ELectrical COupling Information From The Rhythmia HDx Mapping System And DireCtSense Technology In The Treatment Of Paroxysmal AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation
Sponsor: Boston Scientific Corporation

PM007  
  
Confidential   
 
 
 
LOCALIZE protocol, document 92142978, Rev/Ver AB 
 
COVER PAGE 
for posting publicly Localize Protocol on ClinicalTrials.gov web site 
 
 
 
Protocol title: ELectrical COupling Information From The RhythmiaTM HDx 
Mapping System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
 
Protocol code: PM007 
 
Protocol date and version: October 5, 2017 – Ver AB 
 
NCT number: 03232645 
 
 

PM007                                                                        Form/Template 90702637 Rev/Ver AH 
Confidential   
                       LOCALIZE protocol, document 92142978, Rev/Ver AB 
Page 1 of 65 
 
 
 
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study 
(LOCALIZE) 
 
CLINICAL INVESTIGATION PLAN 
 
PM007 
 
 
Sponsored By 
Boston Scientific Corporation 
4100 Hamline Ave. N. 
St. Paul, MN 55112 
 
and 
 
Guidant Europe NV,  
RM 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. 
 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 1 of 65

PM007                                                             PM007 Form/Template 90702637 Rev/Ver AH 
Confidential                                                  LOCALIZE, document 92142978, Rev/Ver AB 
                                                                                                                                 Page 2 of 65 
  
 
 
 
Contact Information 
Role 
Contact  
Clinical Contact 
Clinical Trial Managers, Protocol Authors 
Giovanni Raciti 
Sr. Clinical Trial Manager 
Guidant Europe, a Boston Scientific Company 
Green Square, Lambroekstraat 5D 
 
1831 Diegem 
Belgium 
Tel. +39 34 82 50 26 87 
Giovanni.raciti@bsci.com 
 
Elke Sommerijns 
Sr. Clinical Trial Manager 
Guidant Europe, a Boston Scientific Company 
Green Square, Lambroekstraat 5D 
 
1831 Diegem 
Belgium 
Phone: +32 479 76 71 56 
Elke.sommerijns@bsci.com 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 2 of 65

PM007                                                             PM007 Form/Template 90702637 Rev/Ver AH 
Confidential                                                  LOCALIZE, document 92142978, Rev/Ver AB 
                                                                                                                                 Page 3 of 65 
  
 
Original Release: July 12, 2017 
Current Version: October 5, 2017 
 
Revision History 
Revision 
Number 
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for Change 
AA 
July 12, 2017 
90702637 Ver 
AH 
/ 
/ 
Initial release 
AB 
October 5, 
2017 
90702637 Ver 
AH 
Protocol 
Synopsis and 
Section 8.1 
 
 
Section 20.1 
/ 
The number of sites was 
increased from 5 to 6. 
 
 
Cardiovascular/ Procedure 
Related SAEs were deleted as 
reportable events: since all 
Serious Adverse Events have to 
be reported in the study, 
Cardiovascular /Procedure  
Related SAEs are anyhow 
considered as reportable 
events. 
 
Clarification was added 
regarding reporting 
requirements for additional 
ablation procedures.  
 
Clarification was added 
regarding reporting 
requirements for new 
arrhythmias.  
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 3 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 4 of 65 
  
2. Protocol Synopsis 
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
Study 
Objective(s) 
The objective of the study is to collect data on the use of the Rhythmia™ 
HDx mapping system running commercially available Software Version 
2.0 or any future commercially available Software Version with 
DirectSenseTM technology and the IntellaMap OrionTM mapping catheter 
in patients indicated for ablation treatment for de-novo Paroxysmal Atrial 
Fibrillation (PAF). The study will collect specific information to 
characterize the DirectSense technology in subjects undergoing catheter-
based endocardial mapping and ablation for de-novo PAF using a 
commercial Rhythmia HDx mapping system.  The clinical local 
impedance data will be used in order to generate usage guidance on the 
DirectSense local impedance feature in the management of de-novo PAF 
cases requiring Pulmonary Vein Isolation (PVI) and in order to further 
develop a future lesion indexing feature. 
Planned 
Indication(s) for 
Use  
 The Rhythmia mapping system and IntellaMap Orion mapping 
catheter are indicated for catheter-based atrial and ventricular 
mapping. The mapping system allows real-time visualization of 
intracardiac catheters as well as display of cardiac maps in a 
number of different formats. The IntellaMap Orion high-
resolution mapping catheter is indicated for electrophysiological 
mapping (recording or stimulating only) of the cardiac structures 
of the heart. 
 The IntellaNav MiFi OI ablation catheter is indicated for 
electrophysiological cardiac ablation procedures.  
Subjects undergoing standard of care catheter-based endocardial mapping 
and ablation for de-novo PAF using a commercial RhythmiaTM HDx 
mapping system will be selected for this study.  
Devices Used in 
the Study 
 Commercial Rhythmia HDx System ; 
 Commercially available Software Version 2.0 with DirectSense 
technology or any commercially available updates that are 
released during the course of the study; 
 The IntellaMap Orion mapping catheter;  
 The IntellaNav MiFi OI ablation catheter 
NOTE: the study will not start until all study devices are market 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 4 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 5 of 65 
  
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
released and commercially available in the regions where the study is 
conducted. 
Study Design 
The LOCALIZE study is a prospective, non-randomized, multi-center 
study to assess the DirectSense technology for the Rhythmia HDx 
mapping system. 
Planned 
Number of 
Subjects 
Enrollment will be considered as complete when 60 patients underwent 
the index ablation procedure and had all 4 Pulmonary Veins encircled 
(TREATMENT subjects, protocol section 10.3). To reduce the impact of 
individual center bias, each site may perform up to 30 procedures.  
Planned 
Number of 
Investigational 
Sites / Countries 
Up to  sites in EU. 
Primary 
Endpoint(s) 
Association between baseline Local Impedance/Local Impedance drop 
values per anatomical segment* as recorded at index ablation procedure 
and the proportion of gaps per anatomical segment* as measured at the 
month 3 assessment.  
* Eight segments around each PV pair defined as per  Figure 11.5-2 
Secondary 
Endpoint(s) 
Additional analyses are planned, including but not limited to: 
 Correlate DirectSense parameters and acute PVI gaps  
o Acute isolation gaps per anatomical segment as associated 
with baseline Local Impedance and Local Impedance drop 
values at first pass encircling during the index ablation 
procedure 
 Median  number of gaps per patient (or per PV pair) after initial 
encircling; 
 Statistical characterization of impedance readings for each 
ablation point 
 Anatomical distribution of the gaps and impedance reading 
differences at different anatomical sites (PV segments*) 
* Eight segments around each PV pair defined as per  Figure 
11.5-2 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 5 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 6 of 65 
  
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
Method of 
Assigning 
Patients to 
Treatment 
Subjects indicated for ablation treatment of de-novo PAF will be selected 
based on the inclusion/exclusion criteria and if deemed to be eligible for 
participation, will be asked to sign the Informed Consent Form.  
Subjects who meet the eligibility criteria and have signed and dated the 
Informed Consent Form are considered enrolled in the study.   
For all enrolled subjects who undergo the ablation procedure, the subjects 
will be treated with the commercial Rhythmia HDx System with 
commercially available Software Version 2.0 with DirectSense 
technology (or any commercially available updates that are released 
during the course of the study); the IntellaMap Orion mapping catheter 
and the IntellaNav MiFi OI ablation catheter. 
Follow-up 
Schedule 
Each subject undergoing PVI will be followed at index procedure, at pre-
discharge visit, at the month 3 assessment and at month 4 follow up. The 
visit at three months after index procedure will include an invasive 
evaluation with the Rhythmia Mapping system to evaluate residual 
conduction gaps after PVI.  The study will be considered complete after 
all enrolled subjects have completed the month 4 follow up. 
Data Collection Overview 
Data Collected 
ENROLLMENT/ 
BASELINE 
INDEX PROCEDURE 
(Day 0) 
PRE-DISCHARGE    
(0-7 days  post 
procedure) 
MONTH 3 FOLLOW 
UP 
(90± 21 days) 
MONTH 4 FOLLOW 
UP (120± 30 days) 
ADDITIONAL 
PROCEDURE        
(if applicable) 
ADDITIONAL VISIT 
(if applicable) 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Medication Regimen 
X 
X* 
X* 
X* 
 
X* 
 
Mapping and  
procedure data 
 
X 
 
X 
 
X** 
 
Patient status 
X 
X 
 
X 
X 
X 
 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
Adverse Event/ Device 
Deficiency Reporting*** 
X 
X 
X 
X 
X 
X 
X 
  
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 6 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 7 of 65 
  
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
*Medication changes only will be captured  
**If additional procedure includes an additional ablation procedure in the LA 
with Rhythmia HDx mapping system, IntellaMap Orion mapping catheter and 
IntellaNav MiFi OI ablation catheter. 
*** For details on Adverse Event and Device Deficiency reporting, please refer 
to Section 20. 
Study Duration 
Enrollment is expected to be completed in approximately 6 months; 
therefore the total study duration is estimated to be approximately 10 
months. 
Key Inclusion 
Criteria 
 History of recurrent symptomatic PAF with ≥1 episode reported 
and documented within the 365 days prior to enrollment; PAF is 
defined as AF episodes that last ≥30 seconds in duration and 
terminate within 7 days.   
 Refractory or intolerant to at least one Beta Blocker, Calcium 
Channel Blocker, Class I OR Class III anti-arrhythmic drug 
(AAD); 
 Eligible for an ablation procedure with the Rhythmia  HDx  
mapping system (software version 2.0 or any future commercially 
available Software Version), IntellaMap Orion mapping catheter 
and IntellaNav MiFi OI ablation catheter according to current 
international and local guidelines (and future revisions) and per 
physician discretion;  
 Subjects who are willing and capable of providing informed 
consent;  
 Subjects who are willing and capable of participating in all testing 
associated with this clinical investigation at an approved clinical 
investigational center; 
 Age 18 to 80 
Key Exclusion 
Criteria 
 Diagnosed with any of the following heart conditions within 90 
days (3 months) prior to enrollment:  
a. New York Heart Association (NYHA) Class III or IV 
b. Left ventricular ejection fraction (LVEF) <35% 
c. Left atrial (LA) diameter >5.5 cm 
d. Unstable angina or ongoing myocardial ischemia (OMI) 
e. Transmural myocardial infarction (MI), acute coronary 
syndrome (ACS), percutaneous coronary intervention 
(PCI), or valve or coronary bypass grafting surgery 
 Active systemic infection or sepsis; 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 7 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 8 of 65 
  
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
 Undergone any left atrial heart ablation procedure, either surgical 
or catheter ablation 
 Prosthetic or stenotic valves in the chamber where the intended 
mapping will occur, or in the path of the catheter access route 
 Subject has a Left Atrial Appendage Closure (LAAC) or 
Percutaneous Transcatheter Closure of a Patent Foramen Ovale 
(PFO) 
 Subject has persistent or long-standing persistent atrial fibrillation 
(AF) ( >1 AF episodes lasting greater than 7 days, with no 
episodes having lasted greater than 30 days, within the past year) 
 Life expectancy ≤ 6 months per physician judgment 
 Subjects who are currently enrolled in another investigational 
study or registry that would directly interfere with the current 
study, except when the subject is participating in a mandatory 
governmental registry, or a purely observational registry with no 
associated treatments; each instance must be brought to the 
attention of the sponsor to determine eligibility; 
 The subject is unable or not willing to complete follow-up visits 
and examination for the duration of the study; 
 Women of childbearing potential who are, or plan to become, 
pregnant during the time of the study (method of assessment upon 
physician’s discretion). 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
No formal pre-specified statistical hypotheses will be tested in this study. 
Statistical Test 
Method 
Descriptive statistics will be used for baseline, procedure and follow-up 
data collected throughout the study.  For the primary endpoint, 95% 
confidence intervals for the difference of the means will be used to 
compare DirectSense parameters between segments with and without 
gaps at month 3. 
Sample Size 
Parameters 
A sample size of 60 subjects is chosen to generate 50 patients with usable 
data  (20% attrition) and  have 90% power to detect a minimum 
difference in DirectSense parameters of 3.71 ohms between segments 
with and without gaps at month 3. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 8 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 9 of 65 
  
ELectrical COupling Information From The RhythmiaTM HDx Mapping 
System And DireCtSenseTM Technology In The Treatment Of Paroxysmal 
AtriaL FibrIllation- A Non-RandomiZed, ProspEctive Study (LOCALIZE) 
Required 
Medication 
Therapy 
This study has no specific requirements in terms of medication therapy; 
the standard of care medication regimen at the investigational site is being 
followed. 
Risks and 
Benefits 
The anticipated Adverse Events (AE) and Adverse Device Effects (ADE) 
in the LOCALIZE study are the same shared for the procedures of 
ablation with use of a 3D mapping system. There may be no direct benefit 
to the subject. However, a dedicated workflow to assess ablation gaps at 
index procedure and at the month 3 assessment may ensure durable 
isolation of the Pulmonary Veins, with potential long term effects on 
efficacy of ablation. 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 9 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 10 of 65 
  
 
 
3. Table of Contents 
1. 
TITLE PAGE  ........................................................................................................................ 1 
2. 
PROTOCOL SYNOPSIS .......................................................................................................... 4 
3. 
TABLE OF CONTENTS ........................................................................................................ 10 
3.1. Table of Figures ...................................................................................................... 13 
3.2. Table of Tables ....................................................................................................... 13 
4. 
INTRODUCTION ................................................................................................................. 15 
5. 
DEVICE DESCRIPTION ....................................................................................................... 16 
5.1. Rhythmia HDx Mapping System .......................................................................... 16 
5.1.1. 
Key DirectSense Components. .................................................................. 17 
5.3. The IntellaNav MiFi OI Ablation Catheter ......................................................... 19 
6. 
STUDY OBJECTIVES .......................................................................................................... 20 
7. 
STUDY ENDPOINTS ............................................................................................................ 20 
7.1. Primary Endpoint .................................................................................................. 20 
7.2. Secondary Endpoint ............................................................................................... 20 
8. 
STUDY DESIGN .................................................................................................................. 21 
8.1. Scale and Duration ................................................................................................. 21 
8.2. Treatment Assignment........................................................................................... 23 
8.2.1. 
Treatment and Control ............................................................................... 23 
8.3. Justification for the Study Design ......................................................................... 23 
9. 
SUBJECT SELECTION ......................................................................................................... 24 
9.1. Study Population and Eligibility ........................................................................... 24 
9.2. Inclusion Criteria ................................................................................................... 24 
9.3. Exclusion Criteria .................................................................................................. 24 
10. SUBJECT ACCOUNTABILITY .............................................................................................. 26 
10.1. Point of Enrollment ................................................................................................ 26 
10.2. Withdrawal ............................................................................................................. 26 
10.3. Subject Status and Classification .......................................................................... 26 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 10 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 11 of 65 
  
11. STUDY METHODS .............................................................................................................. 28 
11.1. Data Collection ....................................................................................................... 28 
11.2. Study Candidate Screening ................................................................................... 28 
11.3. Informed Consent/Enrollment Visit ..................................................................... 29 
11.4. Baseline Visit .......................................................................................................... 29 
11.5. Index (ablation) procedure- Ablating physician BLINDED to DirectSense 
technology during initial encircling of PVIs (single blind masking) ................. 30 
11.6. Pre-discharge visits ................................................................................................ 37 
11.7. Additional visits ...................................................................................................... 38 
11.8. Additional procedure ............................................................................................. 38 
11.9. Month 3 Assessment-Ablating physician UNBLINDED to DirectSense 
technology ............................................................................................................... 39 
11.10. 
Month 4 Follow Up .................................................................................. 40 
11.11. 
Study Completion .................................................................................... 40 
11.12. 
Source Documents ................................................................................... 40 
12. STATISTICAL CONSIDERATIONS ....................................................................................... 41 
12.1. Endpoints ................................................................................................................ 41 
12.1.1. Primary Endpoint ....................................................................................... 41 
12.1.1.1. Hypotheses ................................................................................ 41 
12.1.1.2. Sample Size ............................................................................... 41 
12.1.1.3. Statistical Methods .................................................................... 41 
12.2. General Statistical Methods .................................................................................. 41 
12.2.1. Analysis Sets .............................................................................................. 41 
12.2.2. Control of Systematic Error/Bias ............................................................... 42 
12.2.3. Number of Subjects per Investigative Site ................................................ 42 
12.3. Data Analyses ......................................................................................................... 42 
12.3.1. Other Endpoints/Measurements ................................................................. 42 
12.3.2. Changes to Planned Analyses .................................................................... 42 
13. DATA MANAGEMENT ........................................................................................................ 42 
13.1. Data Collection, Processing, and Review ............................................................. 42 
13.2. Rhythmia HDx Electronic Data Management .................................................... 43 
13.3. Data Retention ........................................................................................................ 43 
13.4. Technical Source Forms ........................................................................................ 43 
14. AMENDMENTS ................................................................................................................... 44 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 11 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 12 of 65 
  
15. DEVIATIONS ...................................................................................................................... 44 
16. DEVICE/EQUIPMENT ACCOUNTABILITY .......................................................................... 44 
17. COMPLIANCE ..................................................................................................................... 44 
17.1. Statement of Compliance ....................................................................................... 44 
17.2. Investigator Responsibilities ................................................................................. 45 
17.2.1. Delegation of Responsibility ..................................................................... 46 
17.3. Ethics Committee ................................................................................................... 46 
17.4. Sponsor Responsibilities ........................................................................................ 47 
17.4.1. Role of Boston Scientific Representatives ................................................ 47 
17.5. Insurance ................................................................................................................. 48 
18. MONITORING ..................................................................................................................... 49 
19. POTENTIAL RISKS AND BENEFITS .................................................................................... 49 
19.1. Anticipated Adverse Events and Adverse Device Effects ................................... 49 
19.2. Risks Associated with the Study Device(s) ........................................................... 49 
19.3. Risks associated with Participation in the Clinical Study .................................. 49 
19.4. Risk Minimization Actions .................................................................................... 50 
19.5. Anticipated Benefits ............................................................................................... 50 
19.6. Risk to Benefit Rationale ....................................................................................... 51 
20. SAFETY REPORTING .......................................................................................................... 51 
20.1. Reportable Events by investigational site to Boston Scientific .......................... 51 
20.2. Definitions and Classification ............................................................................... 52 
20.3. Relationship to Study Device(s) ............................................................................ 53 
20.4. Investigator Reporting Requirements .................................................................. 55 
20.5. Boston Scientific Device Deficiencies .................................................................... 56 
20.6. Reporting to Regulatory Authorities / ECs / Investigators ................................ 57 
20.7. Subject Death Reporting ....................................................................................... 57 
21. INFORMED CONSENT......................................................................................................... 58 
22. SUSPENSION OR TERMINATION ........................................................................................ 60 
23.1 Premature Termination of the Study ................................................................... 60 
23.1.1 
Criteria for Premature Termination of the Study ....................................... 60 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 12 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 13 of 65 
  
23.2 Termination of Study Participation by the Investigator or Withdrawal of EC 
Approval ................................................................................................................. 60 
23.3 Requirements for Documentation and Subject Follow-up ................................. 60 
23.4 Criteria for Suspending/Terminating a Study Site ............................................. 61 
23. PUBLICATION POLICY ....................................................................................................... 61 
24. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .................................................. 61 
24.1. Compensation for Subject’s Health Injury ......................................................... 61 
25. BIBLIOGRAPHY .................................................................................................................. 62 
26. ABBREVIATIONS AND DEFINITIONS .................................................................................. 64 
26.1. Abbreviations ......................................................................................................... 64 
26.2. Definitions ............................................................................................................... 65 
27. APPENDICES ...................................................................................................................... 65 
 
 
3.1. Table of Figures 
Figure 5.1-1: The Rhythmia HDx Mapping System overview .......................................... 16 
Figure 5.1-2: Four-electrode impedance measurement on BSC MiFi Catheter ............. 17 
Figure 5.1-3: Local Impedance feature user interface. A) Local impedance vs time 
trace. B) Average impedance widget. C) Power bar. D) Tip graphic. .......... 18 
Figure 8.1-1: LOCALIZE Study Design ............................................................................. 22 
Figure 11.5-1: Index Procedure Workflow ......................................................................... 35 
Figure 11.5-2: 8 Circumferential positions around each PV ............................................ 37 
 
3.2. Table of Tables 
Table 9.2-1: Inclusion Criteria............................................................................................. 24 
Table 9.3-1: Exclusion Criteria ............................................................................................ 25 
Table 11.1-1: Data Collection Schedule .............................................................................. 28 
Table 11.12-1: Source Documentation Requirements ....................................................... 40 
Table 20.2-1: Safety Definitions ........................................................................................... 52 
Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event .................................................................................................... 54 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 13 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 14 of 65 
  
Table 20.4-1: Investigator Reporting Requirements ......................................................... 55 
Table 26.1-1: Abbreviations ................................................................................................. 64 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 14 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 15 of 65 
  
4. Introduction 
The incidence and prevalence of cardiac arrhythmias have seen significant growth in the last 
few decades, largely mirroring a sharp increase in the forms of heart disease known to 
promote rhythm abnormalities. Tachyarrhythmias are estimated to affect well over 6 million 
people in Europe and the US and create an annual multi-billion dollar burden on these 
economies1-2-3. Atrial fibrillation (AF) is the most common tachyarrhythmia.  It currently 
affects approximately 2.3 million people in North America4 and 4.5 million people in 
Europe5-6-7. 
Traditional treatment modalities, such as drug therapy and open heart surgery, have been 
found to be inadequate for a growing number of patients, either because of poor efficacy, 
side effects, or the mere invasiveness of surgery8-9-10. The introduction of specialized 
percutaneous catheters and the development of other enabling technologies have collectively 
led to an improvement in the safety and efficacy of minimally-invasive curative procedures, 
namely catheter ablation of cardiac arrhythmias, a procedure which involves a process of 
Electro-Anatomical Mapping and subsequent ablation of the culprit tissue area11. 
PVI is currently the most prevalent approach for catheter ablation of PAF. Long-term success 
of the procedure is diminished by arrhythmia recurrences occurring predominantly because 
of reconnections in previously isolated Pulmonary Veins (PVs)12-13. 
The Rhythmia HDx mapping system is designed for electroanatomical mapping in catheter 
ablation procedures by optimizing the need for speed and accuracy. The system is able to 
simultaneously acquire data from multiple electrodes.  In addition, based on user-defined 
criteria, the system is able to efficiently acquire data over multiple cardiac beats. When used 
in conjunction with the Rhythmia mapping catheter, the system is able to acquire up to 
hundreds of points per minute leading to fast and detailed map creation. 
Since its market release, physicians and users have gained experience with the Boston 
Scientific Rhythmia HDx mapping system in the human clinical setting.  Boston Scientific 
has recently implemented the DirectSense feature within the Rhythmia HDx mapping system 
to provide a local impedance metric that aids the physician in assessing catheter localization 
relative to cardiac tissue. 
Previous research12-13-14-15-16 has shown a positive correlation between catheter contact force 
and durability of lesions in PVI for PAF. The DirectSense feature within the Rhythmia HDx 
mapping system provides a measure of the resistive load at the catheter-tissue interface and is 
highly sensitive to objects with dissimilar resistivity.  This is different from the mechanical 
contact provided by contact force in that it also represents the potential for resistive heating 
during RF applications. DirectSense thereby provides electrical coupling information and is 
believed to better guide physicians during ablation procedures in order to create durable PVI 
lesions. 
This study will evaluate the correlation between the local impedance information of the 
DirectSense feature during initial procedure and gaps at month 3 follow-up in a clinical 
environment. 
The data of up to 60 subjects who will undergo ablation treatment for de-novo PAF will be 
evaluated; the operating physician will be blinded to the local impedance information of the 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 15 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 16 of 65 
  
DirectSense feature during initial PVI encircling and then receive local impedance 
information during acute and follow-up gap closure for all cases. 
 
5. Device Description 
All devices used in the study, including those described in section 5.1 to 5.3  are market 
released and commercially available in the regions where the study is conducted. 
5.1. Rhythmia HDx Mapping System 
The Rhythmia HDx mapping system and the IntellaMap Orion mapping catheter are 
designed for electroanatomical mapping in catheter ablation procedures. The Rhythmia HDx 
mapping System tracks catheters inside the heart in order to visualize their location and 
construct geometric shells.  The Rhythmia HDx 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 Rhythmia HDx mapping system can display various types 
of electroanatomical maps including geometrical shell only, activation maps, voltage maps, 
and fractionation maps.   
Figure 5.1-1: The Rhythmia HDx Mapping System overview 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 16 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 17 of 65 
  
The System is able to simultaneously acquire data from multiple electrodes.  In addition, 
based on user-defined criteria, the System is able to acquire data over multiple cardiac beats. 
When used in conjunction with the IntellaMap Orion Catheter, the System is able to acquire 
hundreds of points per minute leading to high resolution map creation.  
The maps are constructed using catheter magnetic and impedance location technology and 
data from intracardiac electrograms. Maps may be displayed as anatomical maps, and 
electroanatomical maps. 
The commercially available system operates the latest commercially-available software 
(version 2.0 or newer).  Subsequent versions of the Rhythmia HDx mapping system and 
software may be used during this study as they become commercially available.  
 
 
5.1.1. Key DirectSense Components. 
The DirectSense 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.  
 
In the Rhythmia HDx mapping system, local impedance is measured using a traditional four-
electrode method where a non-stimulatory current is driven between two electrodes (i.e., a 
source and a sink electrode) and the resulting potential field (voltage) is measured across two 
alternate electrodes on an intracardiac catheter. The driven current and the measured voltage 
are used to calculate impedance that represents local dielectric tissue properties nearest the 
source electrode. Using this method, far-field effects (e.g., respiration, patch placement, IV 
fluid infusion, etc.) have less influence on local impedance measurements than the more 
commonly used transthoracic impedance from radiofrequency (RF) generators. Figure 5.1-2 
demonstrates a representative four-electrode impedance measurement on the Boston 
Scientific MiFi catheter. In this example, the source electrode is configured to the tip of the 
catheter and the sink electrode is configured to the proximal ring (i.e., R3). Voltage is 
measured between the mini-electrodes embedded in the tip and the distal ring electrode (i.e., 
R1).  
   
 
Figure 5.1-2: Four-electrode impedance measurement on BSC MiFi Catheter 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 17 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 18 of 65 
  
 
This local impedance system utilizes existing Rhythmia HDx mapping system hardware 
capabilities and is completely independent of the RF generator impedance measurement 
system.  
The graphical user interface (UI) for the Local Impedance feature is displayed in Figure 
5.1-3 during the creation of an anatomical map in the right atrium of a swine. This UI is 
comprised of four central elements: 
(A) a local impedance vs time trace, 
(B) an average impedance widget, 
(C) a power bar, and  
(D) a catheter tip graphic. 
All display elements can be enabled or disabled per physician preference.  
 
 
 
Figure 5.1-3: Local Impedance feature user interface. A) Local impedance vs time 
trace. B) Average impedance widget. C) Power bar. D) Tip graphic. 
 
5.2. The IntellaMap Orion High Resolution Mapping Catheter 
The IntellaMap Orion high resolution mapping catheter is indicated for electrophysiological 
mapping (recording or stimulating only) of the cardiac structures of the heart. The IntellaMap 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 18 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 19 of 65 
  
Orion Catheter is an 8.5F (Ø 2.82 mm), 115 cm working length, 64-electrode steerable 
catheter. The basket-shaped distal region consists of 8 splines that comprise the electrode 
array.  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™ HDx 
mapping system. 
5.3. The IntellaNav MiFi OI Ablation Catheter 
The IntellaNav MiFi OI catheter is a steerable 7F catheter designed to deliver RF energy to 
the 4.5mm catheter tip electrode for cardiac ablation.  It is designed to be used in conjunction 
with the Boston Scientific  Irrigation Tubing Set (M0041160) or equivalent, Biosense 
Webster CoolFlow® Irrigation Pump with software version 1.3 or equivalent (Catalog 
CFP002 or CFP001/Model M-5491-00 or M-5491-01/02), Biosense Webster CoolFlow 
Irrigation Tubing Set (Model CFT001), Stockert EP-Shuttle RF Generator (Catalogue # 
39D76X, software version 1.035, 1.036 and 10.037),  Maestro 4000 Generator (Catalog 
M004 4000 0), MetriQTM Irrigation Pump (Catalog M004 4100 0) and MetriQTM Irrigation 
Tubing Set (Catalog M004117 0).   
The IntellaNav MiFi OI catheter has a distal electrode segment and a proximal handle that are 
connected by a torquable catheter shaft.  The electrode segment is comprised of a tip 
electrode and 3 ring electrodes.  The tip electrode has an embedded temperature sensor and 
delivers RF energy for cardiac ablation. The tip electrode contains 3 embedded  mini-
electrodes that can record EGMs and deliver stimulus for pacing. The ring electrodes record 
electrograms (EGM) signals for mapping and deliver stimulus for pacing.  The handle 
includes the electrical connector for the cable connection to the RF Generator, or 3-
Dimensional (3D) mapping navigational system component, and one luer fitting used to 
connect the catheter to the irrigation system tubing set.  The steering assembly, electrode lead 
wires, thermocouple wires and one cooling fluid lumen reside within the catheter shaft. 
The IntellaNav MiFi OI catheter incorporates an open-irrigated cooling mechanism to 
remove heat from the catheter electrode tip and tip/tissue interface.  Heparinized normal 
saline (0.9%) is delivered via one lumen in the catheter and infuses it into the heart through 
six ports on the distal portion of the catheter electrode tip.   
 
 
 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 19 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 20 of 65 
  
6. Study Objectives 
The objective of the study is to collect data on the use of the Rhythmia HDx mapping system 
running commercially available Software Version 2.0 or any future commercially available 
Software Version with DirectSense technology, the IntellaMap Orion mapping catheter and 
the IntellaNav MiFi OI ablation catheter, in patients indicated for ablation treatment for de-
novo PAF. The study will collect specific information to characterize the DirectSense 
technology in subjects undergoing catheter-based endocardial mapping and ablation for de-
novo PAF using a commercial Rhythmia HDx mapping system.  Direct Sense data will be 
automatically recorded by the Rhythmia HDx mapping system during ablation procedures. 
The clinical local impedance data will be analyzed offline and used in order to generate 
usage guidance on the DirectSense local impedance feature in the management of de-novo 
PAF cases requiring PVI and in order to further develop a future lesion indexing feature. 
 
7. Study Endpoints 
7.1. Primary Endpoint 
Primary endpoint is the association between baseline Local Impedance/Local Impedance 
drop values per anatomical segment as recorded at index ablation procedure and the 
proportion of gaps per anatomical segment as measured at the month 3 assessment. 
Local impedance data will be automatically recorded by the Rhythmia HDx mapping system 
during PVI for each ablation point. Impedance data will be analyzed offline to determine 
Baseline Local Impedance and Impedance drops for each ablation point. For the primary 
endpoint assessment, impedance data will be grouped per 8 anatomical segments around each 
PV pair (please refer to Figure 11.5-2). Distribution of ablation points and gaps during the 
index ablation procedure and at the month 3 assessment will be recorded during mapping and 
ablation with the Rhythmia HDx mapping system. 
 
7.2. Secondary Endpoint 
Additional analyses are planned, including but not limited to: 
 Correlate DirectSense parameters and acute PVI gaps; 
o Acute isolation gaps per anatomical segment as associated with baseline Local 
Impedance and Local Impedance drop values at first pass encircling during 
the index ablation procedure 
 Median  number of gaps per patient (or per PV pair) after initial encircling; 
 Statistical characterization of impedance readings for each ablation point; 
 Anatomical distribution of the gaps and impedance reading differences at different 
anatomical sites (PV segments) 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 20 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 21 of 65 
  
8. Study Design 
The LOCALIZE study is a prospective, non-randomized, multicenter study. 
8.1. Scale and Duration 
Enrollment will be considered as complete when 60 patients undergo the index ablation 
procedure and complete encircling of the 4 PVs (2 PV pairs). Up to 6 sites in EU may 
participate in the study. To reduce the impact of individual center bias, each site may perform 
up to 30 index ablation procedures. This limit of 30 procedures cannot be exceeded, unless 
Boston Scientific gives written approval to do so. 
Each treated subject will be followed for 4 months after the index ablation procedure (index 
procedure); therefore treated subjects will be followed at index procedure, at pre-discharge 
visit, at the month 3 assessment and at month 4 follow up.  
The study will be considered complete upon completion of the final month 4 follow-up. 
A study subject’s participation will be considered complete when all protocol required visits 
have been completed. 
It is anticipated that enrollment will be conducted over a period of 6 months; therefore the 
total study duration is estimated to be 10 months. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 21 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 22 of 65 
  
Figure 8.1-1: LOCALIZE Study Design 
 
 
 
 
 
 
Patient signs 
Informed Consent 
 
Patient meets all of the 
inclusion and 
 none of the exclusion 
criteria  
Do not consider patient 
for enrollment 
Yes 
Yes 
Enrollment 
Demography & Medical history 
Medical assessment & Medication regimen 
Patient status 
Index Procedure 

Point by point PVI ablation  - WACA – remapping for gap assessment after 
20 min   

Please refer to Figure 11.5-1 for more details  
3-Month Assessment 
Electroanatomic mapping to identify isolation gaps; Rhythmia/Orion, IntellaNav 
MiFi OI 
Measure reference local impedances: blood pool and myocardium  
Gap closure: Point-by-point discrete-lesion touch-up unblinded to DirectSense 
Medical assessment & Medication regimen 
No 
Pre-Discharge 
Medical assessment & Medication changes 
4-Month Follow Up 
Patient Status 
Adverse Events  
Study Completion 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 22 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 23 of 65 
  
8.2. Treatment Assignment 
All subjects who meet the eligibility criteria as per 9.2 and 9.3 and sign the informed consent 
will be considered enrolled.  Data will be collected during the baseline visit, the ablation 
(index) procedure, the pre-discharge visit, the month 3assessment and during the month 4 
follow up. In case additional visits or additional ablation procedures take place, this data  will 
also be collected. Please refer to Section 11.2 to 11.10 for an overview of data to be collected 
during these visits.  
 
A study subject can only be enrolled once in the study.  
8.2.1. Treatment and Control 
For all enrolled subjects who undergo the ablation procedure, the subjects will be treated 
with the commercial Rhythmia HDx System with commercially available Software Version 
2.0 with DirectSense technology (or any commercially available updates that are released 
during the course of the study), the IntellaMap Orion mapping catheter and the IntellaNav 
MiFi OI ablation catheter. Initial encircling of the PVs will be performed by Investigators 
who perform the ablation blinded with respect to DirectSense (single blind masking). This 
will not impact the AE assessment by the investigator.  
 
8.3. Justification for the Study Design 
This is a post-market study designed to collect specific information in order to characterize 
the DirectSense technology in subjects undergoing catheter-based endocardial mapping and 
ablation for de-novo PAF using a commercial Rhythmia HDx mapping system.  The 
DirectSense feature generates local impedance data that is automatically stored in the 
Rhythmia HDx mapping system during PVI. In this study local impedance data will be 
retrieved from the system for off-line analysis. As Direct Sense is intended to provide 
information on the localization of the ablation catheter to cardiac tissue (and the ability to 
create durable PV lesions), an additional endocardial mapping procedure at 3 month is 
required in this study in order to assess gaps in the PV, after substrate stabilization. This 
information will be used to evaluate the association between impedance readings at initial 
PVI and a durable isolation at 3 months (primary endpoint). This month 3 assessment is not 
standard of care in clinical practice, but a recognized standard for clinical studies and 
literature18 in order to verify durable isolation of PV (acute assessment is unable to detect 
mid-term gaps).  Subjects will be followed at month 4 for patient status/AE assessment. 
 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 23 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 24 of 65 
  
9. Subject Selection  
9.1. Study Population and Eligibility  
Subjects enrolled in the LOCALIZE study will be clinically indicated for an endocardial 
catheter-based mapping procedure for the treatment of de-novo PAF and meet the study 
inclusion/exclusion criteria as outlined below in section 9.2 and 9.3. The subjects selected for 
participation will be from the investigator’s general patient population. The investigator or its 
designee has the responsibility for screening all potential subjects and selecting those who 
meet study inclusion/exclusion. 
9.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 9.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 9.3) is 
met.  
Table 9.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
 History of recurrent symptomatic PAF with ≥1 episode reported and 
documented within the 365 days prior to enrollment; PAF is defined as 
AF episodes that last ≥30 seconds in duration and terminate within 7 
days.   
 Refractory or intolerant to at least one Beta Blocker, Calcium Channel 
Blocker, Class I OR Class III anti-arrhythmic drug (AAD); 
 Eligible for an ablation procedure with the Rhythmia  HDx  mapping 
system (software version 2.0 or any future commercially available 
Software Version), IntellaMap Orion mapping catheter and IntellaNav 
MiFi OI ablation catheter according to current international and local 
guidelines (and future revisions) and per physician discretion;  
 Subjects who are willing and capable of providing informed consent;  
 Subjects who are willing and capable of participating in all testing 
associated with this clinical investigation at an approved clinical 
investigational center; 
 Age 18 to 80 
 
 
9.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 9.3-1) will be excluded from this 
clinical study. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 24 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 25 of 65 
  
Table 9.3-1: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
 Diagnosed with any of the following heart conditions within 90 days 
(3 months) prior to enrollment:  
a. New York Heart Association (NYHA) Class III or IV 
b. Left ventricular ejection fraction (LVEF) <35% 
c. Left atrial (LA) diameter >5.5 cm 
d. Unstable angina or ongoing myocardial ischemia (OMI) 
e. Transmural myocardial infarction (MI), acute coronary  
syndrome (ACS), percutaneous coronary intervention (PCI), or  
valve or coronary bypass grafting surgery 
 Active systemic infection or sepsis; 
 Undergone any left atrial heart ablation procedure, either surgical or 
catheter ablation 
 Prosthetic or stenotic valves in the chamber where the intended 
mapping will occur, or in the path of the catheter access route 
 Subject has a Left Atrial Appendage Closure (LAAC) or Percutaneous 
Transcatheter Closure of a Patent Foramen Ovale (PFO) 
 Subject has persistent or long-standing persistent atrial fibrillation 
(AF) ( >1 AF episodes lasting greater than 7 days, with no episodes 
having lasted greater than 30 days, within the past year) 
 Life expectancy ≤ 6 months per physician judgment 
 Subjects who are currently enrolled in another investigational study or 
registry that would directly interfere with the current study, except 
when the subject is participating in a mandatory governmental 
registry, or a purely observational registry with no associated 
treatments; each instance must be brought to the attention of the 
sponsor to determine eligibility; 
 The subject is unable or not willing to complete follow-up visits and 
examination for the duration of the study; 
 Women of childbearing potential who are, or plan to become, pregnant 
during the time of the study (method of assessment upon physician’s 
discretion). 
 
 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 25 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 26 of 65 
  
10. Subject Accountability 
10.1. Point of Enrollment 
Subjects who meet the eligibility criteria and have signed and dated the Informed Consent 
Form are considered enrolled in the study.   No further review of eligibility criteria for study 
participation is required beyond this point. It is the investigator’s site responsibility to assess 
eligibility criteria before the index procedure.  
 
10.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) shall be accounted for and documented. If a subject withdraws from the 
clinical investigation, the reason(s) shall be reported. If such withdrawal is due to problems 
related to study device safety or performance, the investigator shall ask for the subject’s 
permission to follow his/her status/condition outside of the clinical study.   
 
Every effort should be made to retain subject enrollment for the duration of the study.  
During the informed consent process, subjects should be fully informed of the data collection 
requirements and duration, and should only be enrolled if willing to fully participate in it.  
Reasons for withdrawal may include physician discretion, subject choice to retire consent, 
lost to follow-up, or death. In the event a subject does decide to withdraw from the study, 
every effort should be made to obtain full information on any on-going reportable Adverse 
Events up to the point of withdrawal.  Subjects should only be considered lost to follow-up 
after significant effort has been made to contact the subject.  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.  Subject withdrawal and lost to 
follow-up will be documented on the “End of Study” electronic Case Report Form (eCRF). 
Additional data may no longer be collected after the point at which a subject has been 
withdrawn from the study or withdraws his/her consent, for whatever reason.  
All open reportable Adverse Events should be closed or documented as chronic. Data 
collected up to the point of subject withdrawal may be used, unless any local regulations 
apply which require removal of the data. 
10.3. Subject Status and Classification 
As subjects are evaluated, enrolled and treated in the study, they will be grouped into one of 
the following several categories. Categorization will help determine how data gathered from 
them will be stored and evaluated. 
 
Consent Ineligible 
A subject who has signed informed consent but does not meet eligibility criteria will be 
classified as “Consent Ineligible”. There are no Follow Up reporting requirements for 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 26 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 27 of 65 
  
consent ineligible subjects. Subjects determined to be Consent Ineligible according to 
statements above do not count towards the enrollment ceiling and will not be used for 
analysis of the endpoints. The original signed Informed Consent must be maintained in the 
center’s patient file.   A subject Identification Number (ID)  is created by Medidata Rave 
upon  entering the subject in the eCRF. For consent ineligible subjects, an enrollment eCRF 
(ICF form and in-and exclusion criteria forms)  and “end of study” eCRF form must be 
completed. If applicable, an Adverse Event eCRF form must be completed.  
 
Intent 
A subject who signs informed consent, meets eligibility criteria, but withdraws or is 
withdrawn prior to starting the encircling of the 4 PVs (prior to the 1st RF application in the 
left atrium) will be classified as “INTENT”. Subjects that are enrolled in the study but do not 
undergo ablation procedure within 60 days from consent signature date are withdrawn from 
the study and classified as “INTENT”. 
There are no Follow Up requirements for Intent subjects. Intent subjects do not count 
towards the enrollment ceiling and will not be used for analysis of the endpoints. The original 
signed Informed Consent must be maintained in the center’s patient file. A subject ID is 
created by Medidata Rave upon  entering the subject in the eCRF. For intent subjects, an 
enrollment, baseline and “end of study” eCRF form must be completed. If applicable, an 
Adverse Event eCRF form must be completed. No index procedure eCRF must be 
completed. 
 
Attempt 
A subject who signs informed consent, meets eligibility criteria and had the encircling of the 
4 PVs started (post the 1st RF application in the left atrium), but did not have the initial 
encircling for all 4 PVs (2 PV pairs) completed will be classified as “ATTEMPT”. Attempt 
subjects will be followed up until Pre-Discharge. A subject ID is created by Medidata Rave 
upon  entering the subject in the eCRF. For Attempt subjects,  all applicable case report 
forms must be completed. If applicable, an Adverse Event eCRF form must be completed. 
Attempt subjects do not count towards the enrollment ceiling and will not be used for 
analyses of the endpoints. The original signed Informed Consent must be maintained in the 
center’s patient file.  
 
Treatment 
A subject who had encircling of the 4 PVs (2 PV pairs) completed will be classified as 
“TREATMENT”. These subjects are followed in accordance with the follow-up schedule 
and included in all study analyses.  A subject ID is created by Medidata Rave upon  entering 
the subject in the eCRF. For Treatment subjects, all applicable case report forms per the 
protocol must be completed. Treatment subjects do count towards the enrollment ceiling and 
will be used for analyses of the endpoints. The original signed Informed Consent and any 
relevant documentation must be maintained in the center’s patient file. 
 
It is the investigational sites’s responsibility to list all Consent Ineligible, Intent, Attempt and 
Treatment subjects on the Screening and Enrollment Log. 
  
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 27 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 28 of 65 
  
11. Study Methods 
11.1. Data Collection 
Each Treatment subject will be followed at index procedure, at pre-discharge visit, at the 
month 3 assessment and at month 4 follow up. In order to reliably capture subject status at 
study end, the month 4 follow up has to be scheduled within 120 ± 30 days following the 
index procedure. If the subject needs to undergo an additional ablation procedure in the LA 
during the follow up period and the Rhythmia HDx mapping system, the IntellaMap Orion 
mapping catheter and the IntellaNav MiFi OI ablation catheter were used for this procedure, 
then this additional ablation procedure will be considered as the month 3 assessment if the 
month 3 assessment was not yet performed. No Protocol Deviation will have to be completed 
for a Visit Out Of Window. In case a different mapping system was used and/or different 
mapping and/or therapeutic catheters will be used for this additional ablation procedure in the 
LA, the subject will have to be withdrawn prior to this additional ablation procedure.  
Table 11.1-1 provides an overview of the data to be collected at each visit. 
 
Table 11.1-1: Data Collection Schedule 
Data Collected 
ENROLLMENT/ 
BASELINE 
INDEX PROCEDURE 
(Day 0) 
PRE-DISCHARGE    
(0-7 days  post 
procedure) 
MONTH 3 FOLLOW 
UP 
(90± 21 days) 
MONTH 4 FOLLOW 
UP (120± 30 days) 
ADDITIONAL 
PROCEDURE (if 
applicable) 
ADDITIONAL VISIT 
(if applicable) 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Medication Regimen 
X 
X* 
X* 
X* 
 
X* 
 
Mapping and procedure data 
 
X 
 
X 
 
X** 
 
Patient status 
X 
X 
 
X 
X 
X 
 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
Adverse Event/ Device 
Deficiency Reporting*** 
X 
X 
X 
X 
X 
X 
X 
*Medication changes only will be captured 
**If additional procedure includes an additional ablation procedure in the LA with Rhythmia HDx 
mapping system, IntellaMap Orion mapping catheter and IntellaNav MiFi OI ablation catheter. 
*** For details on Adverse Event and Device Deficiency reporting, please refer to Section 20. 
11.2. 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 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 28 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 29 of 65 
  
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. 
11.3. Informed Consent/Enrollment Visit 
In order to determine eligibility of a subject, the investigator or designee needs to implement 
the consent process and verify/ document the subject meets the inclusion/exclusion criteria. 
Informed consent is required for all subjects (or their legal representatives) prior to their 
participation in the study. 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 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 will be classified as Intent (see 
section 10.3). The same subject cannot be considered for re-enrollment as re-enrollment is 
not allowed for any subjects in this study. The site will ensure that originally signed ICFs are 
filed in subjects’ binders and that the ICF process is documented in the medical file. 
Originally signed ICFs and the ICF process will be made available for review at Interim 
Monitoring Visits (IMVs). 
 
11.4. Baseline Visit 
Subjects who provide consent and meet all of the study enrollment criteria will have baseline 
data collected.  
The data collection at baseline includes: 
 Visit date; 
 Demographic data, including: age at time of consent, gender; 
 Physical assessment including: height, weight, resting heart rate, systolic and diastolic 
blood pressure;  medical history, including:  
o Underlying cardiovascular disease, including but not limited to hypertension, 
dyslipidaemia, cardiovascular artery disease;  
o Prior history of cardiac events including: acute myocardial infarction, ischemic 
stroke, hemorrhagic stroke or transient ischemic attack; 
o Prior surgical interventions and/or cardiac procedures (ablation excluded) 
including: Percutaneous Trans Catheter Angioplasty (PTCA), Coronary Artery 
Bypass Graft (CABG), pacemaker (PM) implantation, implantable cardioverter-
defibrillator (ICD) implant, Cardiac Resynchronization Therapy (CRT) implant, 
cardiac valve interventions, left atrial appendage closure (LAAC), patent foramen 
ovale (PFO) intervention, heart transplant or procedures for implantation of other 
intracardiac devices;  
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 29 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 30 of 65 
  
o History of cardiac arrhythmias, including but not limited to time of first episode 
of PAF; 
o Detailed history of all 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 Pre-procedure assessment of  Left Ventricular Ejection Fraction, and left atrial 
diameter, if available; 
o Non-cardiac comorbidities 
 CHA2DS2-VASc score 
 Current cardiovascular medication regimen including anti arrhythmic, anticoagulation 
andantiplatelet agents. 
 
11.5. Index (ablation) procedure- Ablating physician BLINDED to DirectSense 
technology during initial encircling of PVIs (single blind masking) 
The index ablation procedure (day 0) should be performed using standard of care methods 
established by the investigational center (e.g. sterile technique, personnel requirements, etc.).  
Study-related mapping and ablation with the Rhythmia HDx mapping system, the IntellaMap 
Orion mapping catheter and the IntellaNav MiFi OI ablation catheter should only be 
performed by physicians trained in Electrophysiology (EP) and authorized by BSC to 
perform study-related activities. 
11.5.1. General information 
The following general information on the procedure should be collected: 
 Procedure date; 
 Identification of study devices:  
o Commercial Rhythmia HDx System; serial number  
o Commercially available Software Version 2.0 with DirectSense technology or 
any commercially available updates that are released during the course of the 
study; 
o The IntellaMap Orion mapping catheter; catheter model, lot number 
o The IntellaNav MiFi OI ablation catheter; catheter model, lot number 
 Identification of non-study devices:  
o Additional diagnostic catheters used during the case other than Orion 
including manufacturer, model and type 
o Sheaths used during the procedure including manufacturer, model and type 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 30 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 31 of 65 
  
o Additional  ablation catheter(s) used during the case other than IntellaNav 
MiFi OI including manufacturer, model, and  type 
 If concomitant procedures occurred during ablation procedure (e.g. ICD implant, PM, 
LAAC); 
 LA access approach (trans septal, retrograde) 
 Was heparin administered prior to or immediately following LA access according to 
guidelines?17 
 Were ACT levels of 300 to 400 seconds achieved during the procedure according to 
guidelines?17 
 The name of the EP physician performing the procedure 
 
11.5.2. Procedural information 
In order to avoid potential bias, the number of ablating physicians performing the index 
procedure and the month 3 assessment per investigational site is restricted to 2. Boston 
Scientific will therefore authorize maximum 2 ablating physicians per site. 
Prior to starting the ablations, Rhythmia HDx + IntellaMap Orion will be used to collect an 
electroanatomic map (i.e. activation and voltage map) of the Left Atrium.   
For all subjects it is preferred that all maps are acquired during pacing from the Coronary 
Sinus.  
11.5.2.1. PVI ablation(s) - Ablating physician blinded to the DirectSense technology during 
initial encircling of PVs  
It is recommended to limit the space between the center of 2 lesions to a maximum of 5 mm. 
The ablating physician   is encouraged to avoid jumps between anatomical locations. 
For the PVI ablation(s) the following information will be collected: 
 Information related to PVI ablation(s): 
o method of access to left atrium for ablation catheter, if applicable (trans-
septal, retrograde, or both); 
o type of PVI ablation application(s) (e.g. point (focal) lesions, dragging 
lesions*); 
 *The usage of dragging lesions for encircling the PVs will result in a Protocol Deviation. 
Dragging lesions or other types of applications are allowed for other arrhythmia(s)/ 
additional lines. 
o specific PVI ablation technique(s) (WACA + information on additional lines 
if applicable) 
o anatomical segments targeted for ablation (please refer to Figure 11.5-2 for 
the 8 circumferential positions around each PV pair) 
**Not targeting all anatomical segments for ablation will result in a Protocol Deviation. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 31 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 32 of 65 
  
 Total number of RF applications per anatomical segment for PVI ablation; 
 Power and duration for each RF application (cfr. printed EP Lab Procedure Report); 
 Occurrence of steam pops;  
 DirectSense data collection:  
o Blood pool impedance measurements for approximately 10 s prior to the 1st 
RF application (reference measurement) 
o Myocardium impedance measurements for approximately 10 s prior to the 1st 
RF application (reference measurement) 
o Local impedance data will be sampled approximately every 50 ms. This data 
will be simultaneously recorded in a digital log file by the BSC representative.  
 
o Single ablation applications will be tagged by the Boston Scientific 
representative under guidance of the operating physician, in the Rhythmia 
HDx mapping system and on the Technical Source Form as:  
 belonging to a specific PV and anatomical segments.  
 resulting in steam pops.  
Single applications in each anatomical segment will be tagged with ordinal 
numbers.  
 
At the end of the PVI ablation(s), PVI will be confirmed by means of entrance block. 
The waiting period before testing entrance block should be approximately 20 minutes. After 
this waiting period, Rhythmia HDx + IntellaMap Orion will be used to collect an 
electroanatomic map (i.e. activation and voltage map) of the Left Atrium. For all subjects it is 
preferred that all maps are acquired during pacing from the Coronary Sinus. 
The following information will be collected in the eCRF:  
 Number and location of gaps for each PV per segment, if any*** 
*** where feasible, the investigator should indicate approximate location respectively to the tagged ablation 
point 
 
The BSC Rhythmia Mapping Specialist (RMS) supporting the procedure will be unblinded to 
the DirectSense technology during the entire procedure.  
 
If the ablating physician becomes unblinded to the DirectSense technology during the initial 
encircling of the PVs, this will have to be documented on the Technical Source Form. For 
more details on the Technical Source Form, please refer to Section 13.4.   
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 32 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 33 of 65 
  
Gap closure, if applicable - Ablating physician UNBLINDED to the DirectSense technology  
If gaps are identified and the ablating physician decides to ablate these gaps, the ablating 
physician will be unblinded to the DirectSense technology.  
It is recommended to limit the space between the center of 2 lesions to a maximum of 5 mm. 
The ablating physician is encouraged to avoid jumps between anatomical locations. 
For the gap closure, the following information will be collected: 
 additional point lesions 
*The usage of dragging lesions for encircling the PVs will result in a Protocol Deviation. 
Dragging lesions or other types of applications are allowed for other arrhythmia(s)/ 
additional lines.  
 anatomical segments targeted for gap closure (please refer to Figure 11.5-2 for the 8 
circumferential positions around each PV)  
**Not targeting all anatomical segments for ablation will result in a Protocol Deviation. 
 Total number of RF applications per anatomical segment for gap closure; 
 Power and duration for each RF application (cfr. Printed EP Lab Procedure Report); 
 Occurrence of steam pops;  
 DirectSense data collection:  
o Local impedance data will be sampled approximately every 50 ms. This data 
will be simultaneously recorded in a digital log file by the BSC representative.  
 
o Single ablation applications will be tagged by the Boston Scientific 
representative, under guidance  of the operating physician, in the Rhythmia 
HDx mapping system and on the Technical Source Form as  
 belonging to a specific PV and anatomical segments 
 resulting in steam pops.  
 Single applications in each anatomical segment will be tagged with 
ordinal numbers.  
o Local impedance data on the prior ablation line on both sides of the gap and 
on the gap itself must be recorded for approximately 10 s.   
 
End of PVI 
After touch ups of the gaps, Rhythmia HDx + IntellaMap Orion will be used to collect an 
electroanatomic map (i.e. activation and voltage map) of the Left Atrium. In case other 
arrhythmia(s)/additional lines will be ablated, these can be ablated prior to obtaining the 
electroanatomic map (i.e. activation and voltage map) of the Left Atrium. For all subjects it is 
preferred that all maps are acquired during pacing from the Coronary Sinus. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 33 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 34 of 65 
  
There is no requirement to implement a waiting period of approximately 20 minutes before 
obtaining this electroanatomic map. At the end of the PVI ablation(s), PVI will be confirmed 
by means of entrance block. 
The following DirectSense data will be collected:  
 Blood pool impedance measurements for approximately 10 s (reference 
measurement) 
 Myocardium impedance measurements for approximately 10 s (reference 
measurement) 
 Local impedance data will be sampled approximately every 50 ms. This data will be 
simultaneously recorded in a digital log file by the BSC representative.  
 
The following information will be collected in the eCRF:  
 
Number of gap touch ups for each PV per each segment, if any****** where feasible, the 
investigator should indicate approximate location respect to the tagged ablation point 
 
11.5.2.2. Ablation of other arrhythmia(s)/additional line(s) 
In case other arrhythmia(s)/additional line(s) will be ablated, the PVI has to be achieved prior 
to ablating other arrhythmia(s)/additional line(s).   
 If the other arrhythmia(s)/additional line(s) will be ablated in the LA, Rhythmia HDx 
+ IntellaMap Orion will be used to collect an electroanatomic map (i.e. activation and 
voltage map) of the Left Atrium prior to ablating the other arrhythmia(s)/additional 
line(s) in the LA.  
 
 If the other arrhythmia(s)/additional line(s) will not be ablated in the LA, the 
electroanatomic map (i.e. activation and voltage map) of the Left Atrium may be 
obtained after ablating the other arrhythmia(s)/additional line(s).  
For the other arrhythmia(s)/additional line(s), the following information will be collected: 
o Type of ablation application(s) (e.g. point (focal) lesions, dragging lesions#); 
#Dragging 
lesions 
or 
other 
types 
of 
applications 
are 
allowed 
for 
other 
arrhythmia(s)/additional lines. 
o Anatomical locations targeted for other arrhythmia(s)/additional line(s); 
o Total number of RF applications per other arrhythmia(s)/additional 
location(s); 
o Technique used to ablate these other arrhythmia(s)/additional line(s); 
o Successful termination of the arrhythmia(s), if applicable; 
o Power and duration for each RF application; 
o Total RF application time for the other arrhythmia(s)/additional line(s); 
o Did steam pops occur; 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 34 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 35 of 65 
  
 
11.5.2.3. 
Data 
collection 
after 
PVI 
ablation(s) 
and 
after 
ablation 
of 
other 
arrhythmia(s)/additional line(s), if applicable 
At the end of the procedure the following information will be entered into the eCRF: 
 Total Fluoroscopy time; 
 Total procedure time will be collected, defined as time elapsed from time first access 
sheath insertion into the subject until the last catheter removed; 
 Assessment of reportable Adverse Events/Device Deficiencies; 
 Protocol Deviations, if applicable 
 
At the end of the procedure, the following data must be saved/printed: 
 The Rhythmia Advanced Export Case Data (the data collected through the Rhythmia 
HDx mapping system) will be saved and stored to external media, as provided by the 
sponsor. 
 The EP Lab Procedure Report will be printed and stored in the center’s patient file.  
Please refer to Table 11.11-1 for an overview of source document requirements. 
 
The Figure below describes the index procedure workflow.  
 
Figure 11.5-1: Index Procedure Workflow 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 35 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 36 of 65 
  
 
PVI ablation 

Measure reference local impedances: blood pool and myocardium 

Point by point lesions of PVs, using WACA 

Limit the space between the center of 2 lesions to a maximum of 5 mm  

Avoid jumps between anatomical segments 
PVI ablation cont’d 
     Waiting period of approximately 20 minutes (20 min waiting period starts after 
initial PV emcircling) 
Gap Closure (if the physician decides to ablate these gaps) 
     Point by point lesions of PVs, using WACA 
     Limit the space between the center of 2 lesions to a maximum of 5 mm 
Map Creation 

Rhythmia HDx + IntellaMap Orion will be used to collect an electroanatomic map 
(i.e. activation and voltage map) of the LA  
Gaps 
identified? 
End of PVI ablation 

Measure reference local 
impedances: blood pool and 
myocardium 
No 
Yes 
Will additional 
lines/arrhythmia(s) in 
the LA* be ablated?
No 
End of index procedure 
Yes 
Ablation additional lines/arrhythmias in the LA 
      No study-specific requirements, per investigator practice  
*If other arrhythmia(s)/additional line(s) will be ablated in the LA, Rhythmia + IntellaMap Orion  will be used to collect 
an electroanatomic map of the LA prior to ablating the other arrhythmia(s)/additional line(s) in the LA. If the other 
arrhythmia(s)/additional line(s) will not be ablated in the LA, Rhythmia + IntellaMap Orion will be used to collect an 
electroanatomic map of the LA after ablating the other arrhythmia(s)/additional line(s). 
Optional Map Creation 
•       Rhythmia HDx + IntellaMap Orion will be used in case an additional  electroanatomic 
map (i.e., activation and voltage map) of the LA is collected 
Will additional 
lines/arrhythmia(s) outside 
of the LA* be ablated 
No 
Yes 
Ablation additional 
lines/arrhythmia(s) 
outside of the LA 
Map Creation 

Rhythmia HDx + IntellaMap Orion will be used to collect an electroanatomic 
map (i.e. activation and voltage map) of the LA 

Entrance block testing PVs by creating an electroanatomic map of the LA* 
Blinded to DirectSense technology 
Unblinded to DirectSense technology 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 36 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 37 of 65 
  
 
Figure 11.5-2: 8 Circumferential positions around each PV  
 
11.6. Pre-discharge visits 
The pre-discharge follow up visit should be done before hospital discharge but no later than 8 
days past index ablation procedure, even if the subject has to remain at the hospital for a longer 
time (e.g. due to an Adverse Event). 
 
The data collection at Pre-Discharge includes: 
• 
Date of visit; 
• 
Rhythm at time of pre-discharge; 
• 
Variations in current medication regimen; 
• 
Reportable Adverse Events, if applicable 
• 
Additional Follow Ups/Procedures, if applicable 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 37 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 38 of 65 
  
11.7. Additional visits 
Additional visits before the month 4 follow up may occur per physician decision. If an 
additional visit should occur, the following information should be collected in the eCRF: 
 Visit date; 
 Type of visit: in-clinic or phone contact,  
 Reportable Adverse Events, if applicable; 
 Reason for additional follow up including standard of care, due to adverse event or 
other. 
11.8. Additional procedure  
In case an additional procedure occurs during the month 4 follow up period, the data of this 
procedure will be entered in the ‘Additional Procedure’ eCRF.  In case this additional 
procedure is an ablation procedure (for the same, or different arrhythmias or for and 
unsuccessful ablation of the arrhythmia presented at index procedure) for which a different 
mapping system was used or different mapping and/or therapeutic catheters were used, 
detailed information about this additional ablation procedure will be entered in the 
‘Additional Procedure’ eCRF: 
 The name of the EP physician performing the procedure 
 Was the additional ablation procedure performed in the LA?  
o For additional ablation procedures performed in the LA: Did this additional 
ablation procedure occur as a result of an unsuccessful or incomplete index 
procedure? 
o Was this additional ablation procedure performed to treat the same arrhythmia 
as the one from the index procedure? If no, specify the arrhythmia type 
o Was the Rhythmia HDx mapping system, IntellaMap Orion mapping catheter 
and IntellaNav MiFi OI ablation catheter used for this additional ablation 
procedure?  
 If yes, this additional ablation procedure will be considered as the 
month 3 assessment if the month 3 assessment was not yet performed. 
This additional ablation procedure must be completed in the month 3 
assessment visit. Please refer to Section 11.9-3 for more details. 
 If no, in case a different mapping system was used and/or different 
mapping and/or therapeutic catheters were used, the subject will have 
to be withdrawn prior to this additional ablation procedure. 
 Please refer to Section 10.2 for more details.  
Any reportable adverse event resulting from additional procedures must be captured on the 
Adverse Event eCRF.  
The additional ablation procedure itself should not be reported as a Serious Adverse Event 
(SAE), unless associated with subject worsening condition. In this case, the additional 
ablation procedure should be reported in the Adverse Event eCRF as corrective action of the 
specific SAE reported for the worsening condition. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 38 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 39 of 65 
  
Additional procedures will not alter the determination of the primary endpoint (acute 
procedural success), that will be based on the index procedure. 
 
11.9. Month 3 Assessment-Ablating physician UNBLINDED to DirectSense 
technology 
Rhythmia HDx + IntellaMap Orion will be used to collect an electroanatomic map (i.e. 
activation and voltage map) of the Left Atrium.  In case gaps are detected and the physician 
decides to ablate these gaps, ablation must be performed with the IntellaNav MiFi OI 
catheter. 
 
For all subjects it is preferred that all maps are acquired during pacing from the Coronary 
Sinus. 
 
Gap sites will be determined for each segment and vein according to Figure 11.5-2. The 
location of each gap will be defined as a site of PV potential on the diagnostic catheter, and 
in the case of retreatment, to be confirmed by a change in PV activation.  
 
The following DirectSense data has to be collected: 
 Blood pool impedance measurements for approximately 10 s. In case the physician 
decides to ablate, this measurement has to be obtained prior to the 1st RF application 
(reference measurement) 
 Non-ablated myocardium impedance measurements for approximately 10 s prior to 
the 1st RF application. In case the physician decides to ablate, this measurement has to 
be obtained prior to the 1st RF application (reference measurement) 
 Local impedance data will be sampled approximately every 50 ms. This data will be 
simultaneously recorded in a digital log file by the BSC representative.  
 
 
For at least 5 points that are considered as gap-free, the following DirectSense data has to be 
collected 
 Ablated myocardium impedance measurements for approximately 10 s. In case the 
physician decides to ablate, this measurement has to be obtained prior to the 1st RF 
application (reference measurement) 
 
For all gaps that are ablated, the following DirectSense data has to be collected: 
 Gap impedance measurement for 10 s prior to first ablation within the gap 
 
In case the ablating physician decides to ablate gaps, if any, the ablating physician can use 
whichever ablation technique he/she prefers. There is also no requirement to perform 
entrance block testing at the end of the ablation of gaps or to implement a waiting time after 
the ablation of gaps, if applicable. Also, there is no need to collect a Rhythmia + IntellaMap 
Orion activation map at the end of the ablation of gaps, if applicable.  
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 39 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 40 of 65 
  
 
11.10. 
Month 4 Follow Up  
Investigators will have to assess subject status at one month (30 days +/-7) after the month 3 
assessment. The month 4 follow up has to be performed in-clinic. The data collection at the 
month 4 follow up includes: 
• Visit date; 
• Current vital status of subject; 
• Reportable Adverse Events, including resolution of ongoing events, if applicable 
 
11.11. 
Study Completion 
Each Treatment subject will be followed until the month 4 follow up. Participation in the study is 
considered complete upon completion of the month 4 follow up. 
In case of premature termination of the study, please refer to Section 23.1.  
Following termination/completion of the study, subjects will be managed according to local 
institution practice. 
 
11.12. 
Source Documents 
Printed, optical or electronic document containing source data shall be used; examples 
include hospital records, laboratory notes, radiographs, records kept at the investigation site, 
and/or at the laboratories involved in the clinical study, technical source forms (as defined in 
section 13.3) 
Where copies of the original source document as well as printouts of original electronic 
source documents are retained, these shall be signed and dated by a member of the 
investigation center team with a statement that it is a true reproduction of the original source 
document. If the Principal Investigator delegates this task to one of the investigational team 
members, the delegation of this task must be documented in the Site Signature and 
Responsibility Log. 
Table 11.12-1: Source Documentation Requirements 
Requirement 
Disposition 
Informed consent documentation process 
Retain at Center 
Documentation  of: 
 
Demographics: age at procedure, gender 
 
Cardiovascular medications 
 
Arrhythmia history 
 
Cardiac disease history 
 
Pregnancy , if applicable 
Retain at Center 
Signed Technical Source Form for Index procedure and 
month 3 assessment 
Retain at Center 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 40 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 41 of 65 
  
Table 11.12-1: Source Documentation Requirements 
Requirement 
Disposition 
Rhythmia Advanced Export Case Data 
Submit to Boston Scientific  
Printed EP Lab Procedure Report  
Retain at Center 
Procedure mapping data (saved  to external media, as 
provided by the sponsor) 
Retain at Center 
In the event of  patient death (if available):  
 
Death narrative 
 
Relevant medical records 
 
Death certificate 
 
Autopsy report 
Submit one copy to Boston Scientific,  
Retain one copy at center 
 
12. Statistical Considerations 
An overview of the study design, sample size and statistical analysis is provided below. 
12.1. Endpoints 
12.1.1. Primary Endpoint 
The primary endpoint is to assess the association between baseline Local Impedance/Local 
Impedance drop values per anatomical segment as recorded at index ablation procedure and 
the proportion of gaps per anatomical segment as measured at the month 3 assessment.  
12.1.1.1. Hypotheses 
No formal pre-specified statistical hypotheses will be tested in this study. 
12.1.1.2. Sample Size  
A sample size of 60 subjects is chosen to generate 50 patients with usable data  (20% 
attrition) and  have 90% power to detect a minimum difference in DirectSense parameters of 
3.71 ohms between segments with and without gaps at month 3. 
12.1.1.3. Statistical Methods 
While no formal hypothesis test will be performed, 95% confidence intervals for the mean 
difference  in baseline Local Impedance/Local Impedance drop values between segments 
with and without gaps will used to compare groups. 
12.2. General Statistical Methods 
12.2.1. Analysis Sets 
The primary endpoint will be assessed in all Treatment subjects who complete the month 3 
gap site assessment. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 41 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 42 of 65 
  
Additional analyses will include all subjects enrolled into the study overall and categorized 
according  to the definitions in section 10.3 or subsets of these categories. 
12.2.2. Control of Systematic Error/Bias 
Selection of patients will be made from the Investigator’s usual patient population. All 
patients meeting the eligibility criteria and having signed the ICF will be enrolled in the 
study. 
12.2.3. Number of Subjects per Investigative Site 
To reduce the impact of individual center, each site may perform up to 30 index ablation 
procedures. This limit of 30 procedures cannot be exceeded, unless Boston Scientific gives 
written approval to do so. 
12.3. Data Analyses  
12.3.1. Other Endpoints/Measurements  
Additional analyses are planned, including but not limited to: 
 Correlation of DirectSense parameters and acute PVI gaps  
o Acute isolation gaps per anatomical segment as associated with baseline Local 
Impedance and Local Impedance drop values at first pass encircling during 
the index ablation procedure 
 Median  number of gaps per patient (or per PV pair) after initial encircling; 
 Statistical characterization of impedance readings for each ablation point 
 Anatomical distribution of the gaps and impedance reading differences at different 
anatomical sites (PV segments) 
12.3.2. Changes to Planned Analyses 
Any changes to the planned statistical analyses outlined in this protocol will be documented 
in the clinical study report along with a reason for the deviation. 
13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data will be recorded in a secure electronic data capture (EDC) system. 
The clinical database will reside on a production server hosted by 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 iMedidata 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 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 42 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 43 of 65 
  
pertaining to the use of electronic records and signatures. Database backups are performed 
regularly. 
The Investigator provides his/her electronic signature on the appropriate eCRFs in 
compliance with local regulations. 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 EDC system and will  
be issued to the site for appropriate response. Site staff will be responsible for resolving all 
queries in the database. 
13.2. Rhythmia HDx Electronic Data Management 
At the conclusion of the case, de-identified case data will be exported in a proprietary format 
from both the Rhythmia HDx mapping system to external storage media (as provided by the 
sponsor) and provided back to the sponsor.   
13.3. Data Retention 
The Investigator or Investigational site will maintain, at the investigative site, in original 
format all essential study documents and source documentation that support the data 
collected on the study subjects in compliance with ICH/GCP guidelines.  Documents must be 
retained until at least 2 years have elapsed since the formal discontinuation of the clinical 
investigation of the product. These documents will be retained for a longer period of time by 
agreement with BSC or in compliance with other local regulations. It is BSC’s responsibility 
to inform the Investigator when these documents no longer need to be maintained. The 
Investigator will take measures to ensure that these essential documents are not accidentally 
damaged or destroyed. If for any reason the Investigator 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.  
 
13.4. Technical Source Forms 
A Technical Source Form (TSF) is developed by Boston Scientific or by the investigational 
site to capture protocol required data elements that are not duplicated in any other source 
documents. This form is to be used by the study sites as a source document. A Boston 
Scientific representative (R&D Representative or Clinical Trial Manager) may complete the 
TSF at the request of the Ablating Physician. The TSF will be reviewed and signed for 
approval by the Ablating Physician at the end of each procedure.  
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 43 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 44 of 65 
  
14. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
EC/CA) of the revised protocol must be obtained prior to implementation. 
15. 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 EC 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 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 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 in the eCRF. Sites may also be 
required to report deviations to the EC, 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 EC notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
16. Device/Equipment Accountability 
The principal investigator or an authorized designee shall keep records documenting the  
 Rhythmia HDx system unit number, software version used, date used 
 Model number, serial number, and date used of the catheters 
17. Compliance 
17.1. Statement of Compliance 
This study will be conducted in accordance with the current version of ISO 14155: Clinical 
Investigation of Medical Devices for Human Subjects – Good Clinical Practice, the relevant 
parts of the ICH Guidelines for Good Clinical Practice, relevant parts of the ICH Guidelines 
for Good Clinical Practices, ethical principles that have their origins in the Declaration of 
Helsinki, and pertinent individual country laws and regulations. The study shall not begin 
until the required approval/favorable opinion from the EC and/or regulatory authority has 
been obtained, if appropriate. Any additional requirements imposed by the EC or regulatory 
authority shall be followed, if appropriate. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 44 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 45 of 65 
  
17.2. 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/, ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing EC, 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.   
 Prior to beginning the study, sign the Protocol Signature page documenting his/her 
agreement to conduct the study in accordance with the protocol. 
 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 eCRFs 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 EC and regulatory authorities any SAEs and device deficiencies that could 
have led to a SADE and potential/USADE or UADE, if required by the national 
regulations or this protocol or by the EC, 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 EC when performing auditing activities. 
 Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local EC requirements. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 45 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 46 of 65 
  
 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 investigational 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. 
 Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
17.2.1. 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 and adequate supervision of those to whom tasks are delegated. The 
investigator is accountable for regulatory violations resulting from failure to adequately 
supervise the conduct of the clinical study.  
17.3. Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational site will provide to the sponsor 
documentation verifying that their EC is registered or that registration has been submitted to 
the appropriate agency, as applicable according to national/regulatory requirements.   
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 46 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 47 of 65 
  
A copy of the written EC and/or competent authority 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 and shipment of investigational product/equipment. 
Prior approval must also be obtained for other materials related to subject recruitment or 
which will be provided to the subject. 
Annual EC approval and renewals will be obtained throughout the duration of the study as 
required by local/country or EC requirements. Copies of the Investigator’s reports and the EC 
continuance of approval must be provided to the sponsor.  
17.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative including, but not limited to Contract Research Organization (CRO) will have 
access to these confidential records. 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. All data used in the analysis and reporting of this study will be 
without identifiable reference to specific subject name. 
Boston Scientific will keep subjects’ identifiable health information confidential in 
accordance with all applicable laws and regulations.  Boston Scientific may use subjects’ 
health information to conduct this research, as well as for additional purposes, such as 
overseeing and improving the performance of its device, new medical research and proposals 
for developing new medical products or procedures, and other business purposes. 
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.  
17.4.1. 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 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 
(including the Rhythmia HDx Mapping System, programmers, analyzers, and other support 
equipment). 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during ablation procedure, assist with the conduct of testing specified 
in the protocol, and interact with the subject to accomplish requested activities. Typical tasks 
may include the following. 
• 
Setting up, calibrating and/or operating parameters to investigator-requested settings 
of the Rhythmia HDx mapping system 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. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 47 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 48 of 65 
  
• 
Interaction with Boston Scientific noninvasive equipment (Rhythmia HDx System 
and, accessories) and interpretation of information contained therein to support the collection 
of required information by the delegated site staff. 
• 
Print out reports directly from the System and provide original to clinical site as 
source documentation. 
• 
Provide technical expertise/support to subjects during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or their 
delegated site staff and the subject.  
• 
The R&D Representative or Clinical Trial Manager may complete the Technical 
Source Form during the procedure, in order to assist the ablating physician with data 
collection during the procedure. 
 
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• 
Observing testing or medical procedures to provide information relevant to clinical 
protocol compliance. 
• 
Reviewing collected data and study documentation for completeness and accuracy. 
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. 
• 
Collect critical study data (defined as primary or secondary endpoint data) without 
review and approval of the ablating physician. 
• 
Enter data in electronic data capture systems or study medical data into paper forms. 
17.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
 
 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 48 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 49 of 65 
  
18. Monitoring 
Monitoring (on-site and remote) will be performed during the study to assess continued 
compliance with the protocol and applicable regulations. 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 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 and audits and that 
sufficient time is devoted to the process. 
 
19. Potential Risks and Benefits 
19.1. Anticipated Adverse Events and Adverse Device Effects 
The anticipated Adverse Events (AE) and Adverse Device Effects (ADE) in the LOCALIZE 
study are the same shared for the procedures of ablation with use of a 3D mapping system. Both 
the index ablation procedure and the three month invasive reassessment (a procedure of mapping 
and potential additional ablation) are associated with the same list of anticipated AE and ADE. 
Please refer to the study devices Directions for Use (DFU) for a listing of anticipated adverse 
events and adverse device effects associated with cardiac catheterization. 
 
19.2. Risks Associated with the Study Device(s)  
There are no incremental risks that are associated with the study devices and those of market 
available products as listed above.  
19.3. Risks associated with Participation in the Clinical Study 
Risks associated with participation to this study are similar to those shared with the standard 
ablation procedures.  The impacts of study-specific differences in procedures are summarized as 
follows: 
 
The index ablation procedure performed in LOCALIZE has the same purpose of an 
ablation procedure of a subject not participating in this study (i.e. 3D mapping and 
ablation of PAF). The technique for ablation of the arrhythmia (WACA) is standard and 
can be further customized with additional ablation lines per physician’s preference. The 
only differences with respect to a non-study  ablation for PAF are: 
o Potential additional time required to collect information and impedance values for 
the DirectSense feature. The collection of impedance data will not affect therapy 
and will not add specific risks. The total prolongation of the procedure will not be 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 49 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 50 of 65 
  
substantial and will not impact patient safety. In any case, the physician can 
decide to interrupt the procedure if any risk for the subject is expected due to the 
potentially prolonged procedure duration. 
o The ablating physician will initially be blinded to the DirectSense feature when 
performing the initial encircling of the PVs. However, DirectSense data will be 
available to the ablating physician after re-mapping  for potential additional gap 
closure. Having the feature blinded during initial encircling will not have an 
impact on patient’s safety as the DirectSense feature is labelled as a localisation 
feature and not supposed to drive/guide the ablation therapy.  
 
The assessment at month 3 will be similar to the initial procedure as requiring mapping 
and potential ablation of the residual gaps. The ablating physician will not be blinded  to 
DirectSense during this procedure. The additional procedure at  month 3 will not present 
additional risks compared to a standard ablation procedure. An additional mapping and 
ablation procedure is currently not indicated for patients who underwent de novo ablation 
for PAF in the absence of symptoms or recurrence of arrhythmia. However,  an additional 
ablation procedure after 2-3 months post initial PVI is currently a  recognized 
standard  used in previous studies12,13   and  has been included  recent literature in order 
to verify durable isolation of PVs18-22.  
 
19.4. Risk Minimization Actions 
Additional unanticipated risks may exist. Risks can be minimized through compliance with 
standard of care treatments, performing procedures in the appropriate hospital environment, 
adherence to subject selection criteria, close monitoring of the subject's physiologic status 
during procedures and/or follow-ups and by promptly supplying BSC with all pertinent 
information required by this protocol. 
19.5. Anticipated Benefits 
There may be no direct benefit to the subject. However, a dedicated workflow to assess 
ablation gaps at index procedure and at three months invasive reassessment may ensure durable 
isolation of the pulmonary veins, with potential long term effects on efficacy of ablation. The 
potential benefit for an additional mapping procedure at three months lies in the fact that the 
success rate after a single procedure is still sub-optimal as PV reconnection is frequently seen 
during repeat ablation18-22. As such, achieving durable chronic PV insulation by delivering 
effective, transmural lesions during the ablation is key to optimize long-term outcomes. Recently, 
the PRESSURE study23 also showed that a strategy of routine repeated assessment with re-
isolation of PV reconnection improved freedom from AT recurrence, AT burden, and quality of 
life compared with current standard care. Additionally, 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. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 50 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 51 of 65 
  
19.6. Risk to Benefit Rationale 
Risk management activities, including hazard analyses, have been performed on Rhythmia 
HDx mapping system, IntellaMap Orion mapping catheter and IntellaNav MiFi OI ablation 
catheter to identify and analyze known and foreseeable hazards 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 instructions for use of the product to reduce the residual risk of each 
hazard as necessary and practicable. The hazard analysis has been reviewed and approved 
and the remaining risks are acceptable when weighed against the intended benefits to the 
patient. 
20. Safety Reporting 
20.1. 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: 
Reportable Events: 
 All Serious Adverse Events; 
 All Events Leading to Death  
 All Thromboembolic Events 
 All Procedure Related AEs 
 All Rhythmia HDx mapping system, IntellaMap Orion mapping catheter and 
IntellaNav MiFi OI ablation catheter Device Related Adverse Events; 
 All Device Deficiencies related to the study devices (Rhythmia HDx mapping system, 
IntellaMap Orion mapping catheter and IntellaNav MiFi OI ablation catheter); 
 Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
previously not defined in the physicians manuals. 
Whenever 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. 
Death should not be recorded as an AE, but should only be reflected as an outcome of one (1) 
specific SAE (see Table 20.2-1 for AE definitions). 
If an additional ablation procedure is required, this additional ablation procedure should not 
be considered as an Adverse Event, unless associated with subject worsening condition or a 
new diagnosis. If the investigator considers this event to be related to any procedure, the 
event needs to be reported. In this case, the additional ablation procedure should be reported 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 51 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 52 of 65 
  
in the Adverse Event eCRF as corrective action of the specific Procedure Related Adverse 
Event reported for the worsening condition or new diagnosis. 
If the patient experiences a new arrhythmia between the index procedure and the end of 
study, and the investigator considers this Adverse Event to be procedure related, it needs to 
be reported.Refer to DFUs for the known risks associated with the study device(s). 
The Boston Scientific Medical Safety group will provide safety oversight by reviewing and 
classifying individual events that are reported to the sponsor. Routine aggregate safety 
reviews will be conducted to ensure subject safety. 
20.2. Definitions and Classification 
Adverse event definitions are provided in Table 20.2-1. Administrative edits were made on 
the definition of serious adverse event from ISO 14155 and MEDDEV 2.7/3 for clarification 
purposes. All events required to be reported in this study are listed in Section 20.1. 
 
Table 20.2-1: 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 investigational 
medical device.  
NOTE 1: This includes events related to the investigational medical device 
or comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of an investigational 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 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational 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 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 52 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 53 of 65 
  
Table 20.2-1: Safety Definitions 
Term 
Definition 
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. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
A inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 
Abbreviations: EC=Ethics Committee 
20.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device or procedure. See 
criteria in Table 20.3-1:   
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 53 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 54 of 65 
  
Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
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 investigational 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 investigational 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 
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 
The relationship with the use of the investigational 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 
The relationship with the use of the investigational device seems relevant and/or the 
event cannot reasonably explained by another cause, but additional information may 
be obtained. 
Causal Relationship 
The serious event is associated with the investigational 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 investigational device use/application or 
procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational 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; 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 54 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 55 of 65 
  
Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the investigational 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. 
 
20.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 20.4-1 
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: 
 
Localize.safety@bsci.com 
 
Table 20.4-1: Investigator Reporting 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 1 business day of first becoming aware of the 
event. 
 
Terminating at the end of the study 
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.  
 
For deaths, within 3 calendar days of site notification 
 
Reporting required through the end of the study 
Provide all relevant 
source documentation 
(unidentified) for 
reported event upon 
request of the sponsor 
 
When documentation is available 
Serious Adverse 
Device Effects 
Complete AE eCRF 
page with all available 
new and updated 
information. 
 
Within 2 business days of first becoming aware of 
the event or as per local/regional regulations. 
 
Reporting required through the end of the study 
Provide all relevant 
 
When documentation is available 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 55 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 56 of 65 
  
Event 
Classification 
Communication 
Method  
Communication Timeline post-market studies*  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE VIGILANCE 
SYSTEM) 
source documentation 
(unidentified) for 
reported event upon 
request of the sponsor. 
Device Deficiencies 
(including but not 
limited to failures, 
malfunctions, and 
product 
nonconformities) 
Note:  Any 
Investigational 
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 eCRF with 
all available new and 
updated information.  
 
Within 2 business days of first becoming aware of 
the event. Reporting required through the end of the 
study 
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 (recommended within 30 
business days after becoming aware of the 
information) 
 
Reporting required through the end of the study 
20.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the manufacturer)  
associated with the study devices (Rhythmia HDx mapping system, IntellaMap Orion 
mapping catheter and IntellaNav MiFi OI ablation catheter) will be documented and reported 
to BSC. If possible, the device(s) should be returned to BSC for analysis. Instructions for 
returning the study catheters will be provided in the Site Initiation Visit slides. 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 failures and malfunctions should also 
be documented in the subject’s medical record. 
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not adverse events. However, a reportable event that results from a 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 56 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 57 of 65 
  
device failure or malfunction, would be recorded as an adverse event on the appropriate 
eCRF. 
For Device Deficiencies, the investigator must assess and report if the device deficiency  
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. 
20.6. Reporting to Regulatory Authorities / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the EC, and regulatory authorities of 
UADE and SAE as required by local/regional regulations. 
20.7. Subject Death Reporting 
A subject death during the study should be reported to Boston Scientific as soon as possible 
and, in any event, within3 calendar days of site notification. The site’s EC must be notified of 
any deaths in accordance with that site’s EC policies and procedures.  
If requested by Boston Scientific, a detailed narrative (death letter) describing the 
circumstances surrounding the death should be included in the death notification. 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 Rhythmia HDx mapping system, the IntellaMap Orion 
mapping catheter, IntellaNav MiFi OI ablation catheter clinical investigation, procedure, or 
subject condition; 
• Whether or not the death was witnessed; 
• Whether the subject had worsening heart failure; if applicable 
• 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. 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 57 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 58 of 65 
  
 
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 IntellaMap Orion mapping catheter and IntellaNav MiFi OI ablation 
catheter should be returned promptly to Boston Scientific RM/EP for analysis.  
  
21. 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 investigational 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 body, as applicable. The ICF must be 
accepted by BSC or its delegate (e.g. CRO), and approved by the site’s EC, or central EC, 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 EC.  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 EC 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, 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 58 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 59 of 65 
  
 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 body 
according to their requirements. Any violations of the informed consent process must be 
reported as deviations to the sponsor and local regulatory authorities (e.g. EC), as 
appropriate. 
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 EC. The new version of the ICF must be approved by the EC. 
Acceptance by Boston Scientific is required if changes to the revised ICF are requested by 
the site’s EC. The EC will determine the subject population to be re-consented. 
The site will ensure that originally signed ICFs are filed in subjects’ binders and that the ICF 
process is documented in the medical file. Originally signed ICFs and the ICF process will be 
made available for review at Independent Monitoring Visits (IMVs). 
 
 
 
 
 
 
 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 59 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 60 of 65 
  
22. Suspension or Termination 
23.1 Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or administrative reasons and reasons 
related to protection of subjects.  Investigators, associated ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of study termination. 
23.1.1 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 of the 
device. 
23.2 Termination of Study Participation by the Investigator or Withdrawal of EC 
Approval 
Any investigator, or EC in the LOCALIZE study may discontinue participation in the study 
or withdraw approval of the study, respectively, with suitable written notice to Boston 
Scientific. Investigators, associated ECs, and regulatory authorities, as applicable, will be 
notified in writing in the event of these occurrences. 
23.3 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 
EC 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 EC terminates participation in the study, participating investigators, 
associated ECs, 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 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 60 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 61 of 65 
  
23.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific Corporation 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 3 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 study 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 EC and regulatory authorities, as applicable, will be notified. 
All subjects enrolled in the study at the site will continue to be followed according to 
standard of care at the site. The Principal Investigator at the site must make provision for 
these follow-up visits unless BSC notifies the investigational site otherwise. 
 
23. 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 Corporation 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. 
 The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
 
24. Reimbursement and Compensation for Subjects 
24.1. Compensation for Subject’s Health Injury 
Boston Scientific Corporation will purchase an insurance policy to cover the cost of potential 
health injury for study subjects, and if required by applicable law.  
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 61 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 62 of 65 
  
25. Bibliography 
1. 
Huang SK, Wood MA, editors.  Catheter ablation of cardiac arrhythmias. 
Philadelphia: Sounders Elsevier; 2006. 
2.    
Kannel WB, Benjamin EJ. Status of Epidemiology of Atrial Fibrillation. Med Clin N 
Am 92 (2008) 17–40 
3.    
Rhythmia Medical’s analysis based on data from: Millennium Research Group.  
4.  
Feinberg WM BJ, Laupacis A, et al. Prevalence, age distribution and gender in 
patients with atrial fibrillation; analysis and implications. Arch Intern Med. 1995;155:469-
473 
5.  
Wann S CA, January C, et al. ACC/AHA/HRS focused update on the management of 
patients with atrial fibrillation (2011 writing group members) (updating the 2006 guideline): 
A report of the American College of Cardiology Foundation/American Heart Association 
task force on practice guidelines. Circulation. 2011;123:104-123  
6.  
Fuster V RL, Cannom DS, et al. ACCF/AHA/ESC 2006 guidelines for the 
management of patients with atrial fibrillation: Executive summary.  A report of the 
American College of Cardiology/American Heart Association task force on practice 
guidelines and the European Society of Cardiology committee for practice guidelines 
(writing committee to revise the 2001 guidelines for the management of patients with atrial 
fibrillation): Developed in collaboration with the North American Society of Pacing and 
Electrophysiology. Circulation. 2006;114:e257-e354 
7.  
Friberg J BP, Scharling H. Rising rates of hospital admissions for atrial fibrillation. 
Epidemiology 2003;14 666-672 
8.  
Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES, Thorpe K, 
Champagne J, Talajic M, Coutu B, Gronefeld GC, Hohnloser SH. Comparison of beta-
blockers, amiodarone plus beta- blockers, or sotalol for prevention of shocks from 
implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA. 
2006;295:165–71. 
9.    
Waldo AL. A perspective on antiarrhythmic drug therapy to treat atrial fibrillation: 
there remains an unmet need. Am Heart J. 2006;151(4):771-8. 
10.    Noheria A, Kumar A, Wylie JV, Josephson ME. Catheter ablation vs antiarrhythmic 
drug therapy for atrial fibrillation. Arch Intern Med. 2008;168(6):581-6. 
11.  
Chen SA, Chiang CE, Tai CT, Cheng CC, Chiou CW, Lee SH, Ueng KC, Wen ZC, 
Chang MS. Complications of diagnostic electrophysiologic studies and radiofrequency 
catheter ablation in patients with tachyarrhythmias: an eight-year survey of 3,966 consecutive 
procedures in a tertiary referral center. Am J Cardiol. 1996;77(1):41-6. 
 
12.  
Neuzil P, Reddy VY, Kautzner J, Petru J, Wichterle D, Shah D, Lambert H, Yulzari 
A, Wissner E, Kuck KH. Electrical reconnection after pulmonary vein isolation is contingent 
on contact force during initial treatment: results from the EFFICAS I study. Circ Arrhythm 
Electrophysiol. 2013 Apr;6(2):327-33. doi: 10.1161/CIRCEP.113.000374. Epub 2013 Mar 
20. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 62 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 63 of 65 
  
13.  
Kautzner J, Neuzil P, Lambert H, Peichl P, Petru J, Cihak R, Skoda J, Wichterle D4, 
Wissner E, Yulzari A, Kuck KH. EFFICAS II: optimization of catheter contact force 
improves outcome of pulmonary vein isolation for paroxysmal atrial fibrillation. Europace. 
2015 Aug;17(8):1229-35. doi: 10.1093/europace/euv057. Epub 2015 Jun 3. 
14.  
Gaspar T, Sih H, Hindricks G, Eitel C, Sommer P, Kircher S, Rolf S, Arya A, 
Teplitsky L, Piorkowski C. Use of electrical coupling information in AF catheter ablation: a 
prospective randomized pilot study. Heart Rhythm. 2013 Feb;10(2):176-81. doi: 
10.1016/j.hrthm.2012.10.010. Epub 2012 Oct 9. 
15. 
Jones MA, Webster D, Wong KC, Hayes C, Qureshi N, Rajappan K, Bashir Y, Betts 
TR. The benefit of tissue contact monitoring with an electrical coupling index during ablation 
of typical atrial flutter--a prospective randomised control trial. J Interv Card Electrophysiol. 
2014 Dec;41(3):237-44. doi: 10.1007/s10840-014-9943-6. Epub 2014 Sep 19. 
16.  
Natale A, Reddy VY, Monir G, Wilber DJ, Lindsay BD, McElderry HT, Kantipudi C, 
Mansour MC, Melby DP, Packer DL, Nakagawa H, Zhang B, Stagg RB, Boo LM, 
Marchlinski FE. Paroxysmal AF catheter ablation with a contact force sensing catheter: 
results of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol. 2014 Aug 
19;64(7):647-56. doi: 10.1016/j.jacc.2014.04.072. 
17.  
Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, 
Damiano RJ Jr, Davies DW, DiMarco J, et al. Europace. 2012 Apr; 14(4):528-606. 2012 
HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial 
Fibrillation: recommendations for patient selection, procedural techniques, patient 
management and follow-up, definitions, endpoints, and research trial design. 
18. Rordorf R, Expert Rev Med Devices. 2017; Liang, Expert Rev Cardiovasc Ther. 2016 , 
Aryana . Heart Rhythm. 2016 , Duytschaever  Europace 2015, Reddy . J Cardiovasc 
Electrophysiol. 2015 
19. Liang JJ, Santangeli P. Contact force sensing during atrial fibrillation ablation: clinical 
experience and effects on outcomes. Expert Rev Cardiovasc Ther. 2016 Jun;14(6):749-59. 
20. Aryana A, Mugnai G, Singh SM, Pujara DK, de Asmundis C, Singh SK, Bowers MR, 
Brugada P, d'Avila A, O'Neill PG, Chierchia GB. Procedural and biophysical indicators of 
durable pulmonary vein isolation during  cryoballoon ablation of atrial fibrillation. Heart 
Rhythm. 2016 Feb;13(2):424-32. 
21. Duytschaever M, Taghji P, Tavernier R. Towards durable pulmonary vein isolation: we 
are closing the gap. Europace. 2015 Aug;17(8):1164-5.  
22.  Reddy VY, Sediva L, Petru J, Skoda J, Chovanec M, Chitovova Z,  Di Stefano P, Rubin 
E, Dukkipati S, Neuzil P. Durability of Pulmonary Vein Isolation with Cryoballoon Ablation: 
Results from the Sustained PV Isolation with Arctic Front Advance (SUPIR) Study. J 
Cardiovasc Electrophysiol. 2015 May;26(5):493-500.  
23. Das M , Wynn GJ, Saeed Y, Gomes S, Morgan M, Ronayne C, Bonnett LJ, Waktare EP 
et al Pulmonary Vein Re-Isolation as a Routine Strategy Regardless of Symptoms The 
PRESSURE Randomized Controlled Trial. JACC 2017, In press. 
 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 63 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 64 of 65 
  
26. Abbreviations and Definitions  
26.1. Abbreviations 
Abbreviations are shown in Table 26.1-1.   
Table 26.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ACT 
Activated Clotting Time 
AE 
Adverse Event 
AF 
atrial Fibrillation 
AFL 
atrial Flutter 
ADE 
Adverse Device Effect 
AV 
Atrio-Ventricular 
BSC 
Boston Scientific Corporation 
CA 
Competent Authority 
CABG 
Coronary Artery Bypass Graft 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRT 
Cardiac Resynchronization Therapy 
CTI 
Computerized Tomography Imaging 
CTM 
Clinical Trial Manager 
DFU 
Directions For Use 
ID 
Identification Number 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
ECG 
Electrocardiogram 
EGM 
Electrogram 
EP 
Elektrophysiology 
GCP 
Good Clinical Practice 
HCP 
Health Care Personnel 
IC 
Intracardiac 
ICD 
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
IMV 
Independent Monitoring Visit 
IRB 
Institutional Review Board 
LAAC 
Left Atrial Appendage Closure 
MRI 
Magnetic Resonance Imaging 
PAF 
Paroxysmal Atrial Fibrillation 
PFO 
Patent Foramen Ovale 
PM 
Pacemaker 
PTCA 
Percutaneous Trans Catheter Angioplasty 
PV 
Pulmonary Vein 
PVI 
Pulmonary Vein Isolation 
RF 
Radiofrequency 
SAE 
Serious Adverse Event 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 64 of 65

PM007                                                                          Form/Template 90702637 Rev/Ver AH 
Confidential                                    LOCALIZE protocol, document 92142978, Rev/Ver AB 
                                                                                                                               Page 65 of 65 
  
Table 26.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
SADE 
Serious Adverse Device Effect 
SR 
Sinus Rhythm 
SVT 
Supraventricular Tachycardia 
VT 
Ventricular Tachycardia 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
26.2. Definitions 
Terms are defined in Table 26.2-2.  
Table 26.2-2: Definitions 
Term 
Definition 
Source Data 
All information in original records and certified copies of original records of 
clinical findings, observations, or other activities in a clinical trial necessary for 
the reconstruction and evaluation of the trial. Source data are contained in the 
source documents (original records or certified copies).   
Source Documents 
Original documents, data, and records   
 
Abbreviations are defined in Table 27.1-1. 
27. Appendices 
Clinical trial organization, including  names and addresses of the CRO(s) involved in 
selected geographies, names and addresses of the sites, names of Principal Investigators and 
clinical research monitors are provided as annex to the  present protocol, and available upon 
request, where needed, to fulfill local requirements. 
Boston Scientific Confidential. Unauthorized use is prohibited.
Released
92142978 B.4
LOCALIZE-Protocol
Page 65 of 65