ANZCTR - Registration

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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]

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

Sleep Apnoea

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Respiratory

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]

Treatment: Devices

Comparator / control treatment

No treatment for OSA, i.e. no CPAP

Control group

Active

Outcomes

Primary outcome [1]

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]

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]

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]

Baseline and at the time of AF ablation.

Secondary outcome [1]

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]

Baseline, 6 and 12 months post ablation

Secondary outcome [2]

24 Holter Monitors: will be used to assess changes of autonomic function

Timepoint [2]

Baseline and 12 months post ablation.

Secondary outcome [3]

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]