Clinical trial NCT04119999: A Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling
Official title: A Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension,Essential
Obstructive Sleep Apnea
Keywords: sleep
remodeling
blood pressure
trial
Lead sponsor: National University of Singapore
Sponsor class: OTHER
Collaborators: name: Ng Teng Fong General Hospital
name: National University Hospital, Singapore
name: National Heart Centre Singapore
First posted: 2019-10-09
Enrollment: 321
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: 24-hour mean BP (24MBP)
timeFrame: 6 months
Secondary outcomes:
measure: 24-hour systolic BP (24SBP)
timeFrame: 6 months and 12 months
measure: 24-hour pulse pressure (24PP)
timeFrame: 6 months and 12 months
measure: Nocturnal dipping
timeFrame: 6 months and 12 months
measure: Ectopic beat
timeFrame: 12 months
measure: Myocardial remodeling
timeFrame: 12 months
measure: Epworth Sleepiness Scale (ESS) score
timeFrame: 6 months and 12 months
measure: Sleep Apnea Quality of Life Index (SAQLI)
timeFrame: 6 months and 12 months
measure: Functional Outcome of Sleep Questionnaire (FOSQ)
timeFrame: 6 months and 12 months
measure: 36-Item Short Form Health Survey (SF-36)
timeFrame: 6 months and 12 months
measure: EuroQol 5Q (EQ5D)
timeFrame: 6 months and 12 months
measure: Daytime systolic BP
timeFrame: 6 months and 12 months
measure: Nighttime systolic BP
timeFrame: 6 months and 12 months
measure: Percentage of patient with 24-hour systolic BP<130 mmHg
timeFrame: 6 months and 12 months
measure: Percentage of patient with 24-hour systolic BP<120 mmHg
timeFrame: 6 months and 12 months
measure: NT-proBNP
timeFrame: 6 months and 12 months
measure: High sensitivity troponin
timeFrame: 6 months and 12 months
measure: High sensitive C-reactive protein
timeFrame: 6 months and 12 months
Other outcomes:
measure: Subgroup analysis
timeFrame: 6 months and 12 months
Locations:
city: Singapore
country: Singapore
facility: NUHS Cardiosleep research laboratory
Study officials:
affiliation: National University of Singapore
name: Chi-Hang Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: