Clinical trial NCT03355456: Low Voltage-Directed Catheter Ablation for Atrial Fibrillation
Official title: Prospective, Multi-center, Randomized, Evaluation Comparing the Protocol Specified Ablation Approach to the Current Standardized Ablation Approach in the Treatment of Non-paroxysmal Atrial Fibrillation.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation - Symptomatic
Keywords: Persistent atrial fibrillation
Medication refractory atrial fibrillation
Pulmonary vein isolation procedure
Low voltage directed ablation
Lead sponsor: MetroHealth Medical Center
Sponsor class: OTHER
Collaborators: name: Biosense Webster, Inc.
First posted: 2017-11-28
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized comparison of two ablation techniques:

1. Pulmonary vein isolation (PVI) alone to
2. PVI plus total left atrial low voltage-directed ablation.
Primary purpose: TREATMENT

Brief summary: A two-pronged approach to evaluate long term success of non-paroxysmal ablation when using a:

1. specified low voltage-directed with pulmonary vein isolation (LD+PVI) approach compared to ,
2. an approach of pulmonary vein isolation (PVI) alone.

Detailed description: Patients that meet both inclusion and exclusion criteria will be randomized by the study clinical center upon determination of low-voltage being present using 3-D mapping during index. Enrolled subjects who do not have low voltage will be followed in a registry and their data will be evaluated separately. Low-voltage patients will be randomized 1:1 into one of the following arms:

* PVI with additional total left atrial low voltage-directed ablation.
* PVI alone.

All patients will receive the best conventional medical therapy and anticoagulation use based upon HRS consensus recommendations taking into account their baseline risk factors for stroke. The need for interruption of anticoagulation and antiarrhythmic drug therapy for the procedure will be determined by the operator and their center guidelines.

The trial requires continuous monitoring for atrial arrhythmias. Investigators will recommend the use of implantable loop recorders (ILR) but continuous 30 day monitoring with auto-trigger function may be substituted at the 6, 9 and 12 month time points. The ILR device will be implanted under sterile conditions at the manufacture's recommended site on the precordium for arrhythmia monitoring. Implantation will occur between 1 month prior and 3 months post ablation since there will be a 3 month post ablation blanking period. If a dual chamber device is already present, implantation will not be required. iWatch, Kardia or other non-FDA approved cardiac monitoring can be used to preliminarily identify AF recurrence but AF recurrence must be separately verifiable by ECG or other FDA-certified monitoring system.

One year follow-up is planned. Post procedure care is per standard of care with follow-up at 1 month, 3 months, 6 months, 9 months and 12 months. ECG at every follow-up is performed. Download of arrhythmia data will occur at each of these visits as well. Investigators will use the typical post ablation blanking period for recurrence of atrial fibrillation of 3 months. Antiarrhythmic medications can be used during the typical "blanking period" of 3 months post procedure. But per protocol are stopped at 3 months post procedure (2 months post procedure in case of amiodarone).

Investigators will compare time freedom from first arrhythmia event, defined as a sustained episode of atrial fibrillation or atrial tachycardia. Secondary endpoints will be compared as well (see secondary end point defined). Re-initiation of an antiarrhythmic drug after 3 months will be considered a failure of primary endpoint of arrhythmia free survival. However, Anti-arrhythmic medication use after the blanking period for ventricular arrhythmias will not be included as an event. Anticoagulation is continued and monitored based on previous guidelines with use stratified by baseline stroke risk. A recording (CD) of the mapping during the procedure is to be obtained and retained for possible future analysis.

Eligibility criteria: Inclusion Criteria:

Subjects must meet all of the following criteria:

1. Non-Paroxysmal Atrial Fibrillation.
2. Failed or intolerable to at least 1 one antiarrhythmic drug (AAD).
3. 18-85 year of age at time of consent.
4. Scheduled to undergo a clinically indicated AF ablation procedure.
5. Able and willing to comply with all protocol visit requirements.
6. Signed Patient Informed Consent (ICF).
7. Presence of low voltage in the left atrium on 3-D map during index catheter ablation procedure

Exclusion Criteria:

Subjects will be excluded if any of the follow criteria are present:

1. History of prior left-sided catheter or surgical ablation for AF or atypical atrial flutter, including MAZE or mini MAZE.

   * Prior ablation for typical atrial flutter or left-sided ablation for WPW, AV node reentry tachycardia or focal ectopic atrial tachycardia may be included.
2. Uncontrolled heart Failure or NYHA Class IIIb or IV heart failure.
3. Ejection Fraction \< 0.20.
4. Active ventricular tachycardia requiring treatment with catheter ablation or anti-arrhythmic drug within the last 6 months.
5. Left atrial size \> 60 mm diameter on echocardiogram.
6. "Long standing" persistent AF defined as \> or = 1 year of continuous atrial fibrillation at the time of enrollment.
7. Severe pulmonary hypertension (PAP \> 70 mmHg)
8. Unstable valvular disease.
9. AF secondary to electrolyte imbalance, thyroid disease or reversible non- cardiac cause.
10. Poor candidate for general anesthesia.
11. Anticipated survival \< 1 year.
12. MI or CABG within 3 months.
13. Left atrial thrombus in pre-procedure imaging within 4 weeks of the ablation procedure.
14. Any documented thromboembolic event within 6 months of the ablation procedure.
15. Contraindication to anticoagulation.
16. Inability to have implantable monitoring device for atrial fibrillation burden with no pre-existing cardiac device that can monitor atrial arrhythmias OR inability to wear external Holter Monitor continuously for 4 weeks.
17. Significant congenital anomaly or medical condition that may affect the integrity of study data.
18. Women who are pregnant - pregnancy test required if pre-menopausal or non-sterile.
19. Active enrollment in another investigational study involving a drug or device.
20. Inability to undergo complete voltage mapping in normal sinus rhythm - see intraprocedural protocol.
21. Presence of any medical or psychological condition or medical non-compliance history that may adversely impact study outcomes.

Primary outcomes:
measure: Freedom from first arrhythmia recurrence defined as sustained symptomatic or asymptomatic atrial fibrillation, atrial flutter or atrial tachycardia.
timeFrame: Any event between the 3 month blanking period and 1 year post-ablation.
Secondary outcomes:
measure: Reduced arrhythmia burden (frequency that arrhythmia occurs).
timeFrame: Between the 3 month blocking period and 1 year post-ablation.
measure: Freedom from sustained AF/AT
timeFrame: Any event between the 3 month blocking period and 1 year post-ablation.
measure: Freedom from any symptomatic AF/AT
timeFrame: Any event between the 3 month blocking period and 1 year post-ablation.
measure: Reduced need for antiarrhythmic drugs (AAD)
timeFrame: Any event between the 3 month blocking period and 1 year post-ablation.
Other outcomes:
measure: Incidence of procedure related adverse events.
timeFrame: Any event up to 1 year post-ablation.
measure: Tertiary endpoints
timeFrame: Any event up to 1 year post-ablation.
Locations:
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
Study officials:
affiliation: MetroHealth System, Ohio
name: Ohad Ziv, MD
role: PRINCIPAL_INVESTIGATOR
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