A Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling

Not Applicable

Completed

• Conditions: Hypertension,Essential; Obstructive Sleep Apnea
• Interventions: Device: Continuous Positive Airway Pressure; Device: Mandibular Advancement Device

• Registration Number: NCT04119999
• Lead Sponsor: National University of Singapore

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-07
• Study First Submitted QC: 2019-10-07
• Study First Posted: 2019-10-09
• Study Start: 2019-10-16
• Primary Completion: 2023-08-31
• Status Verified: 2024-02
• Study Completion: 2024-02-15
• Last Update Submitted: 2024-02-18
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 321

Inclusion Criteria

1. Age of at least 40 years
2. Chinese (based on the Identity Card or other Identity Document if the subject is a non-Singapore citizen or permanent resident)
3. Physician diagnosed essential hypertension, on at least 1 medication for BP control
4. 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.

Exclusion Criteria

1. Known OSA on treatment
2. Cheyne-Stokes breathing or predominantly central sleep apnea (>50%)
3. Known secondary hypertension: from renal (renal artery stenosis, chronic renal failure); endocrine (aldosterone excess, pheochromocytoma, cushing's syndrome, hyperthyroidism) or cardiac causes (aortic coarctation)
4. Contraindications to CMR: implantable devices, cerebral aneurysm clips, cochlear implants, renal impairment (GRF <30ml/min/1.73m2), claustrophobia and pregnant women
5. 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
6. Limited life expectancy (< 1 year)
7. Hypertensive crisis, acute coronary syndromes or acute heart failure in the past 30 days
8. Known AF (not suitable for CMR and affects remodelling analysis)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CPAP	Continuous Positive Airway Pressure	Continuous Positive Airway Pressure
MAD	Mandibular Advancement Device	Mandibular Advancement Device

Primary Outcome Measures

Name	Time	Method
24-hour mean BP (24MBP)	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.

Secondary Outcome Measures

Name	Time	Method
24-hour pulse pressure (24PP)	6 months and 12 months	Difference in 24-hour pulse pressure (24PP) between the patients in the MAD and CPAP groups as determined by 24-hour ambulatory BP monitoring.
Epworth Sleepiness Scale (ESS) score	6 months and 12 months	Difference in change in ESS score between the MAD and CPAP groups
Percentage of patient with 24-hour systolic BP<120 mmHg	6 months and 12 months	Difference in percentage of patients with 24-hour systolic BP\<120 mmHg in the MAD and CPAP groups
24-hour systolic BP (24SBP)	6 months and 12 months	Difference in 24-hour systolic BP (24SBP) between the patients in the MAD and CPAP groups as determined by 24-hour ambulatory BP monitoring.
Ectopic beat	12 months	Difference in prevalence of ectopic beats between the patients in the MAD and CPAP groups as determined by continuous ECG monitoring
Myocardial remodeling	12 months	Difference in LV and LA dimensions between the patients in the MAD and CPAP groups as determined by cardiac MRI
Nocturnal dipping	6 months and 12 months	Difference in prevalence of nocturnal dipping between the patients in the MAD and CPAP groups as determined by 24-hour ambulatory BP monitoring.
Sleep Apnea Quality of Life Index (SAQLI)	6 months and 12 months	Difference in change in SAQLI score between the MAD and CPAP groups
36-Item Short Form Health Survey (SF-36)	6 months and 12 months	Difference in change in SF-36 score between the MAD and CPAP groups
EuroQol 5Q (EQ5D)	6 months and 12 months	Difference in change in EQ5D score between the MAD and CPAP groups
Functional Outcome of Sleep Questionnaire (FOSQ)	6 months and 12 months	Difference in change in SAQLI score between the MAD and CPAP groups
Daytime systolic BP	6 months and 12 months	Difference in change in daytime systolic BP between the patients in the MAD and CPAP
Nighttime systolic BP	6 months and 12 months	Difference in change in nighttime systolic BP between the patients in the MAD and CPAP
High sensitivity troponin	6 months and 12 months	Change in the plasma level of high sensitivity troponin from baseline to 6-month follow-up
Percentage of patient with 24-hour systolic BP<130 mmHg	6 months and 12 months	Difference in percentage of patients with 24-hour systolic BP\<130 mmHg in the MAD and CPAP groups
NT-proBNP	6 months and 12 months	Change in the plasma level of NT-proBNP from baseline to 6-month follow-up
High sensitive C-reactive protein	6 months and 12 months	Change in the plasma level of high sensitive C-reactive protein from baseline to 6-month follow-up

Trial Locations

Locations (1)

NUHS Cardiosleep research laboratory; 🇸🇬 Singapore, Singapore