Exacerbation Prevention in COPD-OSA overlap syndrome (EPiC-OSA)

Introduction:

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to the health system and cause significant morbidity for patients. Patients with COPD who also have obstructive sleep apnoea (OSA), termed COPD-OSA overlap, have more exacerbations than patients with COPD alone. Observational data suggests treating OSA with positive airway pressure (PAP) therapy may reduce exacerbation frequency in these patients.

There are no randomised clinical trials directly evaluating this, limiting evidence available for clinicians and patients to make decisions. Aim:

We will assess the impact of PAP on exacerbation frequency in patients with overlap. We will incorporate health economic and process evaluations to allowing a robust assessment of the intervention and facilitating adoption into clinical practice. Method:

We will use a multi-centre, open label, randomised clinical trial design. Patients with moderate to severe COPD and a high risk of exacerbations (1 severe or 2 moderate exacerbations in the past 12 months) will be screened for the presence of overlap syndrome using a simple home sleep study. Patients with moderate-severe OSA (AHI>15/h) will be randomised to usual care and PAP or usual care alone.

The primary outcome will be frequency of moderate and severe exacerbations in the year after randomisation and will be evaluated on an intention to treat basis. Patients will have baseline clinical and demographic measurements completed with monthly telephone contacts to collect health care utilisation and review PAP usage (active treatment group). Face to face reviews will be conducted at 3 and 12 months to collect lung function.

A pragmatic clinical definition of an exacerbation will be used. Defined by worsening respiratory symptoms in the absence of another pathology with an escalation of therapy including prescription of antibiotic, corticosteroids or both instituted by the clinical team. The severity of an exacerbation will be assessed as moderate (clinician managed in community) severe (hospital admission).

UK data suggests an expected moderate-severe exacerbation rate of 2.8 (SD 2.5) exacerbations per patient per year. A minimal clinically important reduction in exacerbation rate of 25% (0.7 exacerbations/year) has been used in similar trials. A sample size of 600 (300 per group) is required based on a drop-out and lost to follow-up rate of 14%, sensitivity of 0.05 and power of 0.9.

An economic evaluation, in line with NICE recommended methodology, will be completed using the collected health care utilisation and outcome data to evaluate the short-term cost effectiveness of PAP in the UK health system.

The trial will run with an internal pilot with robust feasibility criteria based on proportion of screened patients included, number of patients randomised per site per month and dropout rate. A process evaluation will be completed concurrently to optimise trial design. Timeline:

Initial regulatory approval and site setup will be established in 6 months. Pilot trial including evaluation will be completed in 14 months with decision to proceed to full trial an month 14. Recruitment will take a further 15 months followed by 1-year follow-up. 3 months has been allocated to complete analysis and write up. Total study duration 48 months.

Impact:

The study examines a medical device already in use and if shown to be clinically and cost effective could be rapidly adopted into UK practice.