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

Официальное название

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

Обзор

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.

Подробное описание

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

Вмешательства

• Устройство 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 collapsibilit
• Устройство 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 prot

Первичные конечные точки

• N-terminal pro-B-type natriuretic peptide (NT-pro BNP) [Срок оценки: Baseline and 6 months (primary outcome)]

Вторичные конечные точки (9)

• Left ventricular ejection fraction (LVEF), expressed as percentage (%). [Срок оценки: Baseline and 6 months]
• Kansas City Cardiomyopathy Questionnaire (KCCQ). [Срок оценки: Baseline, 6 months, and 12 months]
• Epworth Sleepiness Scale (ESS) [Срок оценки: Baseline, 6 months, and 12 months]
• Sleep Apnea Quality of Life Index (SAQLI) [Срок оценки: Baseline, 6 months, and 12 months]
• EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L) [Срок оценки: Baseline, 6 months, and 12 months]
• Montreal Cognitive Assessment (MoCA) [Срок оценки: Baseline, 6 months, and 12 months]
• Adverse cardiovascular events [Срок оценки: 6 months, 12 months, and 36 months]
• Ambulatory BP monitoring [Срок оценки: Baseline and 6 months]
• Peak oxygen uptake (VO₂peak) [Срок оценки: Baseline and 6 months]

Критерии участия

Критерии включения

• 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)
• Agree to follow the study protocol
• Able and willing to undergo a hospital-based overnight polysomnography

Критерии исключения

• 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
• Contraindications to MAD: less than six teeth in each arch; inability to advance the mandible and open the jaw widely.
• Pre-existing temporomandibular joint problems, severe bruxism, and advanced periodontal disease (with mobility affecting MAD stability).
• Patients who are planning to have restorations, dental prostheses or implants done in the next 12 months
• Limited life expectancy (< one year)
• Cardiac or cerebrovascular events in the past 6 months, including myocardial infarction, unstable angina leading to hospitalization, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, carotid revascularization, endovascular procedure, or surgical intervention for peripheral vascular disease
• Current or planned mechanical circulatory support or heart transplantation Current or planned (within the next 6 months) hemodialysis or peritoneal dialysis

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Сингапур · 1 центр

• National University Hospital — Singapore

Идентификаторы

NCT: NCT07460505 · ECOS Ref: 2025-1331

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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