Comparing standard and accelerated weaning from non-invasive breathing support in exacerbation of chronic obstructive pulmonary disease
| ISRCTN | ISRCTN64639614 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64639614 |
| IRAS number | 313485 |
| Secondary identifying numbers | CPMS 53277, IRAS 313485, Protocol v1.1 (05/08/2022) |
- Submission date
- 24/08/2022
- Registration date
- 14/09/2022
- Last edited
- 07/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Every year in the UK, over 141,000 people will be admitted to hospital due to exacerbations of chronic obstructive pulmonary disease (ECOPD). Around one-quarter of these patients develop life-threatening respiratory failure, with a build-up of carbon dioxide (waste gas). Non-invasive ventilation (NIV) involves wearing a tightly-fitted mask connected to a ventilator to help patients breathe out more carbon dioxide.
NIV halves the risk of dying but can cause unpleasant side effects including stomach bloating and skin damage. Once the patient is improving, NIV is gradually removed by giving patients progressively longer periods of time off ventilation. This is called ‘weaning’ and usually takes 3-4 days. Faster weaning should reduce side effects and costs. However shorter treatment may be less effective, and respiratory failure (carbon dioxide build-up) may recur. Currently, there is little evidence to guide a safe process for NIV weaning, with concerns highlighted in a National Confidential Enquiry.
Researchers have recently developed the NIV outcomes score, which predicts the risk of death in NIV-treated patients. They showed that three in four patients have a low or medium risk, and therefore it may be possible to remove the ventilator from this group of patients more quickly. They also noticed big differences between hospitals with respect to duration of weaning and patient relapse rates, highlighting the need for better guidance. They have developed an "accelerated weaning protocol" to support faster weaning from NIV, whilst also ensuring that the approach is consistent within the trial across all hospitals. This will be compared to the current standard approach.
The main question is whether "accelerated weaning" reduces the time required to successfully wean from NIV. If NIV is restarted within 48 hours of removal, this will be considered an unsuccessful weaning attempt and will be included in the time to weaning. Patient outcomes, including any increased risk of death, will be carefully monitored. The researchers will also assess the side effects from NIV, relapse, sleep quality, symptoms, quality of life, readmission into hospital, and costs.
Who can participate?
Patients aged 35 years and over, who are in hospital with ECOPD requiring NIV and have a low or medium risk NIV outcomes score will be considered for participation in the study. To ensure the results apply as widely as possible, patients with a clinical diagnosis of COPD, but without breathing tests to confirm this, will be included, and patients will only be excluded when essential.
What does the study involve?
Those who agree to take part will be randomly allocated by computer to a ‘standard’ or ‘accelerated’ weaning protocol. The standard wean involves increasing the amount of time off NIV over 3-4 days, with a final night on NIV after a full day off NIV. The accelerated wean involves a daily 4-hour trial without NIV under close monitoring. If the carbon dioxide levels in the blood are stable and safe, NIV will be stopped early.
What are the possible benefits and risks of participating?
As things stand, it is not known what the best amount of time is to be on NIV, and practice varies around the country. The researchers cannot guarantee any direct benefits, but by taking part, participants will be helping healthcare professionals about how best to treat their patients in the future, which may include the participants.
The researchers will ask participants some extra questions about how they are feeling, which will take up a short amount of their time both in hospital and after they have gone home. They will try and keep this amount of time to a minimum.
Whichever group patients are randomly assigned to there is a risk of needing the ventilator for longer than anticipated, or extra blood tests. The researchers will always try and keep extra tests to a minimum, patient safety is the priority.
Where is the study run from?
The study is being led by Northumbria Healthcare NHS Foundation Trust, but to ensure the results apply across the NHS, we will include several hospitals across England (UK)
When is the study starting and how long is it expected to run for?
April 2022 to June 2025
Who is funding the study?
National Institute for Health Research, Research for Patient Benefit (UK)
Who is the main contact?
Prof. Stephen Bourke, Stephen.Bourke@northumbria-healthcare.nhs.uk
Contact information
Principal Investigator
Department of Respiratory Medicine
North Tyneside General Hospital
Rake Lane
North Shields
NE29 8NH
United Kingdom
 ORCID ID |
0000-0003-0228-0854 |
|---|---|
| Phone | +44 (0)191 2934026 |
| Stephen.Bourke@northumbria-healthcare.nhs.uk |
Scientific
Department of Respiratory Medicine
North Tyneside General Hospital
Rake Lane
North Shields
NE29 8NH
United Kingdom
| Phone | +44 (0)191 2934026 |
|---|---|
| Stephen.Bourke@northumbria-healthcare.nhs.uk |
Public
Research and Development
North Tyneside General Hospital
Rake Lane
North Shields
NE29 8NH
United Kingdom
| Phone | +44 (0)191 2934087 |
|---|---|
| Jemma.Fenwick@northumbria-healthcare.nhs.uk |
Study information
| Study design | Multi-centre open-label parallel randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled 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 | Standard versus accelerated weaning from non-invasive ventilation (NIV) in chronic obstructive pulmonary disease directed by the NIV outcomes score: a randomised controlled trial |
| Study acronym | NIVOW |
| Study objectives | Daily 4-hour unsupported breathing trials, with the removal of non-invasive ventilation (NIV) if the patient remains clinically and physiologically stable, will shorten the time to successful wean from NIV, compared to the standard protocol in exacerbations of chronic obstructive pulmonary disease (ECOPD) with a low or medium mortality risk. |
| Ethics approval(s) | Approved 08/09/2022, West of Scotland Research Ethics Service (Ward 11, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE, UK, +44 (0)141 314 0212; WosRed@ggc.scot.nhs.uk), ref: 22/WS/0091 |
| Health condition(s) or problem(s) studied | Exacerbation of chronic obstructive pulmonary disease (COPD) |
| Intervention | Patients with exacerbation of COPD requiring NIV who have low or medium risk NIV outcomes scores will be assessed against the full selection criteria detailed below. Consenting patients who meet the eligibility criteria will be independently randomised on a 1:1 basis between the two treatment strategies, performed independently (sealedenvelope.com) using minimisation to ensure groups are balanced for: a) NIV Outcomes score: low or medium risk; b) Site; c) HCO₃-: <28 or ≥28; d) pH: <7.18 or ≥7.18; e) previous NIV: yes or no. Standard weaning protocol: Progressively longer periods off NIV, determined by arterial blood gas (or capillary blood gas), with a final night on NIV after a full day off NIV. Accelerated weaning protocol: Daily 4-hour weaning trial, success confirmed by arterial blood gas, with additional transcutaneous carbon dioxide monitoring. The weaning time endpoint is the date and time that the NIV mask is removed from the patient’s face for the final time (provided NIV does not need to be recommenced within 48 hours). |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Time to successful weaning: duration from the baseline arterial blood gas confirming selection criteria met, to final removal of the ventilator. Death on NIV precludes weaning and will be captured in a competing risk analysis. |
| Secondary outcome measures | 1. Relapse requiring NIV (defined as recurrent acute hypercapnic respiratory failure (AHRF) >48 hours after removal of the ventilator) 2. Total duration of ventilation measured from the time the NIV mask is applied to NIV mask removal 3. Length of hospital stay from arrival to discharge measured using medical records/hospital patient administration system 4. NIV complications (incidence and severity) in hospital, measured by daily recording 5. Patient-reported outcome measures at days 7, 30 and 90 post-randomisation: 5.1. How breathless the patient feels, measured using the Modified Borg dyspnoea scale 5.2. Sputum clearance measured using a visual analogue scale 5.3. How well or poorly the patient feels they have slept the previous night, measured using the Richards-Campbell sleep questionnaire (all measured days 1 to 5 from the start of weaning) 5.4. Patient’s mood for anxiety and depression measured using the Hospital Anxiety and Depression Scale (HADS) pre-discharge 5.5. Quality of life related to COPD measured using the St Georges Respiratory Questionnaire for COPD (SGRQ-C) 5.6. Quality of life measured using EQ-5D-5L 6. Mortality in-hospital and 90-days post-randomisation measured using medical and GP records/electronic patient administration system 7. Readmissions 30-days post-discharge measured using patient self-completed health resource use diary and verified with hospital electronic patient administration system and primary care records 8. Health economic analysis: 8.1. Costs to the NHS in terms of provision of the interventions (both on a respiratory support unit and a critical care unit) and cost implications of subsequent resource utilisation up to 90 days follow-up measured by patient health resource use diaries 8.2. Cost-utility analysis using EQ-5D-5L quality-adjusted life years (QALYs) measured by questionnaire at 30 and 90 days post-randomisation 9. Responder analysis within the accelerated weaning group to identify predictors of success/failure |
| Overall study start date | 01/04/2022 |
| Completion date | 30/06/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 35 Years |
| Sex | Both |
| Target number of participants | 164 |
| Total final enrolment | 164 |
| Key inclusion criteria | 1. Clinical diagnosis of Exacerbation of Chronic Obstructive Pulmonary Disease, complicated by acute hypercapnic respiratory failure (pH <7.35 and PaCO₂ >6.5 kPa) 2. Age 35 years or over 3. Smoking history of 10 or more pack years 4. Low or medium risk Non-Invasive Ventilation (NIV) Outcomes score 5. Provision of acute NIV for 24 hours or longer 6. Correction of respiratory acidaemia 7. PaCO₂ <8 kPa, or PaCO₂ 8-9 kPa with at least a 20% fall in PaCO₂ from pre-NIV baseline value 8. Able to tolerate 60 minutes of unsupported breathing, confirmed by arterial blood gas (ABG) 9. Participants must be randomised within 24 hours of meeting the weaning criteria (based on the time of the qualifying ABG) |
| Key exclusion criteria | 1. Poor tolerance of NIV likely to limit adherence to protocol 2. Receiving home ventilation on admission, or planned referral for home ventilation on discharge 3. Inability to provide informed consent 4. Failure of another organ requiring level 2 or 3 organ support 5. Clinically significant pulmonary fibrosis 6. Metastatic cancer, advanced haematological malignancy, or other serious comorbidities, which may influence survival or decisions about ventilation within the time frame of the trial (3 months) |
| Date of first enrolment | 19/09/2022 |
| Date of final enrolment | 02/04/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Cramlington
NE23 6NZ
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
Stockton-on-tees
TS19 8PE
United Kingdom
Bath
BA1 3NG
United Kingdom
Leeds
LS9 7TF
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Leicester
LE3 9QP
United Kingdom
Sponsor information
Hospital/treatment centre
Unit 7/8, Silver Fox Way
Cobalt Business Park
Newcastle Upon Tyne
NE27 0QJ
England
United Kingdom
| Phone | +44 (0)344 811 8111 |
|---|---|
| ResearchAndDevelopment@northumbria-healthcare.nhs.uk | |
| Website | https://www.northumbria.nhs.uk/ |
"ROR" |
https://ror.org/01gfeyd95 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Research for Patient Benefit Programme, RfPB
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Results will be shared with participants, presented at conferences and published in a high-impact peer-reviewed medical journal. The researchers will engage the relevant British Thoracic Society Specialist Advisory Groups, British Lung Foundation (reaching people with COPD). |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be available upon request from the Chief Investigator Prof. Stephen Bourke (Stephen.Bourke@northumbria-healthcare.nhs.uk) from 6 months after the main papers related to this trial have been published, and provided the intended purpose and planned analysis are discussed and agreed in advance. Only anonymised data will be shared. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 1.2 | 03/01/2023 | 02/01/2024 | No | No |
| Statistical Analysis Plan | version 1.6 | 27/01/2025 | 07/02/2025 | No | No |
| Statistical Analysis Plan | version 1.7 | 13/02/2025 | 21/02/2025 | No | No |
Additional files
Editorial Notes
07/05/2025: The following changes were made:
1. The overall study end date was changed from 31/05/2025 to 30/06/2025.
2. The total final enrolment was added.
3. The recruitment end date was changed from 28/02/2025 to 02/04/2025.
21/02/2025: A statistical analysis plan combined with a health economic analysis plan v1.7 file was uploaded
07/02/2025: Derriford Hospital was removed from the study participating centres and a statistical analysis plan combined with a health economic analysis plan v1.6 file was uploaded.
02/01/2024: The following changes have been made:
1. The recruitment end date has been changed from 31/08/2024 to 28/02/2025.
2. A protocol file has been uploaded.
04/01/2023: The trial participating centre Glenfield General Hospital was added.
09/09/2022: Trial's existence confirmed by the NIHR.
