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

NCT07460505 | Not Yet Recruiting DMC

• 1 other identifier: ECOS Ref: 2025-1331
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure; OSA - Obstructive Sleep Apnea

Keywords

heart failure; OSA; clinical trial; biomarker; quality of life

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 6 months (primary outcome)

Secondary Outcomes (9)

• Left ventricular ejection fraction (LVEF), expressed as percentage (%).

  Baseline and 6 months

• Kansas City Cardiomyopathy Questionnaire (KCCQ).

  Baseline, 6 months, and 12 months

• Epworth Sleepiness Scale (ESS)

  Baseline, 6 months, and 12 months

• Sleep Apnea Quality of Life Index (SAQLI)

  Baseline, 6 months, and 12 months

• EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)

  Baseline, 6 months, and 12 months

Other Outcomes (2)

• Office BP

  Baseline, 6 months and 12 months

• Subjective sleep duration

  Baseline, 6 months, and 12 months.

Study Arms (2)

Mandibular advancement device

EXPERIMENTAL

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

Device: Mandibular advancement device

Mandibular advancement device (sham control)

SHAM COMPARATOR

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.

Device: Mandibular advancement device (Sham)

Interventions

Mandibular advancement device 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.

Mandibular advancement device

Mandibular advancement device (Sham) DEVICE

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.

Mandibular advancement device (sham control)

Eligibility Criteria

• Age: 40 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Alexandra Hospital: collaborator
• Ng Teng Fong General Hospital: collaborator

Study Sites (1)

National University Hospital

Singapore, Kent Ridge, 119228, Singapore

Location

MeSH Terms

Conditions

Heart Failure; Sleep Apnea, Obstructive

Interventions

Occlusal Splints

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Orthotic Devices; Orthopedic Equipment; Surgical Equipment; Equipment and Supplies

Central Study Contacts

Chi-Hang Ronald Lee, MBBS, MD

CONTACT

+6567722493; mdclchr@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We designed a randomized, single-blind, placebo-controlled, outcome-assessor-blinded, superiority clinical trial (MARVEL-HF trial) to evaluate the efficacy of treating OSA (defined as AHI ≥15 events/hour) with MAD in reducing NT-proBNP levels in patients with HF. A sham MAD (same device, without mandibular advancement) will be used as the placebo control (standard practice, as in other clinical trials comparing MAD vs sham MAD). Due to the nature of the intervention, double blinding is not feasible. However, all outcome-assessors will be blinded to treatment allocation. The primary endpoint (plasma NT-proBNP level) is an objective measure.

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: March 10, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031
• Last Updated: March 10, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: 1 year after the trial completion
• Access Criteria: Academics

Locations

SG (1)