Humidified nasal high flow to improve clinical outcomes following severe exacerbations of chronic obstructive pulmonary disease

ISRCTN	ISRCTN15949009
DOI	https://doi.org/10.1186/ISRCTN15949009
ClinicalTrials.gov (NCT)	NCT03899558
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	CPMS 40985
Sponsor	Guy's and St Thomas' NHS Foundation Trust
Funder	NIHR Academy; Grant Codes: DRF-2018-11-ST2-037

Submission date: 18/02/2019
Registration date: 19/02/2019
Last edited: 07/01/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease, affecting 1.2 million people in the UK. COPD patients suffer with episodes of worsening breathing symptoms called exacerbations. Exacerbations occur more often as the disease progresses and are a leading cause of emergency hospitalisation. Patients recovering from exacerbations are at high risk of deteriorating, with one quarter readmitted to hospital within 30 days. COPD thus imposes immense burdens on the National Health Service and patients. This study will investigate the effects of using humidified nasal high-flow (HNHF) during recovery from severe COPD exacerbations. HNHF delivers warmed, humidified air under flows of up to 60 litres per minute through a nasal interface. This has been shown to improve clinical outcomes, including exacerbation frequency, hospitalisations, breathlessness and quality of life amongst COPD patients with respiratory failure. It is thought to achieve this by improving secretion clearance and providing positive airways pressure which supports the breathing system.

Who can participate?
Patients admitted to St Thomas’ Hospital, London with COPD exacerbations

What does the study involve?
Before discharge, participants are randomly allocated to receive either usual care alone or usual care plus a HNHF device, which they are trained to use for a regular period daily. Usual care includes inhalers, steroids and may include antibiotics. Participants are followed up for 30 days after hospital discharge using weekly assessments, daily symptom diaries and wrist-worn watch-like devices that detect physical activity. This enables evaluation of the clinical effects of HNHF on re-exacerbations, readmissions, breathlessness, physical activity and quality of life. Device usage is also measured. Participants who receive devices are interviewed to explore their experiences. After the 30-day home follow-up period, a sub-group of participants undergoes detailed breathing tests during and after exercise to explore the effects of HNHF on the respiratory system.

What are the possible benefits and risks of participating?
It is known that HNHF reduces frequency of hospital admissions and exacerbations and improves symptoms and quality of life in stable COPD patients. This study investigates whether it also has these beneficial effects in COPD patients recovering from severe exacerbations. There are no reported adverse side effects of using the device.

Where is the study run from?
Guy’s and St Thomas’ NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
September 2018 to August 2021

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

Who is the main contact?
1. Prof. Nicholas Hart
Nicholas.hart@gstt.nhs.uk
2. Dr Rebecca D’Cruz
Rebecca.DCruz@gstt.nhs.uk

Contact information

Prof Nicholas Hart
Scientific

Lane Fox Research Unit
St Thomas’ Hospital
Westminister Bridge Road
London
SE1 7EH
United Kingdom

Phone	+44 (0)207 188 8070
Email	Nicholas.hart@gstt.nhs.uk

Dr Rebecca D'Cruz
Scientific

Lane Fox Research Unit
St Thomas’ Hospital
Westminister Bridge Road
London
SE1 7EH
United Kingdom

ORCID ID	0000-0001-5245-9911
Phone	+44 (0)207 188 8070
Email	Rebecca.DCruz@gstt.nhs.uk

Study information

Primary study design	Interventional
Study design	Randomized controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	The role of nasal high-flow to reduce 30-day hospital readmissions following severe exacerbations of chronic obstructive pulmonary disease: a mixed-methods feasibility study
Study acronym	NHF Post-AECOPD
Study objectives	The primary objective is to estimate the effects of humidified nasal high flow on clinical outcomes that are important to patients and healthcare services (30-day hospital readmission, re-exacerbation, breathlessness, health-related quality of life and physical activity), explore patients’ experiences of using the device and understand the effects it has on the breathing system during physical exertion.
Ethics approval(s)	Approved 20/03/2019, London – Harrow Research Ethics Committee, Bristol HRA Centre, Level 3, Block B Whitefriars, Lewins Mead, Bristol, BS1 2NT, Tel: +44 (0)2071048056, Email: nrescommittee.london-harrow@nhs.net, ref: 19/LO/0194
Health condition(s) or problem(s) studied	Chronic obstructive pulmonary disease
Intervention	Patients admitted to St Thomas’ Hospital, London with COPD exacerbations will be recruited. Prior to discharge, participants will be randomised to receive either usual care alone or usual care plus a nasal high-flow (NHF) device, which they will be trained to use for a regular period daily. Usual care includes inhalers, and steroids and may include antibiotics. Participants will be followed up for 30 days after hospital discharge using weekly assessments, daily symptom diaries and wrist-worn watch-like devices that detect physical activity. This will enable evaluation of the clinical effects of NHF on re-exacerbations, readmissions, breathlessness, physical activity and quality of life. Device usage will also be quantified. Participants who receive devices will be interviewed to explore their experiences. After the 30-day home follow-up period, a sub-group of participants will undergo detailed breathing tests during and after exercise to explore the effects of NHF on the respiratory system.
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Nasal high-flow (NHF) device
Primary outcome measure(s)	Estimate of the standard deviation for and possible effect size of 30-day hospital readmission to inform the design of a Phase III multicentre RCT: measured using symptom diaries and medical records at weeks 1, 2, 3, 4 following hospital discharge
Key secondary outcome measure(s)	Current secondary outcome measures as of 22/03/2019: Feasibility: 1. Recruitment rate of eligible patients, measured using the number of eligible patients consenting to participate in the study during the period of recruitment. 2. Adherence with completion of outcome measures, measured by reviewing adherence to the study protocol following completion of individual participants’ study completion 3. Participant’s NHF device usage, measured from the device following individual participants’ study completion Clinical: obtaining estimates of standard deviations and possible effect size of: 1. Admission and non-admission re-exacerbation, measured using symptom diaries at weeks 1, 2, 3, 4 2. Breathlessness, measured daily using symptom diaries, modified Borg and VAS scores for 30 days following hospital discharge and weekly Multidimensional Dyspnoea Profile (MDP) in weeks 1, 2, 3, 4 3. Physical activity, measured continuously using wrist-worn physical activity monitors for the 30-day follow-up period 4. Health-related quality of life, measured using COPD Assessment Test and Clinical COPD Questionnaire at admission, discharge and weekly at weeks 1, 2, 3, 4 5. Lung function, measured using weekly measurements of spirometry at weeks 1, 2, 3, 4 Acceptability of NHF, assessed using qualitative evaluation – a semi-structured interview at week 4 Proof-of-concept sub-study: 1. Inspiratory capacity, measured during incremental exercise testing 2. Breathlessness, measured using mBorg score and MDP before, during and after exercise testing 3. Neural respiratory drive, measured continuously using electromyography during exercise testing 4. Pulmonary mechanics, including pulmonary pressures and flow, measured continuously using a pressure transducer and pneumotachograph during exercise testing 4. Time to recover from maximal breathlessness, measured with a timer, as time from maximal mBorg score to pre-exercise baseline score Previous secondary outcome measures: Feasibility: 1, Recruitment rate of eligible patients, measured using the number of eligible patients consenting to participate in the study during the period of recruitment. 2. Adherence with completion of outcome measures, measured by reviewing adherence to the study protocol (completion of all measured variables) following completion of individual participants’ study completion 3. Participant’s NHF device usage, measured directly from the device following individual participants’ study completion Clinical: obtaining estimates of standard deviations and possible effect size of: 1. Non-admission re-exacerbation, measured using symptom diaries at weeks 1, 2, 3, 4 2. Breathlessness, measured daily using symptom diaries, modified Borg and VAS scores for 30 days following hospital discharge and weekly Multidimensional Dyspnoea Profile (MDP) in weeks 1, 2, 3, 4 3. Physical activity, measured continuously using wrist-worn physical activity monitors for the 30-day follow-up period 4. Health-related quality of life, measured using COPD Assessment Test, Clinical COPD Questionnaire at admission, discharge and weekly at weeks 1, 2, 3, 4 5. Lung function, measured using weekly measurements of spirometry at weeks 1, 2, 3, 4 Acceptability of NHF, assessed using qualitative evaluation – a semi-structured interview at week 4 Proof-of-concept sub-study: 1. Peak exercise capacity, measured using peak work during maximal exercise testing 2. Breathlessness, measured during mBorg score and MDP during exercise testing 3. Neural respiratory drive, measured continuously using electromyography during exercise testing 4. Time to recover from maximal breathlessness, measured with a timer, time from maximal mBorg score to pre-exercise baseline score
Completion date	01/08/2021

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	80
Total final enrolment	18
Key inclusion criteria	1. Emergency hospital admission with a primary diagnosis of AECOPD 2. Aged 40-80 years 3. > = 10 pack year smoking history 4. Body mass index < = 35kg/m2 5. Cognitively and linguistically able to follow English instructions, provide informed consent and complete the study protocol 6. To be discharged home following the hospitalisation in a home environment deemed safe by the investigator to perform home assessments 7. Patient lives in the catchment area served by the Integrated Respiratory Team at Guy’s and St Thomas’ NHS Foundation Trust
Key exclusion criteria	1. Chest radiograph shows pneumothorax 2. Requirement for acute NIV during index hospitalisation or established on home PAP 3. Significant chronic respiratory failure (PaCO2 > 7.0) 4. Clinically significant obstructive sleep apnoea requiring treatment 5. Allergies to latex, metals or local anaesthetic 6. Broken or inflamed skin at the second intercostal space parasternal chest wall areas 7. Psychological or social factors that would impair compliance with the study protocol 8. Any major non-COPD chronic co-morbidity that may contribute significantly to risk of readmission, including (but not limited to) severe heart failure (left ventricular ejection fraction < 30%), malignancy (active treatment or palliation), end stage renal failure and significant neuromuscular disease 9. Planned travel away from home in the 30-day post-discharge period
Date of first enrolment	01/04/2019
Date of final enrolment	24/03/2021

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Guy’s and St Thomas’ NHS Foundation Trust

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

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Published as a supplement to the results publication
IPD sharing plan	The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		06/01/2025	07/01/2025	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

07/01/2025: Publication reference added.
09/09/2022: The following changes have been made:
1. The intention to publish date has been changed from 01/08/2022 to 01/01/2023.
2. The final enrolment number has been changed from 20 to 18.
14/04/2021: The ClinicalTrials.gov number was added.
09/04/2021: Recruitment for this study is no longer paused and the following changes have been made:
1. The recruitment end date has been changed from 01/04/2021 to 24/03/2021.
2. The total final enrolment number has been added.
21/04/2020: Due to current public health guidance, recruitment for this study has been paused.
19/07/2019: The ethics approval was added.
22/03/2019: The condition has been changed from "Specialty: Respiratory Disorders, Primary sub-specialty: Chronic Obstructive Pulmonary Disease; Health Category: Respiratory; Disease/Condition: Chronic lower respiratory diseases" to "Chronic obstructive pulmonary disease" following a request from the NIHR.
22/03/2019: The secondary outcome measures were updated.
21/02/2019: Contact details updated.