Continuous Positive Airway Pressure plus Mandibular Advancement Therapy (PAPMAT): study protocol for an adaptive randomised crossover trial comparing the benefits and costs of combining two established treatments for obstructive sleep apnoea

BACKGROUND: Obstructive sleep apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other health impacts. Continuous positive airway pressure (CPAP) therapy is effective first line treatment for moderate to severe OSA. Unfortunately, many patients have difficulty tolerating CPAP and pressure intolerance is probably an important contributing factor. Mandibular advancement devices (MAD) are an alternative to CPAP. They are worn in the mouth during sleep to reduce airway obstruction. There is some evidence that, when used in combination with CPAP, MADs improve airway anatomy enough to reduce the CPAP pressure required to treat OSA and that this combination therapy could improve CPAP adherence. 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 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, patient-reported outcome measures including subjective daytime sleepiness, quality of life, and treatment preference at the trial exit and health service use. Cost-effectiveness analyses will be undertaken. DISCUSSION: If the intervention is shown to be effective and cost-effective in improving adherence in this standard CPAP-eligible OSA patient population it would be relatively straightforward to introduce into existing OSA treatment pathways, within the wider NHS and more widely. 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 health economics analysis would provide cost-effectiveness data to inform service planning and clinical guidelines through policy briefing papers, including those by NICE and SIGN. TRIAL REGISTRATION: PAPMAT was registered with ISRCTN prior to recruitment beginning (ISRCTN Registry 2021): https://www.isrctn.com/ISRCTN33966032. Registered on 17th November 2021.