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Trial registered on ANZCTR


Registration number
ACTRN12616001436460
Ethics application status
Approved
Date submitted
9/10/2016
Date registered
14/10/2016
Date last updated
20/02/2019
Date data sharing statement initially provided
20/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
CAPLA trial: Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein antral isolation (PVAI) vs PVAI with posterior left atrial wall isolation (PWI).
Scientific title
CAPLA trial: Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein antral isolation (PVAI) vs PVAI with posterior left atrial wall isolation (PWI).
Secondary ID [1] 290288 0
Nil known
Universal Trial Number (UTN)
U1111-1188-4736
Trial acronym
CAPLA study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation 300525 0
Condition category
Condition code
Cardiovascular 300389 300389 0 0
Other cardiovascular diseases
Surgery 300391 300391 0 0
Surgical techniques

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. name / Phrase: CAPLA trial: Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation (PVI) vs PVI with post Left Atrial wall isolation (PWI).

2. Goal / Elements: Atrial fibrillation (AF) ablation also known as pulmonary vein isolation (PVI) has become standard practice and recommended for patients with symptomatic paroxysmal AF (PAF). However, the optimal ablation strategy for patients with persistent atrial fibrillation (PsAF) is not known. Current guidelines recommend use of PVI only in this patient population which we also know is ineffective. Recent evidence has shown that posterior wall isolation (PWI) in addition to PVI may offer benefit in patients with PsAF. Hence we have designed this randomised trial comparing PVI alone vs PVI + PWI and assess 12 month outcomes.

3. Materials: This trial incorporates standard practice for patients with PsAF. All patients will be seen at our arrhythmia clinic with written information provided about atrial fibrillation and the management options available as per routine care. If they are selected for intervention based on clinical and standard management guidelines, they will then be offered enrollment in our trial. If they choose to, addition written information will be provided at that point about the interventions. All trial patients will be followed up closely at 3, 6 and 12 months after intervention.

4. Procedures: Standard / Routine pulmonary vein isolation will be performed in all patients. The additional step in those randomised to the posterior wall isolation will involve a roof and inferior line that is also considered routine care in patients with persistent atrial fibrillation. The standard procedure involves minimally invasive procedure in which patient is taken to the cardiac catheter laboratory. Procedure performed under general anaesthesia. femoral venous access obtained through with catheters are advanced into the heart. The pulmonary veins in the left atrium are targeted with radio frequency ablation using special catheters that can deliver radiofrequency energy to the atrial tiuuse. At the end of the procedure, all sheaths and catheters removed from body.

5. Care provided by Cardiologist and Electrophysiologists who will be looking after the patients regardless of whether they are part of the trial.

6 & 7. Modes of delivery locations: Care and intervention will be provided directly. Location will be tertiary hospitals.

8. Intervention: Interventions will be performed once as part of the trial. Subsequent intervention will be based on patients’ clinical indication and the physician recommendation. Approximate duration of procedure in the PVI group is 2.5 hours. The PVI + PWI group is expected to be slightly longer at approximately 3 hours.

9 & 10. Tailoring or modification: During the ablation, the proceduralist will decide if any additional intervention is clinically necessary or recommended as part of patient care. Any intervention required for the benefit of the patient will be undertaken as needed.
Intervention code [1] 296091 0
Treatment: Surgery
Comparator / control treatment
The control arm will be standard pulmonary vein isolation only without the additional posterior wall isolation. The procedure is expected to take approximately 2.5 hours.
Control group
Active

Outcomes
Primary outcome [1] 299836 0
Single procedure success rate (i.e No documented AF >30 seconds) off antiarrhythmic drugs at 12 months. This specific outcome of recurrence of AF is evaluated in all patients. If they require the use of anti arrhythmic therapy after their procedure, it reflects potential recurrence, hence it is a primary outcome. A new secondary outcome is added which reflects the other group: Single procedure success rate (i.e No documented AF >30 seconds) on antiarrhythmic drugs at 12 months. Recurrence of AF for >30 seconds, assessed by 7 day holter monitor, AliveCor rhythm monitoring system, implantable loop recorder or ECG
Timepoint [1] 299836 0
AF or atrial tachyvcardia recurrence over 12 months
Secondary outcome [1] 328251 0
Procedural duration.

Documented in patient records. Assessed by review of medical records
Timepoint [1] 328251 0
Procedural duration, assessed immediately following end of procedure.
Secondary outcome [2] 328298 0
Fluoroscopy time

Documented in patient records at the time of procedure.
Timepoint [2] 328298 0
Assessed immediately following end of procedure.
Secondary outcome [3] 328299 0
Requirement for antiarrhythmic medication beyond 3 months

Documented during the 3, 6 and 12 months follow up visits.
Timepoint [3] 328299 0
Assessed at 3, 6 and 12 months
Secondary outcome [4] 328300 0
Success after multiple procedures at 12 months off Anti arrhythmic drug (AAD)s

Success after multiple procedures refers to pateints who have more than one procedure for their atrial fibrillation either due to recurrence or due to new atrial flutter.

This outcome is measured in all pateints undergoing multiple procedures. Whether it is with or without antiarrhythmic therapy is then further evaluated.

Off antiarrhytmics refers to patients who do not have the need for AADs after their ablation procedures.

Documented during the 3, 6 and 12 months follow up visits.
Timepoint [4] 328300 0
Assessed at 3, 6 and 12 months
Secondary outcome [5] 328301 0
Success after multiple procedures at 12 months on AADs

Success after multiple procedures refers to pateints who have more than one procedure for their atrial fibrillation either due to recurrence or due to new atrial flutter.

This outcome is measured in all pateints undergoing multiple procedures. Whether it is with or without antiarrhythmic therapy is then further evaluated.

Documented at 12 month follow up
Timepoint [5] 328301 0
Assessed at 12 month follow up
Secondary outcome [6] 328303 0
AFEQT and AF6 questionnaires documented at the initial review, then at 3, 6, 9 and 12 months.
Timepoint [6] 328303 0
Assessed prior to ablation procedure and at 12 months follow up
Secondary outcome [7] 328304 0
Canadian Cardiovascular Society Severity in AF Score (CSS-SAF)

Documented at the initial review pre procedure and at 12months follow up visit
Timepoint [7] 328304 0
Assessed prior to ablation procedure and at 12 months follow up
Secondary outcome [8] 328305 0
Echocardiographic dimensions (LA dimensions and volume, left ventricular end-systolic and end-diastlic dimensions)

Documented in patient records at the routine pre procedure echocardiogram
Timepoint [8] 328305 0
Assessed at the initial review prior to ablation procedure
Secondary outcome [9] 328350 0
Single procedure success rate (i.e No documented AF >30 seconds) on antiarrhythmic drugs at 12 months.

Recurrence of AF for >30 seconds, assessed by 7 day holter monitor or ECG
Timepoint [9] 328350 0
AF recurrence - assessed at 12 months post procedure
Secondary outcome [10] 342095 0
Complication rates at 12 months (including pulmonary vein stenosis, perforation, tamponade, stroke) Complications will be documented immediately at the time of procedure and during the follow up visits at 3, 6 and 12 months.
Timepoint [10] 342095 0
Complications: Assessed at time of procedure and during follow up at 3,6 and 12 months.
Secondary outcome [11] 342096 0
Long term outcomes of ablation technique based on percentage of low voltage area or percentage of scar over the posterior wall.
Timepoint [11] 342096 0
This will be assessed as part of usual follow up at 3,6,9 and 12 months
Secondary outcome [12] 342097 0
Echocardiographic dimensions (LA dimensions and volume, left ventricular end-systolic and end-diastolic dimensions) and relation to long term success
Timepoint [12] 342097 0
This will be assessed during follow up at 3, 6 , 9 and 12 months
Secondary outcome [13] 342098 0
Assess cut off of AF burden that impacts on patients quality of life
Timepoint [13] 342098 0
This will be performed once 12 months follow up is complete
Secondary outcome [14] 342099 0
Improvement of AF burden by >90% post ablation
Timepoint [14] 342099 0
This will be oerfoemed once 12 month follow up is completed
Secondary outcome [15] 342100 0
Percentage completion of various linear ablations and posterior wall isolation with linear ablation only.
Timepoint [15] 342100 0
This data will be available immediately post procedure at the end of the procedure.
Secondary outcome [16] 348669 0
In patients with BMI >32, Success (i.e No documented AF >30 seconds) after AF ablation at 12 months with or without AADs This outcome is measured in all patients undergoing multiple procedures. Whether it is with or without antiarrhythmic therapy is then further evaluated. Documented at 12 month follow up
Timepoint [16] 348669 0
Assessed at 12 months
Secondary outcome [17] 367149 0
Percentage success of linear ablations. This will be assessed at the time of ablation procedure. Linear lines will be checked at the completion of procedure an will be docuemented in the procedure report as per usual routine practice.
Timepoint [17] 367149 0
During initial procedure
Secondary outcome [18] 367150 0
Evaluation of change in HADS score during follow up
Timepoint [18] 367150 0
At 12 months
Secondary outcome [19] 367151 0
Long term outcomes of ablation technique based on percentage of low voltage area (<0.5mV) / scar (<0.05mV) over the posterior wall. This will be assessed based on AF recurrence during the follow up period.
Timepoint [19] 367151 0
At 12 months

Eligibility
Key inclusion criteria
Patients aged 18 to 80 yeasr old with symptomatic documented persistent AF who have trialled and failed to antiarrhythmic therapy
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Paroxysmal AF. Patients with permanent or chronic persistent AF > 18months. AF secondary to reversible cause such as thyrotoxicosis or severe untreated sleep apnoea. Patients with contra indication to anticoagulation. Creatinine >200, End stage renal or hepatic failure. Severe valvular heart disease or cyanotic congenital heart disease.

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)
Centralised computer randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using coin-toss
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
We are planning a study of independent cases and controls with 1 control per case. Prior data, indicate that the failure rate among PVI only arm is approximately 60%. If the true failure rate for Box isolation is 15%, we will need to study 152 in each arm to be able to reject the null hypothesis that the failure rates for experimental and control subjects are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05. We will use a continuity-corrected chi-squared statistic or Fisher’s exact test to evaluate this null hypothesis. Assuming a modest drop out rate of 10%, we will need about 167 patients in each group. Comparisons between groups will be performed with either an unpaired Student’s T-Test or where a normal distribution cannot be assumed, the Mann Whitney U test. All statistical analyses will be performed using SPSS or Stata (12 or higher), StataCorp LP, College Station, TX 77845. Data will be expressed as percentages and frequencies for categorical data of patients, and as means +/- SD for normally distributed variables, and ranges for non-normally distributed variables. Differences in proportions will be compared by a chi-squared analysis or Fisher’s Exact Test. Comparisons between groups will be performed with either an unpaired Student’s T-Test or where a normal distribution could not be assumed the Mann Whitney U test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6784 0
The Alfred - Prahran
Recruitment hospital [2] 6785 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 6786 0
Melbourne Private Hospital - Parkville
Recruitment hospital [4] 9813 0
Cabrini Hospital - Malvern - Malvern
Recruitment postcode(s) [1] 14440 0
3004 - Prahran
Recruitment postcode(s) [2] 14441 0
3050 - Parkville
Recruitment postcode(s) [3] 14442 0
3052 - Parkville
Recruitment postcode(s) [4] 18593 0
3144 - Malvern
Recruitment outside Australia
Country [1] 8297 0
United Kingdom
State/province [1] 8297 0
Oxford University Hospital
Country [2] 8298 0
New Zealand
State/province [2] 8298 0
Waikato Hospital, Hamilton
Country [3] 9497 0
Canada
State/province [3] 9497 0
BC

Funding & Sponsors
Funding source category [1] 294660 0
Hospital
Name [1] 294660 0
Alfred Hospital
Address [1] 294660 0
55 Commercial Rd, Melbourne VIC 3004, Australia
Country [1] 294660 0
Australia
Funding source category [2] 294663 0
Hospital
Name [2] 294663 0
Royal Melbourne Hospital
Address [2] 294663 0
300 Grattan St, Parkville VIC 3050, Australia
Country [2] 294663 0
Australia
Funding source category [3] 294664 0
Hospital
Name [3] 294664 0
Melbourne Private Hospital
Address [3] 294664 0
Royal Parade, Parkville VIC 3052, Australia
Country [3] 294664 0
Australia
Funding source category [4] 294665 0
Hospital
Name [4] 294665 0
Royal Adelaide Hospital
Address [4] 294665 0
North Terrace, Adelaide SA 5000, Australia
Country [4] 294665 0
Australia
Funding source category [5] 294666 0
Hospital
Name [5] 294666 0
Papworth Hospital
Address [5] 294666 0
Papworth Everard, Cambridge CB23 3RE, United Kingdom
Country [5] 294666 0
United Kingdom
Funding source category [6] 294667 0
Hospital
Name [6] 294667 0
Waikato Hospital
Address [6] 294667 0
Selwyn Street and Pembroke Street, Hamilton 3204, New Zealand
Country [6] 294667 0
New Zealand
Primary sponsor type
Hospital
Name
Alfred Hospital
Address
55 Commercial Rd, Melbourne VIC 3004, Australia
Country
Australia
Secondary sponsor category [1] 293516 0
None
Name [1] 293516 0
Address [1] 293516 0
Country [1] 293516 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296096 0
Alfred hospital
Ethics committee address [1] 296096 0
55 Commercial road, Melbourne, Vic 3004
Ethics committee country [1] 296096 0
Australia
Date submitted for ethics approval [1] 296096 0
24/10/2016
Approval date [1] 296096 0
11/05/2017
Ethics approval number [1] 296096 0

Summary
Brief summary
What is known?
PVAI for AF is the standard of care in people with symptomatic paroxysmal AF (class I indication) but the next step in ablation for people with persistent AF is unknown. A major international landmark trial has yielded neutral results with some forms of additional ablation but the effect of PWI + PVAI has not been formally assessed in a multicentre randomised trial.

What this study adds?
Multicentre randomised trial assessing the effect of adding PWI to PVAI in persistent AF on 12-month arrhythmia free survival.

Primary Endpoints
Recurrence of AF for >30 seconds. Single procedure success rate off antiarrhythmic drugs at 12 months.
Complication rates at 12 months (including pulmonary vein stenosis, perforation, tamponade, stroke)

Secondary Endpoints
Procedural duration
Fluoroscopy time
Requirement for antiarrhythmic medication beyond 3 months
Success after multiple procedures at 12 months off AADs
Success after multiple procedures at 12 months on AADs
Quality of life (SF-36 questionnaire)27
AF Severity Score (AFSS)28
Canadian Cardiovascular Society Severity in AF Score (CSS-SAF)29
Echocardiographic dimensions (LA dimensions and volume, left ventricular end-systolic and end-diastlic dimensions)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69530 0
Prof Peter Kistler
Address 69530 0
Alfred Hospital
55 Commercial Road, Melbourne Vic 3004
&
Baker IDI Heart & Diabetes institute
75 Commercial Road, Melbourne Vic 3004
Country 69530 0
Australia
Phone 69530 0
+61 3 9076 2000
Fax 69530 0
Email 69530 0
peter.kistler@bakeridi.edu.au
Contact person for public queries
Name 69531 0
Dr Hariharan Sugumar
Address 69531 0
Alfred Hospital
55 Commercial Road, Melbourne Vic 3004
&
Baker IDI Heart & Diabetes institute
75 Commercial Road, Melbourne Vic 3004
Country 69531 0
Australia
Phone 69531 0
+61 3 9076 2000
Fax 69531 0
Email 69531 0
hsugumar@yahoo.com
Contact person for scientific queries
Name 69532 0
Dr Hariharan Sugumar
Address 69532 0
Alfred Hospital
55 Commercial Road, Melbourne Vic 3004
&
Baker IDI Heart & Diabetes institute
75 Commercial Road, Melbourne Vic 3004
Country 69532 0
Australia
Phone 69532 0
+61 3 9076 2000
Fax 69532 0
Email 69532 0
hsugumar@yahoo.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only Anonymous and de-identified patient information will be collected
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 1407 0
Study protocol
Citation [1] 1407 0
Link [1] 1407 0
Email [1] 1407 0
Other [1] 1407 0
Protocol V 18
Summary results
No Results