A Prospective Randomized Pivotal Trial of the FARAPULSE Pulsed Field Ablation System Compared With Standard of Care Ablation in Patients With Paroxysmal Atrial Fibrillation
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation
Sponsor: Boston Scientific Corporation

 
 
 
 
 
 
 
The FARAPULSE ADVENT Trial 
 
A Prospective Randomized Pivotal Trial of the  
FARAPULSE Pulsed Field Ablation System  
Compared with Standard of Care Ablation in  
Patients with Paroxysmal Atrial Fibrillation 
 
 
CLINICAL INVESTIGATION PLAN (CIP) NUMBER: CS0934 REVISION D 
 
SPONSOR: 
FARAPULSE, INC. 
3715 HAVEN AVE. SUITE 110 
MENLO PARK, CA 94025 
USA 
 
ISSUE DATE: OCTOBER 13, 2021 
 
 
This study is to be performed in accordance with the U.S. Code of Federal Regulations, 
Good Clinical Practice (GCP) and ethical principles consistent with the Declaration of 
Helsinki. 
 
This document contains confidential and proprietary information and may not be copied or 
reproduced in whole or in part without the express written permission of FARAPULSE, INC., 
MENLO PARK, CA. 

 
 
 
 
 
PROTOCOL AGREEMENT FORM 
 
 
 
 
Study Title: The FARAPULSE ADVENT Trial, Revision D, October 13, 2021 
 
I, the undersigned, have read and understand this clinical study, including the appendices. I 
will implement and conduct the clinical study in strict compliance with the study protocol 
and in accordance with good clinical practices (GCP) and all applicable laws and regulations. 
I will ensure that all persons assisting in this study are adequately informed about the 
protocol, study product(s) and their clinical study-related duties and functions. 
 
I agree to maintain all study related information supplied by FARAPULSE Inc. in strictest 
confidence. When information regarding this study is submitted to an Institutional Review 
Board (IRB), it will be forwarded with a requirement that all study related material is to be 
held strictly confidential. 
 
 
 
_________________________ 
___________________________ 
_____________ 
Principal Investigator  
 
Signature 
 
 
 
Date 
 
 
 
 
 

FARAPULSE ADVENT TRIAL 
OCTOBER 13, 2021 
CS0934, REVISION D 
 
PAGE ii 
 
 
TABLE OF REVISIONS 
 
Revision 
Date 
DCO # Change Description 
A 
October 20, 
2020 
20-235 
Initial Release for IDE submission 
B 
November 
15, 2020 
20-255 
Modifications for IDE resubmission 
C 
March 17, 
2021 
21-136 
Modifications for IDE resubmission 
Revision approved for trial initiation (April 16, 2021) 
D 
November 
01, 2021 
21-355 
Modifications for Study Design Consideration IDE 
submission, maintenance updates and typographical 
corrections. 
 

FARAPULSE ADVENT TRIAL 
OCTOBER 13, 2021 
CS0934, REVISION D 
 
PAGE iii 
 
TABLE OF CONTENTS 
 
TABLE OF CONTENTS ........................................................................................................ III 
LIST OF TABLES ............................................................................................................... VIII 
LIST OF FIGURES ............................................................................................................... IX 
PRIMARY STUDY CONTACTS ...............................................................................................1 
PROTOCOL SUMMARY .........................................................................................................2 
ABBREVIATIONS AND ACRONYMS .....................................................................................16 
1. 
INTRODUCTION.........................................................................................................18 
1.1 
BACKGROUND AND RATIONALE..................................................................18 
1.2 
IRREVERSIBLE ELECTROPORATION .............................................................18 
1.3 
SUMMARY OF FARAPULSE PRECLINICAL STUDIES ..................................19 
1.4 
SUMMARY OF FARAPULSE CLINICAL STUDIES FOR PAF .........................20 
1.4.1 THE IMPULSE STUDY ...................................................................20 
1.4.2 THE PEFCAT STUDY .....................................................................21 
1.4.3 THE PEFCAT II STUDY ..................................................................23 
1.4.4 CLINICAL SUB-STUDIES ..................................................................24 
1.5 
RATIONALE FOR CONDUCTING THIS PIVOTAL STUDY .................................25 
1.6 
RISKS, BENEFITS AND MITIGATION .............................................................26 
1.6.1 POTENTIAL RISKS ...........................................................................26 
1.6.2 POTENTIAL BENEFITS......................................................................26 
1.6.3 RISK MITIGATION AND SUMMARY ..................................................27 
2. 
INVESTIGATIONAL DEVICES ....................................................................................28 
2.1 
NAMES OF INVESTIGATIONAL DEVICES ......................................................28 
2.2 
INTENDED USE ............................................................................................28 
2.3 
FARAPULSE PULSED FIELD ABLATION SYSTEM ......................................28 
2.3.1 FARAWAVE PULSED FIELD ABLATION CATHETER ......................30 
2.3.2 FARASTAR PULSED FIELD ABLATION GENERATOR .....................32 
2.3.3 FARADRIVE STEERABLE SHEATH ................................................32 
2.4 
DEVICE ACCOUNTABILITY ..........................................................................33 
2.5 
RETURN OF DEVICES ...................................................................................33 
3. 
STUDY POPULATION .................................................................................................34 
3.1 
SUBJECT RECRUITMENT ..............................................................................34 
3.2 
SUBJECT SCREENING ...................................................................................34 
3.2.1 SCREENING PROCEDURES ...............................................................34 
3.2.2 SCREENING LOG .............................................................................34 
3.3 
STUDY ELIGIBILITY CRITERIA .....................................................................34 
3.3.1 INCLUSION CRITERIA ......................................................................34 
3.3.2 EXCLUSION CRITERIA .....................................................................35 
3.4 
SUBJECT STATUS AND DISPOSITION DEFINITIONS .......................................37 
3.4.1 GENERAL PRE-SCREENING .............................................................37 
3.4.2 COVID-19 PRE-SCREENING ...........................................................38 
3.4.3 SCREENED SUBJECTS ......................................................................38 
3.4.4 SCREEN FAILURE SUBJECTS ............................................................38 

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3.4.5 ENROLLED SUBJECTS ......................................................................38 
3.4.6 ROLL-IN SUBJECTS .........................................................................38 
3.4.7 INTENT-TO-TREAT SUBJECTS ..........................................................39 
3.4.8 SAFETY SUBJECTS ...........................................................................39 
3.4.9 MODIFIED INTENT-TO-TREAT SUBJECTS .........................................39 
3.4.10 COMPLETED SUBJECTS ....................................................................39 
3.4.11 INCOMPLETE SUBJECTS ...................................................................39 
3.4.12 PER PROTOCOL SUBJECTS ...............................................................40 
3.5 
SUBJECT DISPOSITION CHART .....................................................................40 
3.6 
SUBJECT INFORMED CONSENT ....................................................................41 
3.7 
SUBJECT ENROLLMENT ...............................................................................41 
3.8 
SUBJECT RANDOMIZATION .........................................................................42 
3.9 
SUBJECT COMPLETION OR EXIT ..................................................................42 
4. 
STUDY SUMMARY AND SCHEDULE...........................................................................43 
4.1 
STUDY OBJECTIVE AND HYPOTHESIS ..........................................................43 
4.2 
STUDY OVERVIEW ......................................................................................43 
4.3 
SUBJECT CONFIDENTIALITY ........................................................................43 
4.4 
SAMPLE SIZE SUMMARY .............................................................................43 
4.5 
INVESTIGATIONAL SITES .............................................................................44 
4.6 
DURATION OF STUDY AND SUBJECT PARTICIPATION ..................................44 
4.7 
SCHEDULE OF EVENTS AND ASSESSMENTS .................................................44 
4.7.1 BASELINE ASSESSMENT ..................................................................45 
4.7.2 INDEX PROCEDURE / RESCHEDULED INDEX PROCEDURE ................45 
4.7.3 PRE-DISCHARGE ASSESSMENT ........................................................46 
4.7.4 DAY 7 ASSESSMENT ........................................................................48 
4.7.5 DAY 30 ASSESSMENT ......................................................................48 
4.7.6 DAY 60 EM TRAINING AND AAD DISCONTINUATION ....................48 
4.7.7 DAY 90 ASSESSMENT ......................................................................49 
4.7.8 MONTH 6 ASSESSMENT ...................................................................50 
4.7.9 MONTH 12 ASSESSMENT .................................................................50 
4.7.10 RE-ABLATION PROCEDURES ...........................................................52 
4.7.11 UNSCHEDULED ASSESSMENTS ........................................................52 
4.7.12 COVID-19-RELATED DISRUPTION OF STUDY ASSESSMENTS .........53 
4.8 
SCHEDULE OF EVENTS ................................................................................54 
4.9 
SUBJECT FLOW CHART ...............................................................................56 
4.10 
CONTROL OF SYSTEMATIC ERROR AND BIAS ..............................................57 
5. 
STUDY PROCEDURES ................................................................................................58 
5.1 
ANTICOAGULATION ....................................................................................58 
5.2 
INDEX PROCEDURE .....................................................................................58 
5.3 
RESCHEDULED INDEX PROCEDURE .............................................................61 
5.4 
RE-ABLATION PROCEDURES .......................................................................61 
5.5 
START DATE, BLANKING PERIOD AND INDEX PROCEDURES .......................62 
5.6 
ROLL-IN SUBJECTS .....................................................................................63 
5.7 
BLINDING ....................................................................................................63 
5.8 
NEUROLOGIC ASSESSMENT SUBJECTS ........................................................64 
5.8.1 NAS SITES ......................................................................................64 

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5.8.2 POST-ABLATION BRAIN MRI SPECIFICATIONS FOR NAS SUBJECTS 
ONLY ..............................................................................................64 
5.8.3 SCE AND SCL ANALYSIS ...............................................................65 
5.8.4 FOLLOW-UP FOR SUBJECTS WITH SCE OR SCL LESIONS ................65 
5.9 
ANTIARRHYTHMIC DRUGS ..........................................................................65 
6. 
STUDY DEFINITIONS .................................................................................................66 
6.1 
STUDY OUTCOMES ......................................................................................66 
6.2 
ADVERSE EVENT DEFINITIONS ....................................................................66 
6.3 
OTHER DEFINITIONS ...................................................................................66 
6.3.1 ACUTE PROCEDURAL SUCCESS .......................................................66 
6.3.2 ACUTE PROCEDURAL FAILURE .......................................................66 
6.3.3 ACUTE VEIN SUCCESS ....................................................................66 
6.3.4 ANTIARRHYTHMIC DRUGS, CLASS I AND III ...................................66 
6.3.5 BLANKING PERIOD ..........................................................................66 
6.3.6 CHRONIC FAILURE ..........................................................................67 
6.3.7 CHRONIC SUCCESS ..........................................................................67 
6.3.8 COVID-19-RELATED DISRUPTIONS ...............................................67 
6.3.9 DATES .............................................................................................67 
6.3.10 DAY (OR STUDY DAY) ....................................................................67 
6.3.11 DETECTABLE AF, AFL OR AT ........................................................67 
6.3.12 INVESTIGATIONAL DEVICES AND PROCEDURES ..............................67 
6.3.13 PRE-ABLATION ADVERSE EVENTS ..................................................68 
6.3.14 PULMONARY VEIN DIAMETER ........................................................68 
6.3.15 PULMONARY VEIN ISOLATION ........................................................68 
6.3.16 PULSED FIELD GROUP / SUBJECTS ..................................................68 
6.3.17 SEVERE COVID-19 SUBJECTS ........................................................68 
6.3.18 STUDY PARTICIPANTS .....................................................................69 
6.3.19 THERMAL GROUP / SUBJECTS .........................................................69 
6.3.20 TREATMENT FAILURE .....................................................................69 
6.3.21 TREATMENT SUCCESS .....................................................................69 
7. 
OUTCOME MEASURES ..............................................................................................70 
7.1 
PRIMARY SAFETY ENDPOINT ......................................................................70 
7.2 
SECONDARY SAFETY ENDPOINT .................................................................72 
7.3 
ADDITIONAL SAFETY ANALYSES ................................................................72 
7.4 
PRIMARY EFFECTIVENESS ENDPOINT ..........................................................73 
7.5 
SECONDARY EFFECTIVENESS ENDPOINT .....................................................73 
7.6 
ADDITIONAL EFFECTIVENESS ANALYSES....................................................74 
7.7 
PROCEDURAL ASSESSMENTS .......................................................................74 
7.8 
QUALITY OF LIFE ASSESSMENTS .................................................................75 
8. 
ADVERSE EVENTS, DEVICE EFFECTS, MALFUNCTIONS AND DEFICIENCIES ..........76 
8.1 
ANTICIPATED ADVERSE EVENTS .................................................................76 
8.2 
ADVERSE EVENT REVIEW AND ADJUDICATION ...........................................77 
8.3 
ADVERSE EVENTS .......................................................................................77 
8.4 
SERIOUS ADVERSE EVENTS ........................................................................78 
8.5 
PROCEDURE, DEVICE AND COVID-19 RELATEDNESS ................................78 
8.6 
DEVICE EFFECTS .........................................................................................79 

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8.6.1 ADVERSE DEVICE EFFECTS .............................................................79 
8.6.2 SERIOUS ADVERSE DEVICE EFFECTS ..............................................79 
8.6.3 UNANTICIPATED ADVERSE DEVICE EFFECTS ..................................79 
8.7 
DEVICE DEFICIENCIES .................................................................................79 
8.8 
USE ERRORS ...............................................................................................79 
8.9 
MALFUNCTIONS ..........................................................................................80 
8.10 
EVENT MANAGEMENT AND REPORTING .....................................................80 
8.10.1 ADVERSE EVENTS ...........................................................................80 
8.10.2 ADVERSE DEVICE EFFECTS .............................................................80 
8.10.3 DEVICE DEFICIENCY AND MALFUNCTIONS .....................................80 
8.10.4 OTHER ASSESSMENT AND REPORTING REQUIREMENTS ..................81 
8.10.5 REPORTING AES, ADES AND DEVICE DEFICIENCIES ......................81 
9. 
STATISTICAL PROCEDURES AND REPORTING .........................................................83 
9.1 
GENERAL STATISTICAL CONSIDERATIONS ..................................................83 
9.2 
RANDOMIZATION ........................................................................................83 
9.3 
SUBJECT DISPOSITION .................................................................................84 
9.4 
POPULATIONS FOR ANALYSIS .....................................................................84 
9.5 
ASSESSMENT OF THE PRIMARY SAFETY ENDPOINT .....................................84 
9.6 
ASSESSMENT OF THE PRIMARY EFFECTIVENESS ENDPOINT ........................84 
9.7 
SAMPLE SIZE CONSIDERATIONS ..................................................................85 
9.8 
ANALYSIS PLAN ..........................................................................................86 
9.9 
ASSESSMENT OF THE SECONDARY SAFETY ENDPOINT ................................87 
9.10 
ASSESSMENT OF THE SECONDARY EFFECTIVENESS ENDPOINT ...................88 
9.11 
ASSESSMENT OF SUBJECT BLINDING ...........................................................88 
10. 
CORE LABORATORIES ..............................................................................................89 
10.1 
ARRHYTHMIA CORE LABORATORY .............................................................89 
10.1.1 PROCEDURES ..................................................................................89 
10.1.2 EVENT MONITORS ...........................................................................89 
10.1.3 HOLTER MONITORS ........................................................................89 
10.1.4 ARRHYTHMIA DATA REVIEW AND TRANSMISSION .........................90 
10.1.5 CEC OVER-READS OF POTENTIAL ENDPOINTS ...............................90 
10.2 
CARDIAC IMAGING CORE LABORATORY .....................................................90 
10.2.1 PROCEDURES ..................................................................................90 
10.2.2 PULMONARY VEIN DIMENSIONS .....................................................90 
10.2.3 CARDIAC IMAGING DATA REVIEW AND TRANSMISSION .................90 
10.2.4 CEC REVIEW OF PULMONARY VEIN STENOSIS RESULTS ................90 
10.3 
BRAIN IMAGING CORE LABORATORY .........................................................90 
10.3.1 PROCEDURES ..................................................................................91 
10.3.2 SCE AND SCL ASSESSMENT ...........................................................91 
10.3.3 BRAIN IMAGING DATA REVIEW AND TRANSMISSION ......................91 
11. 
MONITORING ............................................................................................................92 
11.1 
MONITORS ..................................................................................................92 
11.2 
CLINICAL MONITORING ACTIVITIES ...........................................................92 
11.3 
MONITORING RESPONSIBILITY AND DATA VERIFICATION ..........................92 
11.4 
SITE VISITS .................................................................................................92 
12. 
STUDY MANAGEMENT .............................................................................................94 

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12.1 
ETHICAL CONSIDERATIONS .........................................................................94 
12.1.1 STUDY CONDUCT ............................................................................94 
12.1.2 ETHICS REVIEW ..............................................................................94 
12.1.3 INFORMED CONSENT .......................................................................94 
12.1.4 CONFIDENTIALITY ..........................................................................95 
12.2 
KEY CONTRIBUTORS ...................................................................................95 
12.2.1 SPONSOR .........................................................................................95 
12.2.2 CONTRACT RESEARCH ORGANIZATION...........................................95 
12.2.3 ARRHYTHMIA CORE LABORATORY .................................................95 
12.2.4 CLINICAL EVENTS COMMITTEE .......................................................95 
12.2.5 DATA AND SAFETY MONITORING BOARD .......................................96 
12.3 
SPONSOR RESPONSIBILITIES ........................................................................96 
12.4 
MONITOR RESPONSIBILITIES .......................................................................97 
12.5 
INVESTIGATOR RESPONSIBILITIES ...............................................................98 
12.6 
INVESTIGATOR AND SITE STAFF TRAINING ...............................................100 
12.7 
CONFIDENTIALITY AND PUBLICATION POLICY ..........................................100 
12.8 
DATA MANAGEMENT ................................................................................100 
12.9 
INSURANCE ...............................................................................................101 
12.10 AUDITS AND INSPECTIONS ........................................................................101 
12.11 STUDY SUSPENSION OR EARLY TERMINATION ..........................................101 
12.12 CRITERIA FOR SUSPENDING OR TERMINATING A STUDY SITE ...................101 
12.13 DEVIATIONS FROM THE CLINICAL INVESTIGATION PLAN ..........................102 
12.14 COVID-19 PANDEMIC CONSIDERATIONS .................................................102 
13. 
REGULATORY CONSIDERATIONS ...........................................................................103 
13.1 
MAINTAINING RECORDS ...........................................................................103 
13.2 
DATA HANDLING AND RECORD KEEPING .................................................103 
13.2.1 SOURCE DOCUMENTS ...................................................................103 
13.2.2 DATA COLLECTION .......................................................................103 
13.3 
INSTITUTIONAL REVIEW BOARD AND FDA APPROVAL ............................104 
13.4 
PROCEDURE FOR AMENDING THE CIP .......................................................104 
13.5 
DEVICE ACCOUNTABILITY ........................................................................104 
14. 
BIBLIOGRAPHY .......................................................................................................105 
 

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PAGE viii 
 
LIST OF TABLES 
 
TABLE 1 
IMPACT OF ABLATION ENERGIES ON 3-MONTH PV DIMENSIONS .............................. 25 
TABLE 2 
FARAPULSE PULSED FIELD ABLATION SYSTEM COMPONENTS.............................. 28 
TABLE 3 
SCHEDULE OF EVENTS – ITT SUBJECTS ..................................................................... 54 
TABLE 4 
SCHEDULE OF EVENTS – ROLL-IN SUBJECTS ............................................................. 55 
TABLE 5 
COMPOSITE SAFETY ENDPOINT DEFINITIONS ............................................................ 70 
TABLE 6 
REPORTING AES, ADES AND DEVICE DEFICIENCIES ................................................. 81 
 

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PAGE ix 
 
LIST OF FIGURES 
 
FIGURE 1 
FARAPULSE PULSED FIELD ABLATION SYSTEM COMPONENTS.............................. 29 
FIGURE 2 
FARAWAVE PULSED FIELD ABLATION CATHETER ................................................. 30 
FIGURE 3 
FARAWAVE PULSED FIELD ABLATION CATHETER - DEPLOYED STATES ............... 31 
FIGURE 4 
FARADRIVE STEERABLE SHEATH ........................................................................... 33 
FIGURE 5 
SUBJECT DISPOSITION CHART .................................................................................... 40 
FIGURE 6 
PRE-DISCHARGE STROKE EVALUATION, NON-NAS SUBJECTS ................................. 47 
FIGURE 7 
PRE-DISCHARGE STROKE EVALUATION, NAS SUBJECTS .......................................... 47 
FIGURE 8 
SUBJECT FLOW CHART ............................................................................................... 56 
FIGURE 9 
INDEX PROCEDURE BLANKING AND FOLLOW-UP INTERVALS ................................... 62 
FIGURE 10 
RESCHEDULED INDEX PROCEDURE BLANKING AND FOLLOW-UP INTERVALS .......... 63 
 
 

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CS0934, REVISION D 
 
PAGE 1 
 
PRIMARY STUDY CONTACTS 
 
SPONSOR 
John Allison, Vice President 
Clinical Affairs, Regulatory Affairs and Quality 
Assurance 
FARAPULSE, Inc. 
3715 Haven Ave. Suite 110 
Menlo Park, CA 94025 
USA 
Tel: +1.650.422.3633 
Email: jallison@farapulse.com 
PRINCIPAL INVESTIGATOR 
Vivek Reddy, MD, Principal Investigator 
Mount Sinai Hospital 
One Gustav L Levy Place, Box 1030 
New York, NY 10029 
USA 
Tel:  +1.212.241.7114 
Email: vivek.reddy@mountsinai.org 
CLINICAL RESEARCH 
ORGANIZATION 
Patricia Bobzin, Director, Medical Devices 
Medpace Medical Device 
3787 95th Ave NE 
Suite 100 
Blaine, MN 55014 
USA 
Tel: +1.612.234.8500 
Fax: +1.513.527.0368 
Email: p.bobzin@medpace.com 
ARRHYTHMIA CORE LAB 
HeartcoR Solutions LLC 
2403 Harnish Drive, Suite 201 
Algonquin, IL 60102 
USA 
CARDIAC IMAGING CORE 
LAB 
Medpace Core Laboratories 
5365 Medpace Way 
Cincinnati, OH 45227 
USA 
BRAIN IMAGING CORE LAB 
Medpace Core Laboratories 
5365 Medpace Way 
Cincinnati, OH 45227 
USA 
 
 
 

FARAPULSE ADVENT TRIAL 
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CS0934, REVISION D 
 
PAGE 2 
 
PROTOCOL SUMMARY 
 
SPONSOR NAME 
FARAPULSE, Inc. 
TITLE OF STUDY 
The FARAPULSE ADVENT Trial 
A Prospective Randomized Pivotal Trial of the FARAPULSE Pulsed 
Field Ablation System Compared with Standard of Care Ablation in 
Patients with Paroxysmal Atrial Fibrillation 
CIP NUMBER / 
REVISION  
CS0934 Revision D  
PRIMARY 
OBJECTIVE 
To determine whether there is valid scientific evidence that endocardial 
ablation using the FARAPULSE Pulsed Field Ablation System is both 
safe and effective for treating drug-resistant symptomatic PAF. 
PRIMARY CLINICAL 
HYPOTHESIS 
Pulmonary vein isolation (PVI) created by the FARAPULSE Pulsed 
Field Ablation System is not inferior in safety and effectiveness to 
treatment with approved catheter ablation technologies – force-sensing 
radiofrequency ablation (RFA) or cryoballoon ablation (CBA) – in the 
treatment of drug-resistant symptomatic PAF. 
INVESTIGATIONAL 
DEVICES 
SECTION 2 
FARAPULSE™ Pulsed Field Ablation System 
• FARAWAVE™ Pulsed Field Ablation Catheters and 
FARASTAR™ Catheter Connection Cable  
• FARASTAR™ Pulsed Field Ablation Generator, 
FARASTAR™ Stimulation Module, FARASTAR™ Recording 
System Module and associated cables 
• FARADRIVE™ Steerable Sheath 
INTENDED USE 
SECTION 2.2 
The FARAPULSE Pulsed Field Ablation System is indicated for the 
treatment of drug-resistant, recurrent, symptomatic PAF.  

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PAGE 3 
 
STUDY SUMMARY 
AND SCHEDULE 
SECTION 4 
This is a prospective, adaptive, multi-center, randomized safety and 
effectiveness pivotal study comparing the FARAPULSE Pulsed Field 
Ablation System with standard of care ablation with force-sensing RF 
catheters and cryoballoon catheters indicated for the treatment of PAF.  
Subjects with documented drug-resistant (Class I to IV) PAF who have 
had ≥ 2 PAF episodes within 6 months of enrollment will undergo 
percutaneous endocardial ablation for PVI. Subjects with typical right-
sided (isthmus-dependent) atrial flutter (AFL) may undergo ablative 
interruption of the cavo-tricuspid isthmus (CTI).  
Class I / III antiarrhythmic drugs (AADs) will be discontinued at Day 
60 ± 10, subject to Investigator discretion. 
Safety: Subjects will be followed at 7 days, 30 days, 90 days, 6 months 
and 12 months for adverse events (AEs). A composite device- and 
procedure-related serious adverse event (SAE) rate will be compared 
between randomization groups for non-inferiority. 
Effectiveness: Subjects will be monitored with weekly scheduled plus 
symptom-driven event monitoring, as well as 6 and 12-month Holter 
monitoring, for freedom from recurrent arrhythmia (atrial fibrillation 
[AF], AFL or atrial tachycardia [AT]) after the Blanking Period (Days 
0 - 90). The proportion of subjects free of post-blanking recurrent 
arrhythmia (AF, AFL or AT), re-ablation or Class I / III AAD use will 
be compared between randomization groups for non-inferiority. 
SAMPLE SIZE 
SUMMARY 
SECTION 4.4 
A maximum of 900 subjects may be enrolled in this study.  
Roll-In Subjects: Up to 105 subjects (the first 1-3 Enrolled Subjects at 
each site) will be treated with the FARAPULSE devices in a manner 
consistent with the randomized Pulsed Field Group and will be 
analyzed and reported separately.  
ITT Subjects: An estimated 450 MITT Subjects will be required to 
support the proposed non-inferiority outcomes. Interim sample size re-
estimation may decrease this number to 350 or increase it to a 
maximum of 750. Up to 45 additional subjects (6%) may be enrolled to 
compensate for those ITT Subjects who do not meet the criteria for the 
MITT Population. 
INVESTIGATIONAL 
SITES 
SECTION 4.5 
Up to 35 investigational sites in the United States.  
No site may enroll more than 45 ITT Subjects (excludes Roll-In 
Subjects and ITT Subjects who do not qualify for the MITT 
population) with an intended minimum of 10 subjects per site. Should 
interim sample size re-estimation lead to an increase in the number of 
MITT Subjects greater than 450, each site will be limited to 10% of the 
increased total. 

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DURATION OF 
STUDY AND 
SUBJECT 
PARTICIPATION 
SECTION 4.6 
Study start-up, inclusive of site initiation and Investigator training, is 
estimated to take 6 months. The enrollment period for the first 600 
subjects (105 Roll-Ins plus 495 ITT Subjects) is estimated to take 18 
months and subjects will be followed for up to 13 months. There will 
be a 3-month period of site close-out visits, for a planned study 
duration of approximately 40 months. Coronavirus Disease 2019 
(COVID-19)-related disruptions and interim sample size re-estimation 
may alter this timeframe. 
Subject participation is anticipated to be 13 ± 1 months to allow for 
screening, pre-procedural diagnostic procedures, randomization, 
treatment and 12±1 months of study follow-up. If a subject requires a 
Rescheduled Index Procedure, this may prolong participation by up to 
2 to 3 months. 
SCHEDULE OF 
EVENTS AND 
ASSESSMENTS 
SECTION 4.7 
• Baseline Assessment 
• Index Procedure / Rescheduled Index Procedure: cardiac 
ablation (Day 0) 
• Pre-Discharge Assessment 
• Day 7 Assessment: clinical assessment 
(Window Days 7 to 11) 
• Day 30 Assessment: clinical assessment 
(Window Day 30 ± 7) 
• Day 60 Event Monitor (EM) Training and AAD 
Discontinuation: (Window Day 60 ± 10) 
• Day 90 Assessment: clinical assessment, cardiac magnetic 
resonance imaging (MRI) / computed tomography (CT) scan, 
begin weekly scheduled and symptomatic event monitoring 
(Window Day 90 ± 14) 
• Month 6 Assessment: clinical assessment, Holter 
(Window Day 180 ± 30) 
• Month 12 Assessment: clinical assessment, Holter, QoL and 
cardiac MRI/CT if Day 90 study showed pulmonary vein 
stenosis (PVS) (Window Day 360 ± 30) 
• Re-Ablation Procedure 
• Unscheduled Assessment 
• COVID-19-Related Disruptions of Study Assessments 
ANTICOAGULATION 
SECTION 5.1 
Anticoagulation will be guided by the 2017 Heart Rhythm Society 
Expert Consensus Statement and the 2019 American Heart Association 
/American College of Cardiology / Heart Rhythm Society Focused 
Update relating to this issue.  

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INDEX PROCEDURE 
SECTION 5.2 
Index Procedure / Rescheduled Index Procedure: All subjects will 
be screened for completion of a minimum of 3 weeks of systemic 
anticoagulation and the absence of atrial thrombus just prior to or at the 
time of the Index Procedure and will be rescheduled if these conditions 
are not met.  
PVI: Subjects will undergo an attempt to isolate all PVs or their 
anatomic equivalent with the randomized devices: 
• Pulsed Field Group with the FARAPULSE Pulsed Field 
Ablation System 
• Thermal Group with either a study-approved RFA or CBA 
system. Sites will use either RFA or CBA exclusively to treat 
subjects randomized to the Thermal Group. 
CTI: Subjects in either the Pulsed Field or Thermal Groups with a past 
history of CTI-mediated (typical) AFL, who manifest typical AFL 
during a procedure or within the Blanking Period, or who have 
inducible typical flutter, may undergo ablation of the CTI at the 
discretion of the Investigator using any approved RF catheter during 
the Index / Rescheduled Index Procedure or any re-ablation procedure.  
Other Ablation: Other ablation is not permitted under this protocol 
except when the Investigator determines that subject welfare requires 
ablation for an accessory pathway, atrioventricular nodal reentrant 
tachycardia (AVNRT), treatment-emergent left-sided AFL or incessant 
AT. 
RE-ABLATION 
PROCEDURES 
SECTION 5.4 
Re-ablation under this protocol requires documentation of Detectable 
AF, AFL or AT. When performed, re-ablation will be performed 
utilizing an approved study ablation catheter (RFA or CBA) at 
Investigator discretion.  
Any re-ablation procedure for AF, AFL or AT during study follow-up 
constitutes a Treatment Failure. 
However, CTI ablation or re-ablation for right-sided typical AFL may 
be performed at any time during study follow-up and does not 
constitute a Treatment Failure. 

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NEUROLOGIC 
ASSESSMENT 
SUBJECTS 
SECTION 5.8 
A subset of study sites qualified and willing to perform the 
standardized brain MRI post-ablation will be established and 
designated as NAS sites. NAS sites will be selected to generate a 
minimum of 80 NAS Subjects, balanced approximately equally 
between RFA and CBA control sites.  
All ITT Subjects at NAS sites free of contraindications to MRI will be 
consented for post-procedure MRI until the study enrollment target of 
evaluable scans is met.  
The MRI will be performed using standardized parameters to elicit 
characteristics of silent cerebral events (SCEs) and silent cerebral 
lesions (SCLs). If a post-procedural SCE or SCL is confirmed, then the 
NAS subject will undergo a pre-discharge neurological assessment and 
a follow-up brain MRI during the 90 Day Assessment window. 
ANTIARRHYTHMIC 
DRUGS 
SECTION 5.9 
Antiarrhythmic drugs (AADs), except for amiodarone, may be utilized 
during the Blanking Period at the Investigator’s discretion. On Day 60 
± 10 each subject will be contacted by telephone to stop all AADs. 
Class I / III AADs should be stopped at the Day 60 Assessment. 
However, at the Investigator’s discretion, Class I / III AADs may be 
continued up to Day 90 without creating a Treatment Failure. 
The use of amiodarone at any time during the study, except intra-
procedurally to control an arrhythmia, or the use of Class I / III AADs 
after Day 90, constitute a Treatment Failure. 

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PRIMARY SAFETY 
ENDPOINT 
SECTION 7.1 
The primary safety endpoint is the Composite Safety Endpoint (CSE) 
defined as the proportion of Intent-to-Treat (ITT) Subjects with one or 
more of the following device- or procedure-related SAEs as 
adjudicated by the CEC. 
Early onset: Any of the following with an Onset Date within 7 days of 
the Index / Rescheduled Index procedure: 
• Death  
• Myocardial infarction 
• Persistent phrenic nerve palsy 
• Stroke 
• Transient ischemic attack (TIA) 
• Peripheral or organ thromboembolism  
• Cardiac tamponade / perforation 
• Pericarditis 
• Pulmonary edema 
• Vascular access complications  
• Heart block 
• Gastric motility/pyloric spasm disorders  
Late onset: Either of the following with an Onset Date at any time 
through the completion of 12-month follow-up visit: 
• PVS 
• Atrio-esophageal fistula 
SECONDARY 
SAFETY ENDPOINT 
SECTION 7.2 
1. Aggregate PV Cross-Sectional Area 
ADDITIONAL 
SAFETY ANALYSES 
SECTION 7.3 
1. Severe Ablation Complications 
2. Nonserious / Serious CSEs 
3. Post-Blanking Direct Current Cardioversions 
4. Post-Blanking Arrhythmia Hospitalizations 
5. Any Related SAE 
6. Any Related Stroke or TIA 
7. Categorized PV Dimensional Changes 
8. Thermal Group RF Ablation / Cryoablation Safety Assessment 
9. Learning Curve Safety Assessment 

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PRIMARY 
EFFECTIVENESS 
ENDPOINT 
SECTION 7.4 
The primary effectiveness endpoint is Treatment Success in Modified 
Intent-to-Treat (MITT) subjects, defined as: 
1. Acute Procedural Success AND 
2. Chronic Success, defined as freedom from: 
a. At the Index / Rescheduled Index Procedure: Use of a non-
randomized treatment modality for PVI 
b. After the Blanking Period: 
i. Occurrence of any Detectable AF, AFL or AT (excluding 
CTI-dependent flutter confirmed by EP study) 
ii. Any cardioversion for AF, AFL or AT (excluding for 
CTI-dependent flutter) 
iii. Use of any Type I or Type III antiarrhythmic medication 
for the treatment of AF, AFL or AT 
c. At any time:  
i. Re-ablation for AF, AFL or AT (other than for CTI-
dependent flutter) 
ii. Use of amiodarone, , except intra-procedurally to control 
an arrhythmia  
Endpoint status will be assessed through the Month 12 Assessment 
(Day 360 ± 30). 
SECONDARY 
EFFECTIVENESS 
ENDPOINT 
SECTIONS 7.5 
The secondary effectiveness endpoint is the same as the primary 
effectiveness endpoint but will be tested for superiority rather than 
non-inferiority. 
ADDITIONAL 
EFFECTIVENESS 
ANALYSES 
SECTION 7.6 
 
1. Acute Procedural Success 
2. Acute Vein Success 
3. Chronic Success  
4. Chronic Success Allowing Re-ablation 
5. Chronic Success Allowing AADs 
6. Treatment Success Allowing Re-ablation 
7. Treatment Success Allowing AADs 
8. Treatment Success with PVI/CTI Only 
9. Early Recurrence of AF 
10. Rate of Re-ablation 
11. PVI Durability at Re-ablation 
12. CTI Ablation Failure 
13. Thermal Group RF Ablation/ Cryoablation Effectiveness 
Assessment 
14. AF Symptom Assessment 
15. Learning Curve Effectiveness Assessment 

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PROCEDURAL 
ASSESSMENTS 
SECTION 7.7 
 
1. Assessments of procedure durations  
a. Procedure time (initiation of venous access to venous access 
closure) 
b. Left atrial dwell time (total time an ablation catheter is in the 
left atrium [LA]) 
c. Total ablation time (first ablation to last ablation) 
d. Total mapping time (total time spent mapping) 
e. Fluoroscopy time (total duration of exposure) 
2. Characterization of lesion sets: 
a. PVI ablations 
b. CTI ablations 
c. For subjects undergoing required LA ablation for an 
accessory pathway, AVNRT, left-sided AFL or incessant 
AT, description of lesion sets utilized 
QUALITY OF LIFE 
ASSESSMENT 
SECTION 7.8 
Quality of Life (QoL) will be assessed at baseline and 12 months using 
two assessments. These assessments will be tested for nominal p values 
between Pulsed Field Subjects and Thermal Subjects: 
1. The EuroQol standardized questionnaire of health states 
(EQ-5D-3 L) 
2. The Atrial Fibrillation Effect on Quality of Life (AFEQT) 
instrument for the measurement of health-related quality of life 
RANDOMIZATION 
SECTION 9.2 
Subjects who meet the inclusion and exclusion criteria will be 
randomized using a 1:1 allocation ratio.  
Each site will utilize only one control modality – either RFA or CBA – 
and will use that modality for all subjects randomized to the Thermal 
Group. Site activation and enrollment will be monitored and when 
necessary controlled to maintain a minimum 40% proportion of 
Thermal Subjects in either the RFA or CBA modality. 
POPULATIONS FOR 
ANALYSIS 
SECTION 9.4 
Several analysis populations are defined for this study, including: 
• Safety Subjects 
• Modified Intent-to-Treat (MITT) Subjects 
• Per Protocol (PP) Subjects 
ASSESSMENT OF 
THE PRIMARY 
SAFETY ENDPOINT 
SECTION 9.5 
The primary safety endpoint for this study is the Composite Safety 
Endpoint (CSE) which will be analyzed as a test of non-inferiority of 
the event rate at 12 months using a non-inferiority margin of 8%. 
Statistical methods are Bayesian. 

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ASSESSMENT OF 
THE PRIMARY 
EFFECTIVENESS 
ENDPOINT 
SECTION 9.6 
The primary effectiveness endpoint for this study is Treatment Success 
which will be analyzed as a test of non-inferiority of the event rate at 
12 months using a non-inferiority margin of 15%. Statistical methods 
are Bayesian. 
SAMPLE SIZE 
CONSIDERATIONS 
SECTION 9.7 
Although the pre-specified statistical analysis methods are Bayesian, 
standard frequentist considerations are used to guide sample size 
selection. 
Parameter selection: Published IDE studies with available 
information comparing new devices with approved control devices 
have all used non-inferiority designs with one-sided alpha of 0.05 and 
15% effectiveness margins and either 8% or 9% safety margins. 
Sample size requirements for safety: The sample size for primary 
safety was estimated for a Farrington-Manning test with PASS 13 
indicates that, for 1:1 randomization, 90% power, alpha=0.05 (one-
sided), CSE rate in both Groups of 0.08 and non-inferiority margin of 
0.08. Assuming a 5% rate of loss-to-follow-up (LTFU), 450 subjects 
are needed. Uncertainty in the CSE rate motivates the use of a design 
wherein the sample size is adaptively determined, with possible sample 
sizes ranging from 350 to 750. 
Sample size requirements for effectiveness: The sample size required 
for the primary effectiveness endpoint was estimated by PASS 13 for 
1:1 randomization, 90% power, alpha=0.05 (one-sided), success rates 
in each group of 0.65 and non-inferiority margin of 0.15. Assuming a 
10% rate of LTFU, 382 subjects are needed. Uncertainty in the 
Treatment Success rate motivates the use of a design wherein the 
sample size is adaptively determined, with possible sample sizes 
ranging from 200 to 550.   
Number of Enrolled Subjects: The primary population for the 
analysis of effectiveness is the MITT Population. The Safety 
Population should be similar but will not be smaller. Considering the 
joint sample size needs of the primary safety and effectiveness 
objectives, the primary analysis population may range from a minimum 
of 350 to a maximum of 750. 
To achieve a sample size of 750 MITT Subjects, up to 900 subjects 
may be enrolled consisting of 750 MITT and up to 105 Roll-In 
Subjects and up to 45 ITT Subjects (6%) who do not meet the criteria 
for the MITT Population. 

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ANALYSIS PLAN 
SECTION 9.8 
This trial is designed using Bayesian statistical techniques.  The sample 
size will be determined adaptively via a Goldilocks design, with 
possible sample sizes of N=350, 450, 550, 650, and 750.   
At each of the four interim sample size assessments, the predictive 
probability that the trial will end in a determination of non-inferiority 
for both safety and effectiveness will be computed and compared to 
pre-specified thresholds.  A determination will be made to stop 
enrollment for predicted success, to stop enrollment for predicted 
futility, or to continue enrollment to the next larger sample size. 
Once subject accrual has stopped, all accrued subjects will be followed 
to 12 months, and then the inferential tests of non-inferiority will occur 
as described in Sections 9.5 and 9.6. 
CORE 
LABORATORIES 
SECTION 10 
A qualified Arrhythmia Core Lab (ACL) will be established to receive, 
review and assess all protocol-stipulated ECGs, EMs and Holter 
monitors.  
A qualified Cardiac Imaging Core Lab (CICL) will be established to 
receive, review and assess all protocol-stipulated cardiac MRIs and 
CTs. 
A qualified Brain Imaging Core Lab (BICL) will be established to 
receive, review and assess all protocol-stipulated brain MRIs for NAS 
Subjects. 
CLINICAL EVENTS 
COMMITTEE 
SECTION 12.2.4 
An independent panel of 3 electrophysiologists will review AEs, 
adjudicate seriousness and relatedness of potential SAEs and 
adjudicate primary safety and effectiveness outcomes. 
This group will consist of a panel of 3 experienced, independent 
physicians who are not Investigators and will be supported by one or 
more Medical Monitors and staff as required. 
The CEC will convene regularly during the study to review, classify 
and/or adjudicate AEs reported in this investigation as well as primary 
and secondary study outcomes. 
DATA AND SAFETY 
MONITORING 
BOARD 
SECTION 12.2.5 
An independent panel of physicians, trialists and a statistician will assess 
study progress and key study outcomes. 
This group will include at least 2 experienced, independent physicians 
who are not Investigators and an independent statistician not involved in 
the routine operation of the study.  
The Data and Safety Monitoring Board (DSMB) will convene regularly 
during the study to assess overall event rates to ensure the integrity of 
the clinical study and the rights, safety and welfare of study subjects.  

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INCLUSION 
CRITERIA 
SECTION 3.3.1 
Patients are required to meet all the following inclusion criteria to 
participate in this study: 
1. Patients with drug-resistant symptomatic PAF meeting all the 
following criteria: 
a. Paroxysmal: AF that terminates spontaneously or with 
intervention within 7 days of onset. 
b. Frequency: 
i. Physician documentation of recurrent PAF (two or more 
episodes) within 6 months, AND 
ii. At least one (1) documented episode by a recording such 
as ECG, EM, Holter monitor or telemetry strip within 12 
months of enrollment. 
c. Drug failed: Failed AAD treatment, meaning therapeutic 
failure of at least one (1) AAD (Class I to IV) for efficacy 
and / or intolerance. 
2. Patients who are ≥ 18 and ≤ 75 years of age on the day of 
enrollment. 
3. Patient who are willing and capable of: 
a. Providing informed consent to undergo study procedures 
AND 
b. Participating in all examinations and follow-up visits and 
tests associated with this clinical study. 

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EXCLUSION 
CRITERIA 
SECTION 3.3.2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(CONTINUED NEXT 
PAGE) 
Patients will be excluded from participating in this study if they meet 
any one of the following exclusion criteria: 
1. AF that is any of the following: 
a. Persistent (both early and longstanding) by diagnosis or 
continuous duration > 7 days 
b. Requires four (4) or more direct-current cardioversions in 
the preceding 12 months 
c. Secondary to electrolyte imbalance, thyroid disease, alcohol 
or other reversible / non-cardiac causes 
2. Any of the following atrial conditions: 
a. Left atrial anteroposterior diameter ≥ 5.5 cm (by MRI, CT 
or TTE) 
b. Any prior atrial endocardial or epicardial ablation 
procedure, other than right sided cavotricuspid isthmus 
ablation or for right sided SVT 
c. Any prior atrial surgery 
d. Intra-atrial septal patch or interatrial shunt 
e. Atrial myxoma 
f. Current LA thrombus 
g. LA appendage closure, device or occlusion, past or 
anticipated 
h. Any PV abnormality, stenosis or stenting (common and 
middle PVs are admissible) 
3. At any time, one (1) or more of the following cardiovascular 
procedures, implants or conditions: 
a. Sustained ventricular tachycardia or any ventricular 
fibrillation 
b. Hemodynamically significant valvular disease: 
i. Valvular disease that is symptomatic  
ii. Valvular disease causing or exacerbating congestive 
heart failure 
iii. Aortic stenosis: if already characterized, valve area 
< 1.5cm or gradient > 20 mm Hg 
iv. Mitral stenosis: if already characterized, valve area 
< 1.5cm or gradient > 5 mm Hg 
v. Aortic or mitral regurgitation associated with 
abnormal LV function or hemodynamic measurements 
c. Hypertrophic cardiomyopathy 
d. Any prosthetic heart valve, ring or repair including balloon 
aortic valvuloplasty 
e. Pacemaker, implantable cardioverter defibrillator or cardiac 
resynchronization therapy devices 
f. Any inferior vena cava (IVC) filter, known inability to 
obtain vascular access or other contraindication to femoral 
access 

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PAGE 14 
 
EXCLUSION 
CRITERIA 
SECTION 3.3.2 
 
 
(CONTINUED FROM 
PRIOR PAGE) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(CONTINUED NEXT 
PAGE) 
g. History of rheumatic fever 
h. History of congenital heart disease with any residual 
anatomic or conduction abnormality 
4. Any of the following procedures, implants or conditions: 
a. At baseline: 
i. New York Heart Association (NYHA) Class III/IV 
ii. Left ventricular ejection fraction (LVEF) < 40% 
iii. Symptomatic hypotension 
iv. Uncontrolled hypertension (SBP > 160 mmHg or DBP 
> 95 mmHg on two BP measurements at baseline 
assessment) 
v. Symptomatic resting bradycardia 
vi. Implantable loop recorder or insertable cardiac monitor, 
b. Within the 3 months preceding the Consent Date: 
i. Myocardial infarction 
ii. Unstable angina 
iii. Percutaneous coronary intervention 
iv. Heart failure hospitalization 
v. Treatment with amiodarone 
vi. Pericarditis or symptomatic pericardial effusion 
vii. Gastrointestinal bleeding 
c. Within the 6 months preceding the Consent Date: 
i. Heart surgery 
ii. Stroke, TIA or intracranial bleeding 
iii. Any thromboembolic event 
iv. Carotid stenting or endarterectomy 
5. Diagnosed disorder of blood clotting or bleeding diathesis 
6. Contraindication to, or unwillingness to use, systemic 
anticoagulation 
7. Patient who is not on anticoagulation therapy for at least 3 weeks 
prior to the ablation procedure 
8. Contraindication to both CT and MRI  
9. Sensitivity to contrast media not controllable by premedication 
10. Women of childbearing potential who are pregnant, lactating, not 
using medical birth control or who are planning to become 
pregnant during the anticipated study period 
11. Medical conditions that would prevent participation in the study, 
interfere with assessment or therapy, significantly raise the risk of 
study participation, or modify outcome data or its interpretation, 
including but not limited to: 
a. Body Mass Index (BMI) > 40.0 
b. Solid organ or hematologic transplant, or currently being 
evaluated for an organ transplant 

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EXCLUSION 
CRITERIA 
SECTION 3.3.2 
 
 
(CONTINUED FROM 
PRIOR PAGE) 
 
 
c. Severe lung disease, pulmonary hypertension, or any lung 
disease involving abnormal blood gases or requiring 
supplemental oxygen  
d. Renal insufficiency with an estimated glomerular filtration 
rate (eGFR) < 30 mL/min/1.73 m2, or any history of renal 
dialysis or renal transplant 
e. Active malignancy or history of treated malignancy within 24 
months of enrollment (other than cutaneous basal cell or 
squamous cell carcinoma) 
f. Clinically significant gastrointestinal problems involving the 
esophagus or stomach including severe or erosive esophagitis, 
uncontrolled gastric reflux, gastroparesis, esophageal 
candidiasis or active gastroduodenal ulceration 
g. Active systemic infection 
h. COVID-19 disease 
i. Current confirmed, active COVID-19 disease 
ii. Current positive test for SARS-CoV-2 
iii. Confirmed COVID-19 disease not clinically resolved at 
least 3 months prior to the Consent Date. 
i. Other uncontrolled medical conditions that may modify 
device effect or increase risk, including uncontrolled diabetes 
mellitus (HgbA1c > 8.0% if test result already obtained) or 
active alcohol abuse 
j. Sleep apnea and: 
i. An apnea-hypopnea index (AHI) ≥ 15, or  
ii. An AHI of ≥ 5 and ≤14 with documented symptoms of 
excessive daytime sleepiness, impaired cognition, mood 
disorders or insomnia, or documented hypertension, 
ischemic heart disease or history of stroke, 
unless compliant with continuous positive airway pressure 
(CPAP) treatment. 
k. Predicted life expectancy less than one (1) year 
12. Clinically significant psychological condition that in the 
Investigator’s opinion would prohibit the subject's ability to meet 
the protocol requirements 
13. Current or anticipated enrollment in any other randomized, 
interventional or Food and Drug Administration (FDA)-regulated 
clinical study (data collection for registries or retrospective 
studies is permitted) 
14. Employees / family members of: 
a. FARAPULSE or any of its affiliates or contractors 
b. The Investigator, sub-Investigators, or their medical office or 
practice, or healthcare organizations at which study 
procedures may be performed 

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PAGE 16 
 
Abbreviations and Acronyms 
AAD 
Antiarrhythmic drug 
ACL 
Arrhythmia Core Laboratory 
ACT 
Activated clotting time 
ADC 
Apparent diffusion coefficient 
ADE 
Adverse Device Effect 
AE 
Adverse event 
AF 
Atrial fibrillation 
AFEQT 
Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire 
AFL 
Atrial flutter 
AT 
Atrial tachycardia 
AVNRT 
Atrioventricular nodal reentrant tachycardia 
BICL 
Brain Imaging Core Laboratory 
BMI 
Body Mass Index 
BUN 
Blood urea nitrogen 
CBA 
Cryoballoon ablation 
CEC 
Clinical Events Committee 
CHA2DS2-VASc    A clinical prediction rule for stroke 
CHF 
Congestive heart failure 
CICL 
Cardiac Imaging Core Laboratory 
CIP 
Clinical Investigation Plan (synonymous with study protocol) 
COVID-19 
COrona VIrus Disease 2019: an illness caused by SARS-CoV-2 
CPS 
Chronic Procedural Success 
CRF 
Includes CRF (case report form) and eCRF (electronic CRF) 
CRO 
Clinical research organization 
CSE 
Composite Safety Endpoint 
CT 
Computed tomography 
CTI 
Cavo-tricuspid isthmus 
CXR 
Chest X-ray 
DSMB 
Data and Safety Monitoring Board 
DWI 
Diffusion weighted image 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EM 
Event monitor 
EQ-5D-3 L 
EuroQol standardized questionnaire of health states 
ETW 
Early Termination / Withdrawn 
FDA 
Food and Drug Administration 
FLAIR 
Fluid-attenuated inversion recovery 
HCT 
Hematocrit 
HGB 
Hemoglobin 
ICE 
Intracardiac echocardiography 
ICF 
Informed consent form 
INR 
International normalized ratio 

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IRB 
Institutional Review Board 
IRE 
Irreversible electroporation 
ITT 
Intent(ion)-to-Treat 
IVC 
Inferior vena cava 
LA 
Left atrium or left atrial 
LBBB 
Left bundle branch block 
LTFU 
Lost-to-follow-up 
MITT 
Modified Intent(ion)-to-Treat 
MRI 
Magnetic resonance imaging 
NOAC 
Novel oral anticoagulant 
NIHSS 
National Institutes of Health Stroke Scale 
NYHA 
New York Heart Association 
PAF 
Paroxysmal atrial fibrillation 
PFA 
Pulsed field ablation 
PP 
Per Protocol 
PV 
Pulmonary vein 
PVI  
Pulmonary vein isolation 
PVS 
Pulmonary vein stenosis 
RFA 
Radiofrequency ablation 
SADE 
Serious Adverse Device Effect 
SAE 
Serious adverse event  
SCE 
Silent cerebral events 
SCL 
Silent cerebral lesions 
TEE 
Transesophageal echocardiography 
TIA 
Transient ischemic attack 
TTE 
Transthoracic echocardiography 
UADE 
Unanticipated Adverse Device Effect 
V 
Volts 
 
 
 
 
 

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PAGE 18 
 
1. Introduction 
1.1 
Background and Rationale 
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 
approximately 2.2 million people in the United States and 4.5 million in the European 
Union.1, 2. The incidence increases with advancing age, affecting 6% of the population 
over age 60 and 10% of the population over age 803, 4. Age-adjusted population 
trending projects 16 million people in the United States will have AF by 20505. 
AF remains a significant cause of morbidity and mortality in industrialized societies. 
The annual risk of AF-related stroke is 5% per year and 1 of every 6 strokes diagnosed 
occurs in the presence of AF.6 Therefore, patients with AF require long-term 
anticoagulation to prevent embolic events. Failure to manage AF may also lead to 
anatomic and electrical remodeling of the left atrium (LA), tachycardia-induced 
cardiomyopathy and reduced left ventricular function (heart failure). AF remains an 
extremely costly public health burden, with annual per patient cost of care approaching 
€3000 (approximately $3,200 U.S.)7  
The Heart Rhythm Society (HRS) 2017 Consensus Statement on Catheter and Surgical 
Ablation of Atrial Fibrillation8 defines several different stages of AF. Paroxysmal AF 
(PAF) is defined as AF that terminates spontaneously or with intervention within 7 
days of onset.  
1.2 
Irreversible Electroporation 
Al-Sakere 20079 described irreversible electroporation (IRE) as a non-thermal tissue 
ablation technique in which intense short duration electrical fields are used to 
permanently open pores in cell membranes, thus producing non-thermal tissue ablation. 
Their study, using a mouse model, showed complete regression in 92% of treated 
tumors. IRE ablation has a tissue-specific mechanism of ablation. The tissue injury 
from IRE ablation occurs at the cellular level with loss of homeostasis leading to 
necrosis or apoptosis.10, 11, 12, 13 IRE ablation typically spares the extracellular matrix, 
which facilitates rapid wound healing.14, 15, 16, 17, 18 
Thomson 201119 reported a case-series study (N=38) assessing the safety of IRE for 
treating liver, kidney or lung cancers in humans. The first four patients showed signs of 
transient ventricular arrhythmia, so subsequent patients were all treated using 
electrocardiogram (ECG)-synchronized delivery of electroporation pulses. There were 
2 further arrhythmias and 2 cases of inadvertent damage to neighboring organs. 
Approximately 68% of tumors were completely ablated. The authors concluded that 
IRE is safe for clinical use, provided ECG-synchronized delivery is used.  
A research group led by FHM Wittkampf in Utrecht investigated the potential 
effectiveness and safety of epicardial electroporation in AF ablation procedures using 
porcine models. Wittkampf 201120 (N=10) used a circular ablation catheter and showed 
that PVI was achieved in all animals, with no sign of stenosis at 3-week follow-up. 
Van Driel 201421 (N=6) confirmed this result out to 3-month follow-up. Neven 201422 
(N=5) showed that electroporation lesion depth depended on the level of electrical 
energy applied, reaching 8 mm at 300 joules. 

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Van Driel 201523 (N=20) showed that electroporation could create deep lesions close to 
the phrenic nerve without damage to the nerve. Neven 201424 similarly showed that 
neighboring coronary arteries were undamaged by electroporation (N= 5). These 
animal studies suggest that IRE can safely create deep lesions in heart tissue without 
harming adjacent tissues. 
1.3 
Summary of FARAPULSE Preclinical Studies 
FARAPULSE Inc. (hereinafter FARAPULSE) has performed multiple preclinical 
animal studies investigating the safety and efficacy of the FARAPULSE™ Pulsed 
Field Ablation System. These studies demonstrate that pulsed field ablation (PFA) 
using the FARAPULSE technology reliably produces homogeneous, well-demarcated 
and transmural lesions in porcine atrial tissue. Seven- and 30-day studies show mild to 
moderate inflammatory and healing responses consistent with radiofrequency ablation 
lesions. 
Areas of critical interest that cannot be directly assessed in the clinical studies 
performed to date include: 
• Esophageal Sparing: FARAPULSE performed a preclinical study25 to assess 
the effect of PFA application on the esophagus in a relevant preclinical porcine 
model. A cohort of swine underwent ablation of the esophagus, which was 
mechanically deflected to be in close apposition with the inferior vena cava 
(IVC) which contained the PFA catheter. A control cohort, which underwent 
clinically representative radiofrequency ablation (RFA) was also assessed. After 
a high-dose delivery of the PFA and RFA energies, the animal subjects were 
survived to 25 days.  
Pathological analysis demonstrated that no PFA subjects showed any gross or 
histological sign of ablation-related injury to the esophageal tissues. However, 
all RF control subjects showed ablation-related injury to the esophagus, ranging 
from mucosal lesions to esophageal fistula. 
• Phrenic Nerve Sparing: FARAPULSE performed a preclinical study26 to 
assess the safety and efficacy of the PFA waveform directly adjacent to the 
phrenic nerve. Right superior pulmonary vein (RSPV), inferior common 
pulmonary vein (ICPV) and superior vena cava (SVC) isolation were performed 
using the FARAWAVE Pulsed Field Ablation Catheter in a relevant preclinical 
porcine model.  
None of eleven porcine subjects showed any diminution of phrenic nerve 
function after treatment at the maximum (2.0 kV) and minimum (1.4 kV) 
voltages under investigation. 
• Pulmonary Vein Effects: FARAPULSE performed a preclinical study27 to 
assess the safety and efficacy of ablation using the FARAWAVE Pulsed Field 
Ablation Catheter in a relevant preclinical porcine model. Six porcine subjects 
underwent ablation of the RSPV and ICPV at 2.0 kV and were then survived for 
30 days.  

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Pathological analysis demonstrated that no subjects showed any degree of PV 
narrowing or flow impairment in the treated veins. This study also investigated 
durability of pulmonary vein isolation (PVI) and histological transmurality at 30 
days, showing that both assessments were present in 91.6% of the treated PVs. 
These results support the safety and performance of the system. 
1.4 
Summary of FARAPULSE Clinical Studies for PAF 
1.4.1 
The IMPULSE Study 
FARAPULSE, Inc. conducted a safety and feasibility study28 at Na Homolce Hospital 
in Prague, Czech Republic and Hôpital Cardiologique du Haut-Leveque in Pessac, 
France under the “IMPULSE” Protocol, CS0188. This study was conducted using a 
version of the FARAPULSE Pulsed Field Ablation System which functioned 
similarly to the system which will be used in the IDE investigation and the results are 
summarized below.  
Clinical investigation population: Adult patients with PAF who provided informed 
consent to participate in the study.  
Methodology: In this pre-market, multi-center study, subjects who had signed the 
informed consent underwent baseline assessment, received treatment with the 
investigational device and were assessed prior to discharge, and at 30 days, 3 months, 
6 months and 12 months following the index procedure. A remapping procedure was 
required as part of the 3-month assessment. A core laboratory analyzed ECG data 
from the Event Monitors (EMs) and Holter monitors. Adverse events (AEs) were 
reviewed and where necessary adjudicated by a Clinical Events Committee (CEC). 
Results: A total of 40 subjects enrolled and were treated in this study with a mean 
age of 58.2±9.1 years. A majority of subjects were male, 70% (28/40).  
The primary safety endpoint of the study was the incidence of early-onset (within 7 
days of the PFA ablation procedure) primary adverse events (AEs). One subject had a 
qualifying peri-procedural cardiac tamponade resolving with drainage, for a rate of 
2.5% (1/40).  
The primary feasibility endpoint of the study was the proportion of subjects that 
achieved Acute Procedural Success, defined as the percutaneous endocardial creation 
of electrically isolating lesions around the ostia of the PVs using the FARAPULSE 
Pulsed Field Ablation System. The procedural success rate was 100% (40/40).  
Secondary safety endpoints, included the rate of all serious adverse events (SAEs) 
reported at the different follow-up time points, as adjudicated by the CEC, with 7.5% 
(3/40) of subjects reporting an SAE between index procedure and 30 days (2 AF 
events, 1 cardiac tamponade), 0.0% (0/40) of subjects reporting an SAE between 30 
days and 3 months, 7.5% (3/40) of subjects reporting an SAE between 3 months and 
6 months (1 arteriovenous fistula, 2 ATs) and 2.5% (1/40) of subjects reporting an 
SAE between 6 months and 12 months (1 urinary calculus).  

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No pulmonary vein stenosis (PVS), esophageal lesions or phrenic nerve impairment 
was observed in any subject. 
The secondary feasibility endpoint was long-term technical success, defined as 
electrical isolation of the PVs assessed during an electroanatomical mapping 
procedure performed 3-months following the index procedure, with 41.2% (14/34) of 
subjects achieving technical success.  
For the 40 enrolled subjects, 156 veins were treated at the index procedure, 100% 
(156/156) were successfully isolated and 70% of ablated PVs remained isolated at the 
3-month remapping procedure. Thirty-one (31) of 40 subjects (77.5%) remained free 
from post-blanking AF, atrial flutter (AFL) or atrial tachycardia (AT) after a mean 
follow-up of 356 days. 
Ten (10) device deficiencies were reported in 8 subjects, none of which were deemed 
serious or resulted in any associated AEs in subjects. Of the ten deficiencies, one 
device deficiency was related to a 3rd party guidewire. All procedures were 
completed as planned and all subjects were successfully treated. All deficiencies were 
investigated and most resolved with several others under ongoing investigation. 
Conclusion: These results support the safety and feasibility of the FARAPULSE 
Pulsed Field Ablation System in the treatment of patients with PAF, with a low rate 
of primary AEs through 7 days, a high rate (100%) of procedural success and a rate of 
arrhythmia recurrence consistent with other technologies.  
1.4.2 
The PEFCAT Study 
FARAPULSE, Inc. has completed enrollment in a two-center single arm open label 
safety and feasibility study29 of the treatment of PAF at Na Homolce Hospital in 
Prague, Czech Republic and Hôpital Cardiologique du Haut-Leveque in Pessac, 
France under the “PEFCAT” Protocol, CS0267. This study was conducted using the 
FARAPULSE Pulsed Field Ablation System, very similar in function to the system 
which will be used in the IDE investigation. 
Clinical investigation population: Subjects with documented drug-resistant 
(Class I to IV) symptomatic PAF who have had ≥ 2 episodes within 6 months of 
enrollment.  
Methodology: In this pre-market, multi-center study, subjects who had signed the 
informed consent underwent baseline assessment, received treatment with the 
investigational device and were assessed prior to discharge, and at 30 days, 75 days, 
6 months and 12 months following the index procedure. A remapping procedure was 
required as part of the 75-day assessment. A core laboratory analyzed ECG data from 
the EMs and Holter monitors. AEs were reviewed and where necessary adjudicated 
by the CEC. 
Results: A total of 71 subjects enrolled and were treated in this study with a mean 
age of 57.2±10.5 years. A majority of study subjects were male, 78.9% (56/71).  

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The primary safety endpoint of the study was a composite safety endpoint including 
early-onset and late-onset events. One subject had a prolonged hospitalization for a 
1.5mm AV fistula between the right superficial femoral artery and the right common 
femoral vein that resolved during 5 days of hospitalization. A second subject had a 
pericardial effusion following a protocol-specified remap procedure that included 
PFA, which resolved after drainage. The proportion of subjects with one or more 
composite safety events was 2.8% (2/71).  
The primary feasibility endpoint of the study was Acute Procedural Success, defined 
as the percutaneous endocardial creation of a complete, electrically isolating set of 
lesions around the ostia of the pulmonary veins (PVs) using the FARAPULSE Pulsed 
Field Ablation System during the first procedure, as clinically assessed by entrance 
and/or exit block performed ≥ 20 minutes after the last PVI lesion is made. The 
procedural success rate was 100% (71/71).  
Secondary safety endpoints included the rate of device or procedure-related SAEs at 
30 days, 75, days, 6 months and 12 months, with reported rates between 0.0% and 
4.2%. Additional secondary safety endpoint results at 12 months included: 
stroke/CVA (0.0% [0/71]), transient ischemic attack (TIA) (0.0% [0/71]), major 
bleeding related to anticoagulation treatment (0.0% [0/71]), cardioversion (5.6% 
[4/71]) and arrhythmia-related hospitalization (7.0% [5/71]). 
No PVS, esophageal lesions or phrenic nerve impairment was observed in any 
subject. 
Chronic Procedural Success (CPS) was defined as persistent electrical isolation of all 
initially ablated PVs assessed during an electroanatomical mapping procedure 
performed 75 days following the index procedure. The rate of Chronic Procedural 
Success was found in 74.2% (46/62) of treated and remapped subjects.  
Therapeutic Success was defined as freedom from post-blanking AF, AFL or AT, or 
post-blanking ablation for AF, AFL or AT using the study device, or ablation for AF, 
AFL or AT with a non-study device at any time. The overall rate of Therapeutic 
Success was 67.6% (46/68); for subjects taking antiarrhythmic drugs (AADs) the rate 
was 51.9% (14/27) and for subjects not taking AADs 78.0% (32/41). 
Sixty-eight (68) of 71 subjects remained in the study past Day 90 and as of the cut-off 
date for this analysis 54/68 (79.4%) were free from recurrent arrythmia through a 
mean follow-up of 325 days.  
For the 71 enrolled subjects, 279 veins were treated at the index procedure and 100% 
(279/279) were successfully isolated. Of subjects that attended the 75-day remapping 
procedure, 90.9% (221/243) were durably isolated.  
Device performance was generally excellent, with 16 device deficiencies reported in 
12 subjects, none of which were deemed serious or resulted in any associated AEs in 
subjects. All procedures were completed as planned and all subjects were successfully 
treated. All deficiencies were investigated and most resolved with several others 
under ongoing investigation.  

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Conclusion: These results support the safety and feasibility of the FARAPULSE 
Pulsed Field Ablation System in the treatment of patients with PAF, with a low rate 
of acute and long-term primary safety endpoint events and a high rate (100%) of 
procedural success. 
1.4.3 
The PEFCAT II Study 
FARAPULSE has completed enrollment in the multicenter, single arm open label 
PEFCAT II expanded safety and feasibility study30 of the FARAPULSE Pulsed Field 
Ablation System as well as the FARAFLEX Pulsed Field Ablation Catheter. Subjects 
were enrolled at both the Na Homolce Hospital in Prague, Czech Republic and the 
‘University Hospital in Split Croatia under the “PEFCAT II” Protocol, CS0571. This 
study investigated PVI and cavo-tricuspid isthmus (CTI) ablation using the 
FARAWAVE and FARAFLEX Pulsed Field Ablation Catheters. 
Clinical investigation population: Subjects with documented drug-resistant 
(Class I to IV) symptomatic PAF who have had ≥ 2 episodes within 6 months of 
enrollment.  
Methodology: In this pre-market, multi-center study, subjects who had signed the 
informed consent underwent baseline assessment, received treatment with the 
investigational device and were assessed prior to discharge, and at 30 days, 75 days, 
6 months and 12 months following the index procedure. A remapping procedure was 
required as part of the 75-day assessment. A core laboratory analyzed ECG data from 
the EMs and Holter monitors. AEs were reviewed and where necessary adjudicated 
by the CEC. 
Results: A total of 10 subjects enrolled and were treated in this study with a mean 
age of 56.0±14.2 years. There was equal number of males 50.0% (5/10) and females 
50% (5/10).  
The primary safety endpoint of the study was a CSE including early-onset and late-
onset events. No primary events occurred giving a rate of 0.0% (0/10).  
The primary feasibility endpoint of the study was acute procedural success, defined as 
above. The procedural success rate was 100% (10/10).  
Secondary safety endpoints included the rate of device or procedure-related SAEs, 
stroke, cardioversion and arrhythmia-related hospitalizations. The rates of these 
events were 0.0% (0/10). 
CPS – defined as persistent electrical isolation of all initially ablated PVs – was found 
in 77.8% (7/9) of subjects. 
Acute CTI Success – defined as the creation of bi-directional electrical block across 
the cavotricuspid isthmus – was found in 100% (4/4) of subjects undergoing CTI 
ablation. 
Therapeutic Success – defined as freedom from occurrence of AF, AFL or AT, or 
post-blanking ablation for AF, AFL or AT using the study device, or  ablation for AF, 
AFL or AT with a non-study device at any time – was 80.0% (8/10), 0.0% (0/1) in 

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subjects on AADs and 88.9% (8/9) in subjects off AADs, at a mean follow-up of 200 
days. 
For the 10 enrolled subjects, 39 veins were treated at the index procedure and 100% 
(39/39) were successfully isolated. For subjects that underwent the 75-day remapping 
procedure, 94.3% (33/35) of treated PVs were durably isolated. 
There have been no device deficiencies reported for this study through the analysis 
date. 
Conclusion: These results support the safety and feasibility of the FARAPULSE 
Pulsed Field Ablation System in the treatment of patients with PAF, with a rate of 
0.0% for acute and long-term primary safety endpoint events and a high rate (100%) 
of procedural success.  
1.4.4 
Clinical Sub-Studies 
Several investigator-initiated sub-studies were undertaken during the clinical 
investigations cited above. 
• Esophageal Assessment: Thirty-eight (38) subjects enrolled in the PEFCAT 
study underwent esophagogastroduodenoscopy following ablation using the 
FARAWAVE Pulsed Field Ablation Catheter to isolate all PVs.31  
None (0%) of these studies revealed any ablation-related findings. 
In another study of imaged PVs, Cochet et al compare post-procedure lesion 
imaging from subjects receiving FARAPULSE PFA, radiofrequency and 
cryoballoon ablation for PVI. Consistent with its underlying mechanism, 
FARAPULSE PFA demonstrated no gadolinium enhancement of the esophagus 
suggestive of injury (0/18 subjects). Radiofrequency (6/16 subjects) and 
cryoballoon (4/7 subjects) ablation did create signals for esophageal injury on 
magnetic resonance imaging (MRI).32 
Phrenic Nerve Assessment: An analysis of the first 117 PFA subjects with 
PAF who underwent PVI using the FARAWAVE Pulsed Field Ablation 
Catheter showed 100% of treated veins were isolated acutely. Pre- and post-
ablation phrenic functional testing was performed either by catheter pacing 
proximal to the region of ablation or by free inspiration fluoroscopic imaging of 
the diaphragm.  
No subject (0%, 0/117) showed any diminution of phrenic function.33 
• Pulmonary Vein Morphology: Data regarding baseline and 3-month computed 
tomography (CT) imaging from IMPULSE and PEFCAT (PFA ablated PVs) 
and TOCCASTAR and HEARTLIGHT (control subjects with RF ablated PVs) 
was re-analyzed and compared.34 
A total of 303 PVs showed that the average percent change in PV ostial 
diameters was reduced significantly more in RF subjects compared with PFA 
subjects (p < 0.001). When analyzed in standardized percentile change 

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categories, the distribution of size changes was significantly worse in RF-
treated PVs compared with PF-treated PVs (p < 0.001). 
Table 1 Impact of Ablation Energies on 3-Month PV Dimensions 
Ostial % diameter change 
RFA PVs 
PFA PVs 
p-value 
     Long axis 
-11.8 ± 16.3 
+1.7 ± 9.9 
< 0.001 
     Short axis 
-12.7 ± 18.8 
+3.4 ± 12.7 
< 0.001 
Frequency Distribution of PV Dimensional Change 
Energy 
Total 
Mild 
(30-50%) 
Moderate 
(50-70%) 
Severe 
(70-100%) 
p-value 
RFA (n=166) 
14.5% (24) 
11.4% (19) 
1.8% (3) 
1.2% (2) 
< 0.001 
PFA (n=137) 
0.7% (1) 
0.7% (1) 
0% (0) 
0% (0) 
PV = pulmonary vein. 
Kuroki et al, Ostial Dimensional Changes after PVI: PFA vs RFA. E-published Heart Rhythm Journal 2020. 
• Peri-Procedural Brain MRI: Eighteen (18) subjects enrolled in the IMPULSE 
and PEFCAT studies have undergone peri-procedural post-ablation brain MRI 
scans to assess for silent cerebral events (SCEs) and/or silent cerebral lesions 
(SCLs).  
Two of these subjects (2/18, 11%) showed diffusion-weighted positive lesions 
(SCEs) at approximately one day post procedure. One of these subjects, with a 
prior history of TIA, experienced a possible TIA one day post procedure 
presenting as a complaint of 15 minutes of difficulty speaking that was 
inapparent to observing medical staff; this event was captured in the AE dataset 
as a TIA.35 
These results support the safety and performance of the system. 
1.5 
Rationale for Conducting This Pivotal Study 
Catheter ablation for PAF with a variety of energy sources and catheter configurations 
has been demonstrated to be a safe and effective procedure. The FARAPULSE Pulsed 
Field Ablation System has undergone preclinical and clinical testing to demonstrate its 
preliminary safety and effectiveness for isolating PVs quickly and with minimal 
complications, using a standard catheter-based endocardial procedure. The System has 
undergone preclinical testing in representative models to demonstrate that it can isolate 
PVs and create other cardiac lesions quickly, durably and with minimal complications, 
using a standard catheter-based endocardial procedure. Clinical data from 
131 endocardially ablated human subjects demonstrates the creation durable lesions 
when assessed at 75-day remapping procedures, freedom from recurrent PAF in greater 
than 80% of subjects and an excellent safety profile. 
This pivotal study constitutes the multicenter randomized study of FARAPULSE PFA 
technology compared with existing RFA and CBA technologies for marketing approval 
in the United States and other countries. 
 

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1.6 
Risks, Benefits and Mitigation 
1.6.1 
Potential Risks 
As detailed in Section 1.4, the risk profile associated with the FARAPULSE Pulsed 
Field Ablation System and the ablation procedure is expected to be consistent with 
similar devices currently in clinical use for percutaneous cardiac ablation for treatment 
of PAF.  
The FARAPULSE Pulsed Field Ablation System utilizes PFA to produce continuous 
transmural cardiac lesions to treat AF using an ablation procedure that is similar to 
other commercially available percutaneous ablation catheters. More specifically: 
• The device system is used during percutaneous endocardial ablation procedures 
like other commercially approved catheter systems.  
• The device system is composed of similar biocompatible materials. 
• The device uses standard percutaneous techniques for ablation procedures. 
• The device utilizes a specialized generator to deliver ablation energy.  
• The device has similar procedural properties as compared to the planned 
commercially approved control devices: 
o The device is similar to CBA devices in that it circumferentially ablates an 
entire PV during each delivery 
o The device can be manipulated in the same manner as RFA and CBA 
catheters  
o The device uses metal electrodes for ablation energy delivery (RF 
catheters) and sensing (RFA and CBA catheters.) 
A difference between the FARAPULSE Pulsed Field Ablation System and other 
commercially approved thermal AF ablation systems is that PFA uses non-thermal IRE 
energy for tissue ablation, delivered through electrodes embedded in the FARAPULSE 
Pulsed Field Ablation Catheter for delivery of such energy in the PVs. 
Based on the available preclinical and clinical data and the substantial similarities to 
other approved ablation technologies, the anticipated risks are generally equivalent in 
type, severity and frequency to those associated with commercially released systems 
being used for percutaneous cardiac ablation procedures.  
1.6.2 
Potential Benefits 
There are no guaranteed benefits from participation in this study. European feasibility 
studies of 131 PAF subjects have shown early valid scientific evidence for safety and 
effectiveness similar to existing approved technologies.  
This study may have the following potential benefits: 
• To provide treatment to subjects with PAF using an investigational device 
which has demonstrated the ability to isolate PVs endocardially, to reduce the 
subsequent occurrence of symptomatic AF in treated subjects and potentially to 
reduce the risk for severe ablation complications associated with thermal 
ablation such as phrenic nerve palsy or atrio-esophageal fistula. 

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• To provide information gained from the conduct of this study that may benefit 
other persons with the same medical condition. 
• To generate additional data demonstrating that the endocardial creation of 
electrically isolating lesions via PFA applied using the FARAPULSE Pulsed 
Field Ablation System is a safe and effective treatment for drug-resistant, 
recurrent, symptomatic PAF. 
1.6.3 
Risk Mitigation and Summary 
FARAPULSE has conducted bench, in-vivo and clinical testing to optimize safe use of 
the device during clinical investigation and the devices are in compliance with the 
applicable requirements of the 21 CFR 820 Subpart C, Design Controls of the Quality 
System Regulation, ISO 13485 and ISO 14971. 
The clinical study is designed to mitigate risk by the selection of skilled Investigators, 
experienced sites, eligibility criteria to eliminate higher risk subjects and the carefully 
controlled design of the clinical investigational plan. Careful monitoring and 
comprehensive oversight by independent monitors and physicians are also planned. 
The potential therapeutic improvement associated with the FARAPULSE Pulsed Field 
Ablation System has been recognized by the FDA, which was granted Breakthrough 
Pathway status to the technology in 2019.  
To receive this Breakthrough Pathway designation, the FDA was required to find that 
FARAPULSE Pulsed Field Ablation System: 
“… offers significant advantages over existing approved or cleared alternatives, 
including the potential, compared to existing approved alternatives, to reduce or 
eliminate the need for hospitalization, improve patient quality of life, facilitate 
patients’ ability to manage their own care (such as through self-directed 
personal assistance), or establish long-term clinical efficiencies.” 
Based on the Sponsor’s evaluation of the investigational devices and their performance 
and the design of this pivotal investigation, the Sponsor has conducted an analysis of 
the benefits and risks of the FARAPULSE Pulsed Field Ablation System for the 
treatment of PAF. The conclusion of this review is that this investigation is justified 
because the overall potential benefit to the population outweighs the risks and 
foreseeable risks which have been mitigated as fully described in this submission. 

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2. Investigational Devices 
2.1 
Names of Investigational Devices 
The FARAPULSE Pulsed Field Ablation System is comprised of the following: 
• FARAWAVE Pulsed Field Ablation Catheters and Connection Cables 
• FARASTAR Pulsed Field Ablation Generator, including 
o FARASTAR Stimulation Module 
o FARASTAR Recording System Module 
o Associated cables 
• FARADRIVE Steerable Sheath 
2.2 
Intended Use 
The FARAPULSE Pulsed Field Ablation System is indicated for the treatment of 
drug-resistant, recurrent, symptomatic paroxysmal atrial fibrillation.  
2.3 
FARAPULSE Pulsed Field Ablation System 
The FARAPULSE Pulsed Field Ablation System consists of the FARAWAVE Pulsed 
Field Ablation Catheter, the FARASTAR Pulsed Field Ablation Generator and the 
FARADRIVE Steerable Sheath. These components, sub-components and model 
numbers are listed in Table 2 and depicted in Figure 1 
Table 2 
FARAPULSE Pulsed Field Ablation System Components 
Component 
Subcomponents 
Model Numbers 
FARAWAVE  
Pulsed Field 
Ablation Catheter  
1. FARAWAVE Pulsed Field Ablation Catheter (fully 
deployed diameters of 31mm and 35mm) 
2. FARASTAR Catheter Connection Cable 
41C601 (31mm) 
41C602 (35mm) 
41C604 
FARASTAR  
Pulsed Field 
Ablation 
Generator and 
related equipment 
1. FARASTAR Pulsed Field Ablation Generator  
2. FARASTAR Stimulation Module 
3. FARASTAR Stimulation Module Cable 
4. FARASTAR EGM Cable 
5. FARASTAR Recording System Module 
6. FARASTAR Stimulation Module Auxiliary Cable 
7. FARASTAR Stimulation Module Male Cable 
8. FARASTAR Stimulation Module Female Cable 
9. FARASTAR Stimulation Module Y-Cable – Long 
10. FARASTAR Stimulation Module Y-Cable – Short 
11. FARASTAR Recording System Module Catheter 
Pin Cable  
12. FARASTAR Accessories Cable Set 
61C601 
61C603 
61C604 
61C605 
61C607 
61C608 
61C609 
61C610 
61C611 
61C612 
61C613 
 
61C606 
FARADRIVE  
Steerable Sheath  
 FARADRIVE Steerable Sheath and Dilator 
 
21C602 
 
For Instructions for Use (IFU) documentation please refer to the following: 
• FARAWAVE Pulsed Field Ablation Catheter Instructions for Use - LBL0913 
• FARASTAR Pulsed Field Ablation Generator System Use Manual - LBL0914 
• FARADRIVE Steerable Sheath Instructions for Use - LBL0771 

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Figure 1 
FARAPULSE Pulsed Field Ablation System Components 
 
 
AUX = Stimulation Module output signal that is active during energy delivery and is used by the Recording System Module to disconnect the patient ECG and 
Diagnostic catheter electrodes from the EP Lab Recording system during PFA to reduce the risk of interference, CATH = Generator PFA output to 
FARAWAVE catheter, ECG = electrocardiogram signals, EGM = Generator output of intracardiac signals from the FARAWAVE Electrodes when not delivering 
energy; disconnected from FARAWAVE during energy delivery, EGMs = electrogram signals, EP = Electrophysiology, Lab = laboratory, STIM = Generator output 
of two internal stimulation channels and a trigger output signal active during energy delivery. 

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2.3.1 
FARAWAVE Pulsed Field Ablation Catheter  
The FARAWAVE Pulsed Field Ablation Catheter consists of 2 components: The 
FARAWAVE Pulsed Field Ablation Catheter and the FARASTAR Catheter 
Connection Cable, which are used together. Both components are sterile and single 
use only.  
The FARAWAVE Pulsed Field Ablation Catheter is offered in 2 different sizes 
(31-mm [41C601] and 35-mm [41C602] fully deployed diameters) to accommodate 
varying PV anatomy. Selection of either catheter will be at the Investigator’s 
discretion.  
The FARAWAVE Pulsed Field Ablation Catheter is a multi-electrode catheter that 
connects electrically to the FARASTAR Pulsed Field Ablation Generator (Figure 2). 
It consists of a distal section with electrodes arranged on splines, a shaft section and a 
proximal handle with a manually operated deployment control.  
 
Figure 2 
FARAWAVE Pulsed Field Ablation Catheter 
 
 
 
 
 
 
(Continued next page) 
 
 

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The FARAWAVE Pulsed Field Ablation Catheter has five (5) variably deployable 
splines. The five splines are undeployed during insertion and removal and during use 
can deploy continuously from an undeployed state through a basket-shaped 
configuration to a fully deployed flower-shaped configuration with five petals (See 
Figure 3). 
 
Figure 3 
FARAWAVE Pulsed Field Ablation Catheter - Deployed States 
 
 
 
Each spline has 1 electrode that is separately wired from the others on that spline to 
facilitate connection to a mapping or recording system via a cable supplied with the 
system. The handle includes a flush port for saline infusion, a deployment control 
knob with a guidewire lumen hub that can be connected to a hemostasis valve and a 
short cable that terminates in a single connector for attachment to the FARASTAR 
Catheter Connection Cable. The other end of the Connection Cable attaches to the 
front panel of the FARASTAR Pulsed Field Ablation Generator. The Connection 
Cable is packaged sterile and is single-use only. The PFA energy is delivered from 
the FARASTAR Pulsed Field Ablation Generator over the set of ablation catheter 
electrodes.  
Additional details are provided in the IFU LBL0913 for the specific use and 
procedural steps of the FARAWAVE Pulsed Field Ablation Catheter. 

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2.3.2 FARASTAR Pulsed Field Ablation Generator  
The FARASTAR Pulsed Field Ablation Generator consists of the following 
components: 
• FARASTAR Pulsed Field Ablation Generator 
• FARASTAR Stimulation Module 
• FARASTAR Stimulation Module Cable 
• FARASTAR EGM Cable 
• FARASTAR Recording System Module 
• FARASTAR Stimulation Module Auxiliary Cable 
• FARASTAR Stimulation Module Male Cable 
• FARASTAR Stimulation Module Female Cable 
• FARASTAR Stimulation Module Y-Cable – Long 
• FARASTAR Stimulation Module Y-Cable – Short 
• FARASTAR Recording System Module Catheter Pin Cable 
The FARASTAR Pulsed Field Ablation Generator is a 12-channel output unit that 
generates a pulsed voltage waveform that can be delivered to the FARAWAVE 
Pulsed Field Ablation Catheter. The user selectable voltage options for the 
FARAWAVE Pulsed Field Ablation Catheter are 1800V, 1900V and 2000V. 
The FARASTAR Pulsed Field Ablation Generator includes a 2 channel Cardiac 
Stimulator that can be connected to user supplied pacing catheters through the 
FARASTAR Stimulation Module. While the Generator may be synchronized with the 
Cardiac Stimulator outputs, that feature will not be necessary in this clinical study.  
Details regarding the generator are provided in the FARASTAR Pulsed Field 
Ablation Generator User Manual LBL0914. 
2.3.3 FARADRIVE Steerable Sheath  
The FARAWAVE Pulsed Field Ablation Catheter is used exclusively with the 
FARADRIVE Steerable Sheath. 
The FARADRIVE Steerable Sheath consists of two (2) primary components, the 
Steerable Sheath and the Dilator, which are used together. Both components are 
sterile and single use only. 
The FARADRIVE Steerable Sheath is comprised of a distal steerable section and a 
shaft section which connect to the handle. The handle includes a knob to control the 
deflection of the distal tip and a flush port for infusion of saline or contrast. The 
Dilator is intended for insertion through the sheath lumen and includes a shaped tip 
for dilation for vascular or chamber access (Figure 4). Details regarding the sheath 
are provided in the FARADRIVE Steerable Sheath IFU LBL0771. 
 
 

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Figure 4 FARADRIVE Steerable Sheath 
 
 
2.4 
Device Accountability 
The FARAPULSE Pulsed Field Ablation System will be stored in a secure location and 
access will be controlled. Records will be maintained to document the physical location 
of inventory from shipment to investigational sites by Sponsor or contract 
manufacturing facility through use and / or return or disposal. 
The site will be responsible for maintaining a Device Accountability Log provided by 
the Sponsor or its designated representative. At a minimum the following will be 
recorded: date of receipt, FARAPULSE Pulsed Field Ablation System components 
identification number (Generator, Ablation Catheter and Steerable Sheath lot and / or 
serial number), expiration date, date of use, subject unique identification code and date 
of disposal or return of the device. 
If there is a product Device Deficiency / Malfunction or other need to return the system 
or system components to the Sponsor or contract manufacturer, the Sponsor or designee 
will be contacted for safe product disposal and/ or return details. Appropriate case 
report forms (CRFs) will be completed in the event of a Device Deficiency / 
Malfunction. 
The Investigator is responsible for ensuring that the investigational devices are used 
only under the Investigator’s supervision and are only used according to this protocol, 
training and any subsequent amendments or updates. The Investigator will not supply 
an investigational device to any person not authorized and trained to participate in the 
study. The Investigator shall document on the CRFs the lot numbers and / or serial 
numbers of the devices used during each case. 
2.5 
Return of Devices 
All unused investigational devices will be returned to the Sponsor or designee upon 
completion of the clinical study. Any investigational device that does not meet 
performance specifications will also be returned to the Sponsor or designee for analysis 
per Sponsor procedures. The Investigator or designated representative is responsible for 
device accountability and disposition of all used and unused devices. The Sponsor or its 
designated representative will conduct device reconciliation at the completion of 
subject enrollment or at the conclusion of the study. 

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3. Study Population 
3.1 
Subject Recruitment 
Subjects will be recruited from the clinical practice of, or by referral to, the 
Investigators. Modest compensation may be provided to Enrolled Subjects for their 
participation in the study and travel costs may be reimbursed. 
3.2 
Subject Screening 
3.2.1 
Screening Procedures 
Routine clinical evaluations that would be performed as part of the normal clinical care 
of patients being considered for participation in this study may be performed prior to 
informed consent and the data used as part of the screening assessment. If the subject is 
subsequently consented and enrolled in the study, the results of such tests may be used 
as study data and if used will be entered on the appropriate CRF. 
Site personnel will use care in reviewing the patient’s clinical status in relation to each 
inclusion and exclusion criterion and ensure that appropriately documented results are 
available prior to concluding that the subject meets study inclusion and exclusion 
criteria. 
Screening procedures do not have to be completed on a single day. 
Subjects who become Screen Failures at any time may not be enrolled, randomized or 
participate in any further study procedures unless their disqualifying finding(s) 
becomes fully resolved. 
3.2.2 Screening Log 
A Screening Log will be maintained for all consented subjects who undergo formal 
screening for possible enrollment, identified by a Subject Screen Number, noting the 
date screening was completed and the reason(s) for rejection (the specific inclusion / 
exclusion criteria failed), or that the subject was enrolled. The Investigator will 
maintain the information linking the Subject Screen Number to subject identifiers. 
3.3 
Study Eligibility Criteria 
3.3.1 
Inclusion Criteria 
Patients are required to meet all the following inclusion criteria to participate in this 
study: 
1. Patients with drug-resistant symptomatic PAF meeting all the following criteria: 
a. Paroxysmal: AF that terminates spontaneously or with intervention within 
7 days of onset. 
b. Frequency: 
i. Physician documentation of recurrent PAF (two or more episodes) 
within 6 months, AND 
ii. At least one (1) documented episode by a recording such as ECG, EM, 
Holter monitor or telemetry strip within 12 months of enrollment. 

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c. Drug failed: Failed AAD treatment, meaning therapeutic failure of at least 
one (1) AAD (Class I to IV) for efficacy and / or intolerance. 
2. Patients who are ≥ 18 and ≤ 75 years of age on the day of enrollment. 
3. Patients who are willing and capable of: 
a. Providing informed consent to undergo study procedures, AND 
b. Participating in all examinations and follow-up visits and tests associated 
with this clinical study. 
3.3.2 Exclusion Criteria 
Patients will be excluded from participating in this study if they meet any one of the 
following exclusion criteria: 
1. AF that is any of the following: 
a. Persistent (both early and longstanding) by diagnosis or continuous 
duration > 7 days 
b. Requires four (4) or more direct-current cardioversions in the preceding 
12 months 
c. Secondary to electrolyte imbalance, thyroid disease, alcohol or other 
reversible / non-cardiac causes 
2. Any of the following atrial conditions: 
a. Left atrial anteroposterior diameter ≥ 5.5 cm (by MRI, CT or TTE) 
b. Any prior atrial endocardial or epicardial ablation procedure, other than 
right sided cavotricuspid isthmus ablation or for right sided SVT  
c. Any prior atrial surgery  
d. Intra-atrial septal patch or interatrial shunt 
e. Atrial myxoma 
f. Current LA thrombus 
g. LA appendage closure, device or occlusion, past or anticipated 
h. Any PV abnormality, stenosis or stenting (common and middle PVs are 
admissible) 
3. At any time, one (1) or more of the following cardiovascular procedures, 
implants or conditions: 
a. Sustained ventricular tachycardia or any ventricular fibrillation 
b. Hemodynamically significant valvular disease: 
i. Valvular disease that is symptomatic  
ii. Valvular disease causing or exacerbating congestive heart failure 
iii. Aortic stenosis: if already characterized, valve area < 1.5cm or 
gradient > 20 mm Hg 
iv. Mitral stenosis: if already characterized, valve area < 1.5cm or 
gradient > 5 mm Hg 
v. Aortic or mitral regurgitation associated with abnormal LV function or 
hemodynamic measurements 
c. Hypertrophic cardiomyopathy 
d. Any prosthetic heart valve, ring or repair including balloon aortic 
valvuloplasty 

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e. Pacemaker, implantable cardioverter defibrillator or cardiac 
resynchronization therapy devices 
f. Any IVC filter, known inability to obtain vascular access or other 
contraindication to femoral access 
g. History of rheumatic fever 
h. History of congenital heart disease with any residual anatomic or 
conduction abnormality 
4. Any of the following procedures, implants or conditions: 
a. At baseline: 
i. New York Heart Association (NYHA) Class III or IV 
ii. LVEF < 40% 
iii. Symptomatic hypotension  
iv. Uncontrolled hypertension (SBP > 160 mmHg or DBP > 95 mmHg 
on two (2) BP measurements at baseline assessment) 
v. Symptomatic bradycardia 
vi. Implantable loop recorder or insertable cardiac monitor*
b. Within the 3 months preceding the Consent Date: 
i. Myocardial infarction 
ii. Unstable angina 
iii. Percutaneous coronary intervention 
iv. Heart failure hospitalization 
v. Treatment with amiodarone 
vi. Pericarditis or symptomatic pericardial effusion 
vii. Gastrointestinal bleeding 
c. Within the 6 months preceding the Consent Date: 
i. Heart surgery 
ii. Stroke, TIA or intracranial bleeding 
iii. Any thromboembolic event 
iv. Carotid stenting or endarterectomy 
5. Diagnosed disorder of blood clotting or bleeding diathesis 
6. Contraindication to, or unwillingness to use, systemic anticoagulation 
7. Patient who is not on anticoagulation therapy for at least 3 weeks prior to the 
ablation procedure 
8. Contraindication to both CT and MRI  
9. Sensitivity to contrast media not controllable by premedication 
10. Women of childbearing potential who are pregnant, lactating, not using medical 
birth control or who are planning to become pregnant during the anticipated 
study period 
11. Medical conditions that would prevent participation in the study, interfere with 
assessment or therapy, significantly raise the risk of study participation, or 
modify outcome data or its interpretation, including but not limited to: 
a. Body Mass Index (BMI) > 40.0 
 
* If an implantable loop recorder or insertable cardiac monitor is explanted prior to study enrollment it must not 
be replaced for the duration of the subject’s participation in the study.  

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b. Solid organ or hematologic transplant, or currently being evaluated for an 
organ transplant 
c. Severe lung disease, pulmonary hypertension, or any lung disease 
involving abnormal blood gases or requiring supplemental oxygen 
d. Renal insufficiency with an estimated glomerular filtration rate (eGFR) 
< 30 mL/min/1.73 m2, or any history of renal dialysis or renal transplant  
e. Active malignancy or history of treated malignancy within 24 months of 
enrollment (other than cutaneous basal cell or squamous cell carcinoma) 
f. Clinically significant gastrointestinal problems involving the esophagus or 
stomach including severe or erosive esophagitis, uncontrolled gastric 
reflux, gastroparesis, esophageal candidiasis or active gastroduodenal 
ulceration 
g. Active systemic infection 
h. COVID-19 disease 
i. Current confirmed, active COVID-19 disease 
ii. Current positive test for SARS-CoV-2 
iii. Confirmed COVID-19 disease not clinically resolved at least 3 
months prior to the Consent Date 
i. Other uncontrolled medical conditions that may modify device effect or 
increase risk, including uncontrolled diabetes mellitus (HgbA1c > 8.0% if 
test result already obtained) or active alcohol abuse 
j. Sleep apnea and: 
i. An apnea-hypopnea index (AHI) ≥ 15, or  
ii. An AHI of ≥ 5 and ≤14 with documented symptoms of excessive 
daytime sleepiness, impaired cognition, mood disorders or insomnia, 
or documented hypertension, ischemic heart disease or history of 
stroke, 
unless compliant with continuous positive airway pressure (CPAP) 
treatment. 
k. Predicted life expectancy less than one (1) year 
12. Clinically significant psychological condition that in the Investigator’s opinion 
would prohibit the subject's ability to meet the protocol requirements. 
13. Current or anticipated enrollment in any other randomized, interventional or 
FDA-regulated clinical study (data collection for registries or retrospective 
studies is permitted) 
14. Employees / family members of: 
a. FARAPULSE or any of its affiliates or contractors 
b. The Investigator, sub-Investigators, or their medical office or practice, or 
healthcare organizations at which study procedures may be performed 
3.4 
Subject Status and Disposition Definitions 
3.4.1 
General Pre-Screening 
Potential subjects screened for enrollment prior to signing informed consent who fail 
one (1) or more study eligibility criteria determined by routine clinical assessments or 
the medical record need not be documented. 

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3.4.2 COVID-19 Pre-Screening 
Screening for COVID-19 status will follow each investigational site’s then-current 
requirements.  
Patients may proceed to informed consent and full screening unless any of the 
following conditions exist: 
• They fail the investigational site’s then-current requirements in relation to 
COVID-19 status and study participation. 
• They currently have confirmed, active COVID-19 disease or a positive test for 
SARS-CoV-2. 
• They have had confirmed COVID-19 disease not clinically resolved at least 3 
months prior to the Consent Date. 
The results of COVID-19 screening may be used as study data for any consented 
subject. 
3.4.3 Screened Subjects 
A Screened Subject is any subject who has not failed pre-screening and who has 
signed an informed consent. Each Screened Subject will be recorded in the Screening 
Log with the date of informed consent and the result of the screening process. 
Should an AE occur that is associated with a screening procedure or test and with 
onset prior to randomization, it will be recorded in a Screening AE CRF. Such AEs 
are not part of the ADVENT Trial, its data or analyses and will not be entered into the 
study database. A listing and summary of Screened Subjects will be provided along 
with any screening-associated AEs. 
3.4.4 Screen Failure Subjects 
A Screen Failure Subject is any subject who has signed an informed consent and who 
is then excluded due to failure of one or more study eligibility criteria at any time 
before randomization.  
Subjects who become Screen Failures will be recorded in the Screening Log 
including all eligibility criteria that were the cause of the Screen Failure. Screen 
Failure Subjects will have a Study Exit CRF completed on the date that Screen 
Failure is determined. No study data on events with an onset date after the Exit Date 
may be collected or included as part of the study database or analyses. 
3.4.5 Enrolled Subjects 
An Enrolled Subject is any subject who has signed the informed consent document 
AND who has been determined to meet all pre-procedural study eligibility criteria 
prior to randomization.  
3.4.6 Roll-In Subjects 
Roll-In Subjects are Enrolled Subjects who are treated with the FARAPULSE Pulsed 
Field Ablation System under the provisions of Section 5.6. Roll-In Subjects are not 
randomized and will be analyzed and reported separately. 

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3.4.7 Intent-to-Treat Subjects 
An Intent-to-Treat (ITT) Subject is an Enrolled Subject who is randomized to either 
the Pulsed Field Group or the Thermal (Control) Group. 
3.4.8 Safety Subjects 
A Safety Subject is an ITT Subject who has had a study ablation catheter inserted into 
the body at an Index / Rescheduled Index Procedure. 
3.4.9 Modified Intent-to-Treat Subjects 
A Modified Intent-to-Treat (MITT) Subject is an ITT Subject who receives any 
energy delivery for PVI with the randomized endocardial ablation catheter at an 
Index / Rescheduled Index Procedure. 
3.4.10 Completed Subjects 
A Completed Subject is an ITT Subject who completes the Month 12 Assessment 
either in-person or remotely. The date on which the Month 12 Assessment is 
completed is the Completed Subject’s Exit Date and a Study Exit CRF will be 
completed. No study data on events with an onset date after the Exit Date may be 
collected or included as part of the study database or analyses. 
3.4.11 Incomplete Subjects 
An Incomplete Subject is any ITT Subject who does not become a Completed 
Subject. Anticipated reasons for failure to become Completed Subjects include 
withdrawal of consent by a subject, death or incapacity of a subject, lost-to-follow-up 
(LTFU) status and termination by the Investigator.  
A LTFU Subject is an ITT Subject who ceases to participate in study follow-up 
procedures or who fails to respond to contact attempts. The Investigator will attempt 
to contact such a subject 2 or more times within 60 days and if there is no return to 
study participation, the subject will be deemed LTFU. The Investigator will document 
that a minimum of two attempts were made to contact the subject, including sending a 
certified letter if current address is known, prior to terminating the subject from the 
study.  
The date on which a subject is determined to be an Incomplete Subject is their Exit 
Date, and a Study Exit CRF will be completed including the reason for becoming an 
Incomplete Subject.  
No study data on events with an onset date after the Exit Date may be collected or 
included as part of the study database or analyses. However, if an Incomplete 
Subject’s exit is due to an AE, the Investigator should, if subject consent is 
documented, follow the subject until the AE has resolved or is considered stable, but 
in any case, not more than 390 days have passed since the Index / Rescheduled Index 
Procedure. The data related to that AE may be collected and included in the study 
database and analyses under such consent. 

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3.4.12 Per Protocol Subjects 
A Per Protocol (PP) Subject is a Safety or ITT Subject without major protocol 
deviations that would affect the completeness, accuracy and reliability of the study 
data. Major protocol deviations2 that exclude subjects from a PP Population are the 
following: 
• Failure to meet any of the following study entry criteria: 
o Arrhythmia different than PAF (Inclusion Criterion 1) 
o Prior cardiovascular procedures, implants or conditions (Exclusion 
Criteria 3 and 4) 
o Medical conditions (Exclusion Criterion 11) 
• Failure to receive the randomized ablation treatment for PVI as specified in 
this protocol (Section 5.2 or Section 5.3) 
• Receipt of a prohibited study drug (amiodarone, except intra-procedurally to 
control an arrhythmia ) 
• In addition, the data of Severe COVID-19 Subjects will be censored beginning 
on the Onset Date of infection. 
3.5 
Subject Disposition Chart 
Figure 5 Subject Disposition Chart 
 
MITT = modified intent-to-treat, ITT = intent-to-treat 
 
2 Major protocol deviations also include such events as failure of informed consent, confidentiality violations 
and actions that may affect the subject’s rights, safety or well-being. These, while serious, generally do not 
impact the validity of data collected and so are not part of the per protocol exclusions for outcome assessment. 

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3.6 
Subject Informed Consent 
All subjects must provide documented informed consent using the Institutional Review 
Board (IRB)-approved informed consent form (ICF) / electronic informed consent form 
(eICF) before undergoing any study-related procedures. If electronic consent is utilized 
it will conform to the FDA Guidance Document “Use of Electronic Informed Consent, 
Questions and Answers”, dated December 2016 (or subsequent revised versions as 
applicable). 
Since it may become necessary during this study to access study-specific protected 
healthcare information from remote clinical sites, the ICF / eICF will include this 
permission in the consent process. 
Subjects cannot be asked to sign the ICF / eICF until the study has been fully approved 
by the institution’s IRB and the Sponsor or their clinical research organization (CRO) 
representative has received and reviewed the IRB-approved ICF / eICF. Subjects who 
meet the general eligibility criteria will be asked to sign an ICF / eICF as approved by 
the relevant regulatory authorities before any study-specific tests or procedures are 
performed.  
The Investigator or a designated member of their staff should communicate with the 
subject to obtain written informed consent. As far as possible, non-technical language 
shall be used that is understandable to the subject. The background of the proposed 
study and the benefits and risks of the procedures and study should be explained. The 
subject should be provided with ample time to read the ICF / eICF and discuss it with 
their family and physician. The subject shall be informed that their participation in the 
clinical investigation is confidential. The ICF / eICF must be read and understood by 
the subject and the subject’s questions answered. The ICF / eICF must be signed and 
dated by both the subject and physician / designee overseeing informed consent prior to 
subject enrollment and before the subject undergoes any study-related procedures. All 
subjects are to receive copies of their signed and dated ICF / eICF. A copy of the 
approved ICF / eICF along with a copy of each subject’s signed ICF / eICF will be 
maintained by the Investigator in a designated clinical study administrative file or 
electronic record system. Subjects may not be consented after receiving any medication 
that might alter their ability to comprehend the consent form (e.g., sedatives, narcotics, 
etc.). Study personnel should explain that even if a subject agrees to participate in the 
study and signs the ICF / eICF, the subject may not be eligible to participate if the 
subject fails to meet the screening criteria. 
Written informed consent must be obtained prior to performing any protocol-driven 
tests or any procedures that are not standard of care for a percutaneous ablation 
procedure that the subject is scheduled to undergo. Once written consent has been 
obtained, the subject will be entered on a Screening Log, which will be maintained at 
each site. All subjects who provide written informed consent will be entered into the 
Screening Log regardless of whether they are enrolled in the study. 
3.7 
Subject Enrollment 
Subjects that meet all the eligibility criteria and are deemed suitable by the Investigator 
will be invited to participate in the study.  

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When initial screening indicates that the subject will likely meet the inclusion and 
exclusion requirements and agrees to participate in the study, formal written informed 
consent using the current IRB-approved ICF will be obtained. 
Provisional subject enrollment occurs when the ICF has been signed. Enrollment is 
confirmed when all study eligibility requirements are determined to have been met.  
If one or more of the required pre-enrollment assessments – including cardiac CT/MRI, 
transthoracic echocardiography (TTE), laboratory tests and ECG – have not been 
obtained prior to signing the ICF, then the enrollment is considered provisional until 
that assessment has been obtained and the criteria met.  
Regardless of the sequence of ICF completion and pre-procedural enrollment 
assessments, if study eligibility criteria are not met, the subject is a Screen Failure and 
is not enrolled. 
Study eligibility criteria are determined at the time of study entry. In the instance that 
information received after an Index Procedure / Rescheduled Index Procedure reveals 
that an inclusion or exclusion criterion – determined prior to the Index Procedure / 
Rescheduled Index Procedure to have been met – is found to have been incorrectly 
assessed, this does not change the enrolled status of the subject, who remains in the 
study. 
Each Enrolled Subject will be assigned a unique study identification code to protect 
each subject’s confidential health information. The unique study identification code 
will not include date of birth or subject’s first and last initials and will be used to link 
study data and other study information to the subject in lieu of the subject name. The 
Subject Name Log will be used to link the unique study identity code to the subject and 
will be maintained at the site. This log will remain confidential and will not be provided 
to the Sponsor but only used for reference when monitoring at the study site. 
3.8 
Subject Randomization 
Subjects excluding Roll-In Subjects – who are determined by the Investigator at the 
time of assessment to have met all pre-randomization inclusion and exclusion criteria, 
who have signed an ICF and who are scheduled for the Index Procedure – will be 
randomized. The study staff will confirm documented inclusion / exclusion success 
prior to requesting randomization.  
3.9 
Subject Completion or Exit 
When a subject completes the study at the Month 12 Assessment, exceeds 390 days of 
follow-up without a Month 12 Assessment, or exits prior to such completion, they will 
return to standard medical care and a study termination/exit CRF will be completed, 
including the reason for exit. 
Subjects may voluntarily withdraw from the study at any time for any reason. The 
Investigator may terminate the subject without subject consent at any time to protect 
the subject’s rights, safety or welfare. Subjects leaving the study prior to completion 
will continue to receive appropriate medical care without prejudice. 
 

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4. Study Summary and Schedule 
4.1 
Study Objective and Hypothesis 
The primary objective of this pivotal study is to determine whether there is valid 
scientific evidence that endocardial ablation using the FARAPULSE Pulsed Field 
Ablation System is both safe and effective for treating drug-resistant symptomatic PAF. 
The primary clinical hypotheses of this pivotal study are that PVI created by the 
FARAPULSE Pulsed Field Ablation System is not inferior in safety and effectiveness 
to treatment with approved catheter ablation technologies (force-sensing 
radiofrequency or cryoballoon ablation) in the treatment of drug-resistant symptomatic 
PAF. 
4.2 
Study Overview 
This is a prospective, adaptive, multi-center, randomized safety and effectiveness 
pivotal study comparing the FARAPULSE Pulsed Field Ablation System with standard 
of care ablation with force-sensing RF catheters and cryoballoon catheters indicated for 
the treatment of PAF. Subjects will undergo ablation for PVI with the randomized 
treatment and if indicated CTI ablation using an RF catheter. Subjects will be followed 
at 7 days (telephonic), 30 days, 90 days, 6 months and 12 months for AEs, recurrence 
of arrhythmia after a 90-day Blanking Period and other relevant outcome measures.  
4.3 
Subject Confidentiality 
Enrolled Subjects will be assigned a unique, pseudo-anonymous identifier that will be 
used to maintain confidentiality of each subject’s medical information. Subject names 
will not be captured on the CRFs. All subject identifiers except the unique 
pseudo-anonymous identifier should be redacted from any images or other data 
submitted from the participating site to the Sponsor or the Sponsor’s designated 
reviewers for analysis. All information concerning subjects or their participation in this 
study will be considered confidential. Only the authorized Sponsor, designated 
representative personnel, designated consultants and regulatory agencies will have 
access to these confidential files.  
4.4 
Sample Size Summary 
A maximum of 900 subjects may be enrolled in this study. 
Roll-In Subjects: Up to 105 subjects (the first 1 to 3 Enrolled Subjects at each site) 
will be treated with the FARAPULSE devices in a manner consistent with the 
randomized Pulsed Field Group and will be analyzed and reported separately.  
ITT Subjects: An estimated 450 MITT Subjects will be required to support the 
proposed non-inferiority outcomes. Interim sample size re-estimation may decrease this 
number to 350 or increase it to a maximum of 750. Up to 45 additional subjects (6%) 
may be enrolled to compensate for those ITT Subjects who do not meet the criteria for 
the MITT Population. 

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4.5 
Investigational Sites 
The clinical study will be conducted at up to 35 qualified investigational sites in the 
United States. No site may enroll more than 45 ITT Subjects (excludes Roll-In Subjects 
and ITT Subjects who do not qualify for the MITT population) with an intended 
minimum of 10 subjects per site. Should interim sample size re-estimation lead to an 
increase in the number of MITT Subjects greater than 450, each site will be limited to 
10% of the increased total. 
4.6 
Duration of Study and Subject Participation 
Study start-up, inclusive of site initiation and Investigator training, is estimated to take 
6 months. The enrollment period for the first 600 subjects (105 Roll-Ins plus 495 ITT 
Subjects) is estimated to take 18 months and subjects will be followed for up to 13 
months. There will be a 3-month period of site close-out visits, for a planned study 
duration of approximately 40 months. Coronavirus Disease 2019 (COVID-19)-related 
disruptions and interim sample size re-estimation may alter this timeframe. 
Subject participation is anticipated to be 13 ± 1 months to allow for screening, pre-
procedural diagnostic procedures, randomization, treatment and 12±1 months of study 
follow-up. If a subject requires a Rescheduled Index Procedure, this may prolong 
participation by up to 2 to 3 months. 
4.7 
Schedule of Events and Assessments 
Subjects will complete the following visits and assessments as indicated below and as 
summarized in Table 3, (ITT Subjects) and Table 4, (Roll-In Subjects). 
Assessments that are stipulated as remote may also be performed in-person at the 
investigational site at the Investigator’s discretion with subject agreement. 
All protocol-stipulated assessments below will be entered into the appropriate CRFs. 
Assessments are to be performed within the specified assessment windows.  
When COVID-19-related disruptions (Section 6.3.8) interfere with the performance of 
protocol-stipulated follow-up assessments, study sites and Sponsor personnel will 
adjust procedures to optimize data acquisition while protecting the health, safety and 
welfare of all study participants. Study subjects, sites, IRBs and the FDA will be 
informed of COVID-19-related changes in the study. 
This protocol does not specify how remote assessments should be performed, but these 
will be specified in related study documentation and may be modified as necessary 
during the conduct of the study. The method(s) used during the course of this study to 
interact with study participants and to acquire data remotely will be consistent with 
relevant FDA Guidance Documents and will be reported in the Clinical Study Report. 

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4.7.1 
Baseline Assessment 
Type of Assessment: In-person at investigational site 
The completion of the Baseline Assessment requires an in-person visit. Such 
assessments must be deferred if this is not possible. 
The below baseline data will be generated in the window beginning 30 days prior to the 
Consent Date and ending on the date of the Index Procedure, unless otherwise 
specified. This data will include: 
• Demographics including gender, height and weight 
• Pertinent medical and cardiovascular history 
• AAD and anticoagulation medication history 
• Cardiac physical examination 
• Pregnancy test (all women of child-bearing potential) 
• Hematocrit, hemoglobin, electrolytes, blood urea nitrogen (BUN), creatinine 
• COVID-19 testing by site 
o PCR for SARS-CoV-2 virus or equivalent testing, or  
o Confirmation of successful vaccination with an FDA-approved vaccine 
• 12-lead ECG. ECGs with any arrhythmia will include a rhythm strip for ACL 
submission. 
• Imaging (within the window beginning 90 days prior to the Consent Date and 
ending on the date of the Index Procedure) 
o TTE  
o Cardiac CT or MRI establishing PV dimensions 
• NYHA Classification 
• National Institutes of Health Stroke Scale (NIHSS) score by NIHSS-certified site 
personnel 
• CHA2DS2-VASc score 
• AF symptom assessment 
• Quality of Life Measures: 
o The EuroQol standardized questionnaire of health states (EQ-5D-3 L)  
o The Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire (AFEQT) 
quality of life assessments 
Introduction to the EM / Holter Device: At the Baseline Assessment, the subject 
will receive an introduction to EMs, Holters, the hardware and how it will be utilized 
during the follow-up period. The importance of compliance with these critical 
assessments will be stressed.  
4.7.2 Index Procedure / Rescheduled Index Procedure 
Type of Assessment: In-person at investigational site 
The performance of the Index Procedure / Rescheduled Index Procedure and 
the Pre-Discharge Assessment both require an in-person visit. The Index 
Procedure / Rescheduled Index Procedure must be deferred if this is not 
possible. 

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The Index Procedure will be performed according to Section 5.2. Procedural data will 
be collected including: 
• Transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE) 
will be utilized prior to transseptal puncture for exclusion of LA thrombus. 
• Pregnancy test (all women of childbearing potential if baseline pregnancy test 
obtained more than 30 days prior to procedure) 
• Post-ablation 3D electroanatomical maps (at Investigator discretion) 
• Post-ablation fluoroscopic examination of diaphragm motion to assess phrenic 
nerve response 
• Adverse events 
• Procedural times  
• Lesion set data  
• Peri-procedural anticoagulation data: 
o For subjects on a novel oral anticoagulant (NOAC) whether NOAC therapy 
was interrupted for procedure 
o For subjects on warfarin, a pre-treatment international normalized ratio 
(INR) value 
o Heparin administration and timing 
• Device deficiencies and malfunctions  
• For Thermal Subjects: 
o The specific thermal technology used, including manufacturer/model 
o The use of any esophageal monitoring, cooling or manipulation during the 
ablation procedure 
4.7.3 Pre-Discharge Assessment 
Type of Assessment: In-person at investigational site 
Prior to hospital discharge study data will be collected including: 
• Adverse events 
• Hematocrit, hemoglobin, electrolytes, BUN, creatinine 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications. 
• Cardiac rhythm as determined by a 12-lead ECG. ECGs with any arrhythmia will 
include a rhythm strip for ACL submission. 
• Occurrence, date, indication and outcome of any cardioversion(s) 
• Assessment of subject blinding 
EM Training: The subject will be reminded regarding the use of the EM hardware, the 
importance of event monitoring and of the importance of the Day 60 EM Training. 
Pre-Discharge Stroke Evaluation for non-Neurologic Assessment Subjects: 
• NIHSS score by NIHSS-certified site personnel 
• If either of the following occurs: 
o The post-procedure NIHSS score has increased by 1 or more points over the 
pre-procedure NIHSS score OR 
o There is a clinical suspicion of stroke or TIA 

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Then a consulting neurologist will perform a stroke assessment and include the results 
of a concurrent brain MRI. This assessment will be sufficient to determine with 
reasonable certainty whether a stroke, TIA or neither have occurred, using the 
definitions in Table 5. If a stroke is diagnosed the subject will be assessed using a 
Modified Rankin Scale. Please refer to Figure 6. 
Figure 6 Pre-Discharge Stroke Evaluation, Non-NAS Subjects 
 
Pre-Discharge Stroke Evaluation for Neurologic Assessment Subjects: 
• A post-procedure brain MRI as specified in Section 5.8. 
• NIHSS score by NIHSS-certified site personnel 
• If any of the following occurs: 
o The brain MRI is positive for SCE or SCL findings 
o The post-procedure NIHSS score has increased by 1 or more points over the 
pre-procedure NIHSS score OR 
o There is a clinical suspicion of stroke or TIA 
Then a consulting neurologist will perform a stroke assessment and review the NAS-
stipulated brain MRI. This assessment will be sufficient to determine with reasonable 
certainty whether a stroke, TIA or neither have occurred, using the definitions in Table 
5. If a stroke is diagnosed the subject will be assessed using a Modified Rankin Scale. 
Please refer to Figure 7. 
Figure 7 Pre-Discharge Stroke Evaluation, NAS Subjects 
 
 

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4.7.4 Day 7 Assessment 
Type of Assessment: Remote 
Window: Days 7 – 11 
The Day 7 Assessment is essential to establish the primary safety endpoint and 
every effort must be made to complete this assessment between Day 7 and 
Day 11.  
If the assessment is delayed, the onset date of an AE must be elicited as carefully 
as possible to establish whether it occurred within the interval between the 
ablation procedure and Day 7, or thereafter. 
Subjects will be assessed remotely between Day 7 and 11 post-Index 
Procedure / Rescheduled Index Procedure. Study data will be collected by interview, 
including: 
• Adverse events 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications. 
• Recurrent arrhythmia, cardioversions, ablations or hospital admissions since 
discharge 
• The date, time and communication method(s) used to collect the data remotely 
4.7.5 Day 30 Assessment 
Type of Assessment: Remote 
Window: 30 ± 7 Days 
Discharged subjects will be assessed remotely 30 days (± 7 days) post-Index 
Procedure / Rescheduled Index Procedure. (Any subject who continues to be 
hospitalized 30 days post-ablation will have their 30-Day Visit assessment performed 
in-hospital). Study data will be collected by interview including: 
• Adverse events 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications. 
• Recurrent arrhythmia, cardioversions, ablations or hospital admissions since 7-
day telephonic assessment 
• The date, time and communication method(s) used to collect the data remotely 
4.7.6 Day 60 EM Training and AAD Discontinuation  
Type of Interaction: Remote 
Window: 60 ± 10 Days 
EM Training: At Day 60 ± 10 days following the Index Procedure / Rescheduled 
Index Procedure, the subject will receive an EM and receive remote training regarding 
its use and the importance of event monitoring. The subject will be instructed to begin 

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using the EM at the time of the Day 90 Assessment and weekly thereafter and also for 
any symptomatic episodes throughout the remainder of study follow-up. 
AAD Treatment: During this same subject interaction, Class I / III AADs should be 
stopped – if they have not already been discontinued – to allow assessment of off-drug 
freedom from recurrent AF, AFL or AT (the primary effectiveness endpoint). See 
Section 5.9. 
4.7.7 Day 90 Assessment 
Type of Assessment: In-person at investigational site required; remote only for 
documented COVID-19 related disruption. 
Window: 90 ± 14 Days 
If a COVID-19-related disruption prevents an in-person visit within the visit 
window:  
• As much data as possible may be collected remotely.  
• A cardiac MRI or CT scan performed at another healthcare site may be utilized, 
preferably with the same modality as the baseline scan, or the imaging 
procedure may be delayed for up to 3 months.  
• If a fluoroscopic examination is required due to prior diminished phrenic nerve 
response, an inspiration/expiration chest X-ray (CXR) performed in-person or 
at another healthcare site may be substituted. 
Subjects will be assessed at Day 90 ± 14 days following the Index Procedure / 
Rescheduled Index Procedure.  
EM Review: During this assessment, the subject will be queried as to their 
understanding and use of the EM. Remedial training will be supplied as required. 
The subject will be instructed to begin weekly scheduled and symptomatic use of the 
EM and the critical importance of full compliance for study success will be stressed. 
Study data will be collected at the 90-Day Visit including: 
• Adverse events 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications 
• Recurrent arrhythmia, cardioversions, ablations or hospital admissions since last 
visit 
• Radiologic examination of the diaphragm (fluoroscopic sniff test or 
inspiration/expiration CXR) if the post-Index / Rescheduled Index Procedure 
fluoroscopy indicated diminished phrenic nerve response and resolution has not 
been previously demonstrated 
• Cardiac rhythm as determined by a 12-lead ECG at the time of the visit (in-person 
assessment only). ECGs with any arrhythmia will include a rhythm strip for ACL 
submission. 
• Cardiac CT or MRI scan of the same type as the baseline scan to assess the 
dimensions of the PVs. For subjects with a CICL-confirmed 70% or greater PV 

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diameter reduction, a Month 12 follow-up Cardiac CT or MRI scan of the same 
type as baseline will be scheduled to assess PV dimensions. 
• Follow-up brain MRI as specified in Section 5.8.2 (only for NAS Subjects with a 
confirmed post-procedural SCE or SCL on the post-procedural brain MRI) 
• For any subject diagnosed with stroke during the Pre-Discharge Assessment, a 
Modified Rankin Scale assessment. 
• If data is collected remotely, the date, time and communication method(s) used to 
collect the data remotely. 
4.7.8 Month 6 Assessment 
Type of Assessment: Remote 
Window: 180 ± 30 Days 
If a COVID-19-related disruption interferes with the performance of this 
assessment:  
• As much data as possible may be collected remotely, in or out of window.  
 
Subjects will be assessed remotely at 6 months (180 days ± 30 days) following the 
Index Procedure / Rescheduled Index Procedure.  
Holter Monitor: Within the 180 ± 30-day window for this visit, the subject will be 
contacted, receive remote training regarding the use of the EM hardware for Holter 
monitoring, and complete a 72-hour monitoring session. 
EM Review: During this remote assessment EM compliance will be reviewed for 
weekly scheduled and ad hoc symptomatic monitoring and retraining of the subject 
provided as needed. 
Study data will be collected at the 6-Month Visit including: 
• Adverse events 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications 
• Recurrent arrhythmia, cardioversions, ablations or hospital admissions since last 
visit 
• The date, time and communication method(s) used to collect the data remotely 
4.7.9 Month 12 Assessment 
Type of Assessment: In-person at investigational site required; remote only for 
documented COVID-19 related disruption. 
Window: 360 ± 30 Days 
If a COVID-19-related disruption interferes with the performance of this 
assessment:  
• As much data as possible may be collected remotely, in or out of window. 

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• The absence of a 12-lead ECG during a remote assessment is not a protocol 
deviation but the subject should make an EM transmission at the time of the 
assessment.  
• A cardiac MRI or CT scan, if required because of PVS being detected at the 90 
Day Assessment, may be performed at another healthcare site if required, 
utilizing if at all possible the pre-specified CICL imaging protocol. 
• If a fluoroscopic examination is required due to prior diminished phrenic nerve 
response, an inspiration/expiration chest X-ray (CXR) performed in-person or 
at another healthcare site may be substituted. 
Subjects will be assessed at 360 days ± 30 days following the Index Procedure / 
Rescheduled Index Procedure. The Month 12 Assessment cannot be completed prior to 
the performance of the 72 hour Holter monitor procedure. 
Holter Monitor: Within the 360 ± 30-day window for this visit and prior to the date of 
the Month 12 Assessment, the subject will be contacted, receive remote training 
regarding the use of the EM hardware for Holter monitoring, and complete a 72-hour 
monitoring session. 
Study data will be collected at the 12-Month Assessment including: 
• Adverse events 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications 
• Recurrent arrhythmia, cardioversions, ablations or hospital admissions since last 
visit  
• Radiologic examination of the diaphragm (fluoroscopic sniff test or 
inspiration/expiration CXR) if the post-Index / Rescheduled Index Procedure 
fluoroscopy indicated diminished phrenic nerve response and resolution has not 
been previously demonstrated (in-person assessment only) 
• Cardiac rhythm as determined by a 12-lead ECG at the time of the visit (in-person 
assessment only). ECGs with any arrhythmia will include a rhythm strip for ACL 
submission. 
• AF Symptom Assessment 
• Quality of Life: 
o EQ-5D-3 L  
o AFEQT 
• Assessment of subject blinding 
• For subjects with a 3-month cardiac imaging (MRI or CT) showing a CICL-
confirmed 70% or greater PV diameter reduction, a repeat cardiac imaging 
procedure of the same type to assess PV dimensions. 
• If data is collected remotely, the date, time and communication method(s) used to 
collect the data remotely 
At the completion of all components of the Month 12 Assessment a Study Exit CRF 
will be completed. 
 
 

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4.7.10 Re-Ablation Procedures 
Re-ablation under this protocol requires documentation of Detectable AF, AFL or 
AT.  
Each subject undergoing an anticipated PVI re-ablation procedure on Day 76 or 
later must have a Cardiac CT or MRI scan of the same type as the baseline scan 
obtained prior to the procedure to assess the dimensions of the PVs.3 
When performed, PVI re-ablation will be performed utilizing an approved study 
ablation catheter (RFA or CBA) at Investigator discretion for both Pulsed Field 
and Thermal Subjects. Other energy modalities may not be used. 
Any re-ablation procedure for AF, AFL or AT during study follow-up constitutes a 
Treatment Failure, and therefore during such procedures other sites may be 
ablated at Investigator discretion. 
CTI ablation or re-ablation for right-sided typical AFL may be performed at any 
time during study follow-up and does not constitute a Treatment Failure.  
Other sites may be ablated at Investigator discretion using a commercially 
available ablation system. 
For subjects undergoing a re-ablation procedure the following data will be collected: 
• For subjects with a re-ablation scheduled on Day 76 or later, the Day 90 cardiac 
CT or MRI scan of the same type as the baseline scan will be performed prior to 
re-ablation to assess the dimensions of the PVs.  
• During any re-ablation procedure in which LA access is performed a mapping 
procedure will characterize the reconnection status for each originally treated PV 
to characterize lesion durability. 
• For subjects who received ablation of the CTI, the persistence of nonconductivity 
in targeted tissue will be evaluated with either pacing maneuvers or 
electroanatomical mapping. 
• Lesion set data 
4.7.11 Unscheduled Assessments 
Type of Assessment: Either remote or in-person at investigational site. 
Any unscheduled follow-up assessments that occur throughout study follow-up will be 
documented. Study data will be collected including: 
• Adverse events 
• Data regarding the use, changes in or discontinuation of anticoagulation, rate 
control and/or antiarrhythmic medications 
• Recurrent arrhythmia, cardioversions, ablations or hospital admissions since last 
visit  
• EM compliance will be reviewed for weekly scheduled and ad hoc symptomatic 
monitoring and retraining of the subject provided as needed. 
 
3 The protocol-specified Day 90 cardiac imaging qualifies for this purpose if obtained prior to a re-ablation. 

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• Cardiac rhythm as determined by a 12-lead ECG 
o At the investigational site: required. ECGs with any arrhythmia will include a 
rhythm strip for ACL submission. 
o At another health care site: not required but should be obtained if available. 
The absence of a 12-lead ECG is not a protocol deviation. 
o Remote, not at a health care site: not required. An EM submission should be 
requested. 
• If data is collected remotely, the date, time and communication method(s) used to 
collect the data remotely 
4.7.12 COVID-19-Related Disruption of Study Assessments 
To avoid study disruptions or missing data related to COVID-19 impacts, such as 
COVID-19 illness or COVID-19 restrictions on movement, association or access to 
health care facilities, every effort will be made to gather study data by all available 
means and from any available sources. This includes use of communications media and 
the acquisition of health-related information from other health care facilities and 
providers. 
Telephonic and telemedicine assessments may be used. Important considerations for 
study visits through video conferencing include: 
• The Investigator or study personnel who will conduct remote visits should be 
trained on how to conduct telemedicine video conferencing visits. 
• Procedures should be put in place to maintain a study subject’s privacy, as 
would be done for a clinical visit. 
• Both the Investigator and the study subject should confirm their respective 
identities with one another before engaging in a real-time video conference visit 
according to an identity verification plan developed by the Sponsor. 
The date and time of the real-time video interaction, the location of the study subject 
and the location of the Investigator or personnel conducting the remote visit should be 
documented in the electronic case report form (eCRF). 
Every effort will be made to gather all available study data within the visit window, but 
if that is not possible data will be gathered outside of the visit window. 
Critical assessments to receive priority include: 
• Occurrence and characterization of AEs 
• Symptoms of arrhythmia recurrence 
• Cardiac CT or MRI scans 
• Brain MRIs 
• Follow-up assessments of phrenic nerve function 
• Event monitoring 
• Holter monitoring 
For all such COVID-19-related missed or out of window assessments, specific 
information will be captured that explains the basis of the missing data and its relation 
to COVID-19 for missing information (e.g., from missed visits or subject 
discontinuations) 

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4.8 
Schedule of Events 
Table 3 
Schedule of Events – ITT Subjects 
Assessment 
Baseline1 
(In-
person) 
Index 
Procedure 
(In-person) 
Pre- 
Discharge 
(In-
person) 
Day 7 
(7-11 days) 
(Remote2) 
Day 30  
(± 7 days) 
(Remote2) 
Day 60  
(± 10 days) 
(Remote2) 
Re-
Ablation 
Procedures  
(In-person) 
Day 90 
(90 ± 14 
days)  
(In-person) 
Month 6 
(180 ± 30 
days)  
(Remote2) 
Month 12 
(360 ± 30 
days)  
(In-person) 
Unscheduled 
(In-person/ 
Remote2) 
Informed consent, baseline assessments 
X3 
 
 
 
 
 
 
 
 
 
 
AAD and anticoagulant medications 
X 
 
X 
X 
X 
D/C AADs 
X 
X 
X 
X 
X 
Recurrent arrhythmia, cardioversions, 
ablations, hospital admissions 
 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
Pregnancy test 
X4 
X4 
 
 
 
 
X4 
 
 
 
 
COVID-19 testing by site 
X 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X 
 
 
 
 
X 
 
X 
X 
HCT, HGB, electrolytes, BUN, creatinine 
X 
 
X 
 
 
 
 
 
 
 
 
Transthoracic echocardiogram (TTE) 
X 
 
 
 
 
 
 
 
 
 
 
Event monitors 
Training 
 
Training 
 
 
Training 
 
Weekly + symptomatic transmissions 
X 
72-Hour continuous ECG (Holter) 
Training 
 
Training 
 
 
 
 
 
X 
X 
 
Cardiac CT/MRI for PV dimensions 
X 
 
 
 
 
 
X5 
X 
 
X6 
 
TEE/ICE to exclude LA thrombus 
 
X7 
 
 
 
 
X7 
 
 
 
 
NIHSS 
X 
 
X 
 
 
 
 
 
 
 
 
Radiologic examination of diaphragm 
 
X 
 
 
 
 
X 
X8 
 
X8 
 
AF Symptom Assessment 
X 
 
 
 
 
 
 
 
 
X 
 
EQ-5D-3 L & AFEQT assessments 
X 
 
 
 
 
 
 
 
 
X 
 
Non-NAS subjects: Neuro assessment 
 
 
X9 
 
 
 
 
X9 
 
 
 
NAS subjects: Neuro assessment 
 
 
X10 
 
 
 
 
X10 
 
 
 
Assessment of subject blinding 
 
 
X 
 
 
 
 
 
 
X 
 
Adverse events 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
1   All Baseline Assessments must be generated in the window beginning 30 days (90 days for TTE and cardiac CT/MRI) prior to the Consent Date and ending on the date of the Index Procedure. 
2   Assessments that are defined as remote may also be performed at the investigational site (non-remote) at Investigator discretion and subject agreement. 
3   Baseline assessments include the inclusion/exclusion criteria and the data stipulated in Section 4.7.1. 
4   Females of childbearing potential only. The pre-procedural pregnancy test is not required if the Index Procedure / Rescheduled Index Procedure is within 30 days of the baseline pregnancy test. 
5   For re-ablations occurring Day 1-75, pre-procedural imaging is not required. For re-ablations scheduled for Day 76 or later, ensure the Day 90 cardiac MRI/CT is performed before re-ablation. 
6   Month 12 cardiac MRI/CT only if 3-month imaging revealed any PV with ≥ 70% reduction in PV measured diameter. 
7   Performed at the beginning of the procedure prior to ablation. See Section 5.3 for managing subjects whose procedure is delayed by intracardiac thrombus. 
8   Only if resolution of phrenic nerve palsy has not yet been demonstrated. May be performed either by fluoroscopic sniff test or inspiration/expiration CXR. 
9 Non-NAS subjects: If NIHSS score has increased by 1 or more points or if there is a clinical suspicion of stroke/TIA, then a consulting neurologist will perform a stroke assessment and include the 
results of a concurrent brain MRI. If stroke is diagnosed, a Modified Rankin Scale assessment will be performed prior to discharge and again at 3 months. 
10  NAS subjects: If NIHSS score has increased by 1 or more points, if there is a clinical suspicion of stroke/TIA, or if the post-procedural brain MRI is positive for SCE or SCL findings then a 
consulting neurologist will perform a stroke assessment and include review of the NAS post-procedural brain MRI. If stroke is diagnosed, a Modified Rankin Scale assessment will be performed prior 
to discharge and again at 3 months. 
 

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Table 4 
Schedule of Events – Roll-In Subjects 
 
Assessment 
Baseline1 
(In-
person) 
Index 
Procedure 
(In-person) 
Pre- 
Discharge 
(In-person) 
Day 7 
(7-11 days) 
(Remote2) 
Day 90 
(90 ± 14 
days)  
(In-person) 
Month 6 
(180 ± 30 
days)  
(Remote2) 
Month 12 
(360 ± 30 days)  
(In-person) 
Unscheduled 
(In-person/ 
Remote2) 
Informed consent, baseline assessments 
X3 
 
 
 
 
 
 
 
AAD and anticoagulant medications 
X 
 
X 
X 
X 
X 
X 
X 
Recurrent arrhythmia, cardioversions, 
ablations, hospital admissions 
 
 
X 
X 
X 
X 
X 
X 
Pregnancy test 
X4 
X4 
 
 
 
 
 
 
COVID-19 testing by site 
X 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X 
 
X 
 
X 
X 
HCT, HGB, electrolytes, BUN, creatinine 
X 
 
X 
 
 
 
 
 
Transthoracic echocardiogram (TTE) 
X 
 
 
 
 
 
 
 
Cardiac CT/MRI for PV dimensions 
X 
 
 
 
 
 
 
 
TEE/ICE to exclude LA thrombus 
 
X5 
 
 
 
 
 
 
NIHSS 
X 
 
X 
 
 
 
 
 
Radiologic examination of diaphragm 
 
X 
 
 
X6 
 
X6 
 
AF Symptom Assessment 
X 
 
 
 
 
 
X 
 
Neuro assessment 
 
 
X7 
 
X7 
 
 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
X 
1   All Baseline Assessments must be generated in the window beginning 30 days (90 days for TTE and cardiac CT/MRI) prior to the date of enrollment and ending on the date of the Index Procedure. 
2   Assessments that are defined as remote may also be performed at the investigational site (non-remote) at Investigator discretion and subject agreement. 
3   Baseline assessments include the inclusion/exclusion criteria and the data stipulated in Section 4.7.1.  
4   Females of childbearing potential only. The pre-procedural pregnancy test is not required if the Index Procedure is within 30 days of the baseline pregnancy test. 
5   Performed at the beginning of the procedure prior to ablation. See Section 5.3 for managing subjects whose procedure is delayed by intracardiac thrombus. 
6   Only if resolution of phrenic nerve palsy has not yet been demonstrated. May be performed either by fluoroscopic sniff test or inspiration/expiration CXR. 
7   If NIHSS score has increased by 1 or more points or if there is a clinical suspicion of stroke/TIA, then a consulting neurologist will perform a stroke assessment and include the results of a concurrent 
brain MRI. If stroke is diagnosed, a Modified Rankin Scale assessment will be performed prior to discharge and again at 3 months. 
 
 

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4.9 
Subject Flow Chart 
 
Figure 8 
Subject Flow Chart 
 
 
 
 
Hx = history, PE = physical examination, ECG = electrocardiogram, AAD = antiarrhythmic drug 

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4.10 Control of Systematic Error and Bias 
Subjects will be randomized in this controlled study and key evaluators (CEC, 
Arrhythmia Core Laboratory [ACL] and Cardiac Imaging Core Laboratory [CICL]) for 
primary and secondary outcome assessments will be blinded.  
Error and bias are controlled by additional means, including a comprehensive set of 
study procedures as defined in the protocol which ensure consistent management, site 
and data monitoring and outcome measure assessment. Follow-up Holter monitoring 
and event monitoring data, and all MRI/CT dimensions of PVs, will be assessed 
objectively and without knowledge of subject treatment status by third parties 
according to standard protocols. SAEs and the primary effectiveness and safety 
outcomes will be reviewed by an independent CEC (Section 12.2.4).  
A complete Clinical Study Report and dataset will allow scientific and clinical 
reviewers to independently assess potential error and bias. 

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5. Study Procedures 
5.1 
Anticoagulation 
Anticoagulation will be guided by the 2017 Heart Rhythm Society Expert Consensus 
Statement8 and the 2019 American Heart Association / American College of 
Cardiology / Heart Rhythm Society Focused Update36 relating to this issue.  
Adjustments for subject welfare may be made by Investigators based on clinical 
judgment and do not constitute protocol deviations. 
Throughout the study: 
• Subjects with a CHA2DS2-VASc score ≥ 2 (men) or ≥ 3 (women) should receive 
oral anticoagulants throughout the study.  
• NOACs are recommended over warfarin for eligible subjects.  
• Subjects on warfarin should have at least monthly INR assessment. 
Peri-procedural: 
• Non-anticoagulated subjects will be placed on therapeutic anticoagulation for a 
minimum of 3 weeks prior to an ablation procedure regardless of baseline 
CHA2DS2-VASc score. 
• Subjects taking warfarin should continue warfarin through the procedure. 
• Subjects taking a NOAC should have either continued NOAC (rivaroxaban) or a 
single dose interruption in NOAC with a restart shortly after the procedure, at 
Investigator discretion. 
• A heparin bolus will be delivered prior to or immediately following transseptal 
puncture. Procedural activated clotting times (ACTs) will be sampled regularly 
throughout the procedure and maintained at a minimum of 300 seconds. 
Post-ablation: 
• If the subject is not otherwise indicated for anticoagulation, suitable 
anticoagulation will be maintained for a minimum of 2 months following any 
ablation procedure. 
Thereafter, decisions regarding anticoagulation should be based on the subject’s stroke 
risk and bleeding risk profiles. 
 
5.2 
Index Procedure 
Subjects will be screened for completion of a minimum of 3 weeks of systemic 
anticoagulation prior to the Index Procedure and if this condition has not been met the 
subject will be rescheduled under the procedure defined in Section 5.3. 
Subjects will undergo sedation / anesthesia according to institutional protocol. They 
will then be prepared in conventional sterile fashion for a cardiac catheterization 
procedure.  
Femoral vein access will be obtained via Seldinger technique.  

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Use of ultrasound guidance is recommended, but not required, for femoral venous 
access. 
A heparin bolus will be delivered prior to or immediately after transseptal puncture. 
Procedural ACTs will be regularly monitored and maintained at a minimum of 300 
seconds. 
Commercially approved diagnostic catheters may be placed before or after transseptal 
access is established at the Investigator’s discretion. Transseptal access to the LA will 
be obtained using commercially approved devices, establishing guidewire access to 
the LA. 
TEE within 48 hours of the procedure or ICE during the procedure will be utilized prior 
to transseptal puncture for exclusion of LA thrombus. If the study reveals atrial 
thrombus, the investigational procedure will not begin or will be terminated, no 
ablation will be performed and the subject will be rescheduled under the procedure 
defined in Section 5.3. 
 
Pre-ablation and post-ablation voltage maps are not required. 
Pulsed Field Subjects:  
The use of ICE is required for Pulsed Field Ablation procedures. 
The FARADRIVE Steerable Sheath will be prepared and advanced via guidewire to 
the LA. 
Esophageal temperature monitoring, esophageal cooling and esophageal deviation are 
unnecessary during ablation with the FARAWAVE Pulsed Field Ablation Catheter 
and should not be utilized. 
The FARAWAVE Pulsed Field Ablation Catheter will then be prepared and 
advanced to the LA through the FARADRIVE Steerable Sheath. After confirming an 
ACT of 300 or greater, ablation of the PVs to achieve isolation will be performed 
according to the approved IFU documents and institutional practice.
Ablation will be attempted in every clinically relevant PV, including any vein with an 
active muscular sleeve. Small anomalous PVs that are electrically silent need not be 
attempted. 
PVI ablation may be repeated at the Investigator’s discretion. Each addressable PV 
will be ablated in turn. The isolating effect of the PVI ablation(s) will be checked 
periodically and then finally twenty (20) minutes after the last PVI ablation. 
Adenosine may be used for the final assessment but is not required. 

 
 
At the conclusion of the PVI ablation procedure, the FARAWAVE Pulsed Field 
Ablation Catheter will be undeployed and withdrawn from the FARADRIVE 
Steerable Sheath.  
The functional status of both phrenic nerves will be assessed before the study is 
concluded. 
Thermal Subjects:  
All Investigators at a given site must use only 1 of the 2 categories of Thermal Group 
technology for ablation, either a force-sensing irrigated RFA catheter or a CBA 
catheter, indicated for the treatment of PAF. A site’s Thermal Group technology will 
be determined prior to the initiation of enrollment at that site and maintained without 
exception throughout the study. 
A commercially approved sheath will be prepared and advanced via guidewire to the 
LA. Commercially approved diagnostic catheters may be placed via conventional 
technique at the Investigator’s discretion. A baseline 3D electroanatomical map may 
also be made at the Investigator’s discretion. 
Esophageal protection (temperature monitoring, deviation or cooling) using the site’s 
customary method is required, unless subject welfare precludes such usage. 
The site’s predetermined technology ablation catheter will be prepared and advanced 
to the LA through the sheath. Ablation of the PVs to achieve isolation will be 
performed according to the approved IFU documents and institutional practice.  
Ablation will be attempted in every clinically relevant PV, including any vein with an 
active muscular sleeve. Small anomalous PVs that are electrically silent need not be 
attempted. 
PVI ablation may be repeated at the Investigator’s discretion. The isolating effect of 
the PVI ablation(s) will be checked periodically and then finally twenty (20) minutes 
after the last PVI ablation. Adenosine may be used for the final assessment but is not 
required.  
At the conclusion of the PVI ablation procedure, the ablation catheter should be 
withdrawn from the sheath according to the manufacturer’s instructions. 
The functional status of both phrenic nerves will be assessed before the study is 
concluded. 
All Subjects: 
CTI ablation: Ablation of the CTI may be performed in both Pulsed Field Subjects and 
Thermal Group Subjects using any approved catheter in subjects with a past history of 
cavo-tricuspid isthmus-mediated (typical) AFL, subjects who manifest typical AFL 
during a procedure or within the Blanking Period, or subjects who have inducible 
typical flutter. Bidirectional block should be demonstrated after the last CTI ablation. 

 
 
The CTI ablation data will be documented in the CRF and does not constitute a 
Treatment Failure. 
Other Ablation: Other ablation is not permitted under this protocol except when the 
Investigator determines that subject welfare requires ablation for an accessory pathway, 
AVNRT, treatment-emergent left AFL or incessant AT, using any approved ablation 
catheter. This decision and the associated ablation data will be documented in the CRF 
and does not constitute a Treatment Failure. 
5.3 
Rescheduled Index Procedure 
Subjects found during the Index Procedure to have LA thrombus will have their Index 
Procedure rescheduled to allow treatment of the thrombus, including a minimum of 3 
weeks of continuous therapeutic anticoagulation consistent with Section 5.1. The 
Reschedule Index Procedure will follow the requirements of Section 5.2. 
This rescheduling is permissible and does not create an Acute Procedural Failure. For 
adjustment of follow-up assessments please see Section 5.5 below. References to 
“Index Procedure” in this protocol should be assumed when appropriate to include 
“Rescheduled Index Procedure” as well if not otherwise specified. 
5.4 
Re-Ablation Procedures 
Re-ablation under this protocol requires documentation of Detectable AF, AFL or AT. 
When performed, re-ablation will be performed utilizing an FDA-approved study 
ablation catheter (RFA or CBA) at Investigator discretion.  
Any re-ablation procedure for AF, AFL or AT any time during study follow-up 
constitutes a Treatment Failure. 
 
However, CTI ablation or re-ablation for right-sided typical AFL may be performed at 
any time during study follow-up and does not constitute a Treatment Failure.  
 
Cardiac imaging: 
• For anticipated PVI re-ablations occurring Day 1-75, pre-procedural imaging is not 
required.  
• For anticipated PVI re-ablations scheduled for Day 76 or later, ensure the Day 90 
cardiac MRI/CT is performed before re-ablation to assess the dimensions of the 
PVs. The Cardiac CT or MRI scan must be of the same type as the baseline scan 
obtained prior to the Index / Rescheduled Index Procedure. 
 
TEE within 48 hours of the procedure or ICE during the procedure will be utilized prior 
to transseptal puncture for exclusion of LA thrombus. If the study reveals atrial 
thrombus, the investigational procedure will not begin or will be terminated and no 
ablation will be performed. 
 

 
 
Re-ablation does not reset the Blanking Period or otherwise alter the Schedule of 
Events and Assessments (Section 4.7). 
Remapping will be performed: 
• During any re-ablation procedure in which LA access is performed: 
o Sufficient mapping to establish the durability of isolation of each previously 
treated PV. 
• During any re-ablation procedure in a subject who underwent CTI: 
o Sufficient mapping to establish the durability of a previously treated CTI. 
5.5 
Start Date, Blanking Period and Index Procedures 
The day of the Index Procedure or Rescheduled Index Procedure is the Start Date 
(Day 0) for follow-up scheduling. The Blanking Period consists of a subject’s Day 0 
through and including Day 90. During the Blanking Period, any occurrence of 
Detectable AF, AFL or AT will be documented; however, occurrences of AF, AFL or 
AT during this time will not be considered Treatment Failures.  
For subjects who undergo ablation at the Index Procedure, the follow-up intervals for 
safety and effectiveness are depicted in Figure 9 below: 
Figure 9 
Index Procedure Blanking and Follow-Up Intervals 
 
For subjects who undergo ablation at a Rescheduled Index Procedure the follow-up 
intervals for safety and effectiveness are depicted in Figure 10 below. The follow-up 
intervals for effectiveness and safety are still based on the day of the ablation procedure 
(Day 0). Pre-ablation AEs that occur between the Index Procedure and the day before 
the Rescheduled Index Procedure will not be included in the safety analyses, but will be 
documented and reported separately, with the day of occurrence being enumerated from 
the day of the Index Procedure that was deferred. 

 
 
Figure 10 
Rescheduled Index Procedure Blanking and Follow-Up Intervals 
 
5.6 
Roll-In Subjects 
Up to 105 subjects – to be treated with the FARAPULSE devices – will be consented 
and treated in a manner consistent with the Pulsed Field Group but will be analyzed and 
reported separately from the study population.  
At each site, these Roll-In Subjects will be the first 1 to 3 sequentially enrolled but non-
randomized subjects at that site. Sites with more than 1 Investigator will utilize 
available Roll-In Subjects jointly as required. 
With Sponsor and Investigator agreement, the Roll-In phase at a site will be terminated 
at or before 3 Roll-In Subjects have been treated and all subsequent subjects at the site 
will be randomized as study subjects according to protocol requirements.  
Roll-In Subjects will: 
• Be consented using a Roll-In-specific ICF. 
• Follow the Index Procedures as specified in Section 5.2. 
• Have all study data gathered as specified in Section 4.7.2 and Section 4.7.3. 
• Be followed for 12 months post-ablation, completing Day 7 and Month 3, Month 
6 and Month 12 Assessments for clinically-detected arrhythmias and screening 
for the occurrence of AEs 
• Be managed according to Investigator or referring physician discretion. 
• Have their required study data recorded on a specific and separate CRF set. 
• Be analyzed and reported separately from the ITT Subjects. 
Roll-In Subjects will not: 
• Undergo Quality of Life assessments 
• Undergo NAS assessment 
• Undergo protocol-specified EM or Holter monitoring 
• Undergo protocol-specified cardiac imaging post-procedure 
5.7 
Blinding 
• Investigators: The treating physicians and site-based study personnel are 
necessarily exposed to a subject’s treatment assignment and cannot be blinded. 
As much as possible, site based study personnel who perform follow-up 
evaluations will remain blinded to subject treatment assignment. 

 
 
• Subjects: Study personnel will be trained to avoid disclosing treatment status to 
study subjects. Study subjects will sign an informed consent that states that they 
will not be informed of their treatment status until the conclusion of their 
participation in the study. 
• Core Laboratories: The ACL, CICL and Brain Imaging Core Lab (BICL) will 
remain blinded to treatment assignment throughout the study duration. 
• CEC: The CEC will remain blinded as much as possible consistent with accurate 
adjudication.  
• Data and Safety Monitoring Board (DSMB): In general, the DSMB will review 
unblinded results in order to perform their function of protecting the integrity of 
the study and the rights, safety and welfare of study subjects. 
• Study / CRO staff: Monitoring staff will be unblinded to perform their function. 
Other Sponsor and CRO staff will be unblinded on a documented need-to-know 
basis to allow conduct of the study. 
5.8 
Neurologic Assessment Subjects 
Neurologic Assessment Subjects (NAS) are a subset of ITT Subjects who will undergo 
a post-procedural brain MRI following the ablation procedure. 
5.8.1 
NAS Sites 
A subset of study sites qualified and willing to perform the standardized brain MRI 
post-ablation will be established and designated as NAS sites. NAS sites will be 
selected to generate a minimum of 80 NAS Subjects, balanced approximately equally 
between RFA and CBA control sites. Total NAS enrollment will be limited to a 
maximum of 40 subjects in the PFA group and 40 subjects in the Thermal Group 
(RFA/CBA). 
• An approximately equal number of RF-control sites and cryoballoon-control sites 
will be targeted. 
• All ITT Subjects at NAS sites free of contraindications to MRI will be consented 
for post-procedure MRI until the study enrollment target of evaluable scans is 
met. 
• Roll-In Subjects are excluded from participation in the NAS. 
5.8.2 Post-Ablation Brain MRI Specifications for NAS Subjects Only 
These specification are for the protocol-required brain MRIs of NAS Subjects only. 
• Standards and Quality Control: The BICL will establish specific standards for 
brain MRI performance, train participating sites and interact with sites to ensure 
that standards and scan quality remain within specification. 
• Timing: Post index procedure (between 12 hours to 48 hours post-ablation) brain 
MRIs will be performed on each NAS subject. 
• Parameters: The following scan parameters will be used: 
o 1.5-T scanners 
o 5mm slice thicknesses 
o DWI, FLAIR and ADC assessed for each scan 
o SCE = DWI + and ADC reduced 

 
 
o SCL = DWI + and ADC reduced and FLAIR + 
5.8.3 SCE and SCL Analysis 
The frequency and type of SCEs and SCLs will be reported by randomization group, 
along with potential predictor variables including CHA2DS2-VASc status, duration of 
PAF, history of stroke/TIA, procedure time, LA dwell time and total ablation time, 
anticoagulation regimen and ACT levels, occurrence of cardioversion or air 
introduction, frequency of LA catheter exchanges and maximal sheath size.  
5.8.4 Follow-Up for Subjects with SCE or SCL Lesions 
• Subjects with a site-confirmed post-procedural SCE or SCL will undergo a 
pre-discharge neurologic assessment as specified in Section 4.7.3. 
• Subjects with a site-confirmed or BICL-confirmed post-procedural SCE or 
SCL will undergo a follow-up brain MRI using the parameters specified in 
Section 5.8.2 during the 90 Day Assessment window. 
5.9 
Antiarrhythmic Drugs 
AADs, except for amiodarone, may be utilized during the Blanking Period at the 
Investigator’s discretion.  
On Day 60 ± 10 each subject will be contacted by telephone to stop all AADs. 
Class I / III AADs (see Section 6.3.4) should be stopped at the Day 60 Assessment. 
However, at the Investigator’s discretion, Class I / III AADs may be continued up to 
Day 90 without creating a Treatment Failure. If AADs are required after Day 90 and 
Class I / III AADs are prescribed, the Investigator should document the reason for 
utilizing the medication in the eCRF. Notwithstanding the impact on study outcomes, 
the use of Class I / III AADs for subject welfare as determined by the Investigator 
during and after the Blanking Period do not constitute protocol deviations. 
The use of amiodarone at any time during the study, except intra-procedurally to 
control an arrhythmia , or the use of Class I / III AADs after Day 90, constitute a 
Treatment Failure. 

 
 
6. Study Definitions 
6.1 
Study Outcomes 
The primary and secondary effectiveness endpoints and the primary and secondary 
safety endpoints, along with specified additional analyses, procedural assessments and 
quality of life assessments, are defined in Section 7. 
6.2 
Adverse Event Definitions 
Definitions relating to AEs, SAEs, procedure relatedness, device relatedness, device 
effects, malfunctions and deficiencies are defined in Section 8. 
6.3 
Other Definitions 
6.3.1 
Acute Procedural Success 
Demonstration of Acute Vein Success in all attempted PVs using the randomized 
treatment during the first ablation procedure (Index or Rescheduled Index Procedure). 
(See Section 6.3.3) 
6.3.2 Acute Procedural Failure 
The absence of Acute Procedural Success, including the use of any non-randomized 
energy modality for PVI. 
6.3.3 Acute Vein Success 
Proportion of all attempted PVs isolated using the randomized treatment during the 
first ablation procedure (Index or Rescheduled Index Procedure), as clinically 
assessed by entrance block demonstrated ≥ 20 minutes after the last PVI lesion is 
made with or without adenosine testing. 
6.3.4 Antiarrhythmic Drugs, Class I and III 
AADs are those pharmaceutical agents approved or used in the United States for the 
treatment of cardiac arrhythmia. For the ADVENT Trial, the use of Class I and III 
AADs after the Blanking Period constitute a primary effectiveness endpoint failure. 
Examples of these agents include but are not limited to: 
• Class I, sodium channel blockers: disopyramide, flecainide, procainamide, 
propafenone quinidine. 
• Class III, potassium channel blockers: amiodarone, dofetilide, dronedarone, 
sotalol. 
Should other Class I or III AADs become approved or used in the United States for 
the treatment of cardiac arrhythmia during the ADVENT Trial, they will be included 
in the list of AADs that constitute a Treatment Failure if used after the Blanking 
Period. 
6.3.5 Blanking Period 
An interval in which recurrent AF, AFL or AT does not constitute a Treatment 
Failure beginning on Day 0 and running for 90 days thereafter. 
• The Blanking Period has no impact on the assessment of AEs. 

 
 
• For subjects with only an Index Procedure, the Blanking Period will be Day 0 to 
Day 90 inclusive. 
• For subjects who require a Rescheduled Index Procedure, the Blanking Period 
will be the Study Day of the Rescheduled Index Procedure plus 90 days 
inclusive. 
6.3.6 Chronic Failure 
The absence of Chronic Success. 
6.3.7 Chronic Success 
Defined in Section 7.4. 
6.3.8 COVID-19-Related Disruptions 
A disruption to any study procedure resulting directly or indirectly from the 
COVID-19 pandemic, including but not limited to participant illness, study site 
restrictions and limitations, shipping / manufacturing interruptions, significant 
changes in FDA guidance and / or governmental restrictions on travel, association 
and the prioritization of healthcare resources. 
6.3.9 Dates 
• Consent Date: The date a subject signs the ICF. 
• Exit Date:  The date on which study participation ends. 
• Onset Date: The date on which a condition or AE begins. 
• Start Date: Day 0, the date of the Index or Rescheduled Index Procedure. 
6.3.10 Day (or Study Day) 
A Day is an enumerated day of follow-up that begins on an Enrolled Subject’s Start 
Date (Day 0). 
6.3.11 Detectable AF, AFL or AT 
Detectable AF, AFL or AT is an episode of AF, AFL or AT which: 
• Is permanently recorded for review 
• Contains at least 30 seconds of continuous interpretable signal 
o Exception: Continuous AF, AFL or AT for the entirety of a 12 lead ECG 
constitutes Detectable AF, AFL or AT if the continuous interpretable 
signal is 10 seconds or longer 
• Includes symptomatic and asymptomatic episodes.  
• Excludes CTI isthmus-dependent AFL when the mechanism is confirmed 
electrophysiologically. 
Such episodes are not AEs under this protocol unless deemed to be caused by an 
ablation procedure. 
6.3.12 Investigational Devices and Procedures 
For the purpose of assessing event and outcome rates in study subjects: 

 
 
• Investigational devices include any protocol-specified ablation catheter, 
generator/console or sheath, whether FDA approved (radiofrequency ablation or 
cryoablation systems) or not (FARAPULSE Pulsed Field Ablation System). 
• Investigational procedures include any ablation procedure performed by a study 
investigator for the treatment of AF, AFL or AT, and study-directed CT/MRI 
testing. 
6.3.13 Pre-Ablation Adverse Events 
Defined as those AEs that occur between the date of the deferred Index Procedure and 
the day before the Rescheduled Index Procedure in subjects whose first ablation 
procedure is rescheduled due to intracardiac thrombus. These are not included in 
study safety analyses but will be documented and reported separately. 
6.3.14 Pulmonary Vein Dimensions 
For the purpose of study outcomes: 
• PV dimensions will be measured in two roughly orthogonal diameters 
approximating the longest and shortest diameters at the plane of measurement.  
• The measured PV diameter is defined as the geometric mean of these 
2 measurements.  
• The PV cross-sectional area is computed using the formula for area of an 
ellipse, where the longest and shortest axis measurements of the PV diameter 
serve as the major and minor axes of the ellipse, using half of each axis 
diameter as the radii for calculation. 
• Aggregate PV Cross-Section Area is the sum of the calculated PV cross-
sectional area of each PV ablated at the Index / Rescheduled Index Procedure, 
as detailed in the SAP. 
6.3.15 Pulmonary Vein Isolation 
Complete electrical isolation of a PV confirmed by entrance block, specifically: the 
percutaneous endocardial creation of an electrically isolating set of lesions around the 
ostia of a PV, as clinically assessed by entrance block demonstrated ≥ 20 minutes 
after the last PV lesion is made, with or without adenosine testing. 
6.3.16 Pulsed Field Group / Subjects 
Subjects randomized to treatment with the FARAPULSE Pulsed Field Ablation 
System are Pulsed Field Subjects and collectively comprise the Pulsed Field Group. 
6.3.17 Severe COVID-19 Subjects 
Any study subject who contracts COVID-19 infection during study participation that: 
• Requires supplemental oxygen, positive pressure ventilation, and/or intubation 
OR  
• Is associated with any medically serious sequelae of COVID-19, including but 
not limited to new onset cardiac arrhythmia, heart failure, myocarditis, 
neurologic dysfunction or other organ dysfunction or thromboembolic disease. 

 
 
Such subjects will be initially defined by the Investigator and confirmed by the CEC. 
The Onset Date will be the date of symptom onset in a subsequently clinically 
confirmed case of COVID-19 infection. 
6.3.18 Study Participants 
Study participants include patients being screened, Enrolled Subjects, study site 
personnel, study monitors and other CRO personnel as well as Sponsor personnel. 
6.3.19 Thermal Group / Subjects 
Subjects randomized to treatment with RFA or CBA are Thermal Subjects and 
collectively comprise the Thermal Group. 
6.3.20 Treatment Failure 
The absence of Treatment Success. 
6.3.21 Treatment Success 
Defined in Section 7.4. 
 
 
 

 
 
7. Outcome Measures 
7.1 
Primary Safety Endpoint 
The primary safety endpoint is the Composite Safety Endpoint (CSE) defined as the 
proportion of Safety Subjects with one or more of the following device- or procedure-
related SAEs as adjudicated by the CEC based on the definitions contained in Table 5. 
Early onset: Any of the following with an Onset Date within 7 days of the 
Index / Rescheduled Index procedure: 
• Death  
• Myocardial infarction  
• Persistent phrenic nerve palsy 
• Stroke  
• TIA 
• Peripheral or organ thromboembolism  
• Cardiac tamponade / perforation 
• Pericarditis 
• Pulmonary edema 
• Vascular access complications  
• Heart block 
• Gastric motility/pyloric spasm disorders  
Late onset: Either of the following with an Onset Date any time through the 
completion of 12-month follow-up visit: 
• PVS4 
• Atrio-esophageal fistula 
 
Table 5 Composite Safety Endpoint Definitions 
 
Related SAE 
Description/Criteria 
Death 
AE resulting in subject death 
Myocardial 
infarction 
Deﬁned as the presence of any one of the following criteria:  
(1) detection of ECG changes indicative of new ischemia (new ST- T wave 
changes or new LBBB) that persist for more than 1 hour 
(2) development of new pathological Q waves on an ECG 
(3) imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality 
 
4 For subjects ablated with more than one energy modality, the CEC will – to the extent possible – determine 
which modality(ies) are related to any observed PVS. 

 
 
Related SAE 
Description/Criteria 
Persistent phrenic 
nerve palsy 
Defined as absent phrenic nerve function as assessed by 
a change from baseline in the elevation of a hemidiaphragm, persisting 
beyond the end of the procedure that is: 
• 
Demonstrated radiographically by either an inspiration / expiration 
chest X-ray or fluoroscopic sniff test 
• 
Not due to a demonstrable pulmonary process such as atelectasis or 
pleural disease. 
Persistent: not resolved at the time of the last follow-up visit. 
Stroke 
Rapid onset of a focal or global neurological deficit with at least one of the 
following:  
• 
Change in level of consciousness 
• 
Hemiplegia, hemiparesis, numbness or sensory loss affecting 1 side 
of the body 
• 
Dysphasia or aphasia 
• 
Hemianopia, amaurosis fugax, or  
• 
Other neurological signs or symptoms consistent with stroke  
The diagnosis of stroke requires that there be no other readily identifiable 
non-stroke cause for the clinical presentation (e.g., brain tumor, trauma, 
infection, hypoglycemia, peripheral lesion, pharmacological influences). 
The duration of the defined neurological deficit(s) must be: 
• 
≥ 24-hours; OR  
• 
< 24-hours if  
o Therapeutic intervention(s) were performed (e.g., 
thrombolytic therapy or intracranial angioplasty), OR  
o Available neuroimaging documents a new hemorrhage or 
infarct, OR  
o The neurological deficit results in death. 
Transient ischemic 
attack 
Defined as a new focal neurological deficit with: 
• 
Symptom resolution within 24 hours 
• 
No new tissue injury demonstrated (if neuroimaging is obtained) 
Peripheral or organ 
thromboembolism 
A cardiac thrombus that occludes a more distal arterial site other than the 
central nervous system (see Stroke). Cutaneous petechiae are excluded from 
this definition. 
Cardiac tamponade / 
perforation 
The development of a pericardial effusion post-ablation that results in 
hemodynamic compromise, requires pericardiocentesis or results in a 1-cm 
or more pericardial effusion as documented by echocardiography. Cardiac 
tamponade/perforation should also be classiﬁed as “early” or “late” 
depending on whether it is diagnosed during or following initial discharge 
from the hospital. 
Pericarditis 
The development of pericardial inflammation post-ablation that results in an 
effusion that leads to hemodynamic compromise or requires 
pericardiocentesis, prolongs hospitalization by more than 48 hours, requires 
hospitalization, or persists for more than 30 days following the ablation 
procedure. 

 
 
Related SAE 
Description/Criteria 
Pulmonary edema 
Respiratory compromise resulting from cardiac dysfunction or volume 
overload leading to increased interstitial lung fluid requiring intubation or 
parenteral diuretics. 
Vascular access 
complications 
Vascular access complication (e.g., groin hematoma, AV fistula, 
pseudoaneurysm) requiring a significant and invasive intervention (e.g., 
surgical repair, blood transfusion or thrombin injection). 
Heart block  
Impairment of AV conduction that is related to a protocol-stipulated cardiac 
ablation procedure and that requires permanent pacing. 
Gastric 
motility/pyloric 
spasm disorders 
Evidence of impaired gastric motility or pyloric spasm that prolongs 
hospitalization, requires hospitalization or persists for more than 30 days. 
Pulmonary vein 
stenosis  
>70% reduction of an ablated measured PV diameter* compared to the 
baseline CT/MRI scan, as determined by the CICL. 
Atrio-esophageal 
fistula 
Confirmation of a fistulous connection between the atrium and the lumen of 
the esophagus by radiographic, endoscopic or post-mortem examination 
AV = atrioventricular, CICL = Cardiac Imaging Core Laboratory, CT = computed tomography, ECG = 
electrocardiographic, LBBB = left bundle branch block, MRI = magnetic resonance imaging, PV = pulmonary 
vein, SAE = serious adverse event. 
* See Section 6.3.14 for the definition of PV diameter. 
 
7.2 
Secondary Safety Endpoint 
The secondary safety endpoint is Aggregate PV Cross-Sectional Area, defined as the 
paired comparison of change in the computed Aggregate PV Cross-Sectional Area 
(Section 6.3.14) between baseline and 3 months in MITT subjects compared between 
randomization groups (intent-to-treat, regardless of re-ablation with any second energy 
modality). Supplemental analyses will include MITT single-procedure subjects and the 
PP population. 
7.3 
Additional Safety Analyses 
Each of these assessments will be tested for nominal p values between Pulsed Field 
Subjects and Thermal Subjects: 
1. Severe Ablation Complications: The proportion of subjects in each 
randomization group with one or more of the following CSE components as 
defined in Table 4 will be compared between treatment groups. 
• PVS 
• Persistent phrenic nerve palsy 
• Atrio-esophageal fistula 
2. Nonserious / Serious CSEs: The proportion of subjects in each randomization 
group with any device or procedure-related AE in the CSE definitions table 
without regard for serious or nonserious categorization. 
3. Post-Blanking Cardioversions: The proportion of subjects in each randomization 
group with 1 or more post-Blanking Period direct-current (electrical) 
cardioversions. 

 
 
4. Post-Blanking Arrhythmia Hospitalizations: The proportion of subjects in each 
randomization group with 1 or more post-Blanking Period hospitalizations 
primarily due to arrhythmia or arrhythmia complications. 
5. Any Related SAE: The proportion of subjects in each randomization group with 
any device- or procedure-related SAE. 
6. Any Related Stroke or TIA: The proportion of subjects in each randomization 
group with any device- or procedure-related stroke or TIA. 
7. Categorized PV Dimensional Changes: The distribution of PV dimensional 
changes between baseline and 3-month MRI/CT scans 
a. Categorized by the % change in the PV diameters: 0-29.9%, 30-49.9%, 50-
69.9% and ≥ 70% between randomization groups. 
b. Categorized by the % change in computed cross-sectional areas: 0-49.9%, 
50-74.9%, 75-89.9% and ≥ 90% between randomization groups. 
8. Thermal Group RF Ablation / Cryoablation Safety Assessment: a descriptive 
comparison of safety outcomes between the two Thermal Group technologies. 
9. Learning Curve Safety Assessment: For Pulsed Field Group only, per site and 
per operator learning curve assessment of the primary safety endpoint and 
supportive assessment of the secondary safety assessment and / or components of 
the CSE by enrollment sequence. 
7.4 
Primary Effectiveness Endpoint 
Treatment Success: The primary effectiveness endpoint is Treatment Success in 
MITT Subjects, defined as: 
1. Acute Procedural Success (Section 6.3.1) AND 
2. Chronic Success, defined as freedom from: 
a. At the Index / Rescheduled Index Procedure: Use of a non-randomized 
treatment modality for PVI 
b. After the Blanking Period: 
i. 
Occurrence of any Detectable AF, AFL or AT (Section 6.3.11) 
(excluding CTI-dependent flutter confirmed by EP study) 
ii. 
Any cardioversion for AF, AFL or AT (excluding for CTI-dependent 
flutter) 
iii. 
Use of any Type I or Type III antiarrhythmic medication for the 
treatment of AF, AFL or AT 
c. At any time: 
i. 
Re-ablation for AF, AFL or AT (other than for CTI-dependent flutter)  
ii. 
Use of amiodarone, except intra-procedurally to control an arrhythmia 
Endpoint status will be assessed through the Month 12 Assessment (Day 360 ± 30). 
7.5 
Secondary Effectiveness Endpoint 
The secondary effectiveness endpoint is the same as the primary effectiveness endpoint 
but will be tested for superiority rather than non-inferiority. The proportion of Pulsed 
Field Subjects with Treatment Success will be assessed for superiority to the proportion 
of Thermal Subjects with Treatment Success. 

 
 
7.6 
Additional Effectiveness Analyses 
Each of these assessments will be tested for nominal p values between Pulsed Field 
Subjects and Thermal Subjects: 
1. Acute Procedural Success: (Section 6.3.1) Assessed on a per subject basis. 
2. Acute Vein Success: (Section 6.3.3) Assessed on a per vein basis, for all veins 
and for each category of vein. 
3. Chronic Success (Section 7.4). 
4. Chronic Success Allowing Re-ablation: Chronic Success (Section 7.4) 
including as successes those subjects who failed only because they underwent a 
re-ablation procedure during the Blanking Period. 
5. Chronic Success Allowing AADs: Chronic Success (Section 7.4) including as 
successes those subjects who failed only because they received post-Blanking 
Period treatment with a Type I / III AAD. 
6. Treatment Success Allowing Re-ablation: Treatment Success (Section 7.4) 
including as successes those subjects who failed only because they underwent a 
re-ablation procedure during the Blanking Period. 
7. Treatment Success Allowing AADs: Treatment Success (Section 7.4) including 
as successes those subjects who failed only because they received post-Blanking 
Period treatment with a Type I / III AAD. 
8. Treatment Success with PVI/CTI only: Treatment Success (Section 7.4) 
excluding all subjects whose Index / Rescheduled Index Procedure required atrial 
ablation other than PVI or CTI. 
9. Early Recurrence of AF: The proportion of subjects with early recurrence of AF 
≤ Day 90 after the initial study ablation. 
10. Rate of Re-ablation: The proportion of subjects requiring any re-ablation for 
atrial arrhythmias through 12 months of follow-up. 
11. PVI Durability at Re-Ablation: For those subjects undergoing any re-ablation 
procedure with LA access during study follow-up, a per vein and a per subject 
assessment of PVI durability. 
12. CTI Ablation Failure: Proportion of subjects who undergo a first CTI ablation at 
the Index Procedure / Rescheduled Index Procedure who have recurrent typical 
(right-sided) AFL through 12 months of follow-up. 
13. Thermal Group RF Ablation / Cryoablation Effectiveness Comparison: A 
descriptive comparison of effectiveness measures between the two Thermal 
Group technologies. 
14. AF Symptom Assessment: A descriptive comparison of the change in AF 
symptom frequency from baseline to 12 months. 
15. Learning Curve Effectiveness Assessment: For the Pulsed Field Group only, 
per site and per operator learning curve assessment of the primary effectiveness 
endpoint and supportive analyses of related effectiveness and procedural data by 
enrollment sequence. 
7.7 
Procedural Assessments 
Each of these assessments will be tested for nominal p values between Pulsed Field 
Subjects and Thermal Subjects: 
1. Assessments of procedure durations 

 
 
a. Procedure time (initiation of venous access to venous access closure) 
b. LA dwell time (total time an ablation catheter is in the LA) 
c. Total ablation time (first ablation to last ablation) 
d. Total mapping time (total time spent mapping) 
e. Fluoroscopy time (total duration of exposure) 
2. Characterization of lesion sets: 
a. PVI ablations 
b. CTI ablations 
c. For subjects undergoing required LA ablations for an accessory pathway, 
AVNRT, left-sided AFL or incessant AT, a description of lesion sets 
utilized 
7.8 
Quality of Life Assessments 
Quality of Life (QoL) will be assessed at baseline and 12 months using two 
assessments. These assessments will be tested for nominal p values between Pulsed 
Field Subjects and Thermal Subjects: 
1. The EuroQol standardized questionnaire of health states (EQ-5D-3 L) at baseline 
and 12 months (The EuroQol Group. EuroQol - a new facility for the 
measurement of health-related quality of life. Health Policy 1990;16:199-209) 
2. Atrial Fibrillation Effect on Quality of Life (AFEQT) at baseline and 12 months 
(Spertus J, Dorian P, Bubien R, et al. Development and validation of the Atrial 
Fibrillation Effect on QualiTy-of-LIfe (AFEQT) Questionnaire in patients with 
atrial fibrillation. Circ Arrhythm Electrophysiol 2011;4:15-25) 
 

 
 
8. Adverse Events, Device Effects, Malfunctions and Deficiencies 
8.1 
Anticipated Adverse Events 
The following is a list of AEs that may possibly be caused by or associated with the 
proposed use of the investigational devices and other devices, the failure, misuse or 
malfunction of the investigational devices or other devices, or the related procedures 
stipulated by this protocol or associated with this clinical study.  
Recurrent AF for the purposes of this protocol is not an AE, but a continuation of a 
previous condition that is potentially a failure of effectiveness. 
• Access site complications (e.g., hematoma, fistula, pseudo-aneurysm, laceration, 
bleeding) potentially requiring surgical intervention 
• Air embolism 
• Allergic reaction or fever resulting from contact with catheters or drugs 
• Anemia 
• Arrhythmia, potentially requiring cardioversion, defibrillation, or rhythm 
management device 
• Arteriovenous fistula 
• Back pain 
• Bed sores 
• Bleeding, hematoma, hemorrhage or aneurysm at vascular access sites 
• Blood pressure changes including hypotension or hypertension 
• Cardiac tamponade or perforation 
• Cardiac arrest or cardiac failure  
• Cardiogenic shock 
• Catheter entrapment potentially requiring endovascular or surgical intervention 
• Conduction system injury, either transient or permanent, potentially requiring 
pacemaker insertion 
• Congestive heart failure  
• Coronary artery or vein injury 
• Death 
• Drug allergic reaction or side effects (e.g., from contrast, steroids, analgesics, 
anesthetics, anticoagulants, sedatives) 
• Embolism with damage to body structures due to presence of thrombus, 
particulate, device fragments or the introduction of air 
• Esophageal injury, ulcer or fistula 
• Gastric motility / pyloric spasm disorders 
• Hemorrhage 
• Hemodynamic compromise 
• Hemopericardium 
• Hemoperitoneum 
• Hemothorax 
• Local infection, systemic infection and/or sepsis 
• Muscle contractions due to electric stimulation 
• Myocardial infarction / ischemia 

 
 
• Nerve damage 
• Organ failure 
• Pain 
• Perforation (e.g., of diaphragm, liver, lung and/or vessels). 
• Pericardial irritation with pain 
• Pericardial effusion 
• Pericarditis 
• Peritonitis 
• Phrenic nerve injury with potential paralysis of the diaphragm and breathing 
impairment 
• Pneumomediastinum 
• Pneumopericardium 
• Pneumoperitoneum 
• Pneumothorax 
• PV injury, perforation or stenosis 
• Risk of cancer or birth defect/harm to fetus from x-ray exposure 
• Skin burns/irritation from X-ray exposure  
• Stroke / TIA 
• Surgical procedure to correct any anticipated AE 
• Thrombosis 
• Vessel damage, dissection, or occlusion. 
8.2 
Adverse Event Review and Adjudication 
This study will utilize a CEC for the review and adjudication of AEs. All safety 
analyses will utilize the adjudicated rather than site determination of an AE’s 
characteristics in those instances where the CEC has adjudicated that characteristic to 
be different than the site’s determination. See Section 12.2.4. 
8.3 
Adverse Events 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device. 
NOTE 1: 
This definition includes events related to the investigational medical device or the 
control devices. 
NOTE 2:  This definition includes events related to the procedures involved. 
NOTE 3:  For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
NOTE 4: 
This definition excludes medical conditions, findings or abnormalities which are 
determined to have been present at the time of enrollment, which are defined as 
pre-existing conditions. Pre-existing conditions will not be included in the AE 
dataset. However, a worsening of a pre-existing condition during the study does 
constitute an AE. 
NOTE 5: 
This definition excludes otherwise uncomplicated recurrent AF. 
 

 
 
8.4 
Serious Adverse Events 
An SAE includes any of the following types AEs whether or not related to the 
investigational device or procedures: 
• Any AE resulting in death 
• Any AE which is life-threatening 
• Any AE resulting in hospitalization, or significant prolongation of an existing 
hospitalization 
• Any AE resulting in a persistent, significant impairment 
• Any AE requiring significant medical or surgical intervention to prevent a 
significant impairment 
• Any AE resulting in a congenital anomaly or birth defect 
NOTE 1: 
“Life-threatening” means that the study subject was at a substantial and immediate 
risk of dying due to that AE as it occurred. “Life threatening” AEs do not include 
an AE that – had it occurred in a more severe form – might have caused death.  
NOTE 2: 
“Hospitalization” is a physician-ordered inpatient hospital stay from one calendar 
day to the next or longer. Hospitalization does not include an outpatient facility 
visit or ER visit. 
NOTE 3: 
A “significant” prolongation is related to the AE, excludes delays waiting for 
diagnostic results, is medically necessary and extends the hospital stay by at least 
one calendar day. 
NOTE 4: 
“Persistent” is defined as not resolving by the end of study follow-up. 
NOTE 5:  “Significant impairment” is defined as a substantial disruption of a person’s ability 
to conduct normal life functions. 
NOTE 6: 
A “significant medical or surgical intervention” indicates a procedure or therapy 
with significant novel risk or subject discomfort, that results from the AE. 
A “significant medical or surgical intervention” does not include oral medication, 
noninvasive diagnostic testing or blood testing, routine intravenous fluids, the 
administration of antibiotics, or a pharmacologic or electric cardioversion for AF, 
AFL or AT.  
 
8.5 
Procedure, Device and COVID-19 Relatedness 
The causality of all AEs in relation to 3 types of potential causes – the investigational 
devices, a protocol-stipulated procedure or a confirmed COVID-19 infection – will be 
determined according to four different levels of causality: 
1. Definitely Not Related: An AE for which sufficient information exists to 
determine that it is unrelated to the potential cause. 
2. Unlikely Related: An AE that occurs during or after device use, study procedure 
or COVID-19 infection that could also have been produced by other disease states 
or therapies. The Investigator determines after review of available clinical data 
that the AE is unlikely to have been related to the potential cause. 
3. Likely Related: An AE that occurs during or after device use, study procedure or 
COVID-19 infection that could also have been produced by other disease states or 
therapies. The Investigator  determines after review of the clinical data that the 
AE is likely to have been related to the potential cause. 

 
 
4. Definitely Related: An AE that occurs during or after device use, study 
procedure or COVID-19 infection, is known to be a complication of device use, 
study procedure or COVID-19 infection and for which no other reasonable 
explanation can be determined. 
For the determination of device, procedure and COVID-19 relatedness for this study’s 
outcome measures, “Likely related” and “Definitely related” AEs will be deemed 
“related” and “Definitely not related” and “Unlikely related” AEs will be deemed 
“unrelated.” A listing of all AEs including their relatedness and seriousness will be 
included in the final Clinical Study Report. 
8.6 
Device Effects 
8.6.1 
Adverse Device Effects 
An Adverse Device Effect (ADE) is an AE related to the use of an investigational 
medical device. 
NOTE 1:  This definition includes AEs resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. 
NOTE 2: 
This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
NOTE 3: 
“Related to the uses of an investigational medical device” shall be defined for 
this protocol as a determination that the effects were likely or definitely related to 
an investigational device. 
8.6.2 Serious Adverse Device Effects 
A Serious Adverse Device Effect (SADE) is an ADE that has resulted in any of the 
consequences characteristic of an SAE. 
8.6.3 Unanticipated Adverse Device Effects 
An Unanticipated Adverse Device Effect (UADE) is an SADE which by its nature, 
incidence, severity or outcome has not been identified in the current version of the 
risk analysis report as embodied in Section 8.1. 
NOTE 1: 
An anticipated ADE / SADE is an effect which by its nature, incidence, severity 
or outcome has been identified in the risk analysis report or included in Section 
8.1. 
NOTE 2: 
If an SAE is determined to be likely or definitely related to the device and has not 
been previously anticipated, the clinical finding would be classified as an 
unanticipated adverse device effect (UADE). 
8.7 
Device Deficiencies 
A Device Deficiency is an inadequacy of an investigational medical device related to 
its identity, quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the manufacturer. 
8.8 
Use Errors 
A “Use Error” is an act or omission of an act that results in a different medical device 
response than intended by the manufacturer or expected by the user. 

 
 
NOTE 1: 
Use error includes slips, lapses and mistakes. 
NOTE 2: 
An unexpected physiological response of the subject does not in itself constitute a 
use error. 
8.9 
Malfunctions 
A Malfunction is a failure of an investigational medical device to perform in 
accordance with its design specifications and intended purpose when used in 
accordance with the instructions for use or this protocol. 
8.10 Event Management and Reporting 
8.10.1 Adverse Events 
All AEs, including all SAEs, will be monitored from the time of the Index Procedure 
through study exit.  
All AEs and SAEs must be documented in the subject chart and recorded in the 
appropriate CRF. A description of the event, including the start date, resolution date, 
action taken, and the outcome shall be provided along with the Investigator’s 
assessment of the seriousness of the event and the relationship between the AE and the 
study devices and/or procedures. 
All AEs should be followed until the event is resolved, judged to be chronically stable 
or 12-month study follow-up has been completed, whichever occurs first. The 
investigational site will provide relevant follow-up information to the Sponsor or 
designee upon request. 
Any SAE will be reported to CRO within 24 hours of the site becoming aware of the 
event. 
8.10.2 Adverse Device Effects 
The Investigator shall record an ADE or SADE on the appropriate CRF as an aspect of 
reporting the associated AE. 
An ADE will be reported promptly to the CRO. 
A UADE will be reported to the CRO within 24 hours of the site becoming aware of 
the event. 
8.10.3 Device Deficiency and Malfunctions 
The Investigator shall record a Device Deficiency / Malfunction on the appropriate 
CRF. 
A Device Deficiency or Malfunction that was associated with an SAE, or that could 
have contributed to an SAE, will be reported to the CRO within 24 hours of the site 
becoming aware of the event. 
A Device Deficiency or Malfunction that did not contribute and would not likely 
contribute to an SAE, will be reported to the CRO within 7 days of the site becoming 
aware of the event. 

 
 
8.10.4 Other Assessment and Reporting Requirements 
The Sponsor’s Quality Assurance function shall ensure an assessment is completed for 
each reported Device Deficiency / Malfunction. Such information shall be summarized 
in the final Clinical Study Report. Depending on the local requirements or following 
agreement between both parties, the Sponsor, its designated representative (CRO) or 
the Principal Investigator will be responsible for performing safety reporting to the IRB 
according to the relevant local regulatory requirements. The Sponsor or designated 
representative (CRO) will be responsible for reporting to the FDA according to the 
relevant reporting guidelines.  
8.10.5 Reporting AEs, ADEs and Device Deficiencies 
The following Table summarizes the various reporting requirements for events defined 
in this section. 
Table 6 Reporting AEs, ADEs and Device Deficiencies 
Type of Event 
Process 
Unanticipated adverse device 
effect (UADE) 
Submit within 24 hours after study site personnel 
first learn of the event and to the IRB within the 
IRB required timeframe.  
Serious adverse events, Serious 
Adverse Device Effects 
(SAE, SADE)  
Device deficiencies / malfunctions 
that contributed to or could 
contribute to an SAE 
Device deficiencies / malfunctions 
that did not contribute to or are 
unlikely to contribute to an SAE 
Submit within 7 days after study site personnel 
first learn of the event and to the IRB (if required) 
within the IRB required timeframe.  
Non-serious adverse device effect 
(ADE) 
Submit to the CRO as soon as possible after 
Investigator has become aware of the event and to 
the IRB (if required) within the IRB required 
timeframe. 
 
Documents should be sent electronically to:  
CRO: 
 
Medpace 
  
 
Email: Medpace-safetynotification@medpace.com   
 
Return of Subject Device: 
The device involved in the AE, SAE, Device Deficiency and/or Malfunction as 
described above is to be returned to the Sponsor or Sponsor’s designee for analysis and 
investigation, as appropriate. The Study Coordinator shall contact the Sponsor for 
instructions on returning the device. 

 
 
 

 
 
9. Statistical Procedures and Reporting 
A separate Statistical Analysis Plan (SAP) governs the analysis and reporting of the 
data from this investigation. This section summarizes the essential elements of that 
plan.  
9.1 
General Statistical Considerations 
This study is designed using Bayesian statistical methods, with non-informative prior 
distributions for all parameters. The appropriate sample size is determined adaptively 
via a Goldilocks design36, in which the adequacy of the sample size is assessed at 
several pre-specified enrollment milestones.  All primary and secondary objectives will 
be analyzed using Bayesian methods, though frequentist methods may be used for 
selected analyses such as baseline comparisons, poolability and sensitivity analyses and 
a subset of the pre-specified Additional Analyses. 
When descriptive statistics are used, continuous variables will be summarized using 
standard quantitative statistics: number of available observations, mean, standard 
deviation, median, quartiles and range (minimum and maximum observed values). The 
number of missing observations will also be reported. Categorical variables will be 
summarized using classical frequency statistics: number of available observations and 
percentages by categories. Percentages will be calculated on the number of available 
observations. The number of missing observations will also be specified.  
A full data listing will be prepared. Data will be pooled from all study sites.  
All related and resulting reports, documents and data will be produced and maintained 
in such a way as to ensure their control and the protection of subject privacy. Data files 
and analytic reports will be archived according to requisite regulatory standards. 
Data gathered regarding COVID-19 impacts – including missed, late or alternative 
assessments, COVID-19-related complications, subject withdrawals or Severe COVID-
19 status – will be used as required to address potential biases or to perform sensitivity 
analyses related to the impact of COVID-19 on the study integrity or outcomes. A 
tabulation and listing of all subjects impacted by COVID-19 will be included, with a 
description of how that subject’s participation and/or outcome may have been altered. 
COVID-19-related deviations to the schedule, type of assessment and assessment 
windows will be aggregated and reported. 
9.2 
Randomization 
Subjects meeting all pre-randomization inclusion and exclusion criteria who sign an 
ICF will be randomized. The study staff will confirm documented inclusion / exclusion 
success prior to requesting randomization.  
Randomization will be achieved by an interactive web-based or phone-based system. 
Randomization will be stratified by site and use a permuted block design with 
randomly varying block sizes.  
Subjects who meet the inclusion and exclusion criteria will be randomized using a 1:1 
allocation ratio. 

 
 
Each site will utilize only one control modality – either RFA or CBA – and will use 
that modality for all subjects randomized to the Thermal Group. Site activation and 
enrollment will be monitored and when necessary controlled to maintain a minimum 
40% proportion of Thermal Subjects in either the RFA or CBA modality. 
9.3 
Subject Disposition 
The disposition of all subjects enrolled in the study will be described in tables and 
diagrams, including numbers screened, randomized, excluded, treated and assessed at 
each scheduled follow-up interval. Roll-In Subjects will be assessed separately. Severe 
COVID-19 Subjects will be noted and the potential impacts on the study results 
assessed in sensitivity analyses. Subjects who do not complete the study will be 
enumerated and the reason(s) for their discontinuation will be described. 
9.4 
Populations for Analysis 
Study populations, including those for statistical analysis, are defined in Section 3.4. 
9.5 
Assessment of the Primary Safety Endpoint  
The primary safety endpoint for this study is the CSE defined in Protocol Section 7.1.  
The principal analysis population for the safety endpoints is the Safety Population. 
Analysis in the PP Population will also be conducted as a sensitivity analysis. 
The analysis of the primary safety endpoint is a test of non-inferiority of the event rate 
at 12 months using a non-inferiority margin of 8%. The null and alternative hypotheses 
are presented below for primary safety: 
 
H0: QT ≥ QC + 0.08 versus HA: QT < QC + 0.08 
where QT is the CSE proportion in the Pulsed Field (Treatment) Group and QC is the 
CSE proportion in the Thermal (Control) Group. The differences in the proportion of 
subjects with 1 or more CSE events between the Pulsed Field Group and the Thermal 
Group will be tested with a Bayesian statistical method and the prior distributions for 
QT and QC in these calculations are Beta (0.5, 0.5), which is the Jeffreys non-
informative prior. QT will be deemed to be non-inferior to QC if it can be established 
that the posterior probability Pr(HA | data) > Ψsaf, where Ψsaf is a pre-specified threshold 
value that controls the one-sided type I error rate (under simulation) at level 0.05. In the 
absence of missing data, the posterior distributions for QT and QC would be conjugate 
Beta distributions. However, some missing data are expected. Therefore, Bayesian 
multiple imputation of 12-month outcomes will be employed in the principal analysis. 
The imputation model accounts for primary outcome information up through the time 
of censoring. Details on the modeling for this imputation are given in the SAP. 
9.6 
Assessment of the Primary Effectiveness Endpoint 
The primary effectiveness endpoint for this study is Treatment Success defined at 
Section 7.4.  
The principal analysis population for the primary effectiveness endpoint is the MITT 
Population. Analysis in the PP Population will also be conducted as a sensitivity 
analysis. 

 
 
The primary effectiveness endpoint for this study is Treatment Success, which will be 
analyzed as a test of non-inferiority of the event rate at 12 months using a non-
inferiority margin of 15%. The null and alternative hypotheses are: 
 
H0: PT ≤ PC – 0.15 versus HA: PT > PC – 0.15 
where PT is the Treatment Success rate at 12 months in the Pulsed Field Group and PC 
is the Treatment Success rate at 12 months in the Thermal (Control) Group.  
This study is designed using Bayesian statistical techniques and the prior distributions 
for PT and PC in these calculations are Beta (0.5, 0.5), which is the Jeffreys non-
informative prior. PT will be deemed to be non-inferior to PC if it can be established that 
the posterior probability Pr(HA | data) > Ψeff, where Ψeff is a pre-specified threshold 
value that controls the one-sided type I error rate (under simulation) at level 0.05. In the 
absence of missing data, the posterior distributions for PT and PC would be conjugate 
Beta distributions. However, some missing data are expected. Therefore, Bayesian 
multiple imputation of 12-month outcomes will be employed in the principal analysis. 
The imputation model accounts for primary outcome information up through the time 
of censoring. Details on the modeling for this imputation are given in the SAP. 
9.7 
Sample Size Considerations 
Please refer to the SAP for a full treatment of this topic. 
Parameter selection: IDE pivotal studies for the treatment of drug-resistant 
symptomatic PAF are highly standardized and utilize nearly identical definitions of 
primary effectiveness and similar definitions of primary safety. Published IDE studies 
with available information comparing new devices with approved control devices have 
all used non-inferiority designs with one-sided alpha of 0.05 and 15% effectiveness 
margins and either 8% or 9% safety margins.  
Peer-reviewed studies do not undergo the same scrutiny or utilize the rigor of 
FDA-supervised studies and therefore their estimates of effectiveness and safety are 
not entirely comparable to IDE studies. The consensus regarding high quality 
randomized comparisons between currently approved technologies is that none are 
superior to another. Perhaps the largest non-IDE study comparing RFA and CBA 
technologies (Fire and Ice37) found no difference between the two and also reported 
very similar primary outcomes to IDE studies. 
Sample Size Requirements for Safety: 
Although the pre-specified statistical analysis methods are Bayesian, standard 
frequentist considerations are used to guide sample size selection. The sample size for 
primary safety computed for a Farrington-Manning test with PASS 13 indicates that, 
for 1:1 randomization, 90% power, alpha=0.05 (one-sided), CSE rate in both Groups of 
0.08 and non-inferiority margin of 0.08, the study requires a completed sample size of 
214 subjects in each Group, for a total of 428. Assuming a 5% rate of loss-to-follow-up 
(LTFU), 450 subjects are needed. 
There is uncertainty in the CSE rate, and this can have dramatic impact on sample size 
requirements.  If the CSE rate is 0.07 in the Pulsed Field group but 0.08 in the Thermal 

 
 
group, 326 subjects are required to achieve 90% power (344 after compensating for 5% 
LTFU).  If the CSE rate is 0.10 in the Pulsed Field group but 0.08 in the Thermal 
group, 690 subjects are required to achieve 85% power (727 after compensating for 5% 
LTFU). 
This uncertainty in the CSE rate motivates the use of a design wherein the sample size 
is adaptively determined, with possible sample sizes ranging from 350 to 750. 
Sample Size Requirements for Effectiveness:  
Although the pre-specified statistical methods are Bayesian, standard frequentist 
considerations are used to guide sample size selection. The sample size required for the 
primary effectiveness endpoint obtained by PASS 13 for 1:1 randomization, 90% 
power, alpha=0.05 (one-sided), success rates in each group of 0.65 and non-inferiority 
margin δ=0.15 is 172 subjects in each arm, for a total of 344 subjects.  Similar to the 
safety objective, there is uncertainty in the success rates, especially in the Pulsed Field 
group.  If the success rate in the Pulsed Field group is 0.625 but 0.65 in the Thermal 
group, 502 subjects are required to achieve 90% power (558 after compensating for up 
to 10% missing data).  If the success rate in the Pulsed Field group is 0.70 but 0.65 in 
the Thermal group, only 186 subjects are required to achieve 90% power (207 after 
compensating for missing data).   
This uncertainty in the Treatment Success rate motivates the use of a design wherein 
the sample size is adaptively determined, with possible sample sizes ranging from 200 
to 550.   
Number of Enrolled Subjects: 
The primary population for the analysis of effectiveness is the MITT Population. The 
Safety Population should be similar but will not be smaller. Considering the joint 
sample size needs of the primary safety and effectiveness objectives, the primary 
analysis population may range from a minimum of 350 to a maximum of 750. 
To achieve a sample size of 750 MITT Subjects, up to 900 subjects may be enrolled 
consisting of 750 MITT and up to 105 Roll-In Subjects and up to 45 ITT Subjects (6%) 
who do not meet the criteria for the MITT Population. 
9.8 
Analysis Plan 
This trial is designed using Bayesian statistical techniques.  The appropriate sample 
size is determined adaptively via a Goldilocks design38, with possible sample sizes of 
N=350, 450, 550, 650, and 750.   
The sample size determination algorithm is as follows.  At a pre-defined interim 
analysis point (e.g., when N=Ni subjects have been accrued into the MITT population; 
Ni = 350, 450, 550 and 650), four predictive probabilities are calculated: 
PPint,saf   =  Predictive probability that the trial will establish non-inferiority for safety, 
once the current sample (Ni) is followed to 12 months. 
PPmax,saf  = Predictive probability that the trial will establish non-inferiority for safety, 
assuming the maximum sample size (750) is attained and followed to 12 
months.   

 
 
PPint,eff    = Predictive probability that the trial will establish non-inferiority for 
effectiveness, once the current sample (Ni) is followed to 12 months. 
PPmax,eff  = Predictive probability that the trial will establish non-inferiority for 
effectiveness, assuming the maximum sample size (750) is attained and 
followed to 12 months.   
If PPint,saf exceeds a suitably high threshold Wsaf,i, and if PPint,eff exceeds a suitably high 
threshold Weff,i, subject accrual will stop because final success looks probable with the 
current sample.  On the other hand, if PPmax,saf is less than a suitably low threshold Fsaf,i, 
or if PPmax,eff is less than a suitably low threshold Feff,i, subject accrual will stop 
because final success is unlikely.  In either case, follow-up continues to 12 months for 
all subjects, at which time the final analysis will occur. If neither of these conditions 
obtains, enrollment will continue to the next larger sample size (subject to the 
maximum of 750).  These analyses are termed "Interim Sample Size Looks."  Further 
details on the calculation of these predictive probabilities and specification of the 
thresholds {Weff,i, Feff,i, Wsaf,i, Fsaf,i}are provided in the SAP. 
Once subject accrual has stopped, all accrued subjects will be followed to 12 months, 
and then the inferential tests of non-inferiority will occur as described in Sections 9.5 
and 9.6. This is the only time that non-inferiority is tested. 
9.9 
Assessment of the Secondary Safety Endpoint 
One endpoint – Aggregate PV Cross-Sectional Area (Section 7.2) – will be formally 
tested as a secondary safety endpoint.  
The paired comparison of change in the Aggregate PV Cross-Sectional Area between 
baseline and 3 months will be compared between Pulsed Field Subjects and Thermal 
Subjects, testing whether the reduction in Aggregate PV Cross-Sectional Area is 
significantly less in the Pulsed Field Subjects. Within-subject changes in Aggregate PV 
Cross-sectional Area (3-month minus baseline) will be compared between Pulsed Field 
and Thermal groups via a Bayesian version of a t-test. The null and alternative 
hypotheses are: 
H0: μT – μC = 0  versus HA: μT – μC > 0,  
where μT represents the change (3 months minus baseline) in area in the treatment 
(Pulsed Field) group, and μC represents the corresponding change in area in the control 
(Thermal) group. The null hypothesis will be rejected if the posterior probability P(HA | 
data) exceeds a threshold value ΨPV = 0.975, corresponding to a one-sided significance 
level of 0.025.   
The population for analysis will be MITT Subjects with pre- and post-procedure PV 
dimensional data related to one or more protocol-specified ablation lesions. 
Supplemental analyses will be performed using MITT single procedure subjects and the 
PP population. 

 
 
9.10 Assessment of the Secondary Effectiveness Endpoint 
The secondary effectiveness endpoint is Treatment Superiority, which is Treatment 
Success (Section 7.4) tested for superiority between the Pulsed Field and Thermal 
Groups.  
The principal analysis population for the secondary effectiveness endpoint is the MITT 
Population. Analysis in the PP population will also be conducted as a sensitivity 
analysis.  
The null and alternative hypotheses are provided below. 
H0: PT ≤ PC versus HA: PT > PC 
where PT is the Treatment Success rate at 12 months in the Pulsed Field Group, and PC 
is the Treatment Success rate at 12 months in the Thermal Group. Modeling will be 
identical to the test of non-inferiority, and superiority will be concluded if the posterior 
probability Pr(HA | data) > Ψeff,sup, where the threshold Ψeff,sup is a pre-specified 
threshold value that controls the one-sided type I error rate (under simulation) at level 
0.025. In the absence of missing data, the posterior distributions for PT and PC would be 
conjugate Beta distributions. However, some missing data are expected, and especially 
so at the interim analysis. Therefore, Bayesian multiple imputation of 12-month 
outcomes will be employed in the principal analysis. The imputation model accounts 
for primary outcome information up through the time of censoring. More detail on this 
imputation is given in the Statistical Analysis Plan. 
9.11 Assessment of Subject Blinding 
Subjects will complete a survey regarding their opinion as to which study group they 
were assigned to at the time of Index Procedure / Rescheduled Index Procedure 
discharge and at the 12-month follow-up visit. Self-assessment of treatment status will 
be formally assessed according to the procedures defined by Bang 200439 and 
James 1996.40 
 
 
 
 

 
 
10. Core Laboratories 
10.1 Arrhythmia Core Laboratory 
A qualified ACL will be established to receive, review and assess all protocol-
stipulated ECGs, EMs and Holter monitors.  
10.1.1 Procedures 
Documented procedures will be established for the provision of equipment, the 
training of study subjects, the receipt of outputs, the assessment of arrhythmia and the 
transmission of results for inclusion in the study dataset. 
10.1.2 Event Monitors 
Each subject: 
• Will be introduced to the use and importance of EMs at the Baseline visit 
• Will be fully instructed on the use of an EM at the Day 60 EM training. 
Either the ACL or the site will provide the subject with an EM not later than the 
Day 60 EM training to be used beginning at the time of the Day 90 Assessment and 
weekly thereafter and also for any symptomatic episodes throughout the remainder of 
the 12-month study follow-up. 
Careful monitoring and subject follow-up will be implemented to ensure compliance 
with the required weekly scheduled and ad hoc symptomatic utilization and 
transmission of the EMs. Individual missed weekly transmissions will not be counted 
as protocol deviations, but a subject with less than 80% of weeks covered by at least 
one transmission at the end of follow-up will be considered a protocol deviation. 
The EM will be returned to the ACL or the site at the time of the subject’s exit from 
the study. ECG data from the EM will be analyzed by the ACL. 
10.1.3 Holter Monitors 
Each subject: 
• Will be introduced to the use and importance of the Holter monitoring at the 
Baseline visit and the use of the EM hardware for this purpose. 
• Will be fully instructed on the use of a 72-hour continuous ECG (Holter) 
monitor prior to the 6-Month and 12-Month Holter monitoring.  
Careful monitoring and subject follow-up will be implemented to ensure that the 
device will be utilized by the subject for the nominal 72-hour period for both the 
Month 6 and Month 12 Assessments.  
The 12-Month Holter monitor should be performed prior to the completion of the 
Month 12 Assessment. 
ECG data from the Holter monitor will be analyzed by the ACL.  

 
 
10.1.4 Arrhythmia Data Review and Transmission 
The ACL will analyze all protocol-stipulated ECG, EM and Holter data and will 
make available the primary data for review and transmit the rhythm analyses of each 
monitoring study to the CRO for inclusion in the study dataset. 
10.1.5 CEC Over-Reads of Potential Endpoints 
Any ECG, EM or Holter result that is reported by the ACL to contain a first 
post-Blanking Period occurrence of AF, AFL or AT will be reviewed by the CEC to 
establish the presence or absence of a primary effectiveness endpoint event. Such 
adjudications will be repeated to the extent necessary to confirm the date, duration 
and rhythm of any potential Detectable AF, AFL or AT that will determine a post-
Blanking Period Treatment Failure.  
The CEC’s determination regarding Detectable AF, AFL or AT is final. 
10.2 Cardiac Imaging Core Laboratory 
A qualified CICL will be established to receive, review and assess all protocol-
stipulated cardiac MRIs and CTs.  
10.2.1 Procedures 
Documented procedures will be established for the performance of cardiac imaging, 
the receipt of outputs, the assessment of images – most importantly changes in PV 
dimensions – and the transmission of results for inclusion in the study dataset. 
10.2.2 Pulmonary Vein Dimensions 
Each treated vein will have pre-ablation and 3-month post-ablation assessments of 
standardized diameters (Section 6.3.14). Subjects with documented 3-month PVS 
will have a protocol-mandated 12-month post-ablation assessment. 
10.2.3 Cardiac Imaging Data Review and Transmission 
The CICL will analyze all PV dimensions, calculate changes in dimensions, make 
available the primary data for review and transmit the PV dimensional analyses of 
each imaging study to the CRO for inclusion in the study dataset. 
10.2.4 CEC Review of Pulmonary Vein Stenosis Results 
Any cardiac imaging report that is determined by the CICL to contain a PVS will be 
reviewed by the CEC to confirm the finding of a primary effectiveness endpoint 
event. The CEC may request a review of the finding but will not review the images. A 
proposed change in the CICL finding will require consent from the CICL. 
10.3 Brain Imaging Core Laboratory 
A qualified BICL will be established to receive, review and assess all protocol-
stipulated brain MRIs for NAS Subjects. 
 
 

 
 
10.3.1 Procedures 
Documented procedures will be established for the performance of brain imaging in 
NAS Subjects to allow assessment of SCEs and SCLs, the receipt of outputs, the 
assessment of images – most importantly SCEs and SCLs – and the transmission of 
results for inclusion in the study dataset. 
10.3.2 SCE and SCL Assessment 
Each post-procedural brain MRI in NAS Subjects will be assessed according to 
standardized parameters for SCE and SCL findings. 
10.3.3 Brain Imaging Data Review and Transmission 
The BICL will analyze all diffusion weighted and FLAIR findings in NAS Subjects, 
make available the primary data for review and transmit the brain lesion analyses of 
each imaging study to the CRO for inclusion in the study dataset. 
The CEC will not review brain imaging findings for determination of SCE and SCL 
findings in NAS Subjects. 
 

 
 
11. Monitoring 
11.1 Monitors 
Clinical and medical monitors, qualified by training and experience, will be responsible 
for monitoring and overseeing the conduct of the study in accordance with a study 
monitoring plan.  
11.2 Clinical Monitoring Activities 
The monitors will evaluate compliance with the protocol, any specific 
recommendations made by the site’s IRB and the signed Investigator Agreement. 
Phone contacts and site visits will be conducted to ensure that the protocol is being 
followed and that any protocol deviations are properly documented. Clinical 
monitoring will include a verification that the ICF was properly obtained for all 
enrolled study participants, a review of clinical records for accuracy and completeness, 
resolution of missing or inconsistent results and a review of source documents. The 
clinical monitor will verify that the CRFs agree with the source documentation and 
other records. The Investigator will make available to the monitor for review as 
requested ICFs, completed CRFs, source documentation and other relevant records for 
enrolled study subjects.  
If a deficiency is noted during an on-site monitoring visit or at any other time during 
the study, the monitor is required to discuss the situation with the Investigator and the 
Sponsor to ensure compliance. 
11.3 Monitoring Responsibility and Data Verification 
The Sponsor or its designated representative, qualified by training and experience, will 
be responsible for monitoring and overseeing the conduct of the study. The accuracy of 
all (100%) collected data will be verified for: 
• Eligibility criteria 
• Baseline characteristics 
• Primary safety and effectiveness endpoints 
• Secondary endpoints 
• AEs (including SAEs) and Device Deficiencies / Malfunction Reporting 
Verification will utilize source documents including, but not limited to, medical 
records, office/ clinic notes, procedure reports, laboratory results, and physician and 
nursing progress notes. Verification and quality of data, monitoring of clinical study 
progress and Investigator compliance with the approved protocol will be conducted by 
the Sponsor or its designated representative. 
11.4 Site Visits 
The Sponsor or its designated representative must be allowed to visit the clinical site 
and have direct access to all study records throughout the duration of the study. Where 
this is not possible due to COVID-19-related disruption, every effort will be made by 
Sponsor and site personnel to achieve monitoring goals remotely. Study procedures for 
remote monitoring will be consistent with FDA Guidance Documents. 

 
 
Specific monitoring requirements are detailed in the study-specific Monitoring Plan 
maintained in the FARAPULSE and CRO clinical study project files. The Investigator 
and / or institution will provide direct access to source data / documents for study-
related monitoring, audits and regulatory review and inspection. 
It is important that the Investigator and other relevant site personnel, including the 
research study coordinator, are available for consultation with the monitors during the 
monitoring visits and that sufficient time is devoted at the site for the monitoring 
process.  
Additionally, telephone, email contact, and onsite visits will be conducted on a regular 
basis with the Investigator and the site staff to ensure that the protocol is being 
followed and to address any issues that may occur during the study. 
If a deficiency is noted during the study, the monitor is required to discuss the situation 
with the site and the Sponsor (if required) to secure compliance. A Monitoring Site 
Visit Report will be issued to the Sponsor.  

 
 
12. Study Management 
The Sponsor has overall responsibility for the conduct of the study according to Good 
Clinical Practice Guidelines (ICH E6 Consolidated Guidance to Good Clinical Practice) 
as well as any conditions imposed by local and national regulatory authorities. 
For this investigation, the Sponsor may have certain direct responsibilities and will 
otherwise delegate in writing responsibilities to appropriate and qualified consultants, 
contractors and / or CROs. Together, the Sponsor, consultants and CRO will ensure that 
the study is conducted according to the approved Clinical Investigation Plan (CIP), 
IRB-approved ICF and all applicable governing regulations. All personnel participating 
in the conduct of this clinical study will be qualified by education and/or experience to 
perform their tasks. 
12.1 Ethical Considerations 
It is expected that all parties will share in the responsibility for ethical conduct in 
accordance with their respective roles in the investigation. The Sponsor and the 
Investigator shall avoid improper influence or inducement of the subject, monitor, 
other Investigator or other parties participating in or contributing to the clinical 
investigation. 
12.1.1 Study Conduct 
The study will be performed in accordance with the relevant parts of the Code of 
Federal Regulations, ICH Guidelines for Good Clinical Practices and ethical 
principles consistent with the Declaration of Helsinki. The clinical investigation shall 
not begin until the required approval has been obtained from the FDA and the local 
IRB. Any additional requirements imposed by the regulatory authority or IRB shall 
be followed. These principles shall be understood, observed and applied at every step 
in this clinical investigation. 
12.1.2 Ethics Review 
Before any subject can be enrolled in this study, the local, central or national IRB and 
the FDA must review and approve the CIP and the ICF to be used. A subject cannot 
be asked to sign the ICF until the study has been fully approved by the institution’s 
IRB and by the FDA. The Sponsor or their designated CRO will require a copy of any 
IRB correspondence, as well as the final IRB approval letter and the final IRB-
approved ICF and approvals for the CIP and ICF revisions on amendments from the 
IRB. The Sponsor or their designated CRO will keep all the FDA correspondence as 
well as the FDA approval letter. 
12.1.3 Informed Consent 
Subjects will not sign the ICF until the study has been fully approved by the 
institution’s IRB and the Sponsor or their designated CRO has received and reviewed 
the specific IRB-approved ICF. When the Investigator has determined the eligibility 
of a specific subject to enter the study, the ICF must be completed. The ICF must be 
read and understood by the subject, the subject’s questions answered, and the form 

 
 
signed by the subject before any study-related procedures can be performed. All 
subjects are to receive copies of their signed ICF. 
12.1.4 Confidentiality 
Confidentiality of subjects will be maintained throughout the study. A unique 
identification code will be assigned to each subject participating in this study. Any 
data that may be published in abstracts, scientific journals or presented at medical 
meetings will reference a unique subject code and will not reveal the subject’s 
identity. The Sponsor, CRO, Investigators and site personnel will make every 
reasonable effort to protect the confidentiality of all subjects participating in the 
study. 
12.2 Key Contributors 
12.2.1 Sponsor 
Clinical Affairs, Regulatory Affairs and Quality Assurance 
FARAPULSE, Inc. 
3715 Haven Ave. Suite 110 
Menlo Park, CA 94025 
USA 
John Allison, Vice President 
Tel: +1.650.422.3633 
Email: jallison@farapulse.com 
12.2.2 Contract Research Organization 
Medpace Medical Device 
3787 95th Ave NE 
Suite 100 
Blaine, MN 55014 
USA 
Patricia Bobzin, Director, Medical Devices 
Tel: +1.612.234.8500 
Fax: +1.513.527.0368 
Email: p.bobzin@medpace.com  
 
12.2.3 Arrhythmia Core Laboratory 
HeartcoR Solutions LLC 
2403 Harnish Drive, Suite 201 
Algonquin, IL 60102 
USA 
12.2.4 Clinical Events Committee 
The Sponsor or CRO will establish an external group of expert physicians to serve as 
the CEC. This group will consist of a panel of 3 experienced, independent physicians 

 
 
who are not Investigators and will be supported by one or more Medical Monitors and 
staff as required. The CEC will develop a Charter, which will establish committee 
procedures. 
The CEC will convene regularly during the study to review, classify and/or adjudicate 
AEs reported in this investigation as well as primary and secondary study outcomes. 
The CEC will be provided with case summaries, relevant source documents and any 
other information required to evaluate and adjudicate the AEs and study outcomes.  
12.2.5 Data and Safety Monitoring Board 
The Sponsor will establish an external group of physicians and an independent 
statistician to serve as the DSMB. This group will include at least 2 experienced, 
independent physicians who are not Investigators and an independent statistician not 
involved in the routine operation of the study. The DSMB will develop a Charter, 
which will establish committee procedures. 
The DSMB will convene regularly during the study to assess overall event rates to 
ensure the integrity of the clinical study and the rights, safety and welfare of study 
subjects. The DSMB will also review the results of the interim analyses. 
Should any protocol changes be necessitated by the findings of the DSMB during its 
deliberations, or by the impact of externalities such as the COVID-19 pandemic, the 
DSMB may propose such changes to the Sponsor. The Sponsor will review these 
changes with the DSMB and upon consensus submit such changes to the FDA. 
12.3 Sponsor Responsibilities 
Sponsor has the overall responsibility for the study and will perform the following, 
either directly or by documented delegation to qualified contractors: 
• Select qualified Investigators and study sites. 
• Select qualified monitors. 
• Provide the CIP and any subsequent amendments. 
• Provide appropriate information and investigational system training to the 
Investigator and study site staff. 
• Ensure that all deviations from the CIP are reviewed with the appropriate 
Investigator(s) and reported on the CRFs and the final clinical report and that any 
necessary preventative or corrective action is taken. 
• Ensure that all AEs and all ADEs are reported and reviewed with the 
Investigator(s) and where appropriate, that all SAEs and all SADEs are 
appropriately reported. 
• Ensure that all Device Deficiencies / Malfunctions are reviewed by the Sponsor, 
and properly assessed and investigated, as appropriate. 
• Promptly inform the Investigator and where applicable, any regulatory authorities, 
if the study is prematurely terminated or suspended and the reason for the 
termination or suspension. 
• Ensure proper device usage, uniform data collection and protocol compliance. 
• Provide comprehensive initial and remedial training throughout the study, 
including site initiation training regarding the FARAPULSE Pulsed Field 

 
 
Ablation System, the IFU, the CIP, CRF instructions, CRFs, AE/SAE/Device 
Deficiency reporting and requirements for obtaining informed consent. 
• Provide the FARAPULSE Pulsed Field Ablation System to the participating study 
site, in quantities adequate to support study activities. 
• Coordinate ongoing communication with CROs, consultants and study site to 
resolve any problems concerning the protocol or data collection. 
• Ensure compliance with the protocol. Where repeated efforts have failed to 
correct serious compliance issues, the Sponsor may pause or terminate a site’s 
further enrollment in the study; see Section 12.12. 
• Retain ownership of all clinical data generated in this study and control the use of 
the data for purposes of regulatory submissions. 
• Protect subject confidentiality. 
12.4 Monitor Responsibilities 
Clinical monitors, qualified by training and experience, supervised and coordinated by 
qualified managers, and supplied with appropriate data and instructions, will be 
responsible for monitoring and overseeing the conduct of the study. 
Site Initiation Visit: Sponsor personnel and / or clinical monitors will conduct site 
initiation visits at the investigational site – or if required via effective remote 
communication –  to ensure that the Investigator and other investigational site 
personnel involved in the conduct of this investigation have received and understood 
the requirements and contents of this CIP, the Investigator’s Brochure, the subject ICF, 
the CRFs, CRF Instructions, AE/SAE/Device Deficiency reporting requirements and 
the IFU and the Institution and / or Investigator Agreement. 
Site Monitoring: The clinical monitors will conduct routine on-site monitoring visits 
in-person or when this cannot be achieved by effective remote communications in 
accordance with a study monitoring plan to evaluate compliance with the CIP, any 
specific recommendations made by the site’s IRB and the signed Institution and/or 
Investigator Agreement and to ensure that the CIP is being followed and that any 
protocol deviations are properly documented on the respective CRF. Clinical 
monitoring will include a verification that informed consent was properly obtained and 
documented for all enrolled study participants, a review of clinical records and CRFs 
for accuracy and completeness, resolution of missing or inconsistent results and a 
review of source documents. 
Clinical monitoring will include a review of all AEs, SAEs and Device 
Deficiencies / Malfunctions to ensure that all information has been reported to the 
Sponsor, IRB and regulatory authorities as required by the Clinical Investigational Plan 
and applicable standards and laws. 
The clinical monitor will verify that the CRFs are complete and in agreement with the 
source documentation and other records. The clinical monitor will ensure that all CRFs 
have been signed and dated by the Investigator. 
The Investigator will make available to the clinical monitor for review upon request 
ICFs, CRFs, source documentation and other relevant records for Enrolled Subjects at 
the site. It is important that the Investigator and other relevant site personnel are 

 
 
available for consultation with the clinical monitors during the monitoring visits and 
that sufficient time is devoted at the site for the monitoring process. 
If a deficiency is noted during an on-site visit or at any other time during the course of 
the study, the clinical monitor is required to discuss the situation with the Investigator 
and the Sponsor and to subsequently monitor the implementation of corrective actions 
that are required to address the situation. 
All monitoring activities will be documented by the clinical monitor in a monitoring 
report and will include, at a minimum, the date, investigational site visited, names of all 
personnel involved in the visit and a summary of all findings, facts, deviations, 
conclusions and recommended actions to be taken. Key findings will be reviewed with 
the Investigator.  
Upon completion of the study, a study closeout visit will be conducted to ensure that all 
data collection and study requirements are complete. 
Medical monitors qualified by training and experience will support clinical monitors 
and other study personnel by providing study-related medical judgment regarding such 
subjects as interpretation of eligibility criteria, reviewing and assessment of AEs and 
the review of monitoring and study reports. 
12.5 Investigator Responsibilities 
At a minimum, the following documents will be provided by the investigational site to 
the Sponsor prior to study start (consent of the first subject): 
• Signed Clinical Trial Agreements 
• Signed Financial Disclosure Form 
• Signed CIP signature page 
• Investigator and Sub-Investigator’s current curriculum vitae 
• Investigator and site personnel protocol and device training records 
• Any other additional documents as required by the Sponsor 
The Investigator is responsible for ensuring that the investigation is conducted 
according to all signed agreements, the CIP, governing regulations, data protection 
regulations, medical device laws, the Declaration of Helsinki and any other conditions 
imposed by the relevant regulatory authorities. The Investigator is responsible for 
maintaining medical and study records for every subject participating in the clinical 
study (including information maintained electronically such as digital imaging). The 
Investigator will also maintain original source documents from which study-related 
data are derived. 
The Investigator(s) shall be responsible for the day-to-day conduct of the investigation 
as well as for the safety and well-being of the human subjects involved in the clinical 
investigation. 
The Investigator(s) shall: 
• Have the qualified and trained resources to conduct the investigation properly. 
• Obtain from the Sponsor the information that the Investigator(s) judges essential 
about the device and be familiar with this information. 

 
 
• Be well acquainted with the CIP before signing the signature page. 
• Support the monitor and auditor, if applicable, in their activities to verify 
compliance with the CIP, to perform source data verification and to correct the 
CRF where inconsistencies or missing values are identified. 
• Discuss with the Sponsor management any question of modification of the CIP. 
• Make sure that the CIP is followed by all responsible for the conduct of the study 
at his/ her institution. Any deviation shall be documented and reported to the 
study Sponsor and CRO. 
• Make the necessary arrangements to ensure the proper conduct and completion of 
the investigation. 
• Make the necessary arrangements for emergency treatment, as needed, to protect 
the health and welfare of the subject. 
• Ensure that appropriate IRB and FDA approvals are obtained prior to the start of 
the investigation. 
• Inform Sponsor about AEs and Device Deficiencies / Malfunctions in a timely 
manner; document on applicable CRFs. 
• Endeavor to ensure an adequate recruitment of subjects. 
• Ensure that the subject has adequate information and time to provide informed 
consent. 
• Ensure that informed consent is obtained and documented on the IRB-approved 
ICF. 
• Ensure that clinical records are clearly marked to indicate that the subject is 
enrolled in this study. 
• Provide subjects with well-defined procedures for any emergency situation and 
safeguard the subject’s interest. Under these circumstances, deviations from the 
CIP shall not require the prior approval of the Sponsor or the national and local 
regulatory authorities. Such deviations shall not be considered as a breach of 
agreement but shall be documented and reported to Sponsor. 
• Ensure that information which becomes available as a result of the clinical 
investigation which may be of importance to the health of a subject and the 
continuation of the investigation shall be made known to the Sponsor and, if 
pertinent to the safety or well-being of the subject and the private clinician. 
• Inform the subject and/ or the subject’s physician about any premature 
termination or suspension of the investigation with a rationale for study 
termination. 
• Have primary responsibility for the accuracy, legibility and security of all 
investigation data, documents and subject records both during and after the 
investigation. 
• Sign each subject’s CRF, as applicable. 
• Be responsible for the supervision and assignment of duties at his/ her clinical 
center. The Investigator must maintain a Delegation of Authority Form of 
appropriately qualified persons to whom the Investigator has delegated significant 
study related duties.   

 
 
• Ensure that all investigational devices are kept in a secure location and that all 
Systems are accounted for on the Device Accountability Form (number of devices 
used, discarded and returned to Sponsor). 
12.6 Investigator and Site Staff Training 
The participating Investigator and the relevant staff members at each investigational 
site will be trained in the use of the FARAPULSE Pulsed Field Ablation System prior 
to participating in the study. Device training will be conducted by the Sponsor or its 
representatives. All device training will be documented in a training log that will be 
maintained in the Regulatory Site Binder. 
12.7 Confidentiality and Publication Policy 
This clinical study, its associated documentation and the study data are all confidential 
and should not be discussed or shared with persons outside of the study. Additionally, 
the information in this document and regarding this study contains trade secrets and 
commercially sensitive information that are confidential and may not be disclosed 
unless such disclosure is required by law or regulations. Subject to the foregoing, this 
information may be disclosed only to those persons involved in the study who have a 
need to know, but all such persons must be instructed not to further disseminate this 
information to others. These restrictions of disclosure will apply equally to all future 
information that is indicated as confidential. 
The data generated by this clinical study are the property of the Sponsor and may not be 
disclosed without the prior written permission of FARAPULSE, Inc. These data may be 
used by FARAPULSE, Inc. now and in the future for presentation or publication at 
FARAPULSE, Inc.’s discretion or for submission to governmental regulatory agencies. 
FARAPULSE, Inc. reserves the right of prior review of any publication or presentation 
of data from the subject investigation. 
A final comprehensive Clinical Study Report including these analyses will be prepared 
at the conclusion of the study or at such time as the study may be prematurely 
terminated, regardless of outcome. Publication in the appropriate peer-reviewed 
medical literature of the pre-specified study results will be attempted, based on the 
Clinical Study Report. Copies of the final report will be provided to the Investigator 
and their IRB and to the FDA as applicable. Neither Investigators nor their staff will 
publicize any study results without written permission of the Sponsor. 
12.8 Data Management 
Data management procedures will be included in a data management plan. 
eCRFs will be made available to the participating site. Investigators are responsible for 
the accurate completion of subject eCRFs during the study. The Investigator will ensure 
that complete, accurate and timely data in eCRFs are completed, that protocol 
requirements are followed and that complications, AEs and ADEs are correctly 
reported and investigated, as appropriate. The Investigator is expected to maintain all 
source documents as required by the CIP, including laboratory results, supporting 
medical records and signed ICFs. The source documents will be used during the regular 
monitoring visits to verify information against data contained in the completed eCRFs. 

 
 
eCRF data will be reviewed to identify any inconsistent or missing data and any AEs. 
Any data issues are to be promptly addressed with the Investigator by the CRO. 
After eCRF monitoring has been complete and deficiencies / discrepancies resolved, 
study data in the central database will be updated to reflect any changes.  
12.9 Insurance 
The Sponsor will maintain the appropriate and necessary insurance coverage for the 
duration of the study. 
12.10 Audits and Inspections 
The Investigator will allow representatives of the governing IRB and FDA, with 
appropriate notice, to inspect all study records, CRFs and corresponding portions of the 
subject’s office and / or hospital medical records at intervals throughout the study. 
These inspections are for the purpose of verifying adherence to the CIP, completeness 
and exactness of the data being entered onto the CRFs and compliance with regulatory 
agency regulations. 
The Investigator will inform the Sponsor or the Sponsor’s designee immediately upon 
notice that they are to be audited or inspected by any regulatory agencies. The Sponsor 
or the Sponsor’s designee will also inform the site if they are made aware of a pending 
audit or inspection by a regulatory agency. 
12.11 Study Suspension or Early Termination 
The study can be discontinued at the discretion of the Sponsor for reasons including, 
but not limited to, the following: 
• Occurrence of AEs unexpected as to their nature, severity, or duration, or the 
unexpected incidence of known AEs 
• Obtaining new scientific knowledge that shows that the study is no longer valid or 
necessary 
• Data demonstrates a benefit to subjects who undergo percutaneous ablation with 
the FARAPULSE Pulsed Field Ablation System making treatment without the 
FARAPULSE Pulsed Field Ablation System unethical 
• Insufficient recruitment of subjects 
• UADEs presenting an unreasonable risk to subjects (Sponsor may terminate the 
study immediately) 
If the study is discontinued or suspended prematurely, the Sponsor shall promptly 
inform the Investigators of the termination or suspension and the reason(s) for 
discontinuation / suspension. Regulatory authorities shall also be informed promptly 
and provided with the reason(s) for the termination or suspension by the Sponsor. 
Subjects enrolled up to the date of suspension / termination will continue to be followed 
for safety through the 12-month timepoint.  
12.12  Criteria for Suspending or Terminating a Study Site 
Sponsor reserves the right to stop the screening of subjects at an individual study site at 
any time after the study initiation visit for reasons including the following: 

 
 
• Absent or insufficient enrollment of study subjects 
• Persistent non-compliance with the CIP or regulatory requirements 
• Repeated failure to complete CRFs prior to scheduled monitoring visits 
• Failure to obtain written informed consent using the IRB-approved ICF 
• Failure to report SAEs/ UADEs to Sponsor within 24-hours of knowledge 
• Loss of (or unaccounted for) investigational product inventory or repeated failure 
of device accountability. 
12.13 Deviations from the Clinical Investigation Plan 
Under emergency circumstances, deviations from the CIP to protect the rights, safety, 
and well-being of human subjects may proceed without prior approval of the Sponsor 
or IRB, including but not limited to those required to minimize or eliminate immediate 
hazards or to protect the life and well-being of research participants especially in 
relation to limiting exposure to COVID-19. 
The Investigator must notify the Sponsor and the CRO of any deviation from the CIP 
and document the reason for the deviation in the eCRF. 
The Investigator shall notify the Sponsor and the reviewing IRB of any deviation from 
the CIP to protect the life or physical well-being of a subject in an emergency. Such 
notice shall be given as soon as possible, but in no event later than five (5) working 
days after the emergency occurred.  
12.14 COVID-19 Pandemic Considerations 
This clinical investigation has been designed with consideration given to the impact of 
COVID-19 on the safety of study participants, maintaining compliance with Good 
Clinical Practice (GCP) requirements and minimizing risks to study integrity. The 
design includes input from the HRS/ACC/AHA COVID-19 Task Force 
recommendations41 and the relevant FDA Guidelines.42, 43 
Specific areas of concern include availability of electrophysiology resources for 
non-urgent procedures, governmental limitations on travel or hospital utilization, 
hospital restrictions on procedures and personnel access, illness among study or site 
staff, provision of clinical, rhythm and/ or imaging assessment at locations other than 
the treating center, handling and reporting of protocol deviations, availability of 
investigational devices and analysis and reporting of COVID-19-related deviations and 
missing data. 
Should unforeseen circumstances occur, study-related decision making will prioritize in 
the following order: the safety of study participants, maintaining compliance with GCP 
requirements and minimizing risks to study integrity. 
 
 

 
 
13. Regulatory Considerations 
13.1 Maintaining Records 
The Sponsor and CRO will maintain copies of critical correspondence, regulatory 
approvals, Trial Master Files, clinical data, shipment of devices, AEs, SAEs, SADEs, 
UADEs and other records related to the clinical study.  
Trial records will be maintained for a minimum of 3 years following the completion of 
research activities and closure of the study with IRBs, whichever is longer. 
13.2  Data Handling and Record Keeping 
13.2.1 Source Documents 
The Investigator must maintain detailed source documents on all subjects who are 
enrolled or who undergo screening in the study. Source documents include but are not 
limited to, subject medical records, hospital charts, clinic charts, Investigator subject 
study files, as well as the results of diagnostic tests (e.g., laboratory tests, 
hemodynamic studies). 
The following minimum information should be entered into the subject’s medical 
record: 
• The date the subject entered the study and the subject number. 
• The CIP number and the name of the Sponsor. 
• The date that informed consent was obtained and signed by the subject and 
Investigator. 
• Evidence that the subject meets the study eligibility requirements (e.g., medical 
history, study procedures and/or evaluations). 
• The dates of all study related subject visits. 
• Evidence that required procedures and/or evaluations were completed. 
• Use of any concurrent medications. 
• Documentation of specific device used. 
• Occurrence and status of any AEs or SAEs 
• The date the subject exited the study and a notation as to whether the subject 
completed the study or was discontinued, including the reason for 
discontinuation. 
13.2.2 Data Collection 
The Investigator must maintain detailed records on all subjects who sign the ICF and 
begin the pre-procedure evaluation. Data for Enrolled Subjects are transcribed onto 
eCRFs provided by the Sponsor or designee. All data should be transcribed 
completely and promptly.  
Study exit eCRF will be completed for all Enrolled Subjects, regardless of whether 
they did or did not complete the study (e.g., subject discontinuation, study 
termination). The Sponsor and investigational site will maintain all records pertaining 
to this study in accordance with local and national regulations. Prior to the destruction 
of study records the Investigator or his representative shall contact the Sponsor to 

 
 
ensure that they no longer need to be retained. In addition, Sponsor shall be contacted 
if the Investigator plans to leave the investigational site so that arrangements can be 
made for the handling or transfer of study records. 
13.3 Institutional Review Board and FDA Approval 
Regulatory approvals must be obtained prior to enrollment of the first subject. The 
Sponsor is responsible for obtaining regulatory and local approvals for the study. The 
Sponsor or its designated representative will require a copy of any IRB and FDA 
correspondence as well as the final approval letter from the IRB. 
An Investigator may not make CIP changes without prior approval by the Sponsor. All 
significant CIP changes that may affect the following must be submitted and approved 
by the IRB and FDA before initiating the change: 
• Validity of the data or information resulting from the completion of the approved 
CIP 
• Relationship of the likely subject risk to benefit relied upon to approve the CIP 
• Scientific soundness of the CIP 
• Rights, safety, or welfare of the human subjects involved in the investigation 
The Sponsor will notify the investigational site of such changes to ensure the study 
continues to be conducted consistent with the approved CIP. 
13.4 Procedure for Amending the CIP 
The process of amending the CIP and/or related documents is the responsibility of the 
Sponsor. The procedure for amending the CIP shall be as follows: 
• The Sponsor, Investigator, or other relevant party (e.g., IRB, FDA, CEC, DSMB) 
may recommend modification of the CIP. 
• The Sponsor will then modify as necessary the CIP and any associated documents 
requiring amendment as a result of the modification(s). 
• The Sponsor or designated CRO will then submit the revised CIP and any other 
affected documents to the IRB and FDA for approval. 
• Once all required approvals are obtained, the site will be trained to the latest 
approved version of the CIP and any other affected documents. 
13.5 Device Accountability 
The Sponsor will only ship investigational devices to the site once evidence of required 
regulatory approval has been provided to the Sponsor or designee. 
The Investigator must keep complete, current and accurate records of the receipt, use, 
or disposition of investigational devices (21 CFR 812.140 (a)(2)). 

 
 
14. Bibliography 
 
1  
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