Clinical trial NCT01924377: Characterization and Elimination of Mother Rotors
Official title: Characterization and Elimination of Mother Rotors - A Mechanism-targeted Approach for Catheter Ablation of Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Atrial Fibrillation
Keywords: AF
Lead sponsor: Maria Cecilia Hospital
Sponsor class: OTHER
Collaborators: name: Ettore Sansavini Health Science Foundation
name: Mediolanum Cardio Research
First posted: 2013-08-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recent clinical studies have shown that atrial fibrillation (AF) in humans might be sustained by localized sources called "mother rotors" which exhibit persistent, fast, and well organized activity during AF and play an important role in the generation and maintenance of the fibrillatory activity. In this study, investigators aim to identify the electrophysiological characteristics of mother rotors during atrial fibrillation in patients with paroxysmal and persistent AF and to test whether ablation of such patient-specific substrates might improve the acute and long-term success of conventional catheter ablation therapy.

Detailed description: The present study is designed as a prospective, single-centre, randomized, single-blind, controlled, 2-arm parallel group trial.

The study will consist of:

i) a two-month screening period; ii) randomization and treatment phase; iii) a follow-up phase lasting up to 24 months. Patients with paroxysmal or persistent atrial fibrillation referred to the centre to undergo catheter ablation procedure will be screened. It is expected that approximately 260 patients will be screened in order to have 234 patients fulfilling inclusion criteria at the end of the screening period. The sample will include 154 patients with paroxysmal AF and 80 patients with persistent AF. Paroxysmal and persistent AF will be defined according to current ESC guidelines.

Patients fulfilling selection criteria, will be informed of the study and asked for participation. The study requirements, including required testing, will be discussed with the subject. A signed Informed Consent Form for study participation must be obtained prior to any study-related procedure. Patients will be given a daily diary for recording AF-related signs and symptoms and instructed to bring it back at the inclusion visit.

Eligible patients will be randomised using a web-based randomization system embedded in the electronic CRF (e-CRF).

A randomization schedule, stratified by AF type, using balanced blocks will be established before the start of the trial.

Patients will be randomised to one of the two ablation procedures:

* standard circumferential pulmonary vein isolation (CPVI)
* CPVI followed by rotors' identification and ablation (CPVI + Rotor.

The acute endpoint for AF ablation procedure is electrical isolation of the pulmonary veins and non inducibility of AF by atrial extrastimuli.

Rotors are defined as fast and persistent electrical activation with intracardiac electrograms of regular cycle lengths shorter than 240 ms with stable isoelectric line between two adjacent activation.

The acute endpoints for rotors are their identification by predefined mapping characteristics and their elimination by radiofrequency ablation after circumferential pulmonary vein isolation.

Antiarrhythmic medications may be continued for the first 3 months following the first ablation to avoid early recurrences. At 3 months, antiarrhythmics must be stopped to assess for clinical recurrence.

Freedom from symptomatic AF, atrial tachycardia, and atrial flutter off antiarrhythmic drug therapy as assessed from the end of the 3 months blanking period to 12 months following the ablation procedure, and documented by implantable loop recorder monitoring or trans-telephonic (TT) ECG monitoring.

AF episodes \> 10 minutes documented by implantable loop recorder registrations or daily trans-telephonic (TT) ECG will be recorded in the e-CRF, clearly identified by date and time of occurrence. Total duration of the episode will also be recorded. In addition, presence of symptoms, as reported by the patient in the daily diary will be sought.

A Clinical Events Committee (CEC) made up of three cardiologists and arrhythmologists who are not participants in the study will review and adjudicate, symptomatic and asymptomatic AF recurrences.

The Clinical Research Unit staff will support the Investigator and the Sponsor to maintain a high level of ethical, scientific, technical and regulatory quality in all aspects of the Clinical Trial. At regular intervals during the Clinical Trial, the Clinical Research Unit staff will review study progress and any emergent problems. Random source data verification will be performed.

Data will be collected by means of an electronic e-CRF, FDA 21 CFR part 11 compliant.

A detailed Statistical Analysis Plan will be issued.

Eligibility criteria: Inclusion Criteria:

* Patients with paroxysmal or persistent atrial fibrillation referred to the centre to undergo catheter ablation procedure
* Age between 18 and 85 years
* Ability to provide informed consent for study participation and be willing and able to comply with study evaluations and follow-up schedule
* AF burden equal to or greater than 24 hours in the screening period before enrollment

Exclusion Criteria:

* Previous AF ablation
* Secondary AF
* Hyperthyroidism
* Left ventricular ejection fraction \<30%
* NYHA functional class IV
* Left atrial area \> 35 cm2
* Uncorrected severe valvular heart disease
* Contraindication to anticoagulation
* Presence of left atrial thrombus
* Recent (\<6 Months) myocardial Infarction or unstable angina or coronary artery by-pass
* Thoracic surgery for congenital, valvular or aortic disease
* History of cerebrovascular accidents
* Pregnancy
* Significant comorbidities such as cancer, severe renal insufficiency requiring hemodialysis, severe obstructive lung disease, cirrhosis, with a life expectancy less than 1 year.

Primary outcomes:
measure: freedom from symptomatic AF, atrial tachycardia, and atrial flutter
timeFrame: from the end of the 3 months blanking period to 12 months following the ablation proce
Secondary outcomes:
measure: Freedom from asymptomatic AF, atrial tachycardia, and atrial flutter off antiarrhythmic drug
timeFrame: from the end of the 3 months blanking period to 12 months following the ablation procedure
measure: One year clinical/partial success rate
timeFrame: 12 months following the ablation procedure
measure: Number of Rotors electrograms
timeFrame: at time of pre-ablation electrophysiological mapping
measure: anatomical locations of Rotors electrograms
timeFrame: at time of pre-ablation electrophysiological mapping
measure: characteristics of Rotors electrograms
timeFrame: at time of pre-ablation electrophysiological mapping
Other outcomes:
measure: a potential relationship between baseline AF burden, number of rotors and outcome
timeFrame: up to 12 months following the ablation procedure
Locations:
city: Cotignola
country: Italy
facility: Maria Cecilia Hospital
state: Ravenna
Study officials:
affiliation: Maria Cecilia Hospital
name: Carlo Pappone, MD
role: PRINCIPAL_INVESTIGATOR
References: