Exacerbation prevention in patients with both chronic obstructive pulmonary disease and obstructive sleep apnoea

Plain English summary of protocol

Background and study aims
Patients with chronic obstructive pulmonary disease-obstructive sleep apnoea (COPD-OSA) overlap syndrome have higher rates of COPD exacerbations compared to patients with similar severity COPD without OSA. It is currently unknown whether treating OSA in those with COPD-OSA overlap reduces COPD exacerbation rates. The randomised controlled trial will aim to determine whether giving PAP therapy to patients with COPD-OSA overlap will reduce exacerbations of COPD. Patients with COPD-OSA overlap will be randomised into one of two groups: a) PAP therapy in addition to usual care for COPD compared to b) Usual care for COPD alone.

Who can participate?
Patients with moderate-severe COPD (GOLD grade 2-4), high risk of future exacerbations: 1 severe (hospital assessed) exacerbation or 2 moderate (community clinician assessed) in the last 12 months, and moderate-severe OSA (AHI ≥ 15/h)

What does the study involve?
Participants will be randomised to receive home positive airway pressure (PAP) and COPD usual care or COPD usual care alone with a 12-month follow-up period with an internal pilot.

Usual Care Arm:
If randomised to usual care the following information/advice and management will be delivered: as per NICE (https://www.nice.org.uk/guidance/ng115/resources/chronic-obstructive-pulmonary-disease-in-over-16s-diagnosis-and-management-pdf-66141600098245) and local guidance. This will include as a minimum: a review of pharmacotherapy and consideration of regular, triple-inhaled bronchodilator therapy (long-acting β-agonist, long-acting anti-muscarinic, and steroid), antibiotic prophylaxis, as-needed inhaled short-acting β-agonist therapy, sputum clearance techniques where appropriate, smoking cessation support, pulmonary rehabilitation and education on COPD self-management including non-pharmacological management of COPD, including vaccination additionally advice on sleep quality will be given.

Intervention Arm:
PAP therapy for participants in the intervention arm will be delivered according to local site clinical protocols. All centres involved in the study will be asked for SOPs as part of the process evaluation. Where SOPs are not available senior members of the team will be interviewed to understand the local pathway. As a minimum, the following would be expected for device setup:
1. Face-to-face assessment for mask fitting and device training
2. Mask fit and PAP tolerance check
3. Use of humidification according to patient preference and symptom tolerance
4. Remote review within 1st 30 days to check compliance, troubleshoot technical issues, review mask fit and leak

All participants will undergo face-to-face assessments at 3- and 12-months following randomisation and will complete outcome measures assessments. Trial visits will occur ± 14 days from the scheduled date. Telephone calls will be made monthly (a minimum of 3 attempts will be made over at least three days of the scheduled period of follow-up, after which this the visit will be classed as a missed visit) to collect health care utilisation and PAP therapy (if in the intervention group) data and will be verified at the face-to-face visits.

What are the possible benefits and risks of participating?
Using PAP therapy may reduce participants' risk of having another flare-up of their breathing and improve sleep quality and quality of life. Taking part in the study will help us understand whether PAP therapy is or is not beneficial to patients with COPD and OSA who are at high risk of having repeated exacerbations of their COPD.

All patients taking part in the study will benefit from regular visits with the research team who are experienced in supporting patients with COPD.

There are no expected significant disadvantages to taking part. PAP therapy is used commonly in patients with OSA and severe sleepiness and is tolerated by the majority of patients. However, it can be difficult and uncomfortable for some patients and this is why it is important to understand the potential benefits so patients can make informed decisions on using the treatment. Common side effects are usually minor and include skin discomfort and a runny nose; these may resolve with simple steps, such as additional padding under the mask or a nose spray but also improve over time. If severe they may necessitate stopping PAP and the side effects will then stop. If you do experience any side effects from the machine, please contact your local research team using the telephone numbers on the last page of this leaflet.
Potential risks/side effects of PAP therapy include:
• Skin irritation: the mask can irritate the skin where it is applied. You will be provided with training to fit the mask appropriately to reduce this risk.
• Dry nose, mouth and eyes: The flow of air from the PAP device can sometimes cause drying of the nose, mouth or eyes. This is more common if there is a significant leak from the mask so it will be important to have training to reduce this. Participants will also be offered additional humidification of the air to reduce this problem. Rarely (<5%) nose bleeds can occur following starting PAP.
• Runny nose: It is common when starting PAP therapy to develop a runny nose. This is usually mild and resolves without any treatment but may need treatment with a nasal spray.
• Claustrophobia: Some people can find the mask claustrophobic.
• Swallowing air (called aerophagia): When using the machine, you can sometimes swallow some of the air causing burping or slight discomfort.
All patients receive current “best practice” therapy. All the tests involve little/no discomfort, other than the time taken to perform them. The blowing tests may feel uncomfortable as they require some effort but are safe.
This study will require time and commitment from the patients enrolled, which the research team appreciate and are very grateful for. There are three face-to-face study visits (at the start of the study, 3 months later and at the end of the study at 12 months). These face-to-face visits will take approximately 45 minutes. There are also monthly telephone calls which should take 10 minutes each. All participants will be closely followed up by the research team who are experienced in the management of patients with COPD and OSA.

The study will be under the guidance of a Trial Steering Committee whose job is to ensure that the study is managed well and to monitor safety.
Other potential risks of taking part in the study are felt to be low but could include:
• Distress if you are unable to comply with the PAP treatment or follow-up plans that are part of the trial
• Data risks: Data are collected about participants and their health. These data are collected and stored in line with data protection and clinical trial guidance to reduce the risks but data may be accessed by individuals not directly involved in your care or the trial.

Where is the study run from?
Sponsored by Guys and St Thomas Trust and Trial Management by the University of Oxford, Oxford Respiratory Trials Unit, UK

When is the study starting and how long is it expected to run for?
January 2024 to April 2028

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

Who is the main contact?
Dr Patrick Murphy, Patrick.Murphy@gstt.nhs.uk, epic-osa@ndm.ox.ac.uk

Contact information

Dr Ellie Daly
Public

Trial Manager
ORTU - Churchill Hospital, University Of Oxford
Old Road, Headington
Oxford
OX3 7LE
United Kingdom

Phone	+44 (0)1865 225205
Email	ellie.daly@ndm.ox.ac.uk

Dr Patrick Murphy
Principal Investigator

Consultant in Sleep, Ventilation and Respiratory Medicine
Lane Fox Respiratory Unit
Ground Floor, South Wing, Block C
St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom

ORCID ID	0000-0002-1500-611X
Phone	+44 (0)20 7188 7727
Email	Patrick.Murphy@gstt.nhs.uk

Dr Swapna Mandal
Scientific

FRCP Consultant Respiratory Medicine Clinical Lead- Sleep and Ventilation Service
Royal Free London NHS Foundation Trust
Pond Steet
London
NW3 2QG
United Kingdom

ORCID ID	0000-0002-2232-5880
Phone	+44 (0)7387586126
Email	swapnamandal@nhs.net

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centres

Sponsor information

Guy's and St Thomas' NHS Foundation Trust
Hospital/treatment centre

R&D Dept, 16th Floor, Tower Wing
Great Maze Pond
London
SE1 8RT
England
United Kingdom

Phone	+44 (0)20771887188
Email	r&d@gstt.nhs.uk
Website	https://www.guysandstthomas.nhs.uk/
"ROR"	https://ror.org/00j161312

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

46647_Protocol_v1.0_14Oct2024.pdf

Editorial Notes

10/04/2025: internal review.
06/01/2025: Study's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).