Title: MAD plus CPAP: does combining two established treatments for Obstructive Sleep Apnoea give added benefits?
Funder: Department of Health and Social Care

Abstract: Research question Does combining Mandibular Advancement Devices (MAD) with Continuous Positive Airway Pressure (CPAP) therapy make it easier for patients to tolerate CPAP; thereby increasing adherence to treatment and improving outcomes, and is it cost effective? Background Obstructive Sleep Apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other important health impacts. CPAP therapy is effective first line treatment for moderate to severe OSA (NICE 2008) and the more it is used, the more beneficial it is likely to be. Unfortunately, many patients have difficulty tolerating CPAP and pressure intolerance is probably an important contributing factor. MADs are an alternative to CPAP. They are worn in the mouth during sleep to reduce airway obstruction and are routinely used in milder OSA, or when patients can t tolerate CPAP. There is some evidence that, when used in combination with CPAP, MAD improve airway anatomy enough to reduce the CPAP pressure required to treat OSA; and that this combination therapy could improve CPAP adherence. Aims and Objectives To compare combination therapy with standalone CPAP, in moderate to severe OSA, to see whether the combination reduces CPAP pressure requirements, improves CPAP adherence and is cost effective. Methods Consecutive patients starting on CPAP for moderate to severe OSA will be recruited at a regional NHS sleep service. Patients with high CPAP pressure requirements after initial titration, who satisfy all entry criteria and consent to participate, will undertake a 2-arm randomised crossover trial. The arms will be: i) standalone CPAP and ii) CPAP+MAD therapy. Each arm will last 12 weeks, including 2 weeks acclimatisation. CPAP machines will be auto-titrating (continually adjusting pressure according to need) and with facility for data download, so the impact of MAD on CPAP pressure requirements and CPAP adherence can be easily measured. The primary outcome will be CPAP adherence. Secondary outcomes will include measures of OSA severity and patient reported outcome measures including subjective daytime sleepiness, quality of life and treatment preference at trial exit. A Short-term (trial-based) and life-time (model-based) cost-effectiveness analyses will be undertaken. Timelines for delivery: Study initiation March 2021, anticipated completion of study within 36 months. Anticipated Impact and Dissemination If the intervention is shown to be effective and cost effective in improving adherence and patient outcomes in this standard CPAP-eligible OSA patient population it would be of immediate benefit to all patients with OSA, within the wider NHS and globally. Both MAD and CPAP are already used by sleep services so their combination would require only minor adjustments to existing clinical pathways. It would be straightforward to disseminate the results of the study through regional, national and international respiratory meetings. The lead applicant has previously presented results of NIHR MAD research in these fora, which have been well received and translated into practice with real benefits for patients. The health economics analysis would provide cost effectiveness data to inform service planning and clinical guidelines through policy briefing papers, including to NICE and SIGN.

Lay abstract: This study will investigate whether combining Continuous Positive Airway Pressure (CPAP) therapy with a Mandibular Advancement Device (MAD) for patients with Obstructive Sleep Apnoea is better than using CPAP alone. Obstructive Sleep Apnoea (OSA) occurs when the throat muscles relax excessively during sleep. The upper airway becomes too floppy and blocks off breathing resulting in apnoeas (breathing pauses). These choking episodes usually cause oxygen deprivation; the person then briefly wakes up, reopening the airway and restarting breathing. When apnoeas are frequent the sleep disturbance causes excessive daytime sleepiness, which impairs Quality of Life, increases risk of road traffic accidents and affects work performance. OSA also causes high blood pressure and there is an increased risk of heart attack and stroke. Obstructive sleep apnoea affects up to 24% of men and 9% of women, while 2% to 7% of middle-aged adults have OSA Syndrome , when excessive daytime sleepiness is present. CPAP therapy is the usual treatment for moderate and severe OSA. It pumps air through a mask at a pressure sufficient to stop OSA. For most patients CPAP is highly effective at reducing excessive daytime sleepiness and other symptoms. It also helps high blood pressure. MADs fit around the teeth and move the lower jaw forward to keep the airway open. While useful in mild OSA, MADs are less effective in moderate and severe OSA. However they sometimes help these patients if they can t tolerate CPAP. Between 20% and 83% of patients cannot tolerate CPAP, either due to uncomfortably high pressure or because the pressure needed to keep their throat open exceeds what CPAP can provide, leading to breakthrough OSA. For these patients OSA remains untreated. This study will investigate whether giving patients a MAD to wear at the same time as CPAP holds the airway open enough for a lower CPAP pressure to still be effective at treating OSA, and whether this makes it easier for patients to tolerate CPAP, thereby improving CPAP usage, sleep quality and Quality of Life. Patients newly started on CPAP who require a high pressure will be allocated by chance to use CPAP alone (without the MAD) or to use CPAP + MAD in combination for 12 weeks. At the end of the 12 weeks the effects of the treatment they are on will be assessed, before they are switched to the other treatment for another 12 weeks. The main thing we will measure will be whether there is any difference in CPAP usage (hours per night) between CPAP alone and MAD + CPAP worn together. At the end of the study participants will decide which treatment (if any) they want to continue using. They will return to routine clinical follow-up.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: RESPIRATORY