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Trial registered on ANZCTR

Registration number

ACTRN12614001231639

Ethics application status

Approved

Date submitted

21/10/2014

Date registered

25/11/2014

Date last updated

25/11/2014

Type of registration

Retrospectively registered

Titles & IDs

Public title

Paroxysmal Atrial Fibrillation Ablation: complex fractionated atrial electrograms ablation in addition to pulmonary vein isolation versus pulmonary vein isolation

Scientific title

Patients with paroxysmal Atrial Fibrillation Ablation: complex fractionated atrial electrograms ablation in addition to pulmonary vein isolation versus pulmonary vein isolation alone on maintenance of sinus rhythm. (PAFA-SP)

Secondary ID [1]

none

Universal Trial Number (UTN)

Trial acronym

PAFA-SP

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Paroxysmal atrial fibrillation

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Surgery

Surgical techniques

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Pulmonary vein isolation (PVI) during paroxysmal Atrial Fibrillation (75 patients): During the procedure, 4 catheters were introduced via the right femoral vein under lidocaine local anesthesia. A decapolar catheter (InquiryTM St. Jude Medical Inc., St.Paul, MN, USA) was positioned inside the coronary sinus (CS) and a tetrapolar catheter (SupremeTM CRD-2, St. Jude Medical Inc., St.Paul, MN, USA) on the His bundle. Left atrium access was obtained by a single interatrial septal puncture with a BRK needle (St. Jude Medical Inc., St.Paul, MN, USA). Subsequently a circumferential decapolar catheter for pulmonary vein mapping (AFocusIITM 10 pole with a 20 mm diameter; St. Jude Medical Inc., St.Paul, MN, USA) , and the ablation catheter as were positioned into the left atrium.
The ablation was performed with open irrigated ablation catheter Therapy Cool Path DuoTM (St. Jude Medical Inc., St.Paul, MN, USA). 3-D electroanatomic mapping was performed using EnSite NavXTM-software version 8.0 (St. Jude Medical Inc., St.Paul, MN, USA). The time of the procedure never exceeded four hours.
The first objective was to systematically isolate all segmental ostial pulmonary veins. Pulmonary vein isolation was confirmed by entrance block.
Repeated electrophysiological procedures were carried out for recurrent atrial arrhythmias (after the blanking period or 3 months). The first objective was to assess pulmonary vein reconduction, followed by electrical re-isolation.

Intervention code [1]

Treatment: Surgery

Comparator / control treatment

Complex fractionated atrial electrograms ablation in addition to pulmonary vein isolation (75 patients): During the procedure, 4 catheters were introduced via the right femoral vein under lidocaine local anesthesia. A decapolar catheter (InquiryTM St. Jude Medical Inc., St.Paul, MN, USA) was positioned inside the coronary sinus (CS) and a tetrapolar catheter (SupremeTM CRD-2, St. Jude Medical Inc., St.Paul, MN, USA) on the His bundle. Left atrium access was obtained by a single interatrial septal puncture with a BRK needle (St. Jude Medical Inc., St.Paul, MN, USA). Subsequently a circumferential decapolar catheter for pulmonary vein mapping (AFocusIITM 10 pole with a 20 mm diameter; St. Jude Medical Inc., St.Paul, MN, USA) , and the ablation catheter as were positioned into the left atrium.
The ablation was performed with open irrigated ablation catheter Therapy Cool Path DuoTM (St. Jude Medical Inc., St.Paul, MN, USA). 3-D electroanatomic mapping was performed using EnSite NavXTM-software version 8.0 (St. Jude Medical Inc., St.Paul, MN, USA).
The first objective was to systematically isolate all segmental ostial pulmonary veins. Pulmonary vein isolation was confirmed by entrance block. If atrial fibrillation (AF) persisted after pulmonary vein isolation, the procedure was continued using electrogram-guided ablation for complex fractionated atrial electrograms. Complex fractionated atrial electrograms were defined as atrial electrograms with a cycle length (CL) =120 milliseconds or atrial electrograms with fractionation composed of =2 defections and/or with continuous baseline activity. After the creation of left atrial lesions, radiofrequency application was continued inside the coronary sinus and in the right atrium if the right appendage cycle length was shorter than the left, especially at the cavotricuspid isthmus, superior vena cava, crista terminalis and right atrial septum. The tachycardia cycle length was monitored in both the right and the left atrial appendage to assist in determining the optimal site of ablation. If AF converted into atrial tachycardia (AT), activation mapping and catheter ablation of these tachycardias were performed until restoration of SR. ATs were ablated if a patient had =1 stable AT. Atrial tachycardia was defined as organized atrial rhythm with a stable CL, a consistent endocardial activation sequence in both atria and a monomorphic P wave. The endpoint for complex fractionated electrogram (CFE) ablation was (i) the elimination of all CFE sites in the left atrium (LA), CS, and right atrium (RA), and termination of AF with (ii) non-inducibility of AF post-ablation. If AF did not terminate after eliminating all the CFE sites, sinus rhythm was restored by electrical cardioversion. After the restoration of sinus rhythm, the induction of atrial fibrillation was again attempted; if the arrhythmia was not inducible, the procedure was stopped and if AF was still inducible, the ablation continued until the its noninducibility. Atrial fibrillation was considered inducible if it lasted more than 1 min.The time of the procedure never exceeded four hours.
Repeated electrophysiological procedures were carried out for recurrent atrial arrhythmias (after the blanking period or 3 months). The first objective was to assess pulmonary vein reconduction, followed by electrical re-isolation. The aim of electrogram-guided ablation was the restoration of sinus rhythm , or all complex fractionated atrial electrograms (CFAEs) abolished or reduced in amplitude (>80%).

Control group

Active

Outcomes

Primary outcome [1]

Outcome of atrial fibrillation ablation after pulmonary vein isolation or a stepwise approach.

"Procedure success" is defined as freedom from atrial arrhythmia (atrial fibrillation, atrial flutter, atrial tachycardia) off antiarrhythmic drug during follow-up after first and second ablation.
"Procedure failure" is defined as atrial arrhythmia recurrence during follow-up .

The primary outcome of the study was freedom from AF recurrency 3 and 12 months after ablation (excluding the pre-specified blanking period from months 0 to 3). Evaluation included assessment of arrhythmia-related symptoms, adverse events, treatment adherence and any additional therapy since the previous follow-up visit and a 12-lead electrocardiogram. A 48-hour Holter monitoring was also performed every month, and in addition to clinical examinations (the questionnaire was designed for this study), a structured questionnaire was administered to record arrhythmia recurrence and any other symptom.

Timepoint [1]

Time Frame: After first and second catheter ablation, all patients were followed up in our outpatient clinic at 1week, 2 weeks, 1 month, 2,3,6 and 12 months

Secondary outcome [1]

In patients who experience "procedure failure" (defined above), a re-do ablation may be performed. Then the patients will be followed-up again for atrial arrhythmia (atrial fibrillation, atrial flutter, atrial tachycardia) recurrence.Evaluation included assessment of arrhythmia-related symptoms, adverse events, treatment adherence and any additional therapy since the previous follow-up visit and a 12-lead electrocardiogram. A 48-hour Holter monitoring was also performed every month, and in addition to clinical examinations (the questionnaire was designed for this study), a structured questionnaire was administered to record arrhythmia recurrence and any other symptom.

Timepoint [1]

After first and second catheter ablation, all patients were followed up in our outpatient clinic at 1week, 2 weeks, 1 month, 2,3,6 and 12 months

Eligibility

Key inclusion criteria

The inclusion criteria is paroxysmal atrial fibrillation was defined accordingly to the Task Force for the Management of Atrial Fibrillation of ESC/ECATS 2007

Minimum age

18 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Persistent atrial fibrillation, permanent atrial fibrillation.

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)

Randomization was carried out by the statistical unit using a computer-generated random-table.The code was revealed to the researchers once recruitment, data collection and all analyses were completed.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

The differences in AF/AT recurrence rate according to type of ablation and other recorded variables were initially examined using chi-squared test for categorical variables and t-test for continuous variables. Cox proportional hazards analysis was then used to compute the adjusted relative hazards of AT and/or AF recurrence by each variable, after both the first and the second ablation procedures. The dependent variable was recurrence of either AF or AT in both models. We recorded the following variables, all of which were a priori considered for inclusion in multivariate analysis: age, gender, BMI, current cigarette smoking, hypertension, diabetes, dyslipidemia, ischemic heart disease, left ventricular hypertrophy, valvular heart disease, idiopathic dilated cardiomiopathy, AF duration, number of AF episodes per month, left atrial size and volume, left ventricle ejection fraction, antiarrhythmics, amiodarone, beta-blockers and calcium channel blockers use, procedural, radiofrequency and fluoroscopy time, Complex Fractionated Atrial Electrograms (CFAEs) and ablation complications. Covariates were selected for inclusion in final models using a stepwise forward process with the following inclusion criteria: p-value less than 0.15 at univariate analysis and equal to20% change in the hazard ratio of significant predictors. Age and procedure complications were forced to entry. A minimum events-to-variable ratio of 10 was maintained in multivariate modeling to avoid overfitting, and Schoenfeld’s test was carried out to check the validity of proportional hazards assumption. There were no missing values. A p-value of less than 0.05 was considered significant for all analyses.
The sample size estimation was based on the following conservative assumptions: Alpha equal to 0.05; mean SD maintance of sinus rhythmin both the pulmonary vein isolation and the stepwise ablation groups. Using the above parameters, minimum 100 patients were needed to achieve 90% power with 10% expected withdrawals/dropouts.
Statistical significance was defined as a two-sided p-value less than 0.05; all analyses were carried out using STATA statistical software, version 13.1 (Stata Corporation, College Station, Texas, USA, 2013).

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

1/01/2007

Actual

1/01/2007

Date of last participant enrolment

Anticipated

30/06/2013

Actual

28/06/2013

Date of last data collection

Anticipated

Actual

Sample size

Target

150

Accrual to date

Final

Recruitment outside Australia

Country [1]

Italy

State/province [1]

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

Individual

Name

Massimiliano Faustino

Address

Electrophysiology Operating Unit, Cardiovascular Department, “Spirito Santo” Via Fonte Romana no. 8 Hospital, ASL Pescara, 65124 Pescara, Italy

Country

Italy

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Azienda USL Pescara

Ethics committee address [1]

Via Fonte Romana no.8 Hospital, ASL Pescara, 65124 Pescara, Italy

Ethics committee country [1]

Italy

Date submitted for ethics approval [1]

Approval date [1]

17/10/2006

Ethics approval number [1]

Summary

Brief summary

Paroxysmal atrial fibrillation (PAF), arrhythmogenic activity usually originates in the muscle sleeves of the pulmonary veins (PVs) and may trigger and perpetuate the arrythmias. Randomized trials have shown that catheter ablation is superior to antiarrhythmic drug therapy in maintaining sinus rhythm (SR). Circumferential isolation of the PVs has become the cornerstone strategy for PAF catheter ablation with a success rate ranging from 38 - 70% after a single procedure to 65 - 90% after repeated procedures.
Once initiated from a trigger, PAF will not be maintained if the appropriate substrates are not present. The atria of patients with PAF can present very different patterns during electroanatomic mapping due to atrial myocardial fibrosis which is significantly increased in patients with PAF as compared with those in sinus rhythm. There are multiple potential etiological causes for this relationship. Aging and co-existing cardiovascular diseases (e.g. hypertension) are thought to play an important role in the development of myocardial fibrosis and, consequently, in maintaining PAF. In patients with PAF and structural atrial disease, PVs ablation may fail and cause progressive atrial remodeling which explain the recurrences and the development of ‘new’ arrhythmias. Thus alternative approaches aimed at modifying atrial substrates in order to prevent maintaining PAF has been proposed. There is no consensus about the best catheter ablation strategy. The purpose of this prospective study was to determine whether ablation of both CFAEs and PVs is associated with a higher probability of maintaining sinus rhythm as compared to PV isolation alone in patients with PAF refractory to anti-arrhythmic therapy. One hundred fifty patients with paroxysmal AF refractory to at least one anti-arrhythmic drug, were consecutively enrolled for a first-time catheter ablation at Electrophysiology laboratory of Clinica Pierangeli Pescara and Electrophysiology Unit, Cardiovascular Department, “Spirito Santo” Hospital, Pescara between January 2007 and July 2012.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Massimiliano Faustino

Address

“Spirito Santo” Hospital Via Fonte Romana no. 8 Hospital, ASL Pescara, 65124 Pescara, Italy

Country

Italy

Phone

+393473578209

Fax

[email protected]

Contact person for public queries

Name

Dr Massimiliano Faustino

Address

“Spirito Santo” Hospital Via Fonte Romana no. 8 Hospital, ASL Pescara, 65124 Pescara, Italy

Country

Italy

Phone

+393473578209

Fax

[email protected]

Contact person for scientific queries

Name

Dr Massimiliano Faustino

Address

“Spirito Santo” Hospital Via Fonte Romana no. 8 Hospital, ASL Pescara, 65124 Pescara, Italy

Country

Italy

Phone

+393473578209

Fax

[email protected]

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

Current Study Results

No documents have been uploaded by study researchers.

Update to Study Results

Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
4499	Study results article	Yes		doi: 10.1016/j.hrthm.2015.06.009	367296-(Uploaded-21-11-2018-05-50-41)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Stepwise ablation approach versus pulmonary vein isolation in patients with paroxysmal atrial fibrillation: Randomized controlled trial.	2015	https://dx.doi.org/10.1016/j.hrthm.2015.06.009

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically