Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001213831
Ethics application status
Approved
Date submitted
17/06/2021
Date registered
10/09/2021
Date last updated
2/09/2022
Date data sharing statement initially provided
10/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Does obstructive sleep apnoea treatment improve heart rhythm control in patients after having an Atrial Fibrillation ablation. A randomised controlled trial
Scientific title
Does treatment for moderate to severe obstructive sleep apnoea (OSA) improve heart rhythm control in patients following a catheter ablation for Atrial Fibrillation (AF) (SNORE-AF study)
Secondary ID [1] 304503 0
Nil Known
Universal Trial Number (UTN)
U1111-1266-3391
Trial acronym
SNORE-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 322366 0
Obstructive Sleep Apnoea 322367 0
Condition category
Condition code
Cardiovascular 320032 320032 0 0
Other cardiovascular diseases
Respiratory 320033 320033 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi centre interventional prospective randomised controlled study that aims to evaluate whether patients diagnosed with moderate to severe obstructive sleep apnoea (OSA) have an improvement in AF recurrence with treatment of OSA following ablation therapy for Atrial Fibrillation (AF).

Patients who meet eligibility criteria pending sleep diagnosis of sleep disordered breathing (SDB) will be screened using the ambulatory WatchPAT device. Patients with a study demonstrating moderate to severe predominant OSA (AHI =(equal to or greater than) 15; central apnoea index/total apnoea index <20%) will be randomised to treatment or observational management.

Patient randomised to the treatment arm will commence Continuous Positive Airway Pressure (CPAP) therapy while patients in the observational arm will not. CPAP therapy will commence within 3 months of WatchPAT study (window period of CPAP commencement is within 2 months prior to ablation to 3 months post ablation). Patients will attend the Sleep Laboratory at the participating site to be fitted and provided with a loan Auto Positive Airway Pressure (APAP) device to allow for implementation and titration of pressures (can range from 1-4 weeks). Once titration settings have been stabilized and achieved, patients will return to the sleep laboratory at the participating site and be fitted with a fixed pressure Continuous Positive Airway Pressure (CPAP) machine by the CPAP therapist and will receive CPAP education, mask fitting and acclimatization prior to titration. This may take approximately 2-3hours. CPAP machines will have data chips for remote monitoring of pressures by central core sleep lab and patients sleep physician to reduce burden on patients visiting sites. Education for CPAP device will be available and provided by the study core sleep lab at any time throughout the study. Patients will be required and encouraged to use the CPAP machine for a period of 12 months post AF ablation. After a minimum of 1 month continuous treatment from implementation date, if adherence by documented CPAP use cannot be achieved for a minimum of 4 hours per night for at least 5 nights per week despite review and further encouragement, alternate therapy will be prescribed. Sponsored therapies allowed include a mandibular advancement device or sleep re-positional therapy devices which must be implemented within 3 months post ablation date (during the patients blanking period). Patients will have access to the central core sleep lab technicians for any troubleshooting and questions. Patients randomised to the control group will not receive CPAP therapy or other OSA treatment modalities for the study period unless medically indicated.

Post randomisation, all patients (treatment arm and control arm) will have repeated sleep study monitoring using the WatchPAT device at 3, 6 and 12 months. All monitoring will be reviewed by a central sleep core lab. The central sleep core lab is available throughout the study for patient education. Patients will also receive a Itamar Medical WatchPAT educational booklet and youtube video on how to use the device at each WatchPAT timepoint.

The Ablation procedure is standard of care treatment and there is no alteration of the clinical procedure as part of the study protocol. Ablation procedure is completed as standard of care treatment and not a study related procedure.

All patients will receive an implantable loop recorder or a mobile rhythm monitoring device at the discretion of the treating investigator for heart rhythm monitoring. Implantable loop recorders will be inserted and used as standard of care practice as per each hospital protocols. All patients will undergo 24hr Holter monitoring at 3, 6 and 12 months.
Intervention code [1] 320864 0
Treatment: Devices
Intervention code [2] 320865 0
Prevention
Comparator / control treatment
Observational Arm Management: Patients randomised to the control group will not receive CPAP therapy or other OSA treatment modalities for the study period unless medically indicated by new development of:
• fall-asleep motor vehicle or occupational accident
• near to fall-asleep motor vehicle or occupational accident
• moderate to severe excessive daytime sleepiness
• the treating doctors opinion represents a significant driving risk as a result of a sleep disorder
Control group
Active

Outcomes
Primary outcome [1] 327896 0
Time to AF recurrence following AF ablation (single procedure without antiarrhythmic mediation) assessed as a composite outcome from an implanted loop recorder, daily Kardia Alivecor ECG recordings and 24 hour holter monitoring
Timepoint [1] 327896 0
Documented AF > 30 seconds, occurring 3 months (after 3 month blanking period) to 12 months after ablation. These include, implantable loop recorder assessed continuously for 12 months, daily and symptomatic ECG recordings from Kardia Alivecor device for 12 months and 24 hour holter monitoring occurring at 3, 6 and 12 months.
Secondary outcome [1] 396925 0
AF burden over 12 months post ablation (single procedure) assessed as a composite of implanted loop recorder, daily Kardia Alivecor ECG recordings and 24 hour holter monitoring. AF burden is defined as:
a. Number of AF episodes
b. Frequency of AF episodes
c. Duration of total AF (in minutes and as % of total time)
Timepoint [1] 396925 0
AF burden is assessed 3 months (after 3 month blanking period) to 12 months after ablation via either implantable loop recorder that is assessed continuously for 12 months, daily and symptomatic ECG recordings from Kardia Alivecor device for 12 months and 24 hour holter monitoring occurring at 3, 6 and 12 months.
Secondary outcome [2] 396926 0
Multi procedure AF recurrence (with or without antiarrhythmic medication) will be assessed if patient has had required clinical AF procedures including cardioversion and redo-ablation procedure, determined by medical records and physician consult.
Timepoint [2] 396926 0
Patients will be assessed from 3 months (after 3 month blanking period) to 12 months after ablation at follow up timepoints 6 and 12 months if any required AF procedures had occurred.
Secondary outcome [3] 396929 0
Markers of inflammation including CRP, IL-6 and TNF-a will be collected via blood samples
Timepoint [3] 396929 0
Baseline (pre ablation and randomisation) and 12 months post ablation procedure
Secondary outcome [4] 398714 0
Quality of life marker 1 will be assessed using EQ-5D-5L questionnaire.
Timepoint [4] 398714 0
Patients will complete questionnaire at Baseline (pre ablation procedure) and 6 and 12 months post ablation procedure
Secondary outcome [5] 398716 0
Quality of life marker 2 is assessed using the Epworth sleepiness scale and as a composite of sleep compliance
Timepoint [5] 398716 0
Patients will complete questionnaire at Baseline (pre ablation procedure) and 6 and 12 months post ablation procedure
Secondary outcome [6] 398717 0
Quality of life marker 3 is assessing the patients AF and quality of life and will be assessed using the Toronto University AF symptom severity scale (AFSS)
Timepoint [6] 398717 0
Patients will complete questionnaire at Baseline (pre ablation procedure) and 6 and 12 months post ablation procedure
Secondary outcome [7] 398718 0
Quality of life marker 4 is assessing the patients AF and quality of life and will be assessed using the European Heart Rhythm Association score
Timepoint [7] 398718 0
Patients will complete questionnaire at Baseline (pre ablation procedure) and 6 and 12 months post ablation procedure
Secondary outcome [8] 398719 0
Markers of endothelial function include asymmetric dimethylarginine (ADMA) and ET-1
collected via blood samples
Timepoint [8] 398719 0
Baseline (pre ablation and randomisation) and 12 months post ablation procedure
Secondary outcome [9] 398720 0
Markers of platelet function include asymmetric mean platelet volume (MPV), thrombin-antithrombin complexes (TAT), P-Selectin, ADP, Collagen, Thrombin collected via blood samples
Timepoint [9] 398720 0
Baseline (pre ablation and randomisation) and 12 months post ablation procedure

Eligibility
Key inclusion criteria
1. Paroxysmal or persistent atrial fibrillation referred for AF ablation. By definition this will include highly symptomatic patients with paroxysmal or persistent AF (ablation is completed as standard of care treatment and not a research study related procedure).
2. Moderate to severe predominant OSA defined as AHI 15 or greater and a central apnoea index/total apnoea index less than 20 percent (diagnosed by either in lab Polysomnography (PSG) or at home WatchPAT device)
3. Age 18 years to less than 80 years old
4. Able and willing to provide informed consent and comply with all testing and requirements.
5. Willing to use CPAP if randomised to the treatment arm
6. Willing to defer CPAP treatment by up to 12 months if randomised to the non-treatment arm.
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of prior AF ablation procedure
2. Presence of other significant structural heart disease
a. Valvular heart disease ( moderate valvular regurgitation or stenosis)
b. Heart failure (Ejection fraction less than 45%; NYHA class 3 or 4)
c. Surgically corrected congenital heart disease (eg ASD repair)
d. Hypertrophic cardiomyopathy
e. Unstable coronary artery disease
f. Severe left atrial enlargement (LA diameter greater than 5.5cm)
3. Presence of other major comorbidities
a. Renal failure (eGFR less than 50)
b. Poorly controlled hypertension
c. COPD
4. AF due to a transient or reversible cause ie: postoperative cardiac or non-cardiac surgery, lung disease, hyperthyroidism
5. Long standing Persistent AF (long standing AF greater than 12 months with nil documentation of SR)
6. Patients in whom central apnoea index/total apnoea index make equal and greater than 20% total apnoeas
7. Patients in whom withholding CPAP is considered unethical:
a. these include patients with clinically severe symptoms of OSA defined as a history
of fall-asleep or near to fall-asleep accident.
b. patients with clinically moderate to severe daytime sleepiness
c. patients who frequent self-reported episodes of sleepiness or drowsiness while
driving
d. person has had motor vehicle crash/es caused by inattention or sleepiness
e. patients in the opinion of the treating doctor, represents a significant driving risk as
a result of a sleep disorder
8. Patient whom wish to commence CPAP treatment after diagnosis of OSA
9. Patients who have previously been diagnosed and treated for OSA
10. Vulnerable Patient
11. Use of opiates or other respiratory depressants

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation, stratified allocation is via centre/site
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/09/2021
Actual
10/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
220
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
ACT,SA,VIC
Recruitment hospital [1] 19748 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 19749 0
Melbourne Private Hospital - Parkville
Recruitment hospital [3] 19750 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 19751 0
Ashford Community Hospital - Ashford
Recruitment hospital [5] 19752 0
The Canberra Hospital - Garran
Recruitment hospital [6] 19753 0
St Vincents & Mercy Private Hospital - Mercy campus - East Melbourne
Recruitment hospital [7] 19754 0
Epworth Richmond - Richmond
Recruitment hospital [8] 19758 0
The Alfred - Melbourne
Recruitment hospital [9] 19759 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [10] 19761 0
Western Hospital - Footscray - Footscray
Recruitment hospital [11] 23097 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 34389 0
3050 - Parkville
Recruitment postcode(s) [2] 34390 0
3052 - Parkville
Recruitment postcode(s) [3] 34391 0
5000 - Adelaide
Recruitment postcode(s) [4] 34392 0
5035 - Ashford
Recruitment postcode(s) [5] 34393 0
2605 - Garran
Recruitment postcode(s) [6] 34394 0
3002 - East Melbourne
Recruitment postcode(s) [7] 34395 0
3121 - Richmond
Recruitment postcode(s) [8] 34399 0
3004 - Melbourne
Recruitment postcode(s) [9] 34400 0
3144 - Malvern
Recruitment postcode(s) [10] 34402 0
3011 - Footscray
Recruitment postcode(s) [11] 38452 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 308869 0
Hospital
Name [1] 308869 0
Melbourne Health (Royal Melbourne Hospital)
Country [1] 308869 0
Australia
Funding source category [2] 308871 0
Commercial sector/Industry
Name [2] 308871 0
Itamar Medical
Country [2] 308871 0
Israel
Funding source category [3] 312174 0
Commercial sector/Industry
Name [3] 312174 0
ResMed Pty Ltd
Country [3] 312174 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health (Royal Melbourne Hospital)
Address
300 Grattan Street, Parkville VIC 3050
Country
Australia
Secondary sponsor category [1] 309788 0
None
Name [1] 309788 0
Address [1] 309788 0
Country [1] 309788 0
Other collaborator category [1] 281858 0
Hospital
Name [1] 281858 0
Royal Adelaide Hospital
Address [1] 281858 0
Port Rd, Adelaide SA 5000
Country [1] 281858 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308775 0
Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 308775 0
Ethics committee country [1] 308775 0
Australia
Date submitted for ethics approval [1] 308775 0
Approval date [1] 308775 0
25/05/2021
Ethics approval number [1] 308775 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111838 0
Prof Jonathan Kalman
Address 111838 0
Heart Rhythm Services
Royal Melbourne Hospital
300 Grattan Street, Parkville VIC 3050
Country 111838 0
Australia
Phone 111838 0
+61 393425400
Fax 111838 0
Email 111838 0
[email protected]
Contact person for public queries
Name 111839 0
Danielle West
Address 111839 0
Royal Melbourne Hospital
Clinical Trials Centre, Level 2 SouthWest,
300 Grattan Street, Parkville VIC 3050
Country 111839 0
Australia
Phone 111839 0
+61 457028116
Fax 111839 0
Email 111839 0
[email protected]
Contact person for scientific queries
Name 111840 0
Jonathan Kalman
Address 111840 0
Heart Rhythm Services
Royal Melbourne Hospital
300 Grattan Street, Parkville VIC 3050
Country 111840 0
Australia
Phone 111840 0
+61 393425400
Fax 111840 0
Email 111840 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Raw data from the WatchPAT equipment and study results
When will data be available (start and end dates)?
Raw data and study results will be made available to Itamar Medical Ltd after first publication by the CPI/sponsor. No end date, available once sponsor has done analysis and publication.
Available to whom?
Raw data from the WatchPAT equipment and study results will be shared outside of the investigator team to the manufacture of the WatchPAT device - Itamar Medical Ltd, after investigator has done the analysis and publication of results.
Available for what types of analyses?
Following publication, the study results and raw watchpat data may be used by Itamar for research, development, promotional and/or educational purposes.
How or where can data be obtained?
Raw watchPAT data and study results will be obtained through secured data transfer.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.