A Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 321
- 试验地点
- 1
- 主要终点
- 24-hour mean BP (24MBP)
研究概览
简要总结
The objective of this proposal is to evaluate whether mandibular advancement device (MAD) is non-inferior to continuous positive airway pressure (CPAP) in the treatment of obstructive sleep apnea (OSA) and blood pressure reduction. OSA and hypertension are highly prevalent disorders with profound impacts on health. Apart from improving quality of-life, an effective OSA treatment could improve cardiovascular risk partly through blood pressure reduction, particularly in patients with high cardiovascular risk in whom blood pressure control is often suboptimal. Although CPAP is useful, the high non-acceptance and non-adherence preclude its widespread use.
East Asians have a restrictive craniofacial phenotype that predisposes them to OSA and the associated cardiovascular stress. CPAP, while considered the first-line therapy for OSA, has failed to improve cardiovascular outcomes in randomized trials till date because it is poorly tolerated. MADs are oral appliances that correct the restrictive craniofacial phenotype present in East Asians by protruding the lower jaw to reduce upper airway collapsibility. MADs are better tolerated than CPAP, and this may be an important determinant of the overall effectiveness in treating OSA, and thus ameliorating the downstream adverse health outcomes. We hypothesize that MADs are non-inferior to CPAP in treating OSA and reducing cardiovascular risk by blood pressure reduction in East Asians.
We will recruit East Asian subjects with hypertension and high cardiovascular risk for polysomnography. Patients diagnosed with OSA (n=220) will be randomized to MAD or CPAP groups in a 1:1 ratio for a treatment duration of 6 months. The primary endpoint is the 24-hour mean blood pressure as determined by ambulatory monitoring. The secondary endpoints include sleep-time systolic BP, target blood pressure, cardiovascular biomarkers, and myocardial remodeling. Association between OSA and silent paroxysmal atrial fibrillation will also be determined. If MADs are shown to be effective, the next step is to evaluate our novel device- drug-eluting MAD that the team is developing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age of at least 40 years
- •Chinese (based on the Identity Card or other Identity Document if the subject is a non-Singapore citizen or permanent resident)
- •Physician diagnosed essential hypertension, on at least 1 medication for BP control
- •High cardiovascular risk, as defined by one or more of the following: (a) diabetes mellitus, (b) stroke, (c) significant coronary artery disease (at least one stenosis of >50% diameter in at least one major epicardial artery), (d) chronic kidney disease, excluding polycystic kidney disease, with an estimated glomerular filtration rate of <60 ml/min/1.73m2, or (e) age of 75 years or older.
排除标准
- •Known OSA on treatment
- •Cheyne-Stokes breathing or predominantly central sleep apnea (>50%)
- •Known secondary hypertension: from renal (renal artery stenosis, chronic renal failure); endocrine (aldosterone excess, pheochromocytoma, cushing's syndrome, hyperthyroidism) or cardiac causes (aortic coarctation)
- •Contraindications to CMR: implantable devices, cerebral aneurysm clips, cochlear implants, renal impairment (GRF <30ml/min/1.73m2), claustrophobia and pregnant women
- •Contraindications to MAD: <6 to 10 teeth in each arch, inability to advance the mandible and open the jaw widely, pre-existing temporomandibular joint problems, severe bruxism
- •Limited life expectancy (< 1 year)
- •Hypertensive crisis, acute coronary syndromes or acute heart failure in the past 30 days
- •Known AF (not suitable for CMR and affects remodelling analysis)
结局指标
主要结局
24-hour mean BP (24MBP)
时间窗: 6 months
Difference in 24-hour mean BP (24MBP) between the patients in the MAD and CPAP groups as determined by 24-hour ambulatory BP monitoring.
次要结局
- 24-hour pulse pressure (24PP)(6 months and 12 months)
- EuroQol 5Q (EQ5D)(6 months and 12 months)
- Epworth Sleepiness Scale (ESS) score(6 months and 12 months)
- Percentage of patient with 24-hour systolic BP<120 mmHg(6 months and 12 months)
- 24-hour systolic BP (24SBP)(6 months and 12 months)
- Ectopic beat(12 months)
- Myocardial remodeling(12 months)
- Nocturnal dipping(6 months and 12 months)
- Sleep Apnea Quality of Life Index (SAQLI)(6 months and 12 months)
- 36-Item Short Form Health Survey (SF-36)(6 months and 12 months)
- Functional Outcome of Sleep Questionnaire (FOSQ)(6 months and 12 months)
- Daytime systolic BP(6 months and 12 months)
- Nighttime systolic BP(6 months and 12 months)
- High sensitivity troponin(6 months and 12 months)
- Percentage of patient with 24-hour systolic BP<130 mmHg(6 months and 12 months)
- NT-proBNP(6 months and 12 months)
- High sensitive C-reactive protein(6 months and 12 months)
研究者
Chi-Hang Lee
Professor of Medicine
National University of Singapore