Title: Randomised controlled trial of nasal decongestants versus placebo to prolong treatment free periods from continuous positive airway pressure therapy in mild to moderate obstructive sleep apnoea
Funder: Department of Health and Social Care

Abstract: Obstructive sleep apnoea (OSA) is a common problem affecting 4-8% of UK adults. Continuous positive airway pressure (CPAP) is the most effective treatment for OSA. Understandably CPAP is often not tolerated particularly amongst patients with milder OSA who frequently ask for alternatives even in the short term. Recent research shows that when patients stop CPAP treatment, OSA does not reoccur immediately in all, with 15% of patients estimated to be free from OSA after two weeks. Therefore we aim to test if an alternative, less intrusive treatment instead of CPAP prolongs this OSA free period. OSA produces swelling of the pharynx and histological samples of pharyngeal tissue show oedema and inflammation. CPAP reduces oedema in the pharynx as measured by MRI. Patients with heart failure and OSA are particularly troubled by OSA in the second portion of the night due to a shift peripheral oedema to the neck associated with supine posture. Therefore it is likely that pharyngeal oedema is one of the factors influencing the return of OSA. Nasal application of decongestants has been shown to lead to a slight reduction in the severity of OSA in newly diagnosed patients who have not yet used CPAP. Aims We will evaluate whether Xylometazoline, a decongestant, will prolong the treatment free period after discontinuing CPAP. We will specifically compare the interventions for the following clinically relevant patient focused outcomes: The time to recurrence of OSA and symptoms; measured by daily Karolinska sleep score and weekly Epworth sleepiness score (sleep specific questionnaire) and the impact on quality of life; measured by the Sleep Apnoea Quality of Life Index (baseline and trial-end); a sleep apnoea specific quality of life score incorporated the effects of treatment and our pilot questinnaire of side effects and tolerability of the nasal spray. Plan of investigation Management of OSA with CPAP is standard in the current NHS treatment pathway, but the potential for treatment breaks has never previously been supported through lack of evidence. We will address this question through a 1:1 double-blinded randomised placebo-controlled trial which is pragmatic and applicable in every day current practice. Patients will be recruited from two NHS sleep clinics from over 10,000 patients followed-up on CPAP who are representative of typical OSA patients. Patients will be randomised to nasal and pharyngeal once nightly Xylometazoline or placebo instead of their usual CPAP. Patients will then be followed for a maximum of four weeks or until their OSA has returned (ODI>15 /h) or they have return of symptoms of OSA. Outcomes will be relevant to the intent of treatment &ndash; i.e. patient focused and reported. Alongside nightly pulse oximetry, patients will complete a diary with daily symptom scores, and more in depth weekly assessments of symptoms and quality of life. Summary of Potential Benefits This study will assess whether a simple, readily-available intervention can allow patients to take a longer break from CPAP without return of their OSA or symptoms. It has been designed to address outcomes relevant to patients who continue to ask for such an intervention. It will allow better advice to the 230,000 patients already established on CPAP in the UK. If positive, the results should therefore be immediately taken up in to practice, as the service provision model and clinic population are available in a wide range of NHS Hospitals. In addition to answering the primary question, a positive result may support other therapeutic options for patients with milder disease in future and may test if this withdrawal model is an appropriate design to monitor new treatment strategies in a safe, standardised and reproducible way.

Lay abstract: Around 1 in 20 adults have Obstructive Sleep Apnoea ('OSA'). When you relax during sleep the throat tends to narrow. In OSA patients this narrowing leads to pauses in breathing. During these pauses the oxygen level falls and the patient wakes up. These events can occur every minute in severe cases and so patients sleep very badly; awake unrefreshed and are sleepy in the daytime. OSA is best treated with a Continuous Positive Airway Pressure ('CPAP') machine. These blow air into the throat through a mask worn when asleep. CPAP keeps the airway open. The breathing and sleep are stable. Patients awake refreshed and do not fall asleep in the daytime. CPAP can also help snoring, blood pressure and mood. Although CPAP machines work well they are not always comfortable. Around one in 10 patients cannot use CPAP. Patients who don t like CPAP ask if there are any other treatments or if they can stop CPAP machines for short breaks. We know that snoring is worse if the throat is swollen or the nose is blocked. This can also lead to OSA. Snoring may be improved by nasal decongestants. We hope decongestants will also treat OSA so that patients can come off their CPAP for short breaks. We will ask patients who are treated with CPAP to stop their CPAP for up to a month and see how long it takes for OSA to return. Half the group use a real decongestant spray in their throat and half use an inactive dummy spray. We will see if the decongestant spray stops OSA coming back so quickly. If the nose spray stops OSA coming back for a week or more this will help people to decide if they can go away for a few days without having to take their machine.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY