REVOLUTION (WFCC-133) - Treatment of Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and effectiveness of the Circular and Crescent Mapping and Ablation catheters and the workflow of the Multi-Electrode Irrigated Pulmonary Vein Isolation System when used for the treatment of drug refractory symptomatic paroxysmal atrial fibrillation (PAF).

Detailed Description
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The study will include a Workflow Phase to verify consistent workflow of all study device components and evaluate acute safety. Upon meeting the defined criteria, the Workflow Phase will be closed and further enrollment will be toward the Main Study Phase which includes the roll-in (the first 3 subjects enrolled at each site following the closure of the Workflow Phase) and Subpopulation Neurological Assessments (SNA) substudy subjects. SNA assessment is a prospective, non-randomized, controlled, acute assessment of two ablation devices to determine if intracerebral microemboli are generated during or immediately after radiofrequency ablation therapy for PAF. SNA subjects will remain and complete the Main Study Phase. However, SNA-control subjects will not be considered part of the Main Study Phase. All subjects, including the subjects enrolled under the Workflow Phase will be included in the Safety Cohort (evaluated for Primary Safety endpoint and all Secondary Safety endpoints).

Official Title
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REVOLUTION (WFCC-133): Clinical Workflow Study for the Evaluation of the Multi-Electrode Pulmonary Vein Isolation System for the Treatment of Paroxysmal Atrial Fibrillation (PAF)

Conditions
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Paroxysmal Atrial Fibrillation

Intervention / Treatment
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* Device: nMARQ™ System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic Paroxysmal Atrial Fibrillation (PAF) who have had at least one documented Atrial Fibrillation (AF) episode in the twelve (12) months prior to enrollment. Documentation may include electrocardiogram (ECG), transtelephonic monitor (TTM), Holter Monitor (HM), or telemetry strip. Failure of at least one antiarrhythmic drug for AF (class I or III, or Atrioventricular (AV) nodal blocking agents such as beta blockers and calcium channel blockers), as evidenced by recurrent symptomatic AF, or intolerable side effects. Age 18 years or older. Able and willing to comply with all pre-, post- and follow-up testing and requirements. Signed Patient Informed Consent Form. Exclusion Criteria: AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause. Patients with Persistent or Long-standing AF (AF episode lasting > 30 days in duration. Diagnosed atrial myxoma. Left atrial size > 5.5cm. Left Ventricular ejection fraction < 40%. Contraindication to Computed Axial Tomography/Magnetic Resonance Imaging (CT/MRI) procedures New York Heart Association Class III or IV. Previous ablation for enrolled arrhythmia (AF). Documented left atrial thrombus on imaging (example: transesophageal echocardiography or intracardiac echocardiography). Myocardial Infarction within the previous 60 days (2 months). Any valvular cardiac surgical procedure (that is, valve repair or replacement and presence of a prosthetic valve). Coronary artery bypass graft procedure with the last 180 days 6 months. Cardiac Surgery (that is, ventriculotomy, atriotomy) within the past 60 days (2 months). Awaiting cardiac transplantation or other cardiac surgery within the next 365 days (12 months). History of documented thromboembolic event within the past one (1) year. Significant pulmonary disease, (example: restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunctions of the lungs or respiratory system that produces chronic symptoms. Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study. Active illness or active systemic infection or sepsis. Unstable angina. History of blood clotting or bleeding abnormalities. Contraindication to anticoagulation (that is, Heparin or Warfarin). Life expectancy less than 365 days (12 months) Presence of intramural thrombus, tumor or other abnormality that precludes catheter introduction or manipulation. Women who are pregnant (as evidence by pregnancy test if subject is of child bearing potential) and/or breast feeding. Presence of a condition that precludes vascular access. Enrollment in an investigational study evaluating another device or drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nMARQ™ System<br>The nMARQ™ System (Circular and Crescent Mapping and Ablation Catheters as well as the Multi-Channel Radiofrequency Generator) as part of the Multi-Electrode Irrigated Pulmonary Vein (PV) Isolation System will serve as a treatment method for subjects undergoing radiofrequency catheter ablation for drug refractory, symptomatic Paroxysmal Atrial Fibrillation (PAF). The study later included a Subpopulation Neurological Assessments (SNA) substudy which is a prospective, non-randomized, controlled, acute assessment to compare subjects treated with the nMARQ™ System against control subjects treated with the NAVISTAR® THERMOCOOL® Irrigated Tip Catheter. | Device: nMARQ™ System<br>* The nMARQ™ System is indicated for catheter-based electrophysiological mapping for the treatment of drug refractory recurrent symptomatic paroxysmal atrial fibrillatioon.<br>* Other names: nMARQ™ Multi-Electrode Irrigated Pulmonary Vein (PV);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Early Onset Primary Adverse Events | The primary safety endpoint is the incidence of early onset primary adverse events within 7 days of the mapping and ablation procedure. Primary adverse events include pericardial effusion requiring intervention, atrial perforation, pericarditis requiring intervention, cardiac tamponade, pneumothorax, death, pulmonary edema, diaphragmatic paralysis, heart block, stroke / cerebrovascular accident (CVA), hospitalization (initial and prolonged), thromboembolism, myocardial infarction (MI), transient ischemic attack (TIA), and vascular access complications. In addition, pulmonary vein stenosis and atrio-esophageal fistula that occurs greater than one week (7 days) post-procedure are deemed primary adverse event. | Any of above events occurring within 7 days post-procedure (also including the incidence of pulmonary vein stenosis and atrio-esophageal fistula occurring > 7 days and up to one year post-procedure) | 
| Incidence of Freedom From Documented Symptomatic Atrial Fibrillation | The primary effectiveness endpoint is freedom from documented symptomatic atrial fibrillation based on electrocardiographic data through 8 months post ablation. | Evaluated from Day 91 to Day 240 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Non-Primary Serious Adverse Events (SAEs) up to 12 Months | This secondary safety endpoint includes non-primary serious adverse events within 7 days post-procedure and serious adverse events from 7 days to 12 months post-procedure. | 12 months post study procedure | 
| Assessment of Pulmonary Vein (PV) Narrowing and Stenosis at 3 Months After Index Ablation | Incidence of narrowing of PV and stenosis at 3 months post ablation, for subjects with available CT/MRA scans at 3 months. PV Stenosis is defined as 70% or more PV diameter reduction. | Three months after index ablation | 
| Incidence of Completion of Ablation Procedure | This secondary outcome describes the acute effectiveness, which is defined as pulmonary vein isolation (PVI) documented by confirmed entrance block (with or without the use of a focal catheter). | From 7 days to 12 months post study procedure | 
| Absence of Documented Symptomatic PAF Through 6 Months and 12 Months Post Procedure | This endpoint is defined as the absence of documented symptomatic PAF recurrence through 6 months and 12 months post index ablation procedure. | 6 and12 months post study procedure | 
| Subpopulation Neurological Assessments (SNA) Endpoint 1 - Incidence of Cerebral Embolic (ACE) Lesions Post Ablation | Evaluation of post-ablation generation incidence of asymptomatic cerebral microembolic lesions post ablation, as documented by MRI. All microembolic lesions reported in this study are asymptomatic. | 48 hours post-ablation | 
| Subpopulation Neurological Assessments (SNA) Endpoint 2 - Incidence of New Neurological Findings Post Ablation | All SNA subjects were to be evaluated by expert neurologists for existing neurological deficits prior to ablation procedure. After procedure, those subjects were also to be assessed for new neurological deficits. | 48 hours post-ablation |