Heart failure with reduced ejection fraction (HFrEF) is a serious condition that limits daily activities and often leads to hospital stays and early death. Many patients with HFrEF also have obstructive sleep apnea (OSA), a common but often undiagnosed condition where breathing repeatedly stops during sleep. This causes drops in oxygen, poor sleep, and stress on the heart, which can make heart failure worse.
The investigators are studying whether a device called a mandibular advancement device (MAD)-a mouthpiece worn during sleep that keeps the airway open-can help people with both HFrEF and moderate-to-severe OSA. This device is already approved to treat OSA and is often more comfortable and easier to use than a CPAP machine.
In our study, 328 patients in Singapore will be randomly assigned to use either the MAD or a sham device that looks the same but doesn't move the jaw. They will wear the device for 12 months. We will measure changes in a blood marker linked to heart failure severity, as well as exercise ability, blood pressure, sleep quality, and hospital visits.
The investigators hope this study will show that MAD is a simple and patient-friendly way to improve outcomes in people with heart failure.
Age of at least 40 years old with the capacity to provide signed, written informed consent
Ischemic or non-ischemic cardiomyopathy with a left ventricular ejection fraction of 20% to 40% in the previous 6 months
Stable chronic HF with NYHA functional class I-III symptoms on maximally tolerated background therapy for at least 4 weeks
NT-proBNP >600 pg/mL (for participants in sinus rhythm) or >900 pg/mL (for participants in atrial fibrillation) in the previous 6 months (same as leading HF trials)
Known OSA and already on regular treatment
Moderate or severe valvular stenosis or regurgitation
Severe hypoxemia on polysomnography ODI >60 or min SpO2 <60%
Specific HF etiologies, including hypertrophic cardiomyopathy with left ventricular outflow tract obstruction; pericardial disease; infiltrative or inflammatory myocardial disease; valvular heart disease with severe aortic or primary mitral regurgitation, moderate or severe aortic stenosis, any mitral stenosis requiring surgical repair, or active endocarditis
Parallel
Mandibular advancement device
DeviceMandibular advancement devices (MAD) and continuous positive airway pressure (CPAP) are non-surgical treatments for obstructive sleep apnea (OSA) that maintain upper airway patency during sleep. CPAP delivers pressurized air via a mask to splint the airway and is the gold-standard therapy, providing the greatest reduction in apnea-hypopnea index across all OSA severities. MADs are custom-made oral appliances that advance the mandible forward, enlarging the upper airway and reducing collapsibility, and are most effective in mild to moderate OSA. Both therapies improve snoring, daytime sleepiness, and sleep quality, but differ in efficacy and tolerability. CPAP is more physiologically effective, while MADs are often better tolerated, more portable, and associated with higher real-world adherence. As a result, MADs are an accepted alternative for patients who cannot tolerate CPAP, with overall effectiveness influenced by both efficacy and adherence.
Mandibular advancement device (Sham)
DeviceArm Description: The patients randomized to the sham MAD arm, the same MAD device as described above for the MAD arm will be used. Unlike an active MAD which advances the mandible to maintain airway patency, the sham-MAD is designed to resemble the real device while minimizing therapeutic effects. Its titration process ensures participant comfort while maintaining study blinding. The sham MAD is custom-fitted using standard dental impressions but is adjusted to allow only minimal mandibular protrusion (0-2 mm). During follow-up visits, minor, non-therapeutic adjustments are made to simulate an active titration process. These may involve small, inconsequential changes that do not significantly alter mandibular position.
N-terminal pro-B-type natriuretic peptide (NT-pro BNP)
NT-proBNP (Primary endpoint) is a circulating biomarker released from the cardiac ventricles in response to myocardial wall stress and volume overload. It is commonly used to assess the presence and severity of heart failure. NT-proBNP levels are measured in picograms per milliliter (pg/mL). Higher values indicate greater cardiac wall stress and worse heart failure severity.
Left ventricular ejection fraction (LVEF), expressed as percentage (%).
Transthoracic echocardiography determined parameters
Kansas City Cardiomyopathy Questionnaire (KCCQ).
Quality of life assessment tool for heart failure. The Overall Summary Score ranges from 0 to 100, with higher scores indicating better health status and quality of life.
Epworth Sleepiness Scale (ESS)
The Epworth Sleepiness Scale (ESS) is a self-administered questionnaire used to evaluate daytime sleepiness. The total score ranges from 0 to 24, with higher scores indicating greater daytime sleepiness.
Sleep Apnea Quality of Life Index (SAQLI)
The Sleep Apnea Quality of Life Index (SAQLI) is a disease-specific questionnaire assessing the impact of obstructive sleep apnea on daily functioning, social interactions, emotional functioning, and symptoms. The total score ranges from 1 to 7, with higher scores indicating better quality of life.
Office BP
Office BP will be measured at baseline, 6 months and 12 months using a standardized protocol with an automated sphygmomanometer. Three consecutive readings will be taken after the participant has been seated quietly for at least 5 minutes, and the average of the last two readings will be recorded. Office BP remains a practical and widely used metric in routine clinical care.
Subjective sleep duration
Subjective sleep duration will be assessed via patient self-report using standardized sleep questionnaires and sleep diaries, collected at baseline, 6 months and 12 months. Participants will be asked to estimate their average nightly sleep duration over the past month, as well as on weekdays and weekends separately.
Click on the lead sponsor to view all of their trials.
National University Hospital, Singapore
Lead sponsor
Alexandra Hospital
Collaborator
Ng Teng Fong General Hospital
Collaborator
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