
United Kingdom
WV10 0QP
United Kingdom
SW17 0QT
United Kingdom
BT47 6SB
United Kingdom
ST4 6QG
United Kingdom
G4 0SF
United Kingdom
NR4 7UY
United Kingdom
WF1 4DG
United Kingdom
L9 7AL
United Kingdom
BT41 2RL
United Kingdom
E1 1BB
United Kingdom
G51 4TF
United Kingdom
SW10 9NH
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Belfast
BT9 7JB
United Kingdom
Harrow
HA1 3UJ
United Kingdom
PO6 3LY
United Kingdom
Chelsea
London
SW3 6NP
United Kingdom
Newport
NP20 2UB
United Kingdom
Oldham
OL1 2JH
United Kingdom
Fitzrovia
London
NW1 2BU
United Kingdom
York
YO31 8HE
United Kingdom
Sponsor information
Hospital/treatment centre
Research Office, 2nd Floor King Edward Building
Royal Hospitals, Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom
"ROR" |
https://ror.org/02tdmfk69 |
|---|
Funders
Funder type
Not defined
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 | 31/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from rest@nictu.hscni.net or call 028 90635794 and ask for a member of the REST team |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 15/04/2016 | No | Yes | ||
| Results article | 21/09/2021 | 20/05/2022 | Yes | No | |
| Protocol file | version 6.0 | 15/04/2021 | 23/08/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| HRA research summary | 28/06/2023 | No | No | ||
| Other publications | cost-utility analysis | 23/08/2023 | 17/10/2023 | Yes | No |
Additional files
- ISRCTN31262122_PIS.pdf
- - participant information sheet, uploaded 15/04/2016
- ISRCTN31262122_PROTOCOL_V6.0_15Apr21.pdf
Editorial Notes
17/10/2023: Publication reference added.
23/08/2022: Protocol file uploaded.
20/05/2022: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added.
04/03/2022: The overall trial end date has been changed from 01/08/2021 to 30/04/2022 and the plain English summary has been updated accordingly.
07/04/2020: The recruitment end date was changed from 01/05/2020 to 11/02/2020.
05/03/2019: The interventions, secondary outcome measures, inclusion and exclusion criteria, and trial participating centres were updated.
23/05/2017: Updated ethics approval secondary outcome measures and the Plain English Summary (dates). Added participant level data sharing statement. Removed Southampton General Hospital, Freemans Hospital, Bristol Royal Infirmary, Glenfield Hospital, Great Western Hospital, Southmead Hospital, Whiston Hospital, Royal Derby Hospital, Victoria Hospital, Kircaldy, James Cook University Hospital, Medway Maritime Hospital, Royal Sussex County Hospital, Royal Brompton, West Suffolk Hospital as trial participating centres. Changed Leeds Teaching Hospital to St James Hospital Leeds. Overall trial dates changed from 01/12/2015 - 01/04/2021 to 01/03/2016 - 01/08/2021. Recruitment dates changed from 23/04/2016 - 01/12/2019 to 01/06/2016 - 01/05/2020. Updated the participant inclusion and exclusion criteria.
15/04/2016: Added participant information sheet
