NCT07460505

Mandibular Advancement to Reduce Ventricular Load and Improve Quality-of-life in Heart Failure

Mandibular Advancement to Reduce Ventricular Load and Improve Quality of Life in Heart Failure - a Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 328 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 40 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Heart failure profoundly impacts health, quality-of-life, and survival. Patients with heart failure (HF) experience fatigue, breathlessness, and exercise intolerance. Recurrent hospitalizations due to disease exacerbations further burden patients and healthcare systems. Despite advances in therapies, long-term outcomes remain poor with only 50% survival at 5 years post-diagnosis. Based on the left ventricular ejection fraction, HF is classified into three categories: reduced, mildly reduced, and preserved ejection fraction. This proposal focuses specifically on HF with reduced ejection fraction, which carries the worst prognosis. The term "HF" in this proposal refers exclusively to this subtype. A growing body of evidence highlights the critical role of non-traditional and modifiable risk factors in heart failure progression, with obstructive sleep apnea (OSA) emerging as a particularly important contributor. OSA is highly prevalent in patients with HF, with estimates ranging from 40% to 70%. However, it remains substantially underdiagnosed and undertreated. OSA is characterized by repeated collapse of the upper airway during sleep, resulting in intermittent hypoxia, hypercapnia, serial arousals, and surges in sympathetic activity and blood pressure. These stressors contribute to elevated cardiac afterload, myocardial oxygen demand, and neurohormonal activation-all of which exacerbate ventricular dysfunction and HF progression. The relationship between OSA and HF is bidirectional. OSA not only contributes to the worsening of HF, but HF itself can increase the likelihood of OSA due to pulmonary congestion and fluid redistribution during sleep. Among patients with established HF, the presence of OSA has been linked to worse outcomes, including more frequent hospitalizations and higher mortality. Despite this compelling evidence, the therapeutic potential of treating OSA in HF remains underexplored. While small studies suggest that short-term (3-6 months) treatment with continuous positive airway pressure (CPAP) in HF may improve cardiac function, adherence is suboptimal, with many patients unable to tolerate nightly use of CPAP. Given the rising prevalence of obesity, OSA and HF, there is an urgent need for well-tolerated, effective alternatives to CPAP. The mandibular advancement device (MAD) is an oral appliance approved for the treatment of OSA. Compared with CPAP, more patients accept MAD and use it for long-term with better adherence. Our team previously demonstrated in a randomized trial that MAD was associated with better adherence and improved nighttime blood pressure control compared to CPAP. In a pilot study of HF patients, the investigators found that treatment of OSA with MAD led to a reduction in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP)-a robust prognostic biomarker for HF

Conditions

• Heart Failure
• OSA - Obstructive Sleep Apnea

Interventions

Type	Name	Description
DEVICE	Mandibular advancement device	Mandibular 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.
DEVICE	Mandibular advancement device (Sham)	Arm 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.

Timeline

• Start date: 2026-05-01
• Primary completion: 2031-04-01
• Completion: 2031-04-01
• First posted: 2026-03-10
• Last updated: 2026-03-10

Locations

1 site across 1 country: Singapore