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Trial registered on ANZCTR


Registration number
ACTRN12616000088448
Ethics application status
Approved
Date submitted
20/01/2016
Date registered
27/01/2016
Date last updated
9/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of obstructive sleep apnea treatment in patients with atrial fibrillation having ablation: a randomised controlled trial.
Scientific title
Impact of continuous positive airway pressure (CPAP) on freedom from arrhythmia in patients with obstructive SLEEP apnea (OSA) and Atrial Fibrillation (AF) having catheter ablation. (SLEEP-AF Trial)
Secondary ID [1] 287380 0
Nil
Universal Trial Number (UTN)
U1111-1173-8043
Trial acronym
SLEEP-AF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 296068 0
Sleep Apnoea 296069 0
Condition category
Condition code
Cardiovascular 296330 296330 0 0
Other cardiovascular diseases
Respiratory 296331 296331 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi centre prospective randomised controlled trial that aims to evaluate the impact of continuous positive airway pressure (CPAP) for 1 year on recurrence rates of atrial fibrillation in patients with obstructive sleep apnea (OSA) having ablation therapy.

This study will also comprise a sub-study that will evaluate the impact of the intervention on cardiac electroanatomical remodelling and reverse remodelling.

Following diagnosis of at least moderate OSA, patients randomised to the treatment arm will commence CPAP therapy while patients in the control arm will not. CPAP therapy comprises a mask that is worn while sleeping that provides positive airway pressure. All patients randomized to CPAP therapy will receive CPAP education, hands-on demonstration, careful mask fitting and acclimatization prior to titration. Pressures are titrated in the range of 4-20cm H2O until obstructive events are eliminated or maximum CPAP is reach, based on present guidelines for OSA management. The number of visits required for pressure titration will be based on physician clinical judgement. CPAP therapy will commence a minimum of 1 week prior to AF ablation.

Following successful titration, patients will be followed at 3, 6, 9 and 12 months post ablation to assess compliance, efficacy and symptoms. Patients in the control arm will also be followed at these time points for ongoing review.

CPAP adherence will be monitored by clinical evaluation and by utilising the remote monitoring function on CPAP machines.

Ablation procedure:
There is no alteration of the clinical procedure as part of the study protocol.
All patients will undergo Electrophysiology study to rule out supra ventricular tachycardia (SVT) as a cause for atrial fibrillation (Standard Practice at Royal Melbourne Hospital) If found then this tachycardia will be ablated. At a later date if the patient still requires AF ablation, an EP study will be done with activation mapping of both atrium and then wide encircling pulmonary vein antrum isolation will be performed with the aid of electroanatomic mapping and 3-D LA geometry construction. Radiofrequency current from irrigated tip catheters will be the used as the ablation energy. Pre-procedural anti-coagulation will be managed in accordance with local guidelines.

Substrate sub-study:
The sub study will occur during the first year after enrolment commences. Participants of the sub-study will undergo electroanatomical mapping of the right atrium during the initial electrophysiology study for diagnosis and ablation of supra ventricular tachyarrhythmia. Those participants requiring AF ablation at a later date will have right atrial electroanatomical mapping repeated at the time AF ablation. Participants in the sub-study would have been randomised to OSA treatment versus no OSA treatment. Thus we will be able to evaluate the impact of OSA treatment on the AF substrate.

Electrophysiological changes in conduction velocity/ERP and bipolar voltage: EP study will be done at baseline and at the time of AF ablation. Electrophysiology study using diagnostic EP catheter.

Atrial effective refractory period (ERP) will be evaluated at cycle lengths (CL) of 600 and 450 ms with an 8-beat drive followed by an extra- stimulus, starting with an extra-stimulus coupling interval of 150 ms increasing in 10-ms increments. The ERP will be defined as the longest coupling interval failing to propagate to the atrium. At each site the ERP will be measured 3 times during each CL and averaged. If ERP varied by >10 ms, an additional 2 measurements were made, and the total number was averaged. The ERP was measured from the following sites: 1) distal-CS; 2) proximal-CS; 3) low lateral RA; 4) high lateral RA; 5) high septal RA.

Isochronal activation maps (5-ms intervals) of the atria will be created and regional conduction velocity determined in the direction of the wave-front propagation (least isochronal crowding). An approximation of conduction velocity will be determined by expressing the distance between 2 points as a function of the difference in local activation time. Mean conduction velocity for each region will be determined by averaging the conduction velocity between 5 pairs of points, as previously described. For the purposes of evaluating regional conduction differences, each atrium will be segmented as noted in the preceding text.

AF inducibility will be assessed using a standardized protocol of burst pacing in the proximal followed by distal coronary sinus and during programmed extra stimuli from the same sites. Pacing will be started at 200 ms and will be decreased in 5-ms intervals until either AF initiates or there is loss of 1:1 capture. A fixed rate of decrement will be used at 5 ms per 3 seconds to ensure consistency. AF is defined as rapid irregular atrial rhythm lasting longer than 2 seconds. Mean AF duration will be obtained from the average of all induced AF episodes. If AF persists beyond 5 minutes, no further induction will be tried.

Acquired points will also be used to generate bi-polar voltage maps of the atria.
Intervention code [1] 292724 0
Treatment: Devices
Comparator / control treatment
No treatment for OSA, i.e. no CPAP
Control group
Active

Outcomes
Primary outcome [1] 295984 0
AF or atrial tachycardia lasting > 30 seconds assessed by implanted loop recorder or documented ECG occurring after the first 3 months following ablation will constitute the primary outcome.
Timepoint [1] 295984 0
Any atrial arrhythmia (AF or atrial tachycardia) > 30 seconds, occurring 3 months after ablation but within the first year following ablation will be considered having met the primary endpoint.
Primary outcome [2] 297128 0
Substudy evaluating reverse electroanatomical remodelling in response to OSA therapy: Composite outcome of bi-polar voltage, conduction velocity, effective refractory period and AF inducibility assessed using diagnostic EP cathter.
Timepoint [2] 297128 0
Baseline and at the time of AF ablation.
Secondary outcome [1] 317101 0
Cardiac Structure & Function: Composite outcome assessed using transthoracic echocardiographic measures of left and right atrial size, ventricular dimensions, ventricular hypertrophy, systolic function and diastolic function, including measurements of strain and torsion.
Timepoint [1] 317101 0
Baseline, 6 and 12 months post ablation
Secondary outcome [2] 317102 0
24 Holter Monitors: will be used to assess changes of autonomic function
Timepoint [2] 317102 0
Baseline and 12 months post ablation.
Secondary outcome [3] 317103 0
Sleep questionnaires: The Berlin Questionnaire, The Epworth Sleepiness Scale and the STOP-BANG questionnaires will be used to assess symptoms of sleep apnoea.
Timepoint [3] 317103 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [4] 317104 0
AF Symptom questionnaires: including Toronto AF severity scale and European Heart Rhythm Association AF symptom scale.
Timepoint [4] 317104 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [5] 317105 0
Digital ECG's to assess P wave duration and dispersion.
Timepoint [5] 317105 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [6] 317106 0
Inflammation, assessed by composite outcome of of high-sensitivity C-reactive protein (hs-CRP) and Tumour Necrosis Factor Alpha (TNF-a) from venous blood.
Timepoint [6] 317106 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [7] 320104 0
Profibrotic Markers: Composite outcome of Tissue Growth Factor (TGF-ß) and matrix metalloproteinase-9 (MMP-9) will be quantified as markers of fibrosis.
Timepoint [7] 320104 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [8] 320105 0
Composite outcome of platelet aggregation & thrombotic markers: Given the relationship between AF and embolic stroke, we will quantify circulating thrombotic (fibrinogen, plasminogen activator inhibitor 1) and fibrinolytic markers (tissue-plasminogen activator) and 2) platelet aggregation from venous blood samples collected at specified timepoints.
Timepoint [8] 320105 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [9] 320106 0
Composite outcome of endothelial function. We will quantify soluble VCAM and ADMA from venous blood samples collected at specified timepoints.
Timepoint [9] 320106 0
Baseline, 6 months and 12 months post ablation.
Secondary outcome [10] 320107 0
Cardiovascular Risk Factors: Composite outcome of blood pressure, blood lipids (triglycerides, LDL-C, HDL-C) and glycated haemoglobin (HbA1c) will be quantified by venous sampling. Body mass and height will be measured to determine body mass index. Waist circumference will be measured according to standardised methods.
Timepoint [10] 320107 0
Baseline, 6 months and 12 months post ablation.

Eligibility
Key inclusion criteria
Patients having ablation for AF
Patients with at least moderate obstructive sleep apnea defined AHI of 15 or greater.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant pulmonary disease
Life expectancy < 24 months
Severely elevated Epworth Sleepiness Scores that may pose driving risk
Involvement in another trial that will compromise this trial
Reversible cause of AF

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)
All patients referred for catheter ablation of drug-refractory AF are screens for OSA. Patients with at least moderate OSA (AHI >=15) and who meet the above inclusion criteria will be offered entry into the trial. Consenting patients will will be then randomised using a computerised randomisation tool. Upon enrolment and randomisation a unique numerical identifier code will be allocated to each patient for entry into the database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization between 0 (control) and 1 (active) using an electronic random number generator.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Follow up for 12 months post ablation.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2016
Actual
4/03/2016
Date of last participant enrolment
Anticipated
28/12/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
130
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 4475 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 4476 0
Melbourne Private Hospital - Parkville
Recruitment postcode(s) [1] 12570 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [2] 12571 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 291944 0
Hospital
Name [1] 291944 0
Royal Melbourne Hospital (teaching Hopsital of The University of Melbourne) Department of Electrophysiology
Country [1] 291944 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
300 Grattan Street
Royal Melbourne Hospital
Parkville, 3050
Vic
Country
Australia
Secondary sponsor category [1] 290613 0
University
Name [1] 290613 0
The University of Melbourne
Address [1] 290613 0
Parkville Vic
3010
Country [1] 290613 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293441 0
Melbourne Health, Human Research Ethics Committee
Ethics committee address [1] 293441 0
Ethics committee country [1] 293441 0
Australia
Date submitted for ethics approval [1] 293441 0
27/07/2015
Approval date [1] 293441 0
19/08/2015
Ethics approval number [1] 293441 0
HREC/15/MH/356

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

Contacts
Principal investigator
Name 59686 0
Prof Jonathan Kalman
Address 59686 0
Suite 1, Melbourne Heart Centre
Royal Melbourne Hospital
Royal Parade
Parkville Vic, 3050
Australia
Country 59686 0
Australia
Phone 59686 0
+61 3 9349 5400
Fax 59686 0
Email 59686 0
jon.kalman@mh.org.au
Contact person for public queries
Name 59687 0
Chrishan Nalliah
Address 59687 0
Royal Melbourne Hospital
300 Grattan Street
Parkville Vic, 3050
Australia
Country 59687 0
Australia
Phone 59687 0
+61 415 316 498
Fax 59687 0
Email 59687 0
chrishan.nalliah@mh.org.au
Contact person for scientific queries
Name 59688 0
Chrishan Nalliah
Address 59688 0
Royal Melbourne Hospital
300 Grattan Street
Parkville Vic, 3050
Australia
Country 59688 0
Australia
Phone 59688 0
+61 415 316 498
Fax 59688 0
Email 59688 0
chrishan.nalliah@mh.org.au

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseRoutine screening for sleep apnea in patients with atrial fibrillation: Ready for primetime?.2018https://dx.doi.org/10.1016/j.ijcard.2018.02.083
N.B. These documents automatically identified may not have been verified by the study sponsor.