Prospective Evaluation of Open Irrigated Ablation Catheters With High Resolution Mapping to Treat Paroxysmal Atrial Fibrillation
Conditions: Paroxysmal Atrial Fibrillation
Sponsor: Boston Scientific Corporation

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PROSPECTIVE EVALUATION OF OPEN IRRIGATED ABLATION 
CATHETERS WITH HIGH RESOLUTION MAPPING TO TREAT 
PAROXYSMAL ATRIAL FIBRILLATION 
 
INTERRUPT AF - PM009 
CLINICAL INVESTIGATION PLAN 
 
Version B 
12 February 2019 
 
Sponsored By 
Boston Scientific Corporation  
4100 Hamline Ave. N. 
St. Paul, MN 55112 
 
and 
 
Guidant Europe SA / NV, 
a Boston Scientific Company 
 CRM Clinical Department  
Green Square 
Lambroekstraat 5D  
1831 Diegem,  
Belgium 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 

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Role 
Contact  
Clinical Contact 
Rami Guirguis 
Clinical Trial Manager 
Boston Scientific Corporation  
4100 Hamline Avenue North  
St. Paul, MN 55112-5798  
Tel. 1+ (919) 374-3388 
Rami.Guirguis@bsci.com 
 
Sarfaraz Taher 
Director, Clinical Trials, Electrophysiology 
Boston Scientific Corporation  
4100 Hamline Avenue North  
St. Paul, MN 55112-5798  
Tel: +1 (651) 582-5320 
Sarfaraz.Taher@bsci.com 
 
Coordinating Principal 
Investigator(s) 
Oussama M Wazni, MD 
Cleveland Clinic Foundation  
9500 Euclid Avenue 
Desk J2-2 
Cleveland, OH 44195 
216-444-2131 Office 
216-445-6195 Fax 
waznio@ccf.org  
 
Vendors/Labs 
A list of vendors/laboratories involved in the trial is maintained by the 
sponsor.  
 
 
 
 

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Original Release: 01-NOV-2018 
Current Version: B 
 
Protocol Version 
B 
Protocol Date 
12FEB2019 
Template number and version 
92120219 Ver B 
Protocol 
Section 
Modified 
Existing Text as Written in 
Protocol, Version 
Revised/New Text as 
Written in Protocol, Version 
Justification for 
Modification 
Clinical 
Contact 
Micki Weisman 
REMOVED 
Update of current clinical 
contacts. 
5.1 Reporting 
Timelines, 
Table 2 
 
 
Dates corrected to reflect 
due dates based on FDA 
approval of the initial 
Protocol 
8.5 – Data 
Requirements 
Procedure and fluoroscopy 
times (first catheter inserted 
to ablation catheter removed) 
Total Procedure times (first 
catheter inserted to last 
catheter removed). 
Total Fluoroscopy Time 
Correct Definition of 
when procedure ends. 
Separation of Procedure 
time from Fluoro Time 
 
 
 

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1. Protocol Synopsis 
PROSPECTIVE EVALUATION OF OPEN IRRIGATED ABLATION CATHETERS 
WITH HIGH RESOLUTION MAPPING TO TREAT PAROXYSMAL ATRIAL 
FIBRILLATION 
INTERRUPT AF 
Study 
Objective(s) 
To obtain data for the Rhythmia™ Mapping System in conjunction with 
Boston Scientific Open-Irrigated (OI) Catheters for ablation of Paroxysmal 
Atrial Fibrillation (PAF) according to current international and local 
guidelines. 
Primary objective: To assess acute and long-term outcomes for the 
Rhythmia Mapping System in conjunction with Boston Scientific Open-
Irrigated Ablation Catheters to treat de novo Paroxysmal Atrial Fibrillation.   
De Novo PAF is defined as subjects undergoing first ablation procedure for 
PAF with no prior left atrial ablation (RF, Cryo, Surgical). 
Indication(s) 
for Use  
Study devices will be used per approved Indications for Use for each 
geography.  
Devices / 
System used 
in the study 
The study will include the following Boston Scientific Open-Irrigated 
Catheters in geographies where commercially approved for PAF ablation:  
• Blazer Open-Irrigated Ablation Catheter 
• IntellaNav Open-Irrigated Ablation Catheter 
• IntellaNav MiFi Open-Irrigated Ablation Catheter 
• IntellaTip MiFi Open-Irrigated Ablation Catheter 
• Rhythmia Mapping System Gen 1or Rhythmia HDx, equipped with 
Software 1.4 or any successive commercially approved versions. 
• IntellaMap Orion Catheter 
Control 
Device  
There are no control devices in this study 
 
 

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Study 
Design 
Prospective, non-randomized, multicenter (global), post approval clinical 
study (PAS). 
All subjects fitting the enrollment criteria, signing the consent and undergoing 
the index procedure with the study devices will be followed up for three years 
to complete the PAS design mandated from the FDA to collect post-market 
data for Boston Scientific Open-Irrigated Catheters and will be followed for 
three years. 
 
 
INTERRUPT AF Study Design 
Planned 
Number of 
Subjects 
The study will enroll 415 subjects. 
Planned 
Number of 
Sites / 
Countries 
The study is global (US, EU, Asia-Pacific) with 25-50 centers. A minimum 
of 50% of the sites will be selected from the US.  
No study site will be allowed to contribute more than 41 subjects (10% of 
the 415 enrollments requirement). 
 
 

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Primary Safety 
Endpoint 
The primary safety endpoint is defined as the safety event-free rate at 12 
months post-procedure.  
Primary safety events will consist of a composite of acute primary safety 
events (events occurring within seven days post-procedure or hospital 
discharge, whichever is later), and chronic primary safety events (events 
occurring through 3 or 12 months post-procedure). 
Acute primary safety endpoint events will be defined as the following: 
• 
Death 
• 
Myocardial infarction (MI) 
• 
Vagal Nerve Injury/Gastroparesis  
• 
Transient ischemic attack (TIA) 
• 
Stroke/Cerebrovascular accident (CVA) 
• 
Thromboembolism 
• 
Pericarditis 
• 
Cardiac tamponade/perforation 
• 
Pneumothorax 
• 
Vascular access complications 
• 
Pulmonary edema/heart failure 
• 
AV block 
 
Chronic primary safety endpoint events will be defined as the following: 
• 
Occurring through 3 Months post-procedure 
• 
Atrial esophageal fistula 
• 
Pericardial effusion 
 
• 
Occurring through 12 Months post-procedure 
• 
Pulmonary vein stenosis (symptomatic and requiring 
intervention) 
 
Primary 
Effectiveness 
Endpoint 
The primary effectiveness endpoint is defined as the event-free rate at 12 
months post-procedure. 
Primary effectiveness events are defined as: 
• 
Acute procedural failure 
• 
More than one repeat procedure during the blanking period 
(90 days post index procedure) 
• 
Documented atrial fibrillation, or new onset of atrial flutter or 
atrial tachycardia event (≥ 30 seconds in duration from an 
event monitor or Holter, or from a 10 second 12-lead EKG) 
between 91 days and 365 days post index procedure 
• 
Any of the following interventions for atrial fibrillation, or 
new onset of atrial flutter or atrial tachycardia between 91 
days and 365 days post index procedure: 
• 
Repeat procedure 
• 
Cardioversion 

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• 
Prescribed any AAD*  
*AADs for endpoint will consist of all Class I/III and any Class 
II/IV medications taken for control of AF/AT/AFL recurrence  
Secondary 
Effectiveness 
Endpoint 
The secondary effectiveness endpoint is defined as the event-free at 12 
months post-procedure. 
Secondary effectiveness events are defined as: 
• 
Acute procedural failure 
• 
More than one repeat procedure during the blanking period 
(90 days post index procedure) 
• 
Documented symptomatic atrial fibrillation, or new onset of 
atrial flutter or atrial tachycardia event (≥ 30 seconds in 
duration from an event monitor or Holter, or from a 10 second 
12-lead EKG) between 91 days and 365 days post index 
procedure 
• 
Any of the following interventions for atrial fibrillation, or 
new onset of atrial flutter or atrial tachycardia between 91 
days and 365 days post index procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed a higher dose of any AAD* documented at 
baseline 
• 
Prescribed a new AAD* not documented at baseline  
*AADs for endpoint will consist of all Class I/III and any Class 
II/IV medications taken for control of AF/AT/AFL recurrence 
 
 

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Tertiary 
Endpoint 
Chronic effectiveness: Evaluation of recurrence at 24 months and 36 months  
• 
Recurrence is defined as intervention for atrial fibrillation, or new onset 
of atrial flutter or atrial tachycardia (repeat procedures, use of AADs, 
cardioversion), excluding repeat procedures during the 90-day blanking 
period.   
• 
Data collection to include the diagnostic modality used to identify 
recurrence and the therapeutic intervention 
• 
Chronic effectiveness will be evaluated using Kaplan-Meier 
methodology. The Kaplan-Meier 24 month and 36 month chronic 
recurrence-free rate will be calculated and presented along with the 95% 
confidence interval, calculated as the pointwise confidence limit using 
the log-log methodology Subjects who withdraw from the study prior to 
the specified time point without experiencing an event will be censored 
on the date of withdrawal.   
Center Experience: Primary Safety and Primary Effectiveness outcomes by 
center experience 
• In order to evaluate training effectiveness for investigators outside of the 
ZERO AF IDE study, outcomes in centers performing five or more 
procedures using the Blazer OI catheter during the ZERO AF IDE study 
will be compared to all other centers in the study. Kaplan-Meier rates and 
95% confidence intervals for the Primary Safety and Effectiveness 
endpoints for both groups will be presented with no statistical 
comparison. 
 
Safety:  Reportable Adverse Events rates at 12, 24 and 36 months. 
Adverse events will be collected at all subject follow-up visits. 
Reportable events include: 
• All Serious Adverse Events 
• All Study Procedure-Related Adverse Events 
• All Study Device-Related Adverse Events 
• All Study Device Deficiencies  
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse 
Device Effects previously not defined in the Directions For Use. 
 
Adverse event rates will be calculated using binomial methodology. The 
cumulative number of events and event rate will be included in all study reports. 
Subjects at risk for an adverse event will be determined by the subject treatment 
status; all treatment and attempt subjects will be considered at risk for study 
related adverse events 
 
Effectiveness: Acute procedural Success Rate. 

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Acute Procedural Success is defined as pulmonary vein isolation achieved with a 
Boston Scientific OI ablation catheter as demonstrated by map-based entrance 
block with exit block and other maneuvers (such as adenosine testing) at the 
discretion of the physician. 
Method of 
Assigning 
Patients to 
Treatment 
Any subject that signs the consent form, meets eligibility criteria, has any of the 
specified study devices inserted into the body and successfully completes protocol 
specific treatment for the intended disease will be assigned to the treatment group. 
Follow-up 
Schedule 
Study Follow-ups are at: pre-discharge, 1 month (phone check), 3 months 
(blanking period), 6 months (phone check), 12 months, 24 months and 36 
months. 

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Data collection overview 
Data 
Collected 
 ENROLLMENT/ BASELINE 
 INDEX PROCEDURE 
 (Day 0) 
 PRE-DISCHARGE   
 (0-7 days  post -procedure)   
 1-MONTH FOLLOW-UP     
 (30±7 days) 
 3-MONTH FOLLOW-UP     
 (90±30 days) 
 6-MONTH FOLLOW-UP   
 (180±30 days) 
 12-MONTH FOLLOW-UP     
 (365± 30 days) 
 24  MONTH FOLLOW-UP   
 (730 ± 30 days) 
 36 MONTH FOLLOW-UP   
 (1095 ± 30 days) 
 ADDITIONAL FOLLOW-UP 
 REPEAT PROCEDURE 
Informed 
Consent  
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
Exclusion  
X 
 
 
 
 
 
 
 
 
 
 
Demographic 
data 
X 
 
 
 
 
 
 
 
 
 
 
Medical 
History  
X 
 
 
 
 
 
 
 
 
 
 
Vitals 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
Pre-Procedure 
Assessment 
X 
 
 
 
 
 
 
 
 
 
 
Imaging  
Xa 
 
Xa 
 
Xa 
 
Xa 
 
 
Xa 
Xb 
Medication 
Regimen 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Procedure data 
 
X 
 
 
 
 
 
 
 
 
X 
EQ-5D 
X 
 
 
 
X 
X 
X 
 
 
 
 
AFEQT 
X 
 
 
 
X 
X 
X 
 
 
 
 
12-Lead EKG 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
Event Monitor 
 
 
 
 
X 
X 
X 
 
 
Xc 
 
Holter Monitor 
 
 
 
 
 
 
X 
 
X 
 
 
Documentation 
of Intervention 
for 
AF/AT/AFL 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Protocol 
Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse 
Event/Device 
Deficiency 
Reporting 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
a: If Pulmonary Vein Stenosis suspected or per center standard of care 
b: Required for repeat procedures with non-study catheters only 
c: If completed before the 12-month follow-up visit 

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Study 
Duration 
Study is expected to be completed in approximately five years (12-24 month 
enrollment period with three year follow-up). 
Participant 
Duration 
The study duration for each subject is expected to be approximately three years. 
Inclusion 
Criteria 
1. History of recurrent symptomatic Paroxysmal Atrial Fibrillation, defined as 
AFib that terminates spontaneously or with intervention within seven days of 
onset. Minimum documentation includes a physician’s note indicating 
recurrent 
self-terminating 
Atrial 
Fibrillation 
AND 
one 
electrocardiographically documented AF episode within 6 months prior to 
enrollment. 
2. Subjects who are eligible for an ablation procedure for Paroxysmal Atrial 
Fibrillation with the Rhythmia Mapping system according to current 
international and local guidelines 
3. Subjects who are eligible for an ablation procedure for Paroxysmal Atrial 
Fibrillation with a Boston Scientific Open-Irrigated Ablation Catheter 
according to current international and local guidelines 
4. Subjects who are willing and capable of providing informed consent  
5. Subjects who are willing and capable of participating in all testing associated 
with this clinical investigation at an approved clinical investigational center 
6. Subjects whose age is 20 years or above, or who are of legal age to give 
informed consent specific to state and national law. 
Exclusion 
Criteria 
1. Subjects enrolled in any other concurrent clinical study, with the exception 
of 
local 
mandatory 
governmental 
registries 
and 
observational 
studies/registries, without the written approval from Boston Scientific  
2. Subjects unable or unwilling to complete follow-up visits and examination 
for the duration of the study 
3. Subjects who have undergone any previous left atrial cardiac ablation (RF, 
Cryo, surgical) 
4. Subjects who have undergone any cardiac ablation within 30 days prior to 
enrollment  
5. Unrecovered/unresolved Adverse Events from any previous invasive 
procedure 
6. Life expectancy <= three years per physician opinion  
7. Women of childbearing potential who are, or plan to become, pregnant during 
the time of the study (method of assessment upon physician’s discretion) 
8. Known cardiac thrombus within 60 days prior to enrollment 
9. History of CVA, TIA or PE within 90 days prior to enrollment 
10. Implanted pacemaker, ICD, or CRT leads within 90 days prior to enrollment 
11. Implanted Left atrial appendage closure device prior to the index procedure 
12. Prosthetic mitral or tricuspid heart valves (subjects with successful mitral 
valve repair allowed- annular ring constitutes repair) 
13. Left atrial diameter greater than 5.5cm 

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14. Documented or suspected stenosis of any pulmonary veins. 
15. Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or 
reversible or non-cardiac cause. 
16. Contraindication for anticoagulation  
17. Clinically significant mitral valve regurgitation or stenosis per investigator 
discretion. 
18. Any cardiac surgery ≤ 90 days from consent date. 
19. Any electrocardiographically documented episode of Persistent AFib, 
defined as AFib lasting longer than 7 days from onset. 
Statistical Methods  
Primary 
Statistical 
Hypotheses 
and 
Statistical 
Test 
Methods 
Endpoint 
Hypothesis 
Analysis Method 
Primary Safety 
Endpoint 
The primary safety endpoint 
event-free rate at 12 months 
post-procedure >85% 
Kaplan-Meier rate with pointwise 
log-log confidence limit 
Primary 
Effectiveness 
Endpoint  
The primary effectiveness 
event-free rate at 12 months 
post-procedure >50% 
Kaplan-Meier rate with pointwise 
log-log confidence limit 
Secondary 
Effectiveness 
Endpoint  
The secondary effectiveness 
event-free rate at 12 months 
post-procedure >50% 
Kaplan-Meier rate with pointwise 
log-log confidence limit 
Sample 
Size 
Parameters 
The sample size for the study is driven by the primary safety endpoint which 
requires a minimum sample size of 329 TREATMENT subjects.  The sample size 
estimate was obtained using the normal approximation to the binomial 
distribution and verified through simulations based on Kaplan-Meier 
methodology. The following assumptions were used in the sample size 
calculation: 
Assumptions 
Primary Safety 
Expected rate 
90% 
Performance goal 
85% 
Attrition (per year) 
7.5% 
Significance level  (one-sided) 
5% 
Power 
80% 

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Table of Contents 
1. 
PROTOCOL SYNOPSIS .........................................................................................................4 
2. 
INTRODUCTION.................................................................................................................18 
2.1. Background ............................................................................................................18 
2.2. Study Rationale .....................................................................................................19 
3. 
DEVICE DESCRIPTION ......................................................................................................19 
3.1. Open-Irrigated Ablation Catheters .....................................................................19 
3.2. Rhythmia Mapping System ..................................................................................20 
3.3. IntellaMap Orion High Resolution Mapping Catheter .....................................20 
4. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................21 
4.1. Primary Safety Endpoint ......................................................................................21 
4.2. Primary Effectiveness Endpoint ..........................................................................23 
4.3. Secondary Effectiveness Endpoint.......................................................................23 
4.4. Tertiary Endpoints ................................................................................................24 
5. 
STUDY DESIGN .................................................................................................................25 
5.1. Scale and Duration ................................................................................................25 
5.2. Treatment Assignment ..........................................................................................27 
5.3. Justification for the Study Design ........................................................................27 
6. 
SUBJECT SELECTION ........................................................................................................27 
6.1. Study Population and Eligibility ..........................................................................27 
6.2. Inclusion Criteria ..................................................................................................28 
6.3. Exclusion Criteria .................................................................................................28 
7. 
SUBJECT ACCOUNTABILITY .............................................................................................29 
7.1. Point of Enrollment ...............................................................................................29 
7.2. Withdrawal ............................................................................................................30 
7.3. Subject Status and Classification .........................................................................30 
7.4. End-of-Study Definition........................................................................................31 
8. 
STUDY METHODS .............................................................................................................31 
8.1. Data Collection ......................................................................................................31 
8.2. Study Candidate Screening ..................................................................................33 

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8.3. Informed Consent..................................................................................................33 
8.4. Enrollment/Baseline Visit .....................................................................................33 
 
Medications ...............................................................................................34 
 
Anti-Arrhythmic Drugs ............................................................................34 
 
Anticoagulation .........................................................................................34 
8.5. Ablation (index) procedure ..................................................................................35 
8.6. Pre-Discharge Follow-up ......................................................................................37 
8.7. One-Month Follow-up (Phone Check) ................................................................37 
8.8. Three-Month Follow-up .......................................................................................37 
8.9. Six-Month Follow-up (Phone Check) ..................................................................38 
8.10. 12-Month Follow-up..............................................................................................38 
8.11. 24-Month Follow-up..............................................................................................39 
8.12. 36 Month Follow-up ..............................................................................................39 
8.13. Additional Follow-up Visits ..................................................................................40 
8.14. Repeat Ablation Procedure ..................................................................................40 
8.15. Study Completion ..................................................................................................40 
8.16. Source Documents .................................................................................................41 
9. 
STATISTICAL CONSIDERATIONS ......................................................................................41 
9.1. Endpoints ...............................................................................................................41 
 
Primary Safety Endpoint ...........................................................................42 
9.1.1.1. 
Hypotheses ...............................................................................42 
9.1.1.2. 
Sample Size ..............................................................................43 
9.1.1.3. 
Statistical Methods ...................................................................43 
 
Primary Effectiveness Endpoint ...............................................................43 
9.1.2.1. 
Hypotheses ...............................................................................44 
9.1.2.2. 
Sample Size ..............................................................................44 
9.1.2.3. 
Statistical Methods ...................................................................44 
 
Secondary Effectiveness Endpoint ...........................................................44 
9.1.3.1. 
Hypotheses ...............................................................................45 
9.1.3.2. 
Sample Size ..............................................................................45 
9.1.3.3. 
Statistical Methods ...................................................................45 
 
Tertiary Endpoint ......................................................................................46 
 
Total sample size ......................................................................................47 
9.2. General Statistical Methods .................................................................................47 
 
Analysis Sets .............................................................................................47 
 
Control of Systematic Error/Bias ..............................................................47 

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Study Success and Control of Type I Error ..............................................47 
 
Number of Subjects per Investigative Site ...............................................47 
9.3. Data Analyses ........................................................................................................47 
 
Interim Analyses and Progress Report Content ........................................47 
 
Subgroup Analyses ...................................................................................48 
 
Center Pooling Analysis ...........................................................................48 
 
Catheter Type Pooling Analysis ...............................................................48 
 
Additional Analyses ..................................................................................49 
 
Changes to Planned Analyses ...................................................................49 
10. DATA MANAGEMENT .......................................................................................................49 
10.1. Data Collection, Processing, and Review ............................................................49 
10.2. Data Retention .......................................................................................................50 
10.3. Technical Source Forms .......................................................................................50 
10.4. Core Laboratories .................................................................................................50 
 Event Monitor and 24-Hour Holter Monitors ...........................................50 
10.4.1.1. Event Monitor ..........................................................................50 
10.4.1.2. 24-Hour Holter Monitors .........................................................51 
11. DEVIATIONS......................................................................................................................51 
12. COMPLIANCE ....................................................................................................................51 
12.1. Statement of Compliance ......................................................................................51 
12.2. Investigator Responsibilities ................................................................................52 
 Delegation of Responsibility ....................................................................53 
12.3. Institutional Review Board/ Ethics Committee ..................................................53 
12.4. Sponsor Responsibilities .......................................................................................54 
 Role of Boston Scientific Representatives ...............................................54 
12.5. Insurance ................................................................................................................55 
13. MONITORING ....................................................................................................................55 
14. POTENTIAL RISKS AND BENEFITS ...................................................................................56 
14.1. Directions for Use ..................................................................................................56 
14.2. Risks associated with Participation in the Clinical Study .................................56 
14.3. Risk Minimization Actions ...................................................................................56 
14.4. Anticipated Benefits ..............................................................................................56 
14.5. Risk to Benefit Rationale, if applicable ...............................................................56 

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15. SAFETY REPORTING .........................................................................................................56 
15.1. Reportable Events by investigational site to Boston Scientific .........................56 
15.2. Definitions and Classification...............................................................................57 
15.3. Relationship to Device(s) ......................................................................................59 
15.4. Investigator Reporting Requirements .................................................................62 
15.5. Boston Scientific Device Deficiencies ...................................................................63 
15.6. Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators .......63 
15.7. Subject Death Reporting ......................................................................................64 
16. INFORMED CONSENT ........................................................................................................65 
17. COMMITTEES ...................................................................................................................66 
17.1. Safety Monitoring Process ....................................................................................66 
17.2. Steering Committee ...............................................................................................66 
18. SUSPENSION OR TERMINATION........................................................................................67 
18.1. Premature Termination of the Study ..................................................................67 
18.2. Criteria for Premature Termination of the Study .............................................67 
18.3. Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC/REB Approval .......................................................................................67 
18.4. Requirements for Documentation and Subject Follow-up ................................67 
18.5. Criteria for Suspending/Terminating a Study Site ............................................68 
19. CLINICAL TRIAL REGISTRATION AND RESULTS POSTING .............................................68 
20. PUBLICATION POLICY ......................................................................................................68 
21. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .................................................69 
21.1. Compensation for Subject’s Health Injury.........................................................69 
22. BIBLIOGRAPHY .................................................................................................................69 
23. ABBREVIATIONS AND DEFINITIONS .................................................................................72 
23.1. Abbreviations.........................................................................................................72 
23.2. Definitions ..............................................................................................................72 
24. APPENDICES .....................................................................................................................76 
24.1. Quality of Life Instruments ..................................................................................76 
24.2. Clinical Trial Organization ..................................................................................76 

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Table of Figures 
Figure 5.2-1: INTERRUPT AF Study Design ........................................................................ 26 
 
Table of Tables 
Table 1: Primary Safety Endpoint Definitions ........................................................................ 21 
Table 2: INTERRUPT AF Study Timeline ............................................................................ 26 
Table 3: Inclusion Criteria ...................................................................................................... 28 
Table 4: Exclusion Criteria ..................................................................................................... 29 
Table 5: Data Collection Schedule ......................................................................................... 32 
Table 6: Source Documentation Requirements ...................................................................... 41 
Table 7: Safety Definitions ..................................................................................................... 57 
Table 8: Criteria for Assessing Relationship of Study Device or Procedure to Adverse Event
 ............................................................................................................................. 60 
Table 9: Event Communication Requirements ....................................................................... 62 
Table 10: Abbreviations .......................................................................................................... 72 
Table 11: Definitions .............................................................................................................. 72 
 

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2. Introduction 
2.1. Background 
Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting approximately 2.5 
million people in North America, 4.5 million people in Europe and estimated to affect a total 
of 33.5 million people worldwide1-4. The prevalence and incidence of AF are increasing over 
time due to the aging of the population and a substantial increase in the age-specific occurrence 
of AF3-5.   
 
Mortality risk is 1.5 to 2-fold greater for AF patients after accounting for other factors,  with 
AF accounting for approximately 15 percent of all strokes in the US2,6. In addition, atrial 
fibrillation significantly impairs quality of life, with up to two-thirds of patients reporting that 
it is disruptive to their lives7,8.    
 
Paroxysmal Atrial Fibrillation (PAF) is defined as atrial fibrillation which terminates 
spontaneously or with intervention within seven days of onset; this AF  type comprises between 
25% and 62% of cases2,9.  Patients with PAF may exhibit symptoms including palpitations, 
shortness of breath, syncope, fatigue, and lightheadedness, and have serious adverse effects 
such as hemodynamic compromise, embolic stroke, myocardial ischemia or infarction.  
However, PAF  may also present without symptoms while it retains the same risk of thrombus 
formation with embolic potential10.   
 
Treatment options for AF include medical management, cardioversion, implantable devices, 
surgery, and ablation therapy to eliminate the arrhythmia2,3,11.  The approach to therapy for AF 
has evolved due to an altered view of the pathophysiology of this condition.  While previous 
models of treatment focused on the importance of multiple re-entrant wavelets throughout the 
atria to sustain the arrhythmia, it has been increasingly recognized that focal pulmonary vein 
triggers can account for 80 to 95 percent of paroxysmal AF cases that are drug resistant.  The 
principal objective of AF ablation is the electrical disconnection of the pulmonary vein triggers 
from the atrial substrate which is referred to as pulmonary vein isolation (PVI).  To achieve 
this clinical effect, ablation is performed around the pulmonary vein (PV) orifice on the PV 
antrum12-16.  
 
Several technologies have been developed to date to support PVI ablation with radiofrequency 
(RF) ablation, including the Open Irrigated cooling method, currently available among 
different single point ablation catheters 17-19. Open Irrigated catheters have important 
advantages in RF ablation, as surface cooling during energy delivery reduces heating at the 
point of highest current density where excessive temperatures would normally produce 
charring, crater formation and impedance rises. Thus, higher levels of energy can be delivered 
safely using cooled tip ablation with more reliable delivery of radiofrequency current to the 
tissue18. 
 
The introduction of three-dimensional electro-anatomical mapping systems (EMS) also 
represented an important development in contemporary cardiac electrophysiology20. Electro-
anatomical mapping systems are widely used in PVI to facilitate ablation by integrating 

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functional and anatomical information allowing substrate characterization and individual 
ablation strategies, and also facilitating the tracking of intracardiac electrodes and the 
navigation of catheters during PVI21. More recently ultra-high resolution EMS are also 
specifically used to better characterize and confirm isolation of the pulmonary veins 22.   
2.2. Study Rationale 
The Rhythmia Mapping System’s ability to produce high density maps enables for gap 
detection that is critical for de novo PAF procedures.  Utilizing a Rhythmia map-based 
validation workflow targets the gaps that inherently lead to recurrence following de novo PAF 
ablation.  This study aims to demonstrate the efficacy of this Rhythmia map-based workflow 
by evaluating acute and long-term safety and effectiveness outcomes. 
In December 2017, the Center for Devices and Radiological Health (CDRH) of the Food and 
Drug Administration (FDA) approved a new indication for the Boston Scientific Blazer Open-
Irrigated Ablation Catheter and IntellaNav Open-Irrigated Ablation Catheter to include 
treatment of drug refractory, recurrent, symptomatic, paroxysmal atrial fibrillation 
(P150005/S014). This post-approval study (PAS) has been designed to comply with the request 
of providing continued reasonable assurance of the safety and effectiveness of the approved 
device, by evaluating the short (peri-procedural and one-year) and longer-term (through three 
years) safety and effectiveness of the Boston Scientific Open-Irrigated catheters for de novo 
atrial fibrillation ablation procedures.  
In addition, Boston Scientific has added to this PAS protocol the IntellaTip MiFi Open-
Irrigated Ablation Catheter and IntellaNav MiFi Open-Irrigated Ablation Catheter under 
review for P150005/S035 for the expanded indication of PAF that is identical to the indication 
of P150005/S014. 
3. Device Description  
3.1. Open-Irrigated Ablation Catheters 
The study will include the following Boston Scientific Open-Irrigated Catheters in 
geographies where commercially approved for PAF ablation:  
• Blazer Open-Irrigated Ablation Catheter (Blazer OI)  
• IntellaNav Open-Irrigated Ablation Catheter (IntellaNav OI) 
• IntellaNav MiFi Open-Irrigated Ablation Catheter (IntellaNav MiFi OI) 
• IntellaTip MiFi Open-Irrigated Ablation Catheter (IntellaTip MiFi OI) 
 
The BSC Open-Irrigated catheters are designed to deliver RF energy to catheter tip electrode 
for cardiac ablation.  The BSC OI catheters incorporate an open-irrigated cooling mechanism 
through a tip that is partitioned into two chambers. The proximal chamber circulates normal 
saline (0.9 %) within the tip to cool the proximal electrode and mitigate overheating while the 
distal chamber allows the fluid to flow through six irrigation holes into the patient’s 
vasculature, thereby cooling the tip/tissue interface. A luer connection at the proximal end of 

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the handle connects the catheter to an Irrigation Tubing Set, allowing an Irrigation Pump to 
generate the flow of saline to the catheter. 
The electrode segment of the catheters is comprised of a tip electrode and three ring electrodes. 
The tip electrode of all the BSC OI catheters has an embedded temperature sensor and delivers 
RF energy for cardiac ablation.  Additionally, the IntellaTip MiFi OI and the IntellaNav MiFi 
OI include three mini-electrodes in the catheter tip to provide high-resolution electrograms 
(EGM) and the IntellaNav OI and the IntellaNav MiFi OI catheters include a position sensor 
for magnetic tracking and navigation of the catheter on a Rhythmia Mapping System. The ring 
electrodes record EGM signals for mapping and deliver stimulus for pacing. The catheters 
interface with standard RF generators through the Rhythmia Connection Box. The catheter 
handle includes the electrical connector for the cable connection to the Connection Box and 
one luer fitting used to connect the catheter to the Irrigation Tubing Set. 
3.2. Rhythmia Mapping System 
The RhythmiaTM Mapping System, the Rhythmia HDx Mapping System, and the IntellaMap 
OrionTM mapping catheter are designed for electroanatomical mapping in catheter ablation 
procedures. The Rhythmia Mapping System tracks catheters inside the heart in order to 
visualize their location and construct geometric shells.  The Rhythmia Mapping System is also 
capable of using intra-cardiac location and electrical information to display electroanatomical 
maps - electrical activity information on the constructed geometry.  Such electrical information 
can be visualized in 3D and in color. The commercially available system operates the latest 
commercially-available software (version 1.4 or newer). Rhythmia HDx equipped with 
software version 2.0 may include the DirectSense feature. This feature allows for an 
impedance-based metric that can be used in conjunction with other clinical diagnostic 
measures (e.g., electrogram amplitude, fluoroscopy, intracardiac echocardiography, magnetic 
and impedance navigation, and tactile feedback) to inform catheter stability and navigation 
within the heart. 
Subsequent versions of the Rhythmia Mapping System (including but not limited to the already 
commercially released upgrade, the Rhythmia HDx) and software may be used during this 
study as they become commercially available after regulatory approval in their geography. 
3.3. IntellaMap Orion High Resolution Mapping Catheter 
The IntellaMap Orion High Resolution Mapping Catheter is an 8.5F, 115 cm working length, 
64-electrode steerable catheter. The basket-shaped distal region consists of eight splines that 
comprise the electrode array. The proximal end has a handle that extends to a cable with a 
connector. The handle includes bi-directional articulation controls and a deployment slider that 
activates the electrode array into a basket shape once inside the heart. A flushing port extends 
from the back of the connector for connection to a continuous pressurized saline drip. The 
catheter is supplied with an 8.5F insertion sleeve for insertion through the hemostasis valve of 
an introducer sheath. A sensor in the catheter tip enables the position of the distal region of the 
catheter to be tracked in space when used with the Rhythmia™ Mapping System.  Subsequent 
versions of the IntellaMap Orion mapping catheter may be used during this study as they 
become commercially available after regulatory approval in their geography. 

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4. Study Objectives and Endpoints 
The purpose of the INTERRUPT AF study is to obtain data for the Rhythmia™ Mapping 
System in conjunction with Boston Scientific Open-Irrigated (OI) Catheters for ablation of 
Paroxysmal Atrial Fibrillation according to current international and local guidelines.   
The primary objective of the study is to assess acute and long-term outcomes for the Rhythmia 
Mapping System in conjunction with Boston Scientific Open-Irrigated Ablation Catheters to 
treat Paroxysmal Atrial Fibrillation for de novo cases.  In addition, the study serves to comply 
with the FDA request of a PAS for the Blazer OI, IntellaNav OI, IntellaTip MiFi OI, and 
IntellaNav MiFi OI Ablation catheters.   
4.1. Primary Safety Endpoint 
The primary safety endpoint is defined as the safety event-free rate at 12 months post-
procedure. 
Primary safety events will consist of a composite of acute primary safety events, (events 
occurring within seven days post-procedure or hospital discharge, whichever is later), and 
chronic primary safety events (events occurring through 3 or 12 months post-procedure). 
Acute primary safety endpoint events will be defined as the following: 
• 
Death 
• 
Myocardial infarction (MI) 
• 
Vagal Nerve Injury/Gastroparesis  
• 
Transient ischemic attack (TIA) 
• 
Stroke/Cerebrovascular accident (CVA) 
• 
Thromboembolism 
• 
Pericarditis 
• 
Cardiac tamponade/perforation 
• 
Pneumothorax 
• 
Vascular access complications 
• 
Pulmonary edema/heart failure 
• 
AV block 
 
Chronic primary safety endpoint events will be defined as the following: 
• 
Occurring through 3 Months post-procedure 
• 
Atrial esophageal fistula 
• 
Pericardial effusion 
 
• 
Occurring through 12 Months post-procedure 
• 
Pulmonary vein stenosis (symptomatic and requiring intervention) 
 
Table 1: Primary Safety Endpoint Definitions 
Term 
Definition 
Atrio-Esophageal Fistula 
A connection between the atrium and the lumen of the esophagus 

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Table 1: Primary Safety Endpoint Definitions 
Term 
Definition 
AV block 
A conduction disturbance that results in the partial inability of an electrical 
impulse generated in the atria to reach the ventricles. 
Cardiac tamponade/ 
Perforation 
 
The development of a significant pericardial effusion during or within 30 
days of undergoing an AF ablation procedure. A significant pericardial 
effusion is one that results in hemodynamic compromise, requires elective 
or urgent pericardiocentesis, or results in a 1-cm or more pericardial 
effusion as documented by echocardiography. 27  
Myocardial infarction (in 
the context of AF 
ablation)  
The presence of any one of the following criteria:  
(1) detection of ECG changes indicative of new ischemia (new STT 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. 27 
Pericardial Effusion 
A collection of fluid or blood in the pericardial space around the heart or in 
pleural space around the lungs. 27 
Pericarditis 
Inflammation of the pericardium surrounding the heart.  Pericarditis should 
be considered a major complication following ablation if it 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. 27 
Pneumothorax 
Collapse of the lung due to an abrupt change in the intrapleural pressure 
within the chest cavity. 
Pulmonary edema/heart failure 
Ineffective pumping of the heart leading to an accumulation of fluid in the 
lungs. Typical symptoms include shortness of breath with exertion, 
difficulty breathing when lying flat and leg or ankle swelling. 
Pulmonary Vein Stenosis 
(Significant) 
Pulmonary vein stenosis is defined as a reduction of the diameter of a PV 
or PV branch. For the primary safety endpoint of this study, significant 
pulmonary vein stenosis is defined as symptomatic and requiring 
intervention. 
Stroke/Cerebrovascular accident 
(CVA)  
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 one side of the body, dysphasia 
or aphasia, hemianopia, amaurosis fugax, or other neurological signs or 
symptoms consistent with stroke. 
Duration of a focal or global neurological deficit ≥24 hours; OR <24 hours 
if therapeutic intervention(s) were performed (e.g., thrombolytic therapy or 
intracranial angioplasty); OR available neuroimaging documents a new 
hemorrhage or infarct; OR the neurological deficit results in death. 
No other readily identifiable non-stroke cause for the clinical presentation 
(e.g., brain tumor, trauma, infection, hypoglycemia, peripheral lesion, 
pharmacological influences). 
Confirmation of the diagnosis by at least one of the following: neurology 
or neurosurgical specialist; neuroimaging procedure (MRI or CT scan or 
cerebral angiography); lumbar puncture (i.e., spinal fluid analysis 
diagnostic of intracranial hemorrhage) 27 
Thromboembolism 
The blockage of a blood vessel lumen by air or solid material such as 
device fragments, blood clot or other tissues that have migrated from 
another anatomic site. 

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Table 1: Primary Safety Endpoint Definitions 
Term 
Definition 
Transient Ischemic Attack (TIA)  
New focal neurological deficit with rapid symptom resolution (usually 1 to 
2 hours), always within 24 hours; neuroimaging without tissue injury. 27 
Vagal Nerve 
Injury/Gastroparesis 
Vagal nerve injury is defined as injury to the vagal nerve that results in 
esophageal dysmotility or gastroparesis.  Vagal nerve injury is considered 
to be a major complication if it prolongs hospitalization, requires 
hospitalization, or results in ongoing symptoms for more than 30 days 
following an ablation procedure. 27 
Vascular access complications 
Development of a hematoma, an AV fistula, or a pseudoaneurysm. A 
major vascular complication is defined as one that requires intervention, 
such as surgical repair or transfusion, prolongs the hospital stay, or 
requires hospital admission. 27 
 
 
4.2. Primary Effectiveness Endpoint 
The primary effectiveness endpoint is defined as the event-free rate at 12 months post-
procedure. 
 
Primary effectiveness events are defined as: 
• 
Acute procedural failure 
• 
More than one repeat procedure during the blanking period (90 days post index 
procedure) 
• 
Documented atrial fibrillation, or new onset of atrial flutter or atrial tachycardia 
event (≥ 30 seconds in duration from an event monitor or Holter, or from a 10 
second 12-lead EKG) between 91 days and 365 days post index procedure 
• 
Any of the following interventions for atrial fibrillation, or new onset of atrial 
flutter or atrial tachycardia between 91 days and 365 days post index procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed any AAD*  
*AADs for endpoint will consist of all Class I/III and any Class II/IV medications taken 
for control of AF/AT/AFL recurrence  
4.3. Secondary Effectiveness Endpoint 
Secondary effectiveness endpoint is defined as the event-free at 12 months post-procedure. 
 
Secondary effectiveness events are defined as: 
• 
Acute procedural failure 
• 
More than one repeat procedure during the blanking period (90 days post index 
procedure) 
• 
Documented symptomatic atrial fibrillation, or new onset of atrial flutter or 
atrial tachycardia event (≥ 30 seconds in duration from an event monitor or 

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Holter, or from a 10 second 12-lead EKG) between 91 days and 365 days post 
index procedure 
• 
Any of the following interventions for atrial fibrillation, or new onset of atrial 
flutter or atrial tachycardia between 91 days and 365 days post index procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed a higher dose of any AAD* documented at baseline 
• 
Prescribed a new AAD* not documented at baseline  
*AADs for endpoint will consist of all Class I/III and any Class II/IV medications taken 
for control of AF/AT/AFL recurrence 
 
4.4. Tertiary Endpoints 
Chronic Effectiveness: Evaluation of chronic recurrence at 24 months and 36 months  
• Recurrence is defined as intervention for atrial fibrillation, or new onset of atrial flutter 
or atrial tachycardia (repeat procedures, use of AADs, cardioversion), excluding repeat 
procedures during the 90-day blanking period.   
• Data collection to include the diagnostic modality used to identify recurrence and the 
therapeutic intervention 
• Chronic effectiveness will be evaluated using Kaplan-Meier methodology. The 
Kaplan-Meier 24 month and 36 month chronic recurrence-free rate will be calculated 
and presented along with the 95% confidence interval, calculated as the pointwise 
confidence limit using the log-log methodology Subjects who withdraw from the study 
prior to the specified time point without experiencing an event will be censored on the 
date of withdrawal.   
Center Experience: Primary Safety and Primary Effectiveness outcomes by center experience 
• In order to evaluate training effectiveness for investigators outside of the ZERO AF 
IDE study, outcomes in centers performing five or more procedures using the Blazer 
OI catheter during the ZERO AF IDE study will be compared to all other. Kaplan-
Meier rates and 95% confidence intervals for the Primary Safety and Effectiveness 
endpoints for both groups will be presented with no statistical comparison. 
 
Safety:  Reportable Adverse Events rates at 12, 24 and 36 months 
Adverse events will be collected at all subject follow-up visits. 
Reportable events include: 
• All Serious Adverse Events 
• All Study Procedure-Related Adverse Events 
• All Study Device-Related Adverse Events 
• All Study Device Deficiencies 
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
previously not defined in the Directions For Use. 
 

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Adverse event rates will be calculated using binomial methodology. The cumulative number 
of events and event rate will be included in all study reports. Subjects at risk for an adverse 
event will be determined by the subject treatment status; all treatment and attempt subjects will 
be considered at risk for study related adverse events 
 
Effectiveness: Acute Procedural Success Rate 
Acute Procedural Success is defined as pulmonary vein isolation achieved with a Boston 
Scientific OI ablation catheter as demonstrated by map-based entrance block with exit block 
and other maneuvers (such as adenosine testing) at the discretion of the physician. 
5. Study Design 
The INTERRUPT AF study is a global, prospective, non-randomized, multicenter study. The 
study will serve as the Post Approval Study for the Blazer OI, IntellaNav OI, IntellaTip MiFi 
OI, and IntellaNav MiFi OI Ablation catheters. All study devices will be used per instruction 
as they become commercially available after regulatory approval in their geography. 
Therefore, the index procedure for the INTERRUPT AF study is the same procedure that a 
subject would undergo if they were not participating in this study. 
For the purposes of the study, De Novo is defined as subjects undergoing first ablation 
procedure for PAF with no prior left atrium ablations (RF, Cryo, Surgical). 
5.1. Scale and Duration 
A total of 415 subjects will be included in the study to ensure a minimum of 329 TREATMENT 
subjects.  
The study is global and will include 25-50 sites in the United States, Europe and Asia-Pacific. 
A minimum of 50% of the sites will be selected from the United States. 
To reduce the impact of individual center bias, no study site will be allowed to contribute more 
than 41 subjects (10% of the 415 enrollments requirement). 
Each subject will be followed at specified time points after the ablation procedure (index 
procedure) with a follow-up duration of three years.  A study subject’s participation will be 
considered complete when all protocol required visits have been completed as indicated in 
Figure 5.2-1. 
Accordingly, the study is expected to be completed in approximately five years (two-year 
enrollment period with three-year follow-up. 

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Figure 5.1-1: INTERRUPT AF Study Design 
 
Table 2: INTERRUPT AF Study Timeline 
Milestone 
Forecast Date 
Start 
Upon FDA approval of PAS Protocol 
First Enrollment 
Approximately 120 days after FDA approval of the protocol 
Enrollment Plan 
Given the global prevalence of Paroxysmal Atrial Fibrillation, it is 
estimated that each activated site can each enroll 1 subject per month. 
It is anticipated that it will take 12-24 months to enroll the 415 
subjects. 
Progress Updates 
Progress reports will be provided every six months for the first two 
years from the date of FDA Approval of PAS Protocol, then annually 
thereafter.  Section 9.3.1 contains details of the progress report 
content. 
Primary 
Objective 
Analysis 
Within 3 months of 12-Month Visit Completion for all subjects. 
Final Post 
Approval Study 
Report 
Within 3 months of 36-Month Visit Completion for all subjects. 

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Anticipated 
Reporting Dates 
Assuming FDA Approval of PAS Protocol on 01NOV2018, First 
Patient In on 01APR2019 and 18-month enrollment period: 
 
• 6 Month Interim PAS Status Report (~01MAY2019) 
• 12 Month Interim PAS Status Report (~01NOV2019) 
• 18 Month Interim PAS Status Report (~01MAY2020) 
• 24 Month Interim PAS Status Report (~01NOV2020) 
• 36 Month Interim PAS Status Report (~01NOV2021) 
• 48 Month Interim PAS Status Report (~01NOV2022) 
 
• Primary Objective Analysis (~01DEC2021)* 
• Final Post Approval Study Report (~01DEC2023) 
 
* The Primary Objective Analysis will be provided within 3 months of all 12 
Month visits being completed in a Primary Endpoint Report. If the timing of the 
Primary Endpoint Report aligns with a scheduled interim report, the two will be 
combined. 
5.2. Treatment Assignment 
All subjects who meet the eligibility criteria as per Sections 6.2 and 6.3 and sign the informed 
consent will be considered enrolled. Subjects will be classified based on patient status 
classification as per Section 7.3. 
5.3. Justification for the Study Design 
This post-market study aims to collect acute and long-term data for the Rhythmia Mapping 
System and Boston Scientific OI Catheters for de novo PAF ablation. 
The Blazer OI, IntellaNav OI, IntellaTip MiFi OI, and IntellaNav MiFi OI Ablation Catheters 
have been approved by FDA for ablation treatment of PAF. The present study serves to comply 
with the request of providing continued reasonable assurance of the safety and effectiveness 
of the approved devices in a de novo PAF population.  Any of the BSC Open Irrigated study 
catheters listed in Section 3.1 are allowed for use in the study once they are commercially 
available after regulatory approval in their geography for PAF Ablation. 
6. Subject Selection  
6.1. Study Population and Eligibility  
Subjects included in the INTERRUPT AF study should be selected from the investigator’s 
general patient population indicated for catheter ablation of PAF. Investigators are responsible 
for screening all potential subjects and selecting those who meet the eligibility criteria for the 
study as described in Sections 6.2 and 6.3 below. 

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6.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 3) may be given consideration for 
inclusion in this clinical investigation, provided no exclusion criterion (see Section 6.3) is 
met.  
Table 3: Inclusion Criteria 
Inclusion 
Criteria 
1. History of recurrent symptomatic Paroxysmal Atrial Fibrillation, 
defined as AFib that terminates spontaneously or with intervention 
within seven days of onset. Minimum documentation includes a 
physician’s note indicating recurrent self-terminating Atrial 
Fibrillation AND one electrocardiographically documented AF 
episode within 6 months prior to enrollment. 
2. Subjects who are eligible for an ablation procedure for Paroxysmal 
Atrial Fibrillation with the Rhythmia Mapping system according to 
current international and local guidelines; 
3. Subjects who are eligible for an ablation procedure for Paroxysmal 
Atrial Fibrillation with a BSC Open-Irrigated Ablation Catheter 
according to current international and local guidelines; 
4. Subjects who are willing and capable of providing informed consent;  
5. Subjects who are willing and capable of participating in all testing 
associated with this clinical investigation at an approved clinical 
investigational center; 
6. Subjects whose age is 20 years or above, or who are of legal age to 
give informed consent specific to state and national law. 
 
6.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 4) will be excluded from this 
clinical study. 
 

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Table 4: Exclusion Criteria 
Exclusion 
Criteria 
1. Subjects enrolled in any other concurrent clinical study, with the 
exception of local mandatory governmental registries and 
observational studies/registries, without the written approval from 
Boston Scientific  
2. Subjects unable or unwilling to complete follow-up visits and 
examination for the duration of the study; 
3. Subjects who have undergone any previous left atrial cardiac 
ablation (RF, Cryo, surgical) 
4. Subjects who have undergone any cardiac ablation within 30 days 
prior to enrollment; 
5. Unrecovered/unresolved Adverse Events from any previous invasive 
procedure; 
6. Life expectancy <= three years per physician opinion  
7. Women of childbearing potential who are, or plan to become, 
pregnant during the time of the study (method of assessment upon 
physician’s discretion) 
8. Known cardiac thrombus within 60 days prior to enrollment 
9. History of CVA, TIA or PE within 90 days prior to enrollment 
10. Implanted pacemaker, ICD, or CRT leads within 90 days prior to 
enrollment 
11. Implanted Left atrial appendage closure device prior to index 
procedure 
12. Prosthetic mitral or tricuspid heart valves (subjects with successful 
mitral valve repair allowed- annular ring constitutes repair) 
13. Left atrial diameter greater than 5.5cm 
14. Documented or suspected stenosis of any pulmonary veins. 
15. Atrial fibrillation secondary to electrolyte imbalance, thyroid 
disease, or reversible or non-cardiac cause. 
16. Contraindication for anticoagulation  
17. Clinically significant mitral valve regurgitation or stenosis per 
investigator discretion. 
18. Any cardiac surgery ≤ 90 days from consent date. 
19. Any electrocardiographically documented episode of Persistent 
AFib, defined as AFib lasting longer than 7 days from onset. 
7. Subject Accountability 
7.1. Point of Enrollment 

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Investigators will select subjects who are appropriate for study inclusion as per eligibility 
criteria (Section 6.2 and 6.3). Subjects who meet all eligibility criteria and have signed and 
dated the Informed Consent Form are considered enrolled in the study.  All subject enrollments 
will be counted against the enrollment ceiling for the study.   
7.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the INTERRUPT AF 
study, the reason(s) shall be reported. 
Reasons for withdrawal may include physician discretion, change in inclusion/exclusion status, 
subject choice to withdraw consent, lost to follow-up, or death.  While study withdrawal is 
discouraged, subjects may withdraw from the study at any time, with or without reason, and 
without prejudice to further treatment.  All applicable electronic case report forms (eCRFs) up 
to the point of subject withdrawal and an “End of Study” eCRF must be completed.  For 
subjects who are “lost to follow-up” the investigator/center should have at least three 
documented attempts to contact the subject prior to completion of the “End of Study” eCRF.  
No additional data may be collected after a subject has been withdrawn from the study or 
withdraws his/her consent, for whatever reason.  All open adverse events should be closed or 
documented as chronic.  Data collected up to the point of subject withdrawal may be used.  If 
such withdrawal is due to problems related to device safety or performance, the investigator 
shall ask for the subject’s permission to follow his/her status/condition.  
7.3. Subject Status and Classification 
All enrolled subjects will be classified into one of three categories based on their progress and 
completion of key events. Classification will determine how data gathered from them will be 
stored and evaluated. 
• INTENT: Any subject that signs the consent form but does not have any study devices 
inserted into the body. Subjects who are enrolled in the study but do not undergo 
ablation procedure within 60 days from consent signature date may not be reconsented 
and will be withdrawn from the study and classified as “INTENT”. INTENT subjects 
will count towards the enrollment ceiling and will not be used for analysis of the 
endpoints. INTENT subjects will not be followed for any additional visits after 
withdrawal. For these subjects an “End of Study” form must be completed. The original 
signed Informed Consent must be maintained in the center’s subject file.  
• ATTEMPT: Any subject that signs the consent form, meets eligibility criteria and has 
any protocol defined study device inserted into the body but does not receive RF 
ablation per protocol. Additionally, any subject not treated with a BSC OI Catheter and 
the Rhythmia System will be considered an ATTEMPT.  Use of the IntellaMap Orion 
Catheter is required but will not affect subject classification.  Procedures that do not 
utilize the IntellaMap Orion Catheter will have a protocol deviation entered. Subjects 
will be followed for one month for safety reporting only. Therefore, ATTEMPT 
subjects will not be assigned an event monitor for study purposes. All applicable case 
report forms must be completed, including Baseline, data pertaining to the Index 

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procedure, Adverse Event reporting and one-month follow-up. ATTEMPT subjects 
will count towards the enrollment ceiling and will not be used for analyses of the 
primary endpoint. The original signed Informed Consent must be maintained in the 
center’s study file. 
• TREATMENT: Any subject that signs the consent form, meets eligibility criteria and 
has the specified study devices inserted into the body and undergoes protocol specific 
treatment for the intended disease. 
 
7.4. End-of-Study Definition  
A subject enrolled in INTERRUPT AF is considered to have completed the study if he or she 
has completed all phases of the study including the last visit or the last applicable procedure 
shown in the Data Collection Schedule (table 8.1-1). 
8. Study Methods 
8.1. Data Collection 
The data collection schedule is shown in Table 5. 
 
 

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Table 5: Data Collection Schedule 
Data Collected 
 ENROLLMENT/ BASELINE 
 INDEX PROCEDURE 
 (Day 0) 
 PRE-DISCHARGE   
 (0-7 days  post -procedure)   
 1-MONTH FOLLOW-UP   
 (30±7 days) 
 3-MONTH FOLLOW-UP   
 (90±30 days) 
 6-MONTH FOLLOW-UP   
 (180±30 days) 
 12-MONTH FOLLOW-UP  
 (365± 30 days) 
 24  MONTH FOLLOW-UP   
 (730 ± 30 days) 
 36 MONTH FOLLOW-UP   
 (1095 ± 30 days) 
 ADDITIONAL FOLLOW-UP 
 REPEAT PROCEDURE 
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion  
X 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
 
 
 
Vitals 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
Pre-Procedure 
Assessment 
X 
 
 
 
 
 
 
 
 
 
 
Imaging  
Xa 
 
Xa 
 
Xa 
 
Xa 
 
 
Xa 
Xb 
Medication Regimen 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Procedure data 
 
X 
 
 
 
 
 
 
 
 
X 
EQ-5D 
X 
 
 
 
X 
X 
X 
 
 
 
 
AFEQT 
X 
 
 
 
X 
X 
X 
 
 
 
 
12-Lead EKG 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
Event Monitor 
 
 
 
 
X 
X 
X 
 
 
Xc 
 
Holter Monitor 
 
 
 
 
 
 
X 
 
X 
 
 
Documentation of 
Intervention for 
AF/AT/AFL 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse 
Event/Device 
Deficiency 
Reporting 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
a: If Pulmonary Vein Stenosis suspected or per center standard of care 
b: Required for repeat procedures with non-study catheters only 
c: If completed before the 12-month follow-up visit 
 

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8.2. Study Candidate Screening 
Investigators are responsible for screening all subjects and selecting those who are appropriate 
for study inclusion. The subjects selected for participation should be from the investigator’s 
general patient population.  The investigator is expected to follow standard of care testing to 
diagnose and screen subjects for inclusion in the study.  
8.3. Informed Consent 
Patients who meet all of the inclusion criteria and none of the exclusion criteria and agree to 
participate in the INTERRUPT AF study must provide written informed consent approved by 
the regional regulatory body and the investigational center’s IRB/EC prior to study 
participation and study specific testing or data collection.   
The subject should be given ample time to consider participation and ask questions if 
necessary. An approved informed consent form (ICF) shall be signed and personally dated by 
the subject (or legal representative). The original, signed document is to be kept with the 
subject’s file and a copy of the signed ICF must be provided to the subject.  The index 
procedure must be performed within 60 days post ICF signature. In case the index procedure 
has not been performed within this time period, the subject may not be reconsented and will 
be classified as an INTENT (see section 8.3).  
For additional information regarding the informed consent process, refer to Section 19. 
8.4. Enrollment/Baseline Visit 
Subjects who provide written consent and meet all of the study enrollment criteria are enrolled 
in the study.   
Enrolled subjects will have baseline data collected. The data collection at baseline includes: 
• 
Visit date; 
• 
Demographic data, including: age at time of consent, gender, race and ethnicity; 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure;   
• 
Medical history, including:  
o Underlying cardiovascular disease, if any;  
o Prior history of cardiac events including: acute myocardial infarction, CVA, 
TIA, PE or transient ischemic attack; 
o Prior surgical interventions and/or cardiac procedures including: PTCA, 
CABG, pacemaker implantation, ICD implant, CRT implant, cardiac valve 
interventions, left atrial appendage closure, patent foramen ovale intervention, 
heart transplant or procedures for implantation of other intracardiac devices;  
o Detailed history of all arrhythmias and previous cardiac ablation procedures 
(catheter delivered or surgically performed), if any, including date of latest 
ablation procedure and any concomitant procedures (e.g., valve surgery, left 
atrial appendage closure or ligation, etc.), treated arrhythmia(s) and outcome; 
o Non-cardiac comorbidities. 

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• 
Pre-procedure assessment of Left Ventricular Ejection Fraction, Left Ventricular 
Diastolic Diameter, and Left Atrial Diameter within the past six months including data 
collection methods (if available) 
• 
Current cardiovascular medication regimen including anti arrhythmic, anticoagulation 
and antiplatelet agents. 
• 
Imaging 
• 
12-Lead EKG data including ongoing rhythm 
• 
Quality of Life Instruments (AFEQT and EQ-5D-5L) 
 
Evidence of PAF in the medical history should be documented and reported in the CRFs 
including date of last recorded episode, source of recording (Holter, EKG, etc) and treatment 
history (drug, cardioversion, etc). 
 Medications 
 Anti-Arrhythmic Drugs 
It is recommended that all Anti-Arrhythmic Drugs (AADs) should be stopped at least five half-
lives before the procedure; amiodarone should be stopped one month before the procedure.   
It is recommended that AADs only be prescribed after the procedure if a subject has a 
documented arrhythmia recurrence.  Post-procedure AADs are allowed per physician’s 
discretion but new AADs should not be prescribed unless considered medically necessary.  At 
eight weeks, investigators should remove subjects from AADs to appropriately assess the 
subject for early arrhythmia recurrence that may require a repeat ablation procedure within the 
blanking period (on or before day 90) 
If the investigator determines that the subject must remain on an AAD after the blanking 
period, the subject will be considered a Primary Effectiveness Failure.  
Treatment with Class II/IV medications for conditions other than control of arrhythmia 
recurrence is also permitted and will be documented.  Every effort should be made to keep 
those drugs at a stable dose over the entire course of the study.   
 Anticoagulation 
It is expected that the patient population for the study will have differing anticoagulation 
therapies.  The requirements outlined below represent the minimum requirement of the study.   
Additional screening/testing is allowed if deemed necessary by the investigator. 
The following subject groups should get a trans-esophageal echocardiogram (TEE) or 
equivalent to confirm absence of thrombus in the left atrium within 48 hours prior to the 
ablation: 
• Patient presenting in Atrial Fibrillation at the time of the index procedure 
• Patients presenting in Sinus Rhythm but with unknown anticoagulation pre-procedure 

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• Patient presenting in Atrial Fibrillation that have not been therapeutically 
anticoagulated for three weeks 
• Patients with known cardiac thrombus within the past 90 days 
It is also recommended that the following groups get a trans-esophageal echocardiogram (TEE) 
or equivalent to confirm absence of thrombus in the left atrium within 48 hours prior to the 
ablation: 
• Patient presenting in Atrial Fibrillation and that have been therapeutically 
anticoagulated for three weeks 
• Patient presenting in Sinus Rhythm that have not been therapeutically anticoagulated 
for three weeks 
Confirming the absence of thrombus is not required for subjects in sinus rhythm that have 
therapeutic anticoagulation for three weeks. 
Administration of anticoagulation on the morning of the index procedure is optional and 
investigators are encouraged to follow their standard of care. Per the Instructions For Use of 
the study devices, the activated coagulation/clotting time (ACT) level must be brought to a 
level ≥300 seconds and be checked at clinically appropriate intervals per center’s SOC.  No 
ablation can be performed until a minimum ACT of 300 seconds is obtained. 
After the index procedure, all subjects will be required to be anticoagulated, using the drug 
determined best for the subject by the investigator, for a minimum of 60 days.  All 
anticoagulation medications and INR levels, if applicable, will be collected throughout the 
course of the study. 
8.5. Ablation (index) procedure  
The index procedure for the INTERRUPT AF Study will consist of de novo PAF procedures.  
For the purposes of this protocol, de novo procedures are defined as AF procedures in which 
there has been no prior ablation in the Left Atrium (LA).   
Esophageal temperature monitoring is highly recommended and should be performed per the 
center’s standard of care.  Esophageal temperature should be monitored and ablation delivery 
should be guided by rapid temperature rise or when temperature reaches a predefined threshold 
per standard of care. 
The objective of the procedure is map-based electrical isolation of all pulmonary veins.  
Physicians will follow their preferred ablation workflow utilizing a Boston Scientific Open-
Irrigated Catheter following all applicable Instructions for Use.   
Once isolation of PVs has been attempted, the investigator may check for gaps with a validation 
map (vMap).  This may be done on a per vein, per side, or whole chamber basis according the 
investigator’s discretion.  vMaps must be created while the subject is in sinus rhythm or during 
pacing.  Adenosine or isoproterenol testing may be performed per center’s standard of care and 
will be noted in the CRF. 
Final confirmation of entrance block must be by vMap made at least 20 minutes after the last 
ablation (for that PV).  Exit block verification is also highly recommended and will be noted 
in the CRF if completed. 

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Electrical isolation of the veins must be demonstrated by the absence of electrical propagation 
within the ablation lines.   
Additional ablations may be performed according to medical judgement and clinical practice.   
If gaps are present, additional RF applications can be applied as required.  Ablation of Induced 
Arrhythmias is allowed during the procedure as well as any previously documented 
arrhythmias. All additional ablations will be noted on the CRF.  
Mapping/Ablation data collected during the procedure will include but may not be limited to: 
Data Requirements 
Catheter model(s) and lot/serial number(s) used 
Presenting Rhythm 
Esophageal Temperature Monitoring  
(if applicable) 
Programmed ablation catheter fluid infusion rates 
Location of all previous ablations in any chamber (RF, Cryo, Surgical)  
Primary ablation targets  
Location of and reason for additional ablations performed beyond PVI 
Detection of gaps in ablation lines of index procedure (including locations) 
Number of ablation attempts (See Table 11 for definition) needed to close gap in ablation 
line/per gap for index procedure 
Did PV isolation terminate AF?  
What rhythm did AF terminate to?  
Adenosine testing result (if performed) 
Isoproterenol testing information (if performed)  
Was isolation achieved for each PV at the end of the procedure? (Documented via 
electrogram printouts) 
Name of map(s) that demonstrates PVI 
Acute success verification technique  
Was exit block tested? If, so was exit block achieved? 
Total Procedure Time (first catheter inserted to last catheter removed) 
Total Fluoroscopy Time 
Total RF time for the procedure 
Total fluid infused from ablation catheter  
Total mapping time 
Number of maps created 
Mapping time for each map 
Reason for map creation (list for each map)  
Map Completeness 
Number of points in each map 
Specific use of Rhythmia features  
Rhythm at end of case 
Was Cardioversion performed during the procedure? If so, when? 
Electronic Map Data* 
 

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* At the conclusion of the procedure, the Electronic Map Data collected through the Rhythmia 
Mapping System will be saved and stored in anonymized form by the site or sponsor 
representative onto external media provided by the Sponsor. Media will be returned to the 
Sponsor at the end of the study or at periodic intervals during the study. 
8.6. Pre-Discharge Follow-up 
The pre-discharge follow-up visit should be completed before the subject is discharged from 
the hospital.  The visit should occur within seven days post-index procedure. If the subject is 
to remain in the hospital beyond seven days post-index procedure, then the pre-discharge 
follow-up visit should be conducted before the eighth day. 
 
The data collection at Pre-Discharge includes: 
• 
Date of visit; 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure 
• 
Rhythm at time of visit (12-Lead EKG); 
• 
Variations in current medication regimen 
• 
Imaging (collected only if performed, if PV Stenosis suspected or according to center’s 
practice) 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.7. One-Month Follow-up (Phone Check) 
The one-month follow-up should be completed between 23 and 37 days post-procedure.  The 
one-month follow-up can be performed over the phone or in clinic according to the site’s 
standard practice. 
 
The data collection at the one-month follow-up includes: 
• 
Date of visit 
• 
Review of any symptomatic transmissions (event monitor) 
• 
Variations in current medication regimen 
• 
Documentation of any intervention for AF/AT/AFL (e.g.: Repeat Procedure, 
Cardioversion), if applicable 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.8. Three-Month Follow-up 
The three-month follow-up visit should be completed between 60 and 120 days post-procedure.  
Due to the range for the visit completion and the endpoint requirement for medication, AAD 
medication changes made during the three-month follow-up visit will be counted as being 
made within the blanking period, but efforts should be made to remove subjects from AADs 
by eight weeks post-procedure to allow for complete washout. 

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The data collection at the three-month follow-up visit includes: 
• 
Date of visit 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure 
• 
Rhythm at time of visit (12-Lead EKG) 
• 
Review of any available symptomatic or asymptomatic transmissions (event monitor) 
• 
Variations in current medication regimen 
• 
Imaging (collected only if performed, if PV Stenosis suspected or according to center’s 
practice) 
• 
Quality of Life Instruments (AFEQT and EQ-5D-5L) 
• 
Documentation of any intervention for AF/AT/AFL (e.g.: Repeat Procedure, 
Cardioversion), if applicable 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.9. Six-Month Follow-up (Phone Check) 
The six-month follow-up should be completed between 150 and 210 days post-procedure.  The 
six-month follow-up can be performed over the phone or in clinic according to the site’s 
standard practice. 
 
The data collection at the six-month follow-up includes: 
• 
Date of visit 
• 
Review of any symptomatic or asymptomatic transmissions (event monitor) 
• 
Variations in current medication regimen 
• 
Imaging (collected only if performed, if PV Stenosis suspected or according to center’s 
practice) 
• 
Quality of Life Instruments (AFEQT and EQ-5D-5L) 
• 
Documentation of any intervention for AF/AT/AFL (e.g.: Repeat Procedure, 
Cardioversion), if applicable 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.10. 12-Month Follow-up 
The 12-month follow-up visit should be completed between 335 and 395 days post-procedure.   
 
The data collection at the 12-month follow-up visit includes: 
• 
Date of visit 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure 
• 
Rhythm at time of visit (12-Lead EKG); 

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• 
Review of any symptomatic or asymptomatic transmissions (event monitor); 
• 
Collection and Review of 24-hour Holter Monitor for symptomatic or asymptomatic 
events 
• 
Variations in current medication regimen; 
• 
Imaging (collected only if performed, if PV Stenosis suspected or according to center’s 
practice) 
• 
Quality of Life Instruments (AFEQT and EQ-5D-5L) 
• 
Documentation of any intervention for AF/AT/AFL (e.g.: Repeat Procedure, 
Cardioversion), if applicable 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.11. 24-Month Follow-up  
The 24-month follow-up visit should be completed between 700 and 760 days post-procedure.   
 
The data collection at the 24-month follow-up visit includes: 
• 
Date of visit 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure 
• 
Rhythm at time of visit (12-Lead EKG) 
• 
Variations in current medication regimen 
• 
Documentation of any intervention for AF/AT/AFL (e.g.: Repeat Procedure, 
Cardioversion), if applicable 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.12. 36 Month Follow-up 
36-month follow-up visit should be completed between 1065 and 1125 days post-procedure. 
 
The data collection at the 36-month follow-up visit includes: 
• 
Date of visit 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure 
• 
Rhythm at time of visit (12-Lead EKG) 
• 
Collection and Review of 24-hour Holter Monitor for symptomatic or asymptomatic 
events 
• 
Variations in current medication regimen 
• 
Documentation of any intervention for AF/AT/AFL (e.g.: Repeat Procedure, 
Cardioversion), if applicable 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 

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8.13. Additional Follow-up Visits 
An Additional follow-up visit is any subject visit triggered by subject symptoms that is not 
already defined as one of the study visits. 
If subjects experience symptoms associated with cardiac arrhythmias (e.g. palpitations, 
lightheadedness, syncope, dyspnea) during the first 12 months, they will be instructed to record 
the arrhythmia on the event monitor.  The investigator will review the information transmitted 
and will contact the subject to schedule an additional office visit if necessary.   
In addition to determining the best course of action for the subject (repeat ablation, medication 
adjustment), during the visit, the following will be collected: 
• 
Date 
• 
Vitals including: height, weight, resting heart rate, systolic and diastolic blood pressure 
• 
Rhythm at time of visit (12-Lead EKG) 
• 
Variations in current medication regimen 
• 
Imaging (collected only if performed, if PV Stenosis suspected or according to center’s 
practice) 
• 
If performed before the 12-month visit, review of symptomatic episode event monitor 
transmissions by the subject since the last follow-up 
• 
Any intervention for AF/AT/AFL (e.g.: Repeat Procedure, Cardioversion) 
• 
Reportable Adverse Events, if applicable 
• 
Protocol Deviations, if applicable 
8.14. Repeat Ablation Procedure 
It is known that a repeat ablation procedure may be necessary in certain subjects after the index 
ablation procedure due to recurrences of PAF or other tachyarrhythmias requiring treatment.  
One repeat procedure is allowed within the blanking period if considered medically necessary 
due to subject’s intolerability of the arrhythmia. Data collection requirements for the repeat 
procedure are the same as those for the index procedure. 
If an investigator believes it is in the subject’s best interest to perform the ablation with a non-
study catheter, the investigator may choose to withdraw the subject from the study prior to 
performing the procedure.  Prior to study withdrawal and undergoing the repeat procedure with 
a different (non-study) catheter, imaging of the PVs is required. The appropriate type of 
imaging performed may be determined by the investigator.  As available, the PV images must 
be reviewed against the pre-ablation imaging from the index procedure to rule out PV stenosis 
from the index ablation procedure.  In addition, repeat ablation with a non-study catheter must 
occur ≥30 days after the previous ablation procedure.    
8.15. Study Completion 
Active data collection for each subject will be complete after subjects complete the 36-month 
follow-up visit (including Holter Monitor).  Sites will need to complete the “End of Study” 
CRF to signify study completion.  

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8.16. Source Documents 
It is preferable that original source documents are maintained, when available. In lieu of 
original source documents, certified copies are required to be maintained.  A certified copy is 
a copy (irrespective of the type of media used) of the original record that has been verified (i.e., 
by a dated signature or by generation through a validated process) to have the same 
information, including data that describe the context, content, and structure, as the original. 
Source documentation includes but is not limited to those items noted in Table 6. 
Table 6: Source Documentation Requirements 
Requirement 
Disposition 
Informed consent documentation process 
Retain at Center 
Medical history documents pertaining to eligibility 
criteria 
Retain at Center 
Documentation of demographics data 
Retain at Center 
Vitals 
Retain at Center 
Medication Changes 
Retain at Center  
Medical history 
Retain at Center 
Quality of Life Instruments (AFEQT and EQ-5D-5L) 
Retain in subject binder 
Imaging 
Retain at Center 
12-Lead EKGs data including ongoing rhythm 
Retain at Center 
Imaging, per standard of care 
Retain at Center 
Recording System Print-Outs, showing entrance 
block for each Pulmonary Vein 
Retain in subject binder 
Recording lab logs, showing the time of entrance 
block (20 minutes after last ablation) 
Retain in subject binder 
Signed Technical Source Form 
Retain in subject binder 
Adverse Events 
Retain at Center 
In the event of a subject death: 
• 
Death narrative 
• 
Relevant medical records 
• 
Death Certificate 
• 
Autopsy report 
 
 
Submit one copy to BSC, 
Retain one copy at center 
 
Additional source documentation may be required upon request of BSC. 
9. Statistical Considerations 
9.1. Endpoints 
This study has primary endpoints designed to assess the safety and effectiveness of the Boston 
Scientific family of Open-Irrigated Catheters in the general population of subjects undergoing 

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de novo ablation for PAF. The study will be considered successful if both the primary safety 
and primary effectiveness endpoints are passed. 
 Primary Safety Endpoint 
The primary safety endpoint will be evaluated by the primary safety event-free rate at 12 
months post-procedure.  
Primary safety events will consist of a composite of acute primary safety events (events 
occurring within seven days post-procedure or hospital discharge, whichever is later), and 
chronic primary safety events (events occurring through 3 or 12 months post-procedure). 
Acute primary safety events will be defined as the following: 
• 
Death 
• 
Myocardial infarction (MI) 
• 
Vagal Nerve Injury/Gastroparesis   
• 
Transient ischemic attack (TIA) 
• 
Stroke/Cerebrovascular accident (CVA) 
• 
Thromboembolism 
• 
Pericarditis 
• 
Cardiac tamponade/perforation 
• 
Pneumothorax 
• 
Vascular access complications 
• 
Pulmonary edema/heart failure 
• 
AV block 
 
Chronic primary safety events will be defined as the following: 
• 
Occurring through 3 Months post-procedure 
• 
Atrial esophageal fistula 
• 
Pericardial effusion 
 
• 
Occurring through 12 Months post-procedure 
• 
Pulmonary vein stenosis (symptomatic and requiring intervention) 
 
9.1.1.1. Hypotheses 
The primary safety objective is to demonstrate that the primary safety event-free rate through 
12 months post-procedure is greater than the specified performance goal. 
Ho:  The primary safety event-free rate at 12 months post-procedure  85%24, 25 
Ha:  The primary safety event-free rate at 12 months post -procedure > 85% 

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9.1.1.2. Sample Size  
The sample size estimate was obtained using the normal approximation to the binomial 
distribution and verified through simulations based on Kaplan-Meier methodology. The 
following assumptions were used in the sample size calculation: 
 
Assumptions 
Primary Safety 
Expected rate 
90%26 
Performance goal 
85% 
Attrition (per year) 
7.5% 
Significance level  (one-sided) 
5% 
Power 
80% 
 
Under the hypothesis and assumptions outlined above, the required sample size for this 
endpoint is 329 TREATMENT subjects. 
 
9.1.1.3.  Statistical Methods 
For the primary safety endpoint, the Kaplan-Meier 12 month (365-day) primary safety event-
free rate will be calculated. Subjects who withdraw from the study prior to 12 months without 
experiencing an event will be censored on the date of withdrawal.  The 95% one-sided lower 
confidence limit of the observed safety event-free rate will be compared to the performance 
goal of 85%. If the lower confidence limit is greater than the performance goal, the null 
hypothesis will be rejected. The lower confidence limit will be calculated as the pointwise 
confidence limit using the log-log methodology. 
 Primary Effectiveness Endpoint 
The primary effectiveness endpoint will be evaluated by the primary effectiveness event-free 
rate at 12 months post-procedure. 
Primary effectiveness events will be defined as the following: 
• 
Acute procedural failure 
• 
More than one repeat procedure during the blanking period (90 days post index 
procedure) 
• 
Documented atrial fibrillation, or new onset of atrial flutter or atrial tachycardia 
event (≥ 30 seconds in duration from an event monitor or Holter Monitor, or 
from a 10 second 12-lead EKG) between 91 days and 365 days post index 
procedure 
• 
Any of the following interventions for atrial fibrillation, or new onset of atrial 
flutter or atrial tachycardia between 91 days and 365 days post index procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed any AAD*  

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*AADs for endpoint will consist of all Class I/III and any Class II/IV medications taken 
for control of AF/AT/AFL recurrence  
 
9.1.2.1. Hypotheses 
The primary effectiveness objective is to demonstrate that the primary effectiveness event-free 
rate through 12 months post-procedure is greater than the specified performance goal. 
Ho:  The primary effectiveness event-free rate at 12 months post-procedure  50%27 
Ha:  The primary effectiveness event-free rate at 12 months post-procedure > 50% 
 
9.1.2.2. Sample Size  
The sample size estimate was obtained using the normal approximation to the binomial 
distribution and verified through simulations based on Kaplan-Meier methodology. The 
following assumptions were used in the sample size calculation: 
 
Assumptions 
Primary Effectiveness 
Expected rate 
60%26,28,29 
Performance goal 
50% 
Attrition (per year) 
7.5% 
Significance level  (one-sided) 
5% 
Power 
80% 
 
Under the hypothesis and assumptions outlined above, the required sample size for this 
endpoint is 183 TREATMENT subjects. 
9.1.2.3.  Statistical Methods 
For the primary effectiveness endpoint, the Kaplan-Meier 12 month (365-day) primary 
effectiveness event-free rate will be calculated. Subjects who withdraw from the study prior to 
12 months without experiencing an event will be censored on the date of withdrawal.  The 95% 
one-sided lower confidence limit of the observed primary effectiveness event-free rate will be 
compared to the performance goal of 50%. If the lower confidence limit is greater than the 
performance goal, the null hypothesis will be rejected. The lower confidence limit will be 
calculated as the pointwise confidence limit using the log-log methodology. 
 Secondary Effectiveness Endpoint 
The secondary effectiveness endpoint will be evaluated by the secondary effectiveness event-
free rate at 12 months post-procedure. 
Secondary effectiveness events will be defined as the following: 
• 
Acute procedural failure 

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• 
More than one repeat procedure during the blanking period (90 days post index 
procedure) 
• 
Documented symptomatic atrial fibrillation, or new onset of atrial flutter or 
atrial tachycardia event (≥ 30 seconds in duration from an event monitor or 
Holter, or from a 10 second 12-lead EKG) between 91 days and 365 days post 
index procedure 
• 
Any of the following interventions for atrial fibrillation, or new onset of atrial 
flutter or atrial tachycardia between 91 days and 365 days post index procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed a higher dose of any AAD* documented at baseline 
• 
Prescribed a new AAD* not documented at baseline  
*AADs for endpoint will consist of all Class I/III and Class II/IV medications taken for 
control of AF/AT/AFL recurrence  
9.1.3.1. Hypotheses 
The secondary effectiveness objective is to demonstrate that the secondary effectiveness event-
free rate through 12 months post procedure is greater than the specified performance goal. 
Ho:  The secondary effectiveness event-free rate at 12 months post-procedure  50% 
Ha:  The secondary effectiveness event-free rate at 12 months post-procedure > 50% 
9.1.3.2. Sample Size  
The sample size estimate was obtained using the normal approximation to the binomial 
distribution and verified through simulations based on Kaplan-Meier methodology. The 
following assumptions were used in the sample size calculation: 
 
Assumptions 
Secondary Effectiveness 
Expected rate 
65%26 
Performance goal 
50% 
Attrition (per year) 
7.5% 
Significance level  (one-sided) 
5% 
Power 
80% 
 
Under the hypothesis and assumptions outlined above, the required sample size for this 
endpoint is 83 TREATMENT subjects. 
9.1.3.3.  Statistical Methods 
For the secondary effectiveness endpoint, the Kaplan-Meier 12 month (365-day) secondary 
effectiveness event-free rate will be calculated. Subjects who withdraw from the study prior to 
12 months without experiencing an event will be censored on the date of withdrawal.  The 95% 
one-sided lower confidence limit of the observed secondary effectiveness event-free rate will 
be compared to the performance goal of 50%. If the lower confidence limit is greater than the 

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performance goal, the null hypothesis will be rejected. The lower confidence limit will be 
calculated as the pointwise confidence limit using the log-log methodology. 
 Tertiary Endpoint 
Chronic Effectiveness: Evaluation of chronic recurrence at 24 months and 36 months  
• 
Recurrence defined as intervention for atrial fibrillation, or new onset of atrial 
flutter or atrial tachycardia (repeat procedures, use of AADs, cardioversion), 
excluding repeat procedures during the blanking period.   
• 
Data collection to include the diagnostic modality used to identify 
recurrence and the therapeutic intervention 
• 
Chronic effectiveness will be evaluated using Kaplan-Meier methodology. The 
Kaplan-Meier 24 month and 36 month chronic recurrence-free rate will be calculated 
and presented along with the 95% confidence interval, calculated as the pointwise 
confidence limit using the log-log methodology Subjects who withdraw from the study 
prior to the specified time point without experiencing an event will be censored on the 
date of withdrawal.   
Center Experience: Primary Safety and Primary Effectiveness outcomes by center 
experience 
• In order to evaluate training effectiveness for investigators outside of the ZERO AF 
IDE study, outcomes in centers performing five or more procedures using the Blazer 
OI catheter during the ZERO AF IDE study will be compared to all other centers in 
the study. Kaplan-Meier rates and 95% confidence intervals for the Primary Safety 
and Effectiveness endpoints for both groups will be presented with no statistical 
comparison. 
 
Safety:  Reportable Adverse Events rates at 12, 24 and 36 months 
Adverse events will be collected at all subject follow-up visits. 
Reportable events include: 
• All Serious Adverse Events 
• All Study Procedure-Related Adverse Events 
• All Study Device-Related Adverse Events 
• All Study Device Deficiencies 
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
previously not defined in the Directions For Use. 
• Adverse event rates will be calculated using binomial methodology. The cumulative 
number of events and event rate will be included in all study reports. Subjects at risk 
for an adverse event will be determined by the subject treatment status; all treatment 
and attempt subjects will be considered at risk for study related adverse events 
Effectiveness: Acute Procedural Success Rate 

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Acute Procedural Success is defined as pulmonary vein isolation achieved with a Boston 
Scientific OI ablation catheter as demonstrated by map-based entrance block with exit block 
and other maneuvers (such as adenosine testing) at the discretion of the physician. 
 Total sample size 
A total of 415 subjects will be enrolled in the study to ensure a minimum of 329 
TREATMENT subjects. 
9.2. General Statistical Methods 
 Analysis Sets 
While each endpoint was individually powered, each endpoint analysis will use all available 
data from all eligible subjects, regardless of original calculated sample size. 
 Control of Systematic Error/Bias 
Selection of patients will be made from the Investigator’s usual patient load. All patients 
meeting the eligibility criteria and having signed the ICF will be eligible for enrollment in the 
study.   
 Study Success and Control of Type I Error 
Each primary endpoint can be tested at the significance level of 5% while still maintaining the 
overall type I error level at no greater than 5%. This follows the methodology of the 
Intersection-Union Test (IUT).  If both primary endpoints are passed then a gating approach 
will be employed to test the secondary effectiveness endpoint at a significance level of 5%. 
 Number of Subjects per Investigative Site 
To avoid any center effect and bias, one center will not be authorized to enroll more than 41 
subjects (10% of the minimum 415 enrollment total). 
9.3. Data Analyses 
 Interim Analyses and Progress Report Content 
No formal interim analyses are planned for the purpose of stopping the study early for declaring 
effectiveness or for futility.  Analysis of each endpoint will be performed when all applicable 
data for that endpoint has been collected. Analysis of the 12-month endpoints (Primary Safety, 
Primary Effectiveness, Secondary Effectiveness and all additional analyses pertaining to these 
endpoints) will be included in a Primary Endpoint Report. Additionally, Kaplan-Meier 
analyses for the Primary Safety Endpoint events using all available data at the time of the report 
will be included in interim progress reports to the FDA.  These analyses will use the same 
definition of safety events used in the Primary Safety Endpoint but will censor active subjects 
who have not experienced an endpoint event and have not completed their 12-month follow-
up on the day of the data snapshot.  

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Progress reports will be provided to the FDA every 6 months for the first two years and 
annually thereafter. Reports will include sections outlined in the relevant FDA guidance 
pertaining to Post Approval Studies. At minimum, the progress reports will contain the 
following: 
• Number of study sites with enrolled subjects 
• Summary of subject enrollment, subject status, and demographics 
• Analysis of Primary Safety Endpoint events 
• Summary of adverse events, deaths, deviations, and device deficiencies 
 
Results from the progress reports will be posted on the FDA PAS website 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma_pas.cfm).   
 Subgroup Analyses 
An analysis will be performed for the primary endpoints to determine whether significant 
differences exist in endpoint results between subgroups.  The list of covariates (with applicable 
subgroups in parentheses) includes the following: 
• Sex (Female vs. Male) 
• Age at time of consent (subjects > 60 years vs subjects ≤60 years and subjects > 70 
years vs subjects ≤70) 
• Repeat procedures in the blanking period (Repeat procedure within 90 days of index 
procedure vs. no repeat procedure within 90 days of index procedure) 
• Ablation technique (PVI only vs. PVI + additional ablations) 
• Use of device features (DirectSense used in the index procedure vs DirectSense not 
used in the index procedure). 
Each subgroup covariate will be included as a single independent variable in a logistic 
regression model with the primary endpoint outcome as the dependent variable and a test for 
significance at the 15% level will be performed.  
 Center Pooling Analysis 
Center-to-center heterogeneity will be assessed for the primary endpoints by performing a 
random effects logistic regression analysis.  Centers with less than five enrollments will be 
combined to form “supercenters”. Small centers will be combined until the newly created 
supercenter has five enrollments, and then a new supercenter will be created. Centers will be 
deemed to be heterogeneous if the variance of the random center effect is found to significantly 
differ from zero.  A significance level of 15% will be used for this test. 
 Catheter Type Pooling Analysis 
Heterogeneity of outcomes by catheter type will be assessed for the primary endpoints by 
performing a logistic regression analysis with the primary endpoint outcome as the dependent 
variable and Catheter Type as the independent variable.  Outcomes for the Blazer 
OI/IntellaNav OI catheters will be deemed to be heterogeneous with outcomes for the 

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IntellaTip MiFi OI/IntellaNav MiFi OI catheters if no statistical association is found between 
catheter type and the primary endpoint outcomes through the logistic models.   A significance 
level of 15% will be used for this test. 
 Additional Analyses 
An analysis will be done for each primary endpoint stratifying results by catheter type (Blazer 
OI/IntellaNav OI and IntellaTip MiFi OI/IntellaNav MiFi OI). 
Additional analyses will also be done to characterize the procedural workflow data in AF 
ablation cases with the Rhythmia Mapping System. Procedural workflow data will include, 
but not be limited to: 
• electro-anatomical mapping information 
• ablation gap detection (including gap detection techniques)  
• ablation techniques (including use of DirectSense)  
 Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan approved prior to performing the analyses.  
Changes from the planned statistical methods after performing the analyses will be 
documented in the clinical study report along with a reason for the deviation. 
10. Data Management 
10.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case report 
forms (eCRFs) in compliance with local regulations. A written signature on printouts of the 
eCRFs must also be provided if required by local regulation. Changes to data previously 
submitted to the sponsor require a new electronic signature by the Investigator acknowledging 
and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data discrepancies. 
Manual and/or automatic queries will be created in the Medidata EDC system and will be 
issued to the site for appropriate response. Site staff will be responsible for resolving all queries 
in the database. 

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10.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all essential 
study documents and source documentation that support the data collected on the study 
subjects in compliance with applicable regulatory requirements.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or his/her 
designee withdraws responsibility for maintaining these essential documents, custody must be 
transferred to an individual who will assume responsibility and BSC must receive written 
notification of this custodial change. Sites are required to inform Boston Scientific in writing 
where paper or electronic files are maintained in case files are stored off site and are not readily 
available. 
10.3. Technical Source Forms 
The Technical Source Form (TSF) is the approved document to capture protocol required data 
elements that are not duplicated in any other source documents. This form requires review and 
approval by the investigator and is to be used by the study sites as a source document. 
Collection and completion of all information on the Technical Source Form is the 
responsibility of the appropriately delegated site personnel. If available, the mapping specialist 
will provide the delegated site personnel with the study related data collected during the case 
directly from the Rhythmia Mapping system. 
At the conclusion of the procedure, the completed technical source form must be signed (and 
initialed as needed) by the following people: 
• the Delegated Site Personnel completing the forms 
• the Delegated Investigator conducting and/or supervising the case 
• the Rhythmia Mapping Specialist supporting the case 
10.4. Core Laboratories 
 Event Monitor and 24-Hour Holter Monitors  
10.4.1.1. Event Monitor 
A centralized research company will provide the center and/or subject all necessary 
instructions and/or materials related to the use of the event monitor.  Only TREATMENT 
subjects will be provided with an event monitor, such as a Trans-Telephonic Monitor (TTM), 
either prior to discharge from the hospital or will be sent to the subject’s residence immediately 
following discharge.  Subjects will be instructed to collect any symptomatic ECG recordings 
with the event monitor and transmit the recordings to the centralized research company.  All 
events will be analyzed by the centralized research company to determine if the episodes are 
associated with arrhythmia recurrence.   
Within the first 90 days (3 months) after the index ablation procedure (blanking period), 
TREATMENT subjects will be instructed to transmit all symptomatic episodes for detection 
and treatment of early recurrences.  All subjects will be instructed to submit at least two 

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transmissions every month from their 3 month follow-up visit until their 12 month follow-up 
visit to ensure continued symptomatic reporting compliance.  If a subject has a symptomatic 
episode within the month, that transmission will count towards the required transmissions.  The 
centralized research company will work with the investigational site and directly with the 
subject to ensure reporting compliance.   
All event monitors must be returned to the centralized research company upon completion of 
a subject’s 12-month follow-up or withdrawal from the study.   
10.4.1.2. 24-Hour Holter Monitors 
All TREATMENT subjects will be provided with 24-Hour Holter Monitors during the 12-
month and 36-month follow-up visit window.  
Investigational centers will be trained on the set-up of the monitors and will provide the 
subjects with the instructions necessary to complete the test.  If a subject has a symptomatic 
episode while wearing the Holter Monitor, they will be strongly encouraged to report the 
symptoms to their physician.  Once the Holter Monitor is returned to the centralized research 
company, the monitor will be analyzed for all symptomatic and asymptomatic arrhythmia 
episodes, and investigators will be informed of the results.   
11. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect the 
life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC/REB of any deviation from the investigational plan to 
protect the life or physical well-being of a subject in an emergency, and those deviations which 
affect the scientific integrity of the clinical investigation. Such notice shall be given as soon as 
possible, but no later than five working days after the emergency occurred, or per prevailing 
local requirements, if sooner than five working days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using EDC.  Sites may also be 
required to report deviations to the IRB/EC/REB, per local guidelines and government 
regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/EC/REB/FDA notification, site re-training, 
or site discontinuation/termination) will be put into place by the sponsor. 
12. Compliance 
12.1. Statement of Compliance 
This study will be conducted in accordance with post market clinical follow-up guidelines and 
will follow the applicable sections of ISO 14155 (Clinical Investigation of Medical Devices 
for Human Subjects – Good Clinical Practice), the relevant parts of the ICH Guidelines for 
Good Clinical Practices, ethical principles that have their origins in the Declaration of Helsinki, 

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and applicable individual country laws and regulations. The study shall not begin until the 
required approval/favorable opinion from the IRB/EC/REB and/or regulatory authority has 
been obtained, if appropriate. Also, the study shall not begin prior to issuance of the site 
Authorization to Enroll, as provided by the sponsor. Any additional requirements imposed by 
the IRB/EC/REB or regulatory authority shall be followed, if appropriate.  
12.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation plan, 
the spirit of ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, 
any conditions of approval imposed by the reviewing IRB/EC/REB, and prevailing local and/or 
country laws and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to sponsor, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
• Report to the IRB/EC/REB and regulatory authorities any SAEs and device 
deficiencies that could have led to a SADE and potential/USADE or UADE, if required 
by applicable laws or regulations or this protocol or by the IRB/EC/REB, and supply 
BSC with any additional requested information related to the safety reporting of a 
particular event. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to 
the clinical research monitor or auditor and respond to questions during monitoring 
visits or audit(s). 
• Allow and support regulatory authorities and the IRB/EC/REB when performing 
auditing activities. 

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• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC/REB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in 
a clinical study in the case of adverse events, as described in the Informed Consent 
Form (ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the device when it is used/operated by the subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, 
as needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together 
with identification and compliance information for concomitant treatment measures 
(contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained 
and documented during the clinical investigation. 
 Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, ensuring delegates are competent to perform the tasks they have been 
delegated and adequate supervision of those to whom tasks are delegated. Where there is a 
sub-Investigator at a site, the sub-Investigator should not be delegated the primary supervisory 
responsibility for the site. The Principal Investigator is accountable for regulatory violations 
resulting from failure to adequately supervise the conduct of the clinical study.  
12.3. Institutional Review Board/ Ethics Committee 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB/EC/REB for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 

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A copy of the written IRB/EC/REB and/or competent authority (CA) approval of the protocol 
(or permission to conduct the study) and Informed Consent Form, must be received by the 
sponsor before recruitment of subjects into the study. Prior approval must also be obtained for 
other materials related to subject recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/EC/REB before 
the changes are implemented to the study.  All changes to the ICF will be IRB/EC/REB 
approved; a determination will be made regarding whether a new ICF needs to be obtained 
from participants who provided consent, using a previously approved ICF.  
Annual IRB/EC/REB approval and renewals will be obtained throughout the duration of the 
study as required by applicable local/country laws or regulations or IRB/EC/REB 
requirements. Copies of the study reports and the IRB/EC/REB continuance of approval must 
be provided to the sponsor.  
12.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
 Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during index procedure, testing required by the 
protocol, and follow-ups. Support may include HCP training, addressing HCP questions, or 
providing clarifications to HCPs concerning the operation of BSC equipment/devices. 
 
At the request of the investigator and while under investigator supervision, typical tasks of 
BSC personnel may include the following as allowed by local regulations: 
• Setting up, calibrating and/or operating parameters to investigator-requested settings of the 
RhythmiaTM Mapping System and other supporting equipment during the preparation and 
execution of the mapping and ablation procedure. 
• Clarifying device behavior, operation or diagnostic output as requested by the investigator 
or other health care personnel. 
• Interaction with Boston Scientific noninvasive equipment (Rhythmia workstation and 
accessories) and interpretation of information contained therein to support the collection 

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of required information by the delegated site staff. BSC Personnel may review for 
completeness and accuracy. 
• Collect/Archive anonymized data directly from the Rhythmia Mapping System or other 
supporting equipment, print reports and/or provide any original documentation to the 
clinical site as source. 
• Interact with the subject to accomplish requested activities. 
• Assist with the conduct of testing specified in the protocol. 
• Observe any testing or medical procedures to provide information relevant to protocol 
compliance. 
 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
• Discuss a subject’s condition or treatment with a subject without the approval and presence 
of the investigator 
• Record data on Source documents 
• Independently collect critical study data (defined as primary or secondary endpoint data) 
• Enter data in electronic data capture systems or on paper case report forms 
12.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC for 
subjects in the study will be obtained. 
13. Monitoring 
Monitoring will be performed by Boston Scientific or its designees during the study. A 
combination of on-site, remote, or central monitoring will be used to assess continued 
compliance with the protocol and applicable regulations. This includes ensuring proper 
informed consent process, review of safety data, and adherence to protocol defined visit 
schedule. In addition, the clinical research monitor verifies that study records are adequately 
maintained, that data are reported in a satisfactory manner with respect to timeliness, adequacy, 
and accuracy, and that the Principal Investigator continues to have sufficient staff and IRB 
approved facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 

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14. Potential Risks and Benefits 
14.1. Directions for Use 
Please refer to the Directions for Use for an overview of anticipated adverse (device) effects, 
and risks associated to the commercial device(s).   
14.2. Risks associated with Participation in the Clinical Study 
Risks associated with participation in the study are those applicable to paroxysmal RF ablation 
and mapping procedures.   
14.3. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject selection 
criteria, close monitoring of the subject's physiologic status during research procedures and/or 
follow-ups and by promptly supplying BSC with all pertinent information required by this 
protocol. 
14.4. Anticipated Benefits 
There may be no benefit to the subject. However, currently enrolled subjects may benefit from 
their participation in this study due to a closer follow up. Medical science and future patients 
may benefit from the results of this clinical protocol. 
14.5. Risk to Benefit Rationale, if applicable 
Risk management activities, including Hazard Analyses (HA) and Failure Mode Effects 
Analyses (FMEA), have been performed on the Blazer OI catheters and cables (used with 
Stockert 70/EP-Shuttle Generator/Cool Flow Pump system) to identify and analyze known and 
foreseeable hazards (in both normal and fault conditions) and reasonably foreseeable 
sequences or combinations of events that could result from using this product and the risks 
associated with each hazard.  Mitigations have been implemented in the design, processes, 
and/or labeling and Directions For Use of the product to reduce the residual risk of each hazard 
as necessary and practicable.  The HA has been reviewed and approved and the remaining risks 
are acceptable when weighed against the intended benefits to the subject. 
15. Safety Reporting 
15.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All Serious Adverse Events 
• All Study Procedure-Related Adverse Events 

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• All Study Device-Related Adverse Events 
• All Study Device Deficiencies 
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
previously not defined in the Directions For Use. 
 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms.  If it is unclear whether or not an event fits one of the above categories, 
or if the event cannot be isolated from the device or procedure, it should be submitted as an 
adverse event and/or device deficiency. 
All Events related to the study device or study procedure must be reported as Adverse Events. 
Pre-existing conditions and pre-planned hospitalizations at time of enrollment (including AFib, 
AFl, ATach) are not considered Adverse Events, however if they meet the criteria for Serious 
Adverse Events, they should be reported as an SAE. As stated in Table 7, all medical 
interventions are considered Serious Adverse Events, however medical intervention due to 
arrhythmia recurrence is only considered a Serious Adverse Event if the intervention takes 
place after the 90-day Blanking Period.  
Death should not be reported as an Serious Adverse Event, but should only be reflected as an 
outcome of one (1) specific SAE (see Table 7 for AE definitions). 
The following definitions will be used for defining in-patient or prolonged hospitalizations for 
SAE classification purposes: 
• In-patient hospitalizations will be defined as ≥24 hours in duration or <24 hours with 
medical intravenous therapy or surgical intervention 
• Prolonged hospitalization will be defined as ≥72 hours after the index procedure for 
reasons other than anticoagulation 
Refer to Directions for Use for the known risks associated with the commercial device(s). 
15.2. Definitions and Classification 
Adverse event definitions are provided in Table 7. Administrative edits were made on the 
safety definitions from ISO 14155 and MEDDEV 2.7/3 for clarification purposes. 
 
Table 7: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
 
 
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the study 
medical device.  
NOTE 1: This includes events related to the study medical device or 
comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 

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Table 7: Safety Definitions 
Term 
Definition 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the study medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of the study medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
study medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the study medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Note: This definition meets the reporting objectives and requirements of  
ISO 14155  and  MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to serious deterioration in the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk analysis report. 

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Table 7: Safety Definitions 
Term 
Definition 
Device Deficiency 
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
An inadequacy of the study 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. 
15.3. Relationship to Device(s) 
The Investigator must assess the relationship of the reportable AE to the device, or procedure. 
See criteria in Table 8:  
 

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Table 8: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event 
Classification 
Description 
Not Related 
Ref: MEDDEV 2.7/3 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the study device or the 
procedures; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the device 
or procedure;  
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the study device used for 
diagnosis, when applicable; harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Unlikely Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). 
Cases were relatedness cannot be assessed or no information has been obtained 
should also be classified as possible. 
Probably Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device seems relevant and/or the event 
cannot be reasonably explained by another cause, but additional information may be 
obtained. 

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Table 8: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event 
Classification 
Description 
Causal Relationship 
Ref: MEDDEV 2.7/3 
The serious event is associated with the study device or with procedures beyond 
reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, 
when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the serious event. 
 
 

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15.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 9. 
Adverse events and device deficiencies must always be reported through the eCRF system. 
However, in the event that an alternative method of reporting is necessary (i.e. the eCRF system 
is unavailable), please report the adverse event or device deficiency to Boston Scientific by 
sending the Event Notification Form via email to the following email address: 
INTERRUPTAF.Safety@bsci.com 
 
Table 9: Event Communication Requirements 
Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/2:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Unanticipated Adverse 
Device Effect / Unanticipated 
Serious Adverse Device 
Effect  
 
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within one business day of first 
becoming aware of the event. 
• 
Terminating at the end of the study. 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
Upon BSC request.  
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 10 business days after becoming 
aware of the event or as per local/regional 
regulations.  
• 
All Death Events must be reported within 
3 calendar days 
• 
For Austria: within two business days of 
first becoming aware of the event. 
• 
Reporting required through End of Study.  
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
Upon BSC request. 
Serious Adverse Device 
Effects 
Complete AE eCRF page 
with all available new and 
updated information. 
• 
Within two business days of first 
becoming aware of the event or as per 
local/regional regulations. 
• 
Reporting required through End of Study. 
Provide all relevant source 
documentation 
(unidentified) for reported 
event.  
• 
Upon BSC request. 

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Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/2:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Device Deficiencies 
(including but not limited to 
failures, malfunctions, and 
product nonconformities) 
Note:  Any Device Deficiency 
that might have led to a 
serious adverse event if a) 
suitable action had not been 
taken or b) intervention had 
not been made or c) if 
circumstances had been less 
fortunate is considered a 
reportable event. 
Complete Device 
Deficiency CRF with all 
available new and updated 
information.  
• 
Within two business days of first 
becoming aware of the event. Reporting 
required through End of Study. 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event. 
• 
At request of sponsor  
Adverse Event including 
Adverse Device Effects 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• 
In a timely manner (e.g. recommend 
within 30 business days) after becoming 
aware of the information 
• 
Reporting required through End of Study. 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
15.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failure, malfunction, use errors, product 
non-conformities, labeling errors and inadequacy in the information associated with the study 
devices) will be documented and reported to BSC. If possible, the device(s) should be returned 
to BSC for analysis. Instructions for returning the device(s) will be provided upon request. If 
it is not possible to return the device, the investigator should document why the device was not 
returned and the final disposition of the device. Device deficiencies should also be documented 
in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency would be recorded as an adverse event on the appropriate eCRF in addition 
to completing a Device Deficiency CRF. 
15.6. Reporting to Regulatory Authorities / IRBs / ECs / REBs/ Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs/ECs/REBs and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC/REB, and regulatory 
authorities of UADEs and SAEs as required by local/regional regulations. 

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15.7. Subject Death Reporting  
A subject death during the study should be reported to Boston Scientific as soon as possible 
and, in any event, within three (3) calendar days of site notification. The site’s IRB/EC must 
be notified of any deaths in accordance with that site’s IRB/EC policies and procedures.  
Notification of death must include a detailed narrative (death letter) that provides detailed 
information describing the circumstances surrounding the death. A death narrative in the local 
language is acceptable, if accompanied by a translation in English. The details listed below 
should be addressed in the death narrative, in order for BSC to understand the circumstance 
surrounding the death:  
• Date and time of death; 
• Place death occurred; 
• Immediate cause of death; 
• Rhythm at the time of death, if known (include any available documentation); 
• Whether the death was related to the study devices, clinical investigation, procedure, 
or subject condition; 
• Whether or not the death was witnessed; 
• Whether the subject had worsening heart failure; 
• Any other circumstances surrounding the death; 
• Approximate time interval from the initiating event to death (temporal course) – items 
to consider include, but are not limited to: information regarding last time subject was 
seen by investigator, last office visit, etc. 
• Investigator or co-Investigator signature and date. 
 
Also submit the following documentation, upon request from sponsor:  
If the subject expired in the hospital:  
• A copy of the medical records for that admission (e.g., H&P, consults, test results, 
operative reports, and/or progress notes from the hospital chart); 
• Death certificate (if available); 
• Autopsy report (if applicable); 
• If the subject expired outside of the hospital (e.g., home): 
• A copy of the most recent clinic visit (if not already submitted to Boston Scientific); 
• Death certificate (if available); 
• If applicable, the Boston Scientific catheters should be returned promptly to Boston 
Scientific CRM/EP for analysis. 

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16. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any study devices, study-required 
procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO), and approved by the site’s IRB/EC/REB, or central IRB, if 
applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB/EC/REB.  Any modification requires acceptance from BSC prior to 
use of the form.  The ICF must be in a language understandable to the subject and if needed, 
BSC will assist the site in obtaining a written consent translation. Translated consent forms 
must also have IRB/EC/REB approval prior to their use.  Privacy language shall be included 
in the body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, as 
well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her legal 
representative, 
• provide ample time for the subject to consider participation and ask questions if necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed consent 
process. If a legal representative signs, the subject shall be asked to provide informed consent 
for continued participation as soon as his/her medical condition allows. The original signed 
ICF will be retained by the site and a copy of the signed and dated document and any other 
written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory authority 
according to their requirements (e.g., FDA requirement is within five working days of learning 
of such an event). Any violations of the informed consent process must be reported as 
deviations to the sponsor and local regulatory authorities (e.g. IRB/EC/REB), as appropriate. 

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If new information becomes available that can significantly affect a subject's future health and 
medical care, that information shall be provided to the affected subject(s) in written form via 
a revised ICF or, in some situations, enrolled subjects may be requested to sign and date an 
addendum to the ICF. In addition to new significant information during the course of a study, 
other situations may necessitate revision of the ICF, such as if there are amendments to the 
applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC/REB. The new version of the ICF must be approved 
by the IRB/EC/REB. Acceptance by Boston Scientific is required if changes to the revised ICF 
are requested by the site’s IRB/EC/REB. The IRB/EC/REB will determine the subject 
population to be re-consented. 
17. Committees 
17.1. Safety Monitoring Process 
Clinical Sites will report all study device related AEs, study procedure related AEs, and serious 
AEs to the sponsor as assessed by the clinical investigator. Investigators will be tasked to 
determine whether a subject has experienced one of the events specified in Section 4.1, 
counting towards the primary safety endpoint. 
Since device and procedure relatedness do not affect the study endpoints, an independent CEC 
is not necessary to eliminate bias. The determination of relatedness is used for BSC safety 
assessment, but not in determining endpoint events. NOTE: The primary safety endpoint 
includes all deaths within 7 days or pre-discharge (whichever is later) regardless of relatedness 
to study device or procedure. 
All reported adverse events will be reviewed on a regular basis by BSC’s Medical Safety Group 
and study team to evaluate subject safety. The BSC Medical Safety group includes physicians 
with expertise in Electrophysiology and with the necessary therapeutic and subject matter 
expertise to evaluate and classify the events. During scheduled monitoring activities, clinical 
research monitors will support this continuous review through their review of source document 
and other data information. 
17.2. Steering Committee 
A Steering Committee composed of the sponsor’s Clinical Management, the study Principal 
Investigator, and other prominent Electrophysiologists from around the globe has been 
convened for this study.  Responsibilities for the Committee may include oversight of the 
overall conduct of the study with regard to protocol development, study progress, subject 
safety, overall data quality and integrity, and first line review and final decision making of 
independent medical reviewer recommendations, as well as disseminating any study results 
through appropriate scientific sessions and publications.  Steering Committee members may 
participate in the review and approval of all requests for data analysis, abstract and manuscript 
preparation, and submission.   

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18. Suspension or Termination 
18.1. Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs/REBs, and regulatory authorities, as applicable, 
will be notified in writing in the event of study termination. 
18.2. Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the following. 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue 
development/marketing of the device. 
18.3. Termination of Study Participation by the Investigator or Withdrawal of IRB/ 
EC/REB Approval 
Any investigator, or associated IRB/ EC/ REB or regulatory authority in the INTERRUPT AF 
Study may discontinue participation in the study or withdraw approval of the study, 
respectively, with suitable written notice to Boston Scientific. Investigators, associated 
IRBs/ECs/REBs, and regulatory authorities, as applicable, will be notified in writing in the 
event of these occurrences. 
18.4. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC/REB and regulatory authorities, as applicable, will be notified. Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB/EC/REB terminates participation in the study, participating investigators, 
associated IRBs/ECs/REBs, and regulatory authorities, as applicable, will be notified in 
writing. Detailed information on how enrolled subjects will be managed thereafter will be 
provided by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled subjects 
will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
devices, if supplied by Boston Scientific, unless this action would jeopardize the rights, safety, 
or welfare of the subjects. 

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18.5. Criteria for Suspending/Terminating a Study Site 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time 
after the study initiation visit if no subjects have been enrolled for a period beyond six months 
after site initiation, or if the site has multiple or severe protocol violations/noncompliance 
without justification and/or fails to follow remedial actions. 
In the event of termination of site participation, all devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB/EC/REB and regulatory authorities, as applicable, will be 
notified. Study participants will be contacted, as applicable, and be informed of changes to 
study visit schedule. 
19. Clinical Trial Registration and Results Posting 
This research-study is registered on http://www.ClinicalTrials.gov, as required by U.S. Law 
and other jurisdictions.  
In Japan, Investigator shall register a summary of this research-study in one public database 
operated by the National University Hospital Council of Japan, the Japan Pharmaceutical 
Information Center, or the Japan Medical Association. Below are the lists of public database 
available: 
• UMIN-CTR: http://www.umin.ac.jp/ctr/index-j.htm 
• Iyaku Search: http://database.japic.or.jp/is/top/index.jsp 
• JMA CCT: https://dbcentre3.jmacct.med.or.jp/jmactr/ 
Investigator shall update the registered contents appropriately according to revisions of the 
research-study protocol, the progress of the research-study, and shall register the results of 
the research-study when the research is completed. 
20. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC will submit study results 
for publication (regardless of study outcome) following the conclusion or termination of the 
study. Boston Scientific adheres to the Contributorship Criteria set forth in the Uniform 
Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed.  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should be 
discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 

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• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available to 
other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/).  
21. Reimbursement and Compensation for Subjects 
21.1. Compensation for Subject’s Health Injury 
Boston Scientific will purchase an insurance policy to cover the cost of potential health 
injury for study subjects, if required by applicable law.  
22. Bibliography 
1. Rosamond, W., Flegal, K., Friday, G., et al. Heart disease and stroke statistics—2007 update: 
a report from the American Heart Association Statistics Committee and Stroke Statistics 
Subcommittee. Circulation, 2007;115:e69–e171. 
2. January CT, Wann LS, Alpert JS, et al. American College of Cardiology/American Heart 
Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the 
management of patients with atrial fibrillation: a report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart 
Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76.  
3. Friberg J BP, Scharling H. Rising rates of hospital admissions for atrial fibrillation. 
Epidemiology 2003;14 666-672 
4. Chugh SS, Havmoeller R, Narayanan K, Singh et al. Worldwide epidemiology of atrial 
fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129(8):837-47 
5. Wolf PA BEaBA. Secular trends in the prevalence of atrial fibrillation: The framingham 
study. Am heart J 1996;131:790-795 
6. Benjamin E, Wolf, PA, D'Agostino, RB, et al. Impact of atrial fibrillation on the risk of 
death: The framingham heart study. Circulation. 1998;98:946-952 
7. Hamer M, Blumenthal, JA, McCarthy EA, et al. Quality-of-life assessment in patients with 
paroxysmal atrial fibrillation or paroxysmal supraventricular tachycardia. Am J Cardiol. 
1994;74:826-829 
8.Dorian P M, I. Quality of life variables in the selection of rate versus rhythm control in 
patients with atrial fibrillation: Observations from the canadian trial of atrial fibrillation. Card 
Electrophysiol. 2003;Rev 7:276-279 
9. Lip GY, Hee FL. Paroxysmal atrial fibrillation. QJM. 2001 Dec;94(12):665-78 
10 .Wijffels M, Kirchhof CJ, Dorland, R, et al. Atrial fibrillation begets atrial fibrillation.  A 
study in awake chronically instrumented goats. Circulation. 1995;92:1954-1968 

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11. Wazni O, Wilkoff, B, Saliba, W. Catheter ablation for atrial fibrillation. New Engl J Med. 
2011;365:2296-2304 
12. Hassiguierre M J, P, Shah DC, et al. Electrophysiological end point for catheter ablation of 
atrial fibrillation initiated from multiple pulmonary venous foci. Circulation. 2000;101:1409-
1417 
13. Hassiguierre M, Shah, DC, Jais, P, et al. Electrophysiological breaktrhough from the left 
atrium to the pulmonary veins. Circulation. 2000;102:2463-2465 
14.Keane D R, J. Pulmonary vein isolation for atrial fibrillation. Rev Cardiovasc Med. 
2002;3:167-175 
15.Chen SA H, MH, Tai, CT, et al. Initation of atrial fibrillation by ectopic beats originating 
from the pulmonary veins: Electrophysiolgical characteristics, pharmacological responses, and 
effects of radiofrequency ablation. Circulation. 1999;100:1879-1886 
16. Calkins H, Hindricks G, Cappato R, Kim YH, Saad EB, Aguinaga L, Akar JG, Badhwar 
V, Brugada J, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement 
on catheter and surgical ablation of atrial fibrillation: Executive summary. Europace. 
2018;20(1):157-208. 
17.Nakagawa H,  Yamanashi WS,  Pitha JV, et al. Comparison of in vivo tissue temperature 
profile and lesion geometry for radiofrequency ablation with a saline-irrigated electrode versus 
temperature control in a canine thigh muscle preparation, Circulation , 1995, 91 (pg. 2264-
2273) 
18. Thomas SP, Aggarwal G, Boyd AC, Jin Y, Ross DL. A comparison of open irrigated and 
non-irrigated tip catheter ablation for pulmonary vein isolation. Europace. 2004;6:330-5. 
19. Yamamoto T, Yamada T, Yoshida Y, Inden Y, Tsuboi N, et al. Comparison of the change 
in the dimension of the pulmonary vein ostia immediately after pulmonary vein isolation for 
atrial fibrillation-open irrigated-tip catheters versus non-irrigated conventional 4 mm-tip 
catheters. J Interv Card Electrophysiol. 2014;4:83-90. 
20. Ben-Haim SA, Osadchy D, Schuster I, Gepstein L, Hayam G, Josephson ME. 
Nonfluoroscopic, in-vivo, Navigation and Mapping Technology. Nature Medicine 
1996;2:1393-5 
21. Knackstedt C, Schauerte P, Kirchhof P Electro-anatomic mapping systems in arrhythmias. 
Europace. 2008 Nov; 10 Suppl:iii28-34. 
22. Kosiuk J, Hilbert S, John S, Bertagnolli L, Hindricks G, Bollmann A. Preliminary 
experience with high-density electroanatomical mapping for ablation of atrial fibrillation - 
Comparison of mini-basket and novel open irrigated magnetic ablation catheter in consecutive 
patients. International journal of cardiology. 2017;228:401-405. 
24. NAVISTAR® THERMOCOOL® Catheter Post Approval Registry (AF Registry). 
ClinicalTrials.gov Web site: 
https://www.clinicaltrials.gov/ct2/show/results/NCT00964392?term=navistar+ablation&draw
=1&rank=4&sect=X01256#all . Accessed December 1, 2017. 

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25. SMART-SF Radiofrequency Ablation Safety Study. CinicalTrials.gov Web site. 
https://www.clinicaltrials.gov/ct2/show/NCT02359890?term=atrial+fibrillation+ablation+sm
arttouch&rslt=With&rank=1.  Accessed December 1, 2017. 
26. ZERO-AF clinical study data (P150005/S014) 
27. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and 
surgical ablation of atrial fibrillation: Executive summary; Calkins H., et al. (2017)  Heart 
Rhythm,  14  (10) , pp. e445-e494  
28. Dukkipati SR, et al. Pulmonary vein isolation using the visually guided laser balloon: a 
prospective, multicenter, and randomized comparison to standard radiofrequency ablation. J 
Am Coll Cardiol 2015;66(12):1350–60. 
29. Kuck KH, et al. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. 
N Engl J Med 2016;374(23):2235–45. 
30. Lo LW et al , Predictors and Characteristics of Multiple (More Than 2) Catheter Ablation 
Procedures for Atrial Fibrillation. J Cardiovasc Electrophysiol. 2015 26(10):1048-56.  
 
 

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23. Abbreviations and Definitions  
23.1. Abbreviations 
Abbreviations are shown in Table 10.   
Table 10: Abbreviations 
Abbreviation/Acronym 
Term 
AAD 
Anti-Arrhythmic Drug 
CABG 
Coronary artery bypass grafting 
CRT 
Cardiac Resynchronization Therapy 
CVA 
Cerebral Vascular Accident 
EDC 
Electronic Data Capture 
ICD 
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
OI 
Open-Irrigated 
PAF  
Paroxysmal Atrial Fibrillation 
PE 
Pulmonary Embolism 
PTCA 
Percutaneous transluminal coronary angioplasty 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
TEE 
Trans-esophageal echocardiography 
TIA 
Transient Ischemic Attack 
 
 
23.2. Definitions 
Terms are defined in Table 11.  
Table 11: Definitions 
Term 
Definition 
Ablation Attempt 
One or more RF ablations targeted at a single gap closure. An attempt is 
considered complete once isolation is tested. 
Activated Coagulation/Clotting 
Time 
ACT is a test that is used to monitor the effectiveness of high dose heparin 
therapy. 
Arterial-Venous Fistula 
Abnormal communication between an artery and a vein. 
Atrio-Esophageal Fistula 
A connection between the atrium and the lumen of the esophagus 
ATTEMPT Subject 
Any subject that signs the consent form, meets eligibility criteria and has 
any study device inserted into the body but does not receive RF ablation 
per protocol.  
AV block 
A conduction disturbance that results in the partial inability of an electrical 
impulse generated in the atria to reach the ventricles. 
Blanking Period 
90-day period between ablation procedure and the initiation of the 
Effectiveness Evaluation Period during which up to one additional ablation 
procedures can be performed and subjects can be prescribed 
antiarrhythmic drugs as determined necessary by the investigator. 

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Table 11: Definitions 
Term 
Definition 
Cardiac tamponade/ 
perforation 
 
The development of a significant pericardial effusion during or within 30 
days of undergoing an AF ablation procedure. A significant pericardial 
effusion is one that results in hemodynamic compromise, requires elective 
or urgent pericardiocentesis, or results in a 1-cm or more pericardial 
effusion as documented by echocardiography.  
Embolism 
The sudden blocking of an artery by a clot or foreign material which has 
been brought to its site of lodgment by the blood current. 
Enrolled Subject 
A subject who is eligible for enrollment and signs an informed consent 
document to participate in the study. 
Hematoma 
A localized collection of blood, usually clotted, in an organ, space or 
tissue, due to a break in the wall of a blood vessel. 
INTENT Subject 
Any subject that signs the consent form but does not have any study 
devices inserted into the body. Subjects who are enrolled in the study but 
do not undergo ablation procedure within 60 days from consent signature 
date may not be reconsented and will be withdrawn from the study. 
In-patient Hospitalization 
Hospitalizations ≥24 hours in duration or <24 hours with medical 
intravenous therapy or surgical intervention 
Myocardial infarction (in 
the context of AF 
ablation) 
The presence of any one of the following criteria:  
(1) detection of ECG changes indicative of new ischemia (new STT 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 
Paroxysmal Atrial Fibrillation 
(PAF) 
Recurrent symptomatic Atrial Fibrillation that terminates spontaneously or 
with intervention within seven days of onset. 
Pericardial Effusion 
A collection of fluid or blood in the pericardial space around the heart or in 
pleural space around the lungs. 
Pericarditis 
Inflammation of the pericardium surrounding the heart.  Pericarditis should 
be considered a major complication following ablation if it 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. 
Pneumothorax 
Collapse of the lung due to an abrupt change in the intrapleural pressure 
within the chest cavity. 
Primary Effectiveness Failure 
A TREATMENT subject being an acute procedure failure, having more 
than one repeat procedure during the blanking period, or having any of the 
following between 91 days and 12 months post-procedure: 
• documented atrial fibrillation, or new onset of atrial flutter or atrial 
tachycardia event (≥ 30 seconds in duration from an event monitor or 
Holter, or from a 10 second 12-lead EKG) 
any of the following interventions for atrial fibrillation, or new onset of 
atrial flutter or atrial tachycardia between 91 days and 365 days post index 
procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed any AAD 

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Table 11: Definitions 
Term 
Definition 
Procedural Success 
Pulmonary vein isolation achieved with a Boston Scientific OI ablation 
catheter as demonstrated by map-based entrance block with exit block and 
other maneuvers (such as adenosine testing) at the discretion of the 
physician. 
Prolonged Hospitalization 
Hospitalization ≥72 hours after the study procedure for reasons other than 
anticoagulation 
Pseudoaneurysm 
A dilation of an artery with disruption of one or more layers of its walls. 
Pulmonary Vein Stenosis 
(Significant) 
 
Pulmonary vein stenosis is defined as a reduction of the diameter of a PV 
or PV branch. For the primary safety endpoint of this study, significant 
pulmonary vein stenosis is defined as symptomatic and requiring 
intervention. 
Pulmonary edema/heart failure 
Ineffective pumping of the heart leading to an accumulation of fluid in the 
lungs. Typical symptoms include shortness of breath with exertion, 
difficulty breathing when lying flat and leg or ankle swelling. 
Secondary Effectiveness Failure 
A TREATMENT subject being an acute procedure failure, having more 
than one repeat procedure during the blanking period, or having any of the 
following between 91 days and 12 months post-procedure: 
• documented symptomatic atrial fibrillation, or new onset of atrial flutter 
or atrial tachycardia event (≥ 30 seconds in duration from an event monitor 
or Holter, or from a 10 second 12-lead EKG) 
• any of the following interventions for atrial fibrillation, or new onset of 
atrial flutter or atrial tachycardia between 91 days and 365 days post 
study procedure: 
• 
Repeat procedure 
• 
Cardioversion 
• 
Prescribed a higher dose of any AAD documented at baseline 
• 
Prescribed a new AAD not documented at baseline 
Source Data 
All information in original records of clinical findings, observations, or 
other activities in a clinical investigation, necessary for the reconstruction 
and evaluation of the clinical study (original records or certified copies). 
Source Document 
Printed, optical or electronic document containing source data. Examples: 
Hospital records, laboratory notes, device accountability records, 
radiographs, records kept at the investigation site, and at the laboratories 
involved in the clinical study. 

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Table 11: Definitions 
Term 
Definition 
Stroke/Cerebrovascular accident 
(CVA) 
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 one side of the body, dysphasia 
or aphasia, hemianopia, amaurosis fugax, or other neurological signs or 
symptoms consistent with stroke. 
Duration of a focal or global neurological deficit ≥24 hours; OR <24 hours 
if therapeutic intervention(s) were performed (e.g., thrombolytic therapy or 
intracranial angioplasty); OR available neuroimaging documents a new 
hemorrhage or infarct; OR the neurological deficit results in death. 
No other readily identifiable non-stroke cause for the clinical presentation 
(e.g., brain tumor, trauma, infection, hypoglycemia, peripheral lesion, 
pharmacological influences). 
Confirmation of the diagnosis by at least one of the following: neurology 
or neurosurgical specialist; neuroimaging procedure (MRI or CT scan or 
cerebral angiography); lumbar puncture (i.e., spinal fluid analysis 
diagnostic of intracranial hemorrhage) 
Symptomatic AF 
Required symptom(s) of AF that were experienced by the subject, made 
them seek medical attention, and were concurrent with a documented 
episode by ECG, event monitoring and/or Holter monitor. Symptoms may 
have included palpitations, irregular pulse (i.e. rapid, racing, pounding, 
fluttering, bradycardic), dizziness, weakness, chest discomfort, and 
breathlessness. 
Thrombus 
An aggregation of blood factors, primarily platelets and fibrin with 
entrapment of cellular elements, frequently causing vascular obstruction at 
the point of its formation. 
Thromboembolism 
The blockage of a blood vessel lumen by air or solid material such as 
device fragments, blood clot or other tissues that have migrated from 
another anatomic site. 
Transient Ischemic Attack (TIA) 
New focal neurological deficit with rapid symptom resolution (usually 1 to 
2 hours), always within 24 hours; neuroimaging without tissue injury 
TREATMENT Subject 
Any subject that signs the consent form, meets eligibility criteria and has 
the specified study devices inserted into the body and undergoes protocol 
specific treatment for the intended disease. 
Vagal Nerve 
Injury/Gastroparesis  
Vagal nerve injury is defined as injury to the vagal nerve that results in 
esophageal dysmotility or gastroparesis.  Vagal nerve injury is considered 
to be a major complication if it prolongs hospitalization, requires 
hospitalization, or results in ongoing symptoms for more than 30 days 
following an ablation procedure 
Vascular access complications 
Development of a hematoma, an AV fistula, or a pseudoaneurysm. A 
major vascular complication is defined as one that requires intervention, 
such as surgical repair or transfusion, prolongs the hospital stay, or 
requires hospital admission. 

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24. Appendices 
24.1. Quality of Life Instruments 
Clinical trials increasingly recognize the value of including patient reported outcome measures 
in their design. To understand the impact of atrial fibrillation ablation procedures on patient’s 
quality of life, the quality of life instruments used for the trial will be the EQ-5D-5L for a 
generic questionnaire and the AFEQT for disease specific. Subjects will be asked to complete 
the questionnaires at the Enrollment visit as well as at the three, six, and 12 month follow-ups.   
The EQ-5D, generic quality of life measure, will be used to assess health utilities. It is a 
descriptive system of health-related quality of life states consisting of five dimensions 
(mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can 
take one of five responses. The responses record five levels of severity (no problems/slight 
problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D 
dimension. 
The Atrial Fibrillation Effect on Quality of Life (AFEQT) was developed to evaluate disease-
specific quality of life for patients with atrial fibrillation. The 20-item questionnaire is 
subdivided into three domains: symptoms, daily activities, and treatment concerns with 
responses provided on a seven-point Likert scale.  
24.2. Clinical Trial Organization 
Any Clinical Trial Organization used will be documented and available on a separate 
document.