Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol

INTRODUCTION: Obstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number. METHODS AND ANALYSIS: Adult subjects with newly diagnosed OSA (Apnoea-Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student's t-test to compare changes in sympathetic tone between groups. ETHICS AND DISSEMINATION: The protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03428516; Pre-results.