Department of Medicine, National University of Singapore, Singapore.
Department of Endodontics, Operative Dentistry and Prosthodontics, National University of Singapore, Singapore.
BMJ Open. 2023 May 31;13(5):e072853. doi: 10.1136/bmjopen-2023-072853.
Although treatment of obstructive sleep apnoea (OSA) using continuous positive airway pressure (CPAP) reduces blood pressure (BP), adherence to CPAP is often suboptimal. A mandibular advancement device (MAD) is a guideline-endorsed alternative therapy for OSA. Still, there is limited evidence on the relative efficacy between MAD and CPAP on BP reduction. We evaluate whether treatment of moderate-to-severe OSA using MAD can improve BP and other health-related outcomes compared with CPAP.
This is a randomised, controlled, non-inferiority trial conducted. We will recruit 220 Asians with a history of hypertension and high cardiovascular risk for an overnight polysomnography screening. Those with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events/hour) will be randomised to treatment with either MAD or CPAP in a 1:1 ratio. Stratified by age (60 vs <60 years old), body mass index (25 vs <25 kg/m) and apnoea-hypopnoea index (30 vs <30 events/hour), an adaptive randomisation scheme with permuted blocks constructed in real-time is implemented to restrict imbalance. The overall study duration is 12 months. The primary endpoint is the 24-hour mean arterial BP difference between baseline and 6-month follow-up. The secondary endpoints include other measures of ambulatory BP monitoring, arrhythmia based on a 4-day electrocardiographic monitoring, biomarker and proteomic analysis, cardiovascular magnetic resonance-derived myocardial fibrosis and remodelling and quality-of-life questionnaires. Recruitment began in October 2019 and ended in December 2022. Comparison between MAD and CPAP will be performed using covariance (ANCOVA) analysis of the changes in 24-hour mean arterial BP while adjusting for the baseline 24-hour mean arterial BP. We will compare the 95% CIs around the treatment difference point estimate with the prespecified non-inferiority margin (1.5 mm Hg). If the upper limit of the 95% CI is <1.5 mm Hg and crosses 0, non-inferiority of the MAD relative to CPAP will be established.
The Domain Specific Review Board-C, National Healthcare Group under approved the study protocol (NHG DSRB Ref: 2019/00359, approved on 28 August 2019). Study findings will be disseminated to various local, national, and international audiences through abstract presentations and publication in peer-reviewed journals.
NCT04119999.
虽然使用持续气道正压通气（CPAP）治疗阻塞性睡眠呼吸暂停（OSA）可降低血压（BP），但 CPAP 的依从性往往并不理想。下颌前伸装置（MAD）是 OSA 的一种经指南认可的替代治疗方法。尽管如此，关于 MAD 和 CPAP 对降低血压的相对疗效的证据仍然有限。我们评估使用 MAD 治疗中重度 OSA 是否可以改善 BP 和其他与健康相关的结果，与 CPAP 相比。
这是一项随机、对照、非劣效性试验。我们将招募 220 名有高血压病史和高心血管风险的亚洲人进行一夜多导睡眠图筛查。那些患有中重度 OSA（呼吸暂停低通气指数≥15 次/小时）的人将被随机分为 MAD 或 CPAP 治疗组，比例为 1:1。按年龄（60 岁与<60 岁）、体重指数（25 与<25 kg/m）和呼吸暂停低通气指数（30 与<30 次/小时）分层，采用实时构建的置换块自适应随机分配方案限制不平衡。总体研究持续时间为 12 个月。主要终点是从基线到 6 个月随访的 24 小时平均动脉血压差异。次要终点包括其他动态血压监测测量、基于 4 天心电图监测的心律失常、生物标志物和蛋白质组学分析、心血管磁共振衍生的心肌纤维化和重塑以及生活质量问卷。招募于 2019 年 10 月开始，2022 年 12 月结束。使用调整基线 24 小时平均动脉血压后的 24 小时平均动脉血压变化的协方差（ANCOVA）分析来比较 MAD 和 CPAP 之间的差异。我们将比较治疗差异点估计值的 95%置信区间（CI）与预设的非劣效性边界（1.5 mmHg）。如果 95%CI 的上限<1.5 mmHg 且跨越 0，则 MAD 相对于 CPAP 的非劣效性将得到确立。
国立医疗保健集团域特定审查委员会-C 批准了研究方案（NHG DSRB Ref：2019/00359，2019 年 8 月 28 日批准）。研究结果将通过摘要报告和在同行评议期刊上发表的方式向当地、国家和国际各个受众进行传播。
NCT04119999。
