Obstructive Sleep Apnoea and Cardiac Arrhythmias (OSCA)

Obstructive Sleep Apnoea and Cardiac Arrhythmias and the Impact of an Implantable Loop Recorder

This study is a prevelance trial looking at how sleep apnoea affects the heart especially heart rhythms.

Previous research shows that patients suffering from sleep apnoea are much more likely to get heart disease and abnormal heart rhythms (arrhythmias). These defects are sometimes missed by the traditional methods of monitoring i.e. 24-hour Holter monitor and ECGs. This means potentially dangerous arrhythmias may not be detected. Additionally, standard therapy for sleep apnoea does not significantly reduce the risk of heart disease.

This study will recruit 200 participants over a period of 18 months. The research team will observe the heart rhythms of sleep apnoea patients by inserting an implantable loop recorder (ILR) in up to 100 participants. The other 100 patients will simply have standard care. This device will monitor the heart continuously for 3 years allowing us to detect abnormal heart rhythms and treat as necessary.

Demonstrating the incidence of arrhythmia can lead onto a larger study which may change future sleep apnoea management improving their cardiovascular outcomes. Other markers of heart disease such as; blood tests, Magnetocardiography and Echocardiography will be performed on participants to shed more light on the mechanisms which link sleep apnoea and heart disease/arrhythmia.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Obstructive Sleep Apnea; Arrhythmia; Atrial Fibrillation New Onset
• Intervention / Treatment: Device: Reveal LINQ

Detailed Description

Sleep apnoea affects up to 1.5 million adults in the United Kingdom (UK). This puts this population at risk of reduced oxygen levels during sleep, poor sleep and increased breathing effort . All of the above put stress on the body and are proven to increase the risk of high blood pressure, heart failure and vascular problems. This can lead to strokes, heart disease and death.

Sleep apnoea patients are at much higher risk of abnormal heart rhythms. Even with continuous positive airways pressure (CPAP) treatment (which is the mainstay in sleep apnoea and does help to reduce arrhythmias) patients are still at higher risk of heart disease and stroke.

An implantable loop recorder (Reveal-LINQ) inserted into sleep apnoea patients will be able to continuously monitor a patient's heart rhythm. This will determine the incidence of arrhythmia in sleep apnoea patients. Any significant abnormalities in either arm of the study will be treated as per National Health Service guidelines and best care. The cost associated with this method of intervention will also be considered.

If there is a high prevalence of arrhythmia a future larger trial, involving much larger numbers and multiple centres, could be conducted to demonstrate reduced risk of stroke or heart attack using this method of arrhythmia detection and management.

Cardiovascular biomarkers, cardiac function, autonomic function and magnetocardiography in these patients could shed light on the mechanisms which cause increased cardiovascular morbidity and mortality.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hejie He, MBBS; Phone Number: 24693 02476964000; Email: hejie.he@nhs.net

Study Locations

• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry & Warwickshire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with moderate to severe sleep apnoea who require CPAP as standard care (AHI >15)
• Patients between the age of 18 and 75

Exclusion Criteria:

• Patients with a diagnosis of atrial fibrillation (AF), atrial flutter and/or ventricular tachycardia (VT)
• Patients with an ILR already in-situ or an established indication for ILR
• Patients with a palliative diagnosis i.e. life expectancy less than 3 years
• Patients who lack capacity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ILR; Participants who will receive the Implantable Loop Recorder (Reveal-LINQ) inserted just after baseline. This is single intervention and lasts for 3 years after which the patient has the option to have it removed.	Device: Reveal LINQ; Insertion of monitoring device called Reveal-LINQ (an implantable loop recorder)
No Intervention: No ILR; Participants who will not get the Implantable Loop Recorder (Reveal-LINQ).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of arrhythmia	Incidence of arrhythmia in sleep apnoea patients as recorded by ILR vs a no ILR group	3 years
Autonomic function before and after CPAP	Assess the changes to the heart in sleep apnoea patients before and after CPAP in terms of heart rate variability as measured on 24 hour holter monitors. The raw data is taken from the monitor and then analysed manually. The first data set will be from baseline studies which will be compared to studies done at the 1 year follow-up.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset and frequency of atrial fibrillation	Explore the onset and frequency of atrial fibrillation in sleep apnoea patients in order to determine what method of detection is efficient and cost effective.	3 years
Rate of Cardiovascular Morbidity	Explore the impact of inserting an ILR in patients with sleep apnoea on cardiovascular morbidity (stroke and myocardial infarction) compared to those without ILR	3 years
Rate of Cardiovascular Mortality	Explore the impact of inserting an ILR in patients with sleep apnoea on cardiovascular mortality (stroke and/or myocardial infarction resulting in death) compared to those without ILR	3 years
Cardiovascular biomarkers before and after CPAP	Explore the changes to the heart in sleep apnoea patients before and after CPAP in terms of vascular biomarkers - high sensitivity C-Reactive Protein, high sensitivity Troponin-T, N-terminal pro B-type Natriuretic Peptide, Tumour Necrosis Factor-alpha, Matrix Metalloproteinase-9, Interleukin-6, Fibroblast Growth Factor-23. The first data set will be from baseline studies which will be compared to studies done at the 1 year follow-up.	3 years
Echocardiography before and after CPAP	Explore the changes to the heart in sleep apnoea patients before and after CPAP in terms of echocardiogram measures.	3 years
Quality of life: EQ-5D-5L questionnaire	Quality of life measures before and after CPAP as measured by the EQ-5D 5 level questionnaire. This measures various quality of life points from a scale of 1-5. 1 represents poor quality of life and 5 represents good quality of life for each factor. This data will be analysed as per the EuroQol algorithm. The first data set will be from baseline studies which will be compared to studies done at the 1 year follow-up.	3 years

Collaborators and Investigators

• Sponsor: University Hospitals Coventry and Warwickshire NHS Trust

Publications and helpful links

General Publications

• McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, Chen G, Du B, McArdle N, Mukherjee S, Tripathi M, Billot L, Li Q, Lorenzi-Filho G, Barbe F, Redline S, Wang J, Arima H, Neal B, White DP, Grunstein RR, Zhong N, Anderson CS; SAVE Investigators and Coordinators. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016 Sep 8;375(10):919-31. doi: 10.1056/NEJMoa1606599. Epub 2016 Aug 28.
• Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017 Feb 21;69(7):841-858. doi: 10.1016/j.jacc.2016.11.069.
• Yeung C, Drew D, Hammond S, Hopman WM, Redfearn D, Simpson C, Abdollah H, Baranchuk A. Extended Cardiac Monitoring in Patients With Severe Sleep Apnea and No History of Atrial Fibrillation (The Reveal XT-SA Study). Am J Cardiol. 2018 Dec 1;122(11):1885-1889. doi: 10.1016/j.amjcard.2018.08.032. Epub 2018 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2019
• Primary Completion (Actual): April 15, 2023
• Study Completion (Estimated): April 15, 2025

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Obstructive Sleep Apnea; Heart Rate Variability; Implantable Loop Recorder; Interleukin-6; Fibroblast Growth Factor-23; Extended Cardiac Monitoring; Matrix Metalloproteinase-9; Tumour Necrosis Factor-Alpha; High sensitivity C-Reactive Protein; High sensitivity Troponin-T; N-Terminal pro B-type Natriuretic Peptide
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Cardiovascular Diseases; Apnea; Atrial Fibrillation; Arrhythmias, Cardiac
• Other Study ID Numbers: FO409918

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No