LUX-Dx Insertable Cardiac Monitor Remote Programming and Performance Study
Conditions: Atrial Fibrillation, Syncope, Cryptogenic Stroke
Sponsor: Boston Scientific Corporation

Form/Template 92120219_Rev/Ver D 
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   LUX-Dx PERFORM Protocol, 92557593, Rev/Ver C 
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LUX-DxTM Insertable Cardiac Monitor  
Remote Programming and Performance Study 
LUX-Dx PERFORM 
C2045 
CLINICAL INVESTIGATION PLAN 
 
 
NCT #: 04732728 
 
Sponsored By 
Boston Scientific Corporation 
St. Paul, MN 55112, USA 
Tel: 1.800.CARDIAC 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Contact Information 
Role 
Contact 
Clinical Contact 
 
 
1-800-CARDIAC (227-3422) 
   
Coordinating Principal 
Investigator(s) 
Mark Richards MD, PhD, FACC, FHRS  
  
 
Vendors/Labs/External 
Organizations 
A list of vendors/laboratories/External Organizations involved 
in the trial is maintained by the sponsor.  
 
 
 
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Form/Template 92120219_Rev/Ver D 
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Original Release: June 4, 2020 
Current Version: November 3, 2020 
 
 
 
Revision 
Version 
Protocol 
Date 
Template 
number 
and version 
Protocol Section 
Modified 
Summary of Changes 
Justification for 
Modification 
A 
June 4, 
2020 
92120219, 
Rev C 
N/A 
N/A 
Initial release for 
WIRB review and 
approval 
B 
November 
3, 2020 
92120219, 
Rev D 
2. Protocol Synopsis 
 
4.2 Study Rationale 
 
5. LUX-Dx ICM 
Device/System 
Description 
 
6. Study Objectives 
and Endpoints 
 
7.1. Scale and 
Duration 
 
 
7.3. Justification for 
the Study Design 
 
8.2. Inclusion Criteria 
 
 
8.3. Exclusion Criteria 
 
9.2. Enrollment 
Control 
 
9.3. Withdrawal 
 
 
 
9.5. Subject Status and 
Classification 
 
 
Synopsis is updated to reflect changes 
made in the protocol main text. 
Adding safety rationale and 
description of trial population. 
Adding future device and system use. 
 
 
Description of the safety endpoints and 
performance goals. 
Enrollment number, number of sites, 
definition of “Safety Cohort” and 
“Holter Cohort”, and the resulting 
trial flowchart changes are described. 
Provide update and justification of the 
new enrollment number requirement. 
Clarify the 1st inclusion criteria and 
the new indication subgroup; list 
Holter study criteria separately for 
Holter subjects. 
List Holter study criteria separately 
for Holter subjects. 
Update enrollment control to 3 levels: 
Safety Cohort control, Holter Cohort 
control, and site control. 
Adding 2 new withdrawal criteria to 
account for additional circumstances 
which subjects are considered 
withdrawn.  
Eligibility violation is considered a 
study deviation; safety check window 
is from 30 to 60 days after the 
attempted implant. 
N/A 
Adding 
clarification. 
Adding 
clarification. 
 
Addition of the 
safety endpoints 
and performance 
goals.  
Changes reflecting 
the new trial 
design. 
 
Study design 
update. 
Clarification; 
modification of 
indication 
subgroups. 
Clarification. 
 
Updates due to 
design changes. 
 
Addition of 
withdrawal criteria. 
 
 
Clarifications. 
 
 
 
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Revision 
Version 
Protocol 
Date 
Template 
number 
and version 
Protocol Section 
Modified 
Summary of Changes 
Justification for 
Modification 
10.1. Data Collection 
 
 
 
10.4. Enrollment Visit 
 
10.5. ICM Implant 
Procedure 
 
 
10.6. ICM 
Reprogramming 
 
 
 
10.7. 2-Month Holter 
Study Visit 
 
 
 
 
10.8. 6-Month and 12-
Month EMR Review 
 
 
10.9. LUX-Dx ICM 
Not in Service, 
Disabled, or Explanted 
 
11.1.1.  Primary 
Effectiveness 
Objective 1 
11.1.2. Primary 
Effectiveness 
Objective 2 
 
11.1.3. Primary Safety 
Endpoint – Acute 
Visit activities and consolidated in the 
Data Collection Schedule table; virtual 
health visit option is added. 
 
Clarify “Reason for Monitoring” 
determination. 
Adding implanter authorization 
requirement, R-wave amplitude 
collection, and evidence of device 
registration. 
Remove remote reprogramming 
required for the first 25-30 subjects, 
add cap of only requiring the first 5 
reprogramming data entries, and 
clarify the requirement of finalization 
of the reprogrammed settings.  
Provide option to conduct “Virtual 
Health Visit” in Holter study. Clarify 
two 6-day Holter are required for each 
Holter subject. Discuss the sample size 
requirement for the Holter study. 
 
Provide option to conduct “Virtual 
Health Visit”. Clarify lost to follow-up 
consideration due to lack of Clarity 
data transmission.  
Safety check window is from 30 to 60 
days after the applicable events. 
 
Sample size and statistical 
methodology for effectiveness 
objectives are updated to reflect the 
new trial design. 
 
Adding 2 new sections discussing the 
newly added safety endpoints for the 
study. 
 
Modifications and 
providing subject 
with additional 
visit option (virtual 
health visit). 
Clarifications. 
 
Addition of 
requirement and 
clarifications. 
 
Modifications of 
requirement and 
clarifications. 
 
 
Providing subject 
with additional 
visit option (virtual 
health visit); 
clarifications of 
Holter requirement 
and sample size 
needs. 
Providing subject 
with additional 
visit option (virtual 
health visit); 
clarifications. 
Clarifications of 
requirement. 
 
 
Update due to new 
trial design. 
 
 
 
 
Addition of safety 
endpoints for the 
study. 
 
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Revision 
Version 
Protocol 
Date 
Template 
number 
and version 
Protocol Section 
Modified 
Summary of Changes 
Justification for 
Modification 
11.1.4. Primary 
Safety Endpoint - 
Chronic 
 
11.3.1. Interim 
Analyses 
 
13.1. Data Collection, 
Processing, and 
Review 
 
13.3. Technical Source 
Forms (TSF) 
 
16.1. Statement of 
Compliance 
 
16.2. Investigator 
Responsibilities 
 
16.4.1. Role of Boston 
Scientific 
Representatives 
 
18. Potential Risks and 
Benefits 
 
 
 
 
 
 
19.1. Reportable 
Events by Study Site 
to Boston Scientific 
 
19.2. Definitions and 
Classification 
19.3. Relationship to 
Device(s) 
 
 
 
Provide option for sample size 
re-estimation. 
Provide additional information on 
database lock. 
 
New section is added to provide 
additional information on TSF. 
Provide additional information on 
clinical study agreement. 
Provide additional information on 
investigator responsibilities. 
Clarify the role of Boston Scientific 
Representatives. 
 
Adding “Refer to the currently 
available LUX-Dx ICM User’s Manual 
for an updated list of potential adverse 
events”, and adding “Subject who 
participates in the Holter study may 
receive additional arrhythmia 
monitoring in the 14-day monitoring 
period by wearing the Holter monitor” 
as a potential benefit. 
Adding “Serious Adverse Device 
Effects” as reportable safety event for 
the study. 
Definitions and Classification of 
adverse events and event relationship 
are updated per new ISO requirement. 
 
 
 
 
 
Addition of study 
option. 
 
Additional 
information. 
 
 
Additional 
information. 
 
Additional 
information. 
Additional 
information. 
 
Clarifications. 
 
 
Update the 
reference to the 
currently available 
User’s Manual 
mid-study and 
addition of 
potential benefit. 
 
Addition of 
reportable event. 
 
Update per new 
ISO requirement. 
 
 
 
 
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Form/Template 92120219_Rev/Ver D 
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Revision 
Version 
Protocol 
Date 
Template 
number 
and version 
Protocol Section 
Modified 
Summary of Changes 
Justification for 
Modification 
19.4. Investigator 
Reporting 
Requirements 
 
 
 
21.1. Safety 
Monitoring Process 
 
21.3. Independent 
Medical Reviewers – 
Arrhythmia Episodes 
21.4. Independent 
Medical Reviewers – 
Safety Endpoints 
 
22.1.1. Criteria for 
Premature 
Termination of the 
Study 
 
23. Study Registration 
and Results 
 
24. Bibliography 
25. Abbreviations and 
Definitions 
26. 1. Preliminary 
Data Collection Items 
Adding reporting requirement for 
“Serious Health Threat” and updating 
reporting timeframe for “Serious 
Adverse Event”, “Serious Adverse 
Device Effects”, “Device Deficiencies”, 
and “Adverse Event”. 
Clarify the safety monitoring process. 
 
Adding independent medical reviewers 
for arrhythmia episodes review and 
safety endpoints review. 
 
 
Adding additional criteria for study 
termination. 
 
Adding clinical study registration and 
clinical study report requirement. 
Tables and references are updated 
from Section 24 to 26.  
Updated 
study-specific 
requirement. 
 
 
Clarifications. 
 
 
Adding 
independent 
medical reviewers. 
 
 
 
Addition of study 
criteria. 
 
 
Addition of study 
requirement. 
 
Updated 
information.  
C 
November
4, 2020 
92120219, 
Rev C 
Version number 
Updating document version number to 
correct a version error. 
Administrative 
update. 
 
 
 
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2. Protocol Synopsis 
LUX-Dx Insertable Cardiac Monitor Remote Programming and 
Performance Study (LUX-Dx PERFORM) 
Study 
Objective(s) 
The LUX-Dx PERFORM Study will characterize, in a general patient 
population, the utilization of the remote programming feature of the 
Boston Scientific (BSC) Insertable Cardiac Monitor (ICM) device. The 
study will also collect data to characterize the performance of 
arrhythmia detection algorithms. Finally, data collected will be used to 
analyze and characterize the ICM system-related safety events.  
Indication(s) for 
Use  
The LUX-Dx Insertable Cardiac Monitor (ICM) is intended to monitor 
and record subcutaneous electrocardiogram (S-ECG). The recorded 
S-ECG is used for the clinical evaluation and diagnosis of cardiac 
arrhythmias. The LUX-Dx is indicated for use in patients that have a 
known heart condition and are at risk of developing an abnormal heart 
rhythm, or have symptoms that may suggest a cardiac arrhythmia such 
as dizziness, palpitations, syncope, chest pain, and/or shortness of 
breath. The LUX-Dx ICM has not been tested specifically for pediatric 
use. LATITUDE ClarityTM is intended to remotely program and 
interrogate a compatible Boston Scientific device via the myLUXTM 
patient application (patient app) or LUX-Dx Clinic Assistant application 
(clinic app) and transfer data to a central database. The LATITUDE 
Clarity Data Management System provides patient data that can be used 
as part of the clinical evaluation of the patient.   
Test 
Device/System 
The test devices consist of the LUX-Dx ICM, Patient and Clinic Mobile 
Applications, and LATITUDE Clarity Data Management System. The 
number of devices expected to be used are approximately the same as 
the number of total enrollment of the subjects in the study. 
Study Design 
The LUX-Dx PERFORM Study is a prospective, multi-center, single 
arm, post-market, observational study. 
Planned 
Number of 
Subjects 
Approximately 600 to 827 subjects will be enrolled in the study. This 
includes approximately 600 subjects participating in the extended Holter 
monitoring part of the study (Holter study), of which 300 subjects will 
come from the “Atrial fibrillation (AF) management, Post-AF ablation, 
or Suspected AF” indication subgroup, and 300 subjects will come from 
the other two indication subgroups: “Cryptogenic stroke” and 
“Syncope”.  
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LUX-Dx Insertable Cardiac Monitor Remote Programming and 
Performance Study (LUX-Dx PERFORM) 
Planned 
Number of Sites 
/Countries 
This study is planned to be conducted at up to 35 sites in the United 
States to support the required study enrollment. It is possible that sites in 
Europe or Asia Pacific may join the study upon product approval in 
those geographies.  
Study Objectives 
Primary 
Effectiveness 
Objective 1 
Characterize the utilization of the remote programming feature 
Primary 
Effectiveness 
Objective 2 
Characterize the performance of the arrhythmia detection algorithms 
Primary Safety 
Endpoint -
Acute 
ICM System-related Complication-free Rate (CFR) at 30 days 
post-implant 
Primary Safety 
Endpoint - 
Chronic 
ICM System-related Complication-free Rate (CFR) at 12 months 
post-implant 
Method of 
Assigning 
Patients to 
Treatment 
Patient who will be implanted with a BSC LUX-Dx ICM based on 
labelled indications and meet study-specific eligibility criteria will be 
considered for enrollment. To be enrolled in the study, subjects must 
meet all study-specific eligibility criteria and sign the study-specific 
Informed Consent Form (ICF). 
Follow-up 
Schedule 
All subjects must complete the enrollment visit before receiving 
implantation of the LUX-Dx ICM. Following consent into the study, 
relevant data including reportable adverse events and ICM device data 
from the LATITUDE Clarity will be collected during the subject’s study 
participation period. Specifically, participating sites will be requested to 
review each enrolled subject’s electronic medical record (EMR) and 
communicate with the subject by conducting telephone call/virtual 
health visit or in-office visit if scheduled per standard of care to the 
subject at two primary time points (6 months and 12 months 
post-implant) for relevant adverse events. Each subject’s study 
participation period will be approximately one year or until BSC notifies 
all sites that data collection is complete.  
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LUX-Dx Insertable Cardiac Monitor Remote Programming and 
Performance Study (LUX-Dx PERFORM) 
Additionally, extended Holter monitoring (defined as a monitoring 
period of 14 days) will be conducted with a subset of subjects at the 
2-month in-office visit or remotely by telephone/virtual health visit. To 
determine which subjects are required to join the Holter study, the 
following study cohorts are specified: 
• The first 227 subjects enrolled in the study belong to the “Safety 
Cohort”. The number of subjects is required to fulfill the sample 
size requirement of the primary safety endpoint. The “Safety 
Cohort” subjects are not required to participate in the Holter 
study. 
• Once the “Safety Cohort” enrollment is completed, all 
subsequent subjects are required to participate in the Holter 
study. 
• All subjects who participate in the Holter study belong to the 
“Holter Cohort”, which is to fulfill the sample size requirement 
of the primary effectiveness objective 2.  
 
Study Duration The study is expected to last approximately 3.5 years from the first 
enrollment to study closure. 
Participant 
Duration 
The study duration for each enrolled subject is expected to be 
approximately 12 months. 
Inclusion 
Criteria 
• Patient is indicated to be implanted with the LUX-Dx ICM for one 
of the following reasons (grouped in three “Reason for Monitoring” 
subgroups): 
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LUX-Dx Insertable Cardiac Monitor Remote Programming and 
Performance Study (LUX-Dx PERFORM) 
o Cryptogenic stroke 
o Syncope 
o AF management, Post-AF ablation, or Suspected AF 
• Patient is willing to enroll and be monitored in LATITUDE Clarity.  
• Patient is willing and able to be followed remotely via the ICM 
patient mobile app. 
• Patient is willing and capable of providing informed consent (which 
is not to include the use of a legally authorized representative (LAR) 
for documentation of informed consent) and agrees to participate in 
all protocol required activities.  
• Patient is age 18 years or above, or of legal age to give informed 
consent specific to state and national law. 
The following inclusion criterion is applicable for patients participating 
in the Holter study:  
• Patient can tolerate the adhesive used in the Holter monitoring for an 
extended period of time. 
Exclusion 
Criteria 
• Patient is indicated for implantation of, or is currently implanted 
with an active implantable cardiac device (e.g., LVAD, ICD, 
CRT-D, PPM*). 
• Patient cannot tolerate a subcutaneous, chronically-inserted device 
due to medical condition. 
• Patient has a documented life expectancy of less than 12 months (per 
investigator’s discretion). 
• Patient is known to be pregnant at the time of study enrollment 
(method of assessment upon investigator’s discretion). 
• Patient is currently enrolled in another clinical study including 
observational studies/registries, unless prior written approval from 
BSC is obtained. Mandatory governmental registries are accepted for 
co-enrollment without approval by BSC. 
The following exclusion criteria are applicable for patients participating 
in the Holter study:  
• Patient has known allergies to the adhesive materials or hydrogel 
used in the extended Holter monitoring. 
• Patient has broken, damaged, or irritated skin over the chest area 
where the extended Holter monitor will be attached. 
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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................7 
3. 
TABLE OF CONTENTS .......................................................................................................14 
3.1. Table of Figures .....................................................................................................18 
3.2. Table of Tables ......................................................................................................18 
4. 
INTRODUCTION .................................................................................................................19 
4.1. Background ............................................................................................................19 
4.2. Study Rationale .....................................................................................................19 
5. 
LUX-DX ICM DEVICE/SYSTEM DESCRIPTION ...............................................................19 
5.1. LUX-Dx ICM .........................................................................................................20 
5.2. Mobile Applications ..............................................................................................20 
5.3. LATITUDE Clarity Data Management System .................................................21 
5.4. Additional Required Medical Equipment and the Associated Procedures .....22 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................22 
7. 
STUDY DESIGN .................................................................................................................23 
7.1. Scale and Duration ................................................................................................23 
7.2. Treatment Assignment ..........................................................................................24 
7.3. Justification for the Study Design ........................................................................24 
8. 
SUBJECT SELECTION ........................................................................................................25 
8.1. Study Population and Eligibility ..........................................................................25 
8.2. Inclusion Criteria ..................................................................................................25 
8.3. Exclusion Criteria .................................................................................................26 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................27 
9.1. Point of Enrollment ...............................................................................................27 
9.2. Enrollment Control ...............................................................................................27 
9.2.1. 
Enrollment Control of the “Safety Cohort” Subjects ...............................27 
9.2.2. 
Enrollment Control of the Holter Study ...................................................28 
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9.2.3. 
Enrollment Control at Each Site ...............................................................28 
9.3. Withdrawal ............................................................................................................28 
9.4. Lost to Follow-Up ..................................................................................................28 
9.5. Subject Status and Classification .........................................................................29 
9.6. End-of-Study Definition........................................................................................29 
10. STUDY METHODS .............................................................................................................29 
10.1. Data Collection ......................................................................................................29 
10.2. Study Candidate Screening and Recruitment ....................................................30 
10.3. Informed Consent ..................................................................................................30 
10.4. Enrollment Visit ....................................................................................................30 
10.5. ICM Implant Procedure (within 30 days of Enrollment Visit) .........................31 
10.6. ICM Reprogramming (throughout the study) ...................................................32 
10.7. 2-Month Holter Study Visit (±30 days) ...............................................................33 
10.8. 6-Month and 12-Month EMR Review (±30 days) ..............................................34 
10.9. LUX-Dx ICM Not in Service, Disabled, or Explanted .......................................35 
10.10. 
End of Study ............................................................................................35 
10.11. 
Source Documents ..................................................................................35 
11. STATISTICAL CONSIDERATIONS ......................................................................................36 
11.1. Objectives ...............................................................................................................36 
11.1.1. Primary Effectiveness Objective 1 ...........................................................36 
11.1.1.1. Hypotheses ...............................................................................36 
11.1.1.2. Sample Size ..............................................................................36 
11.1.1.3. Statistical Methods ...................................................................36 
11.1.2. Primary Effectiveness Objective 2 ...........................................................36 
11.1.2.1. Hypotheses ...............................................................................36 
11.1.2.2. Sample Size ..............................................................................36 
11.1.2.3. Statistical Methods ...................................................................37 
11.1.3. Primary Safety Endpoint - Acute ..............................................................37 
11.1.3.1. Hypotheses ...............................................................................37 
11.1.3.2. Statistical Methods ...................................................................37 
11.1.3.3. Sample Size ..............................................................................38 
11.1.4. Primary Safety Endpoint - Chronic ..........................................................38 
11.1.4.1. Hypotheses ...............................................................................38 
11.1.4.2. Statistical Methods ...................................................................38 
11.1.4.3. Sample Size ..............................................................................39 
11.1.5. Overall Sample Size .................................................................................39 
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11.2. General Statistical Methods .................................................................................39 
11.2.1. Analysis Sets .............................................................................................39 
11.2.2. Control of Systematic Error/Bias ..............................................................39 
11.2.3. Number of Subjects per Investigative Site ...............................................40 
11.3. Data Analyses ........................................................................................................40 
11.3.1. Interim Analyses .......................................................................................40 
11.3.2. Subgroup Analyses ...................................................................................40 
11.3.3. Justification of Pooling .............................................................................40 
11.3.4. Multivariable Analyses .............................................................................40 
11.3.5. Changes to Planned Analyses ...................................................................40 
12. HEALTH ECONOMICS OUTCOMES ...................................................................................41 
13. DATA MANAGEMENT .......................................................................................................41 
13.1. Data Collection, Processing, and Review ............................................................41 
13.2. Data Retention .......................................................................................................41 
13.3. Technical Source Forms (TSF) ............................................................................42 
13.4. Core Laboratories .................................................................................................42 
14. DEVIATIONS ......................................................................................................................42 
15. DEVICE ACCOUNTABILITY ..............................................................................................42 
16. COMPLIANCE ....................................................................................................................43 
16.1. Statement of Compliance ......................................................................................43 
16.2. Investigator Responsibilities ................................................................................43 
16.2.1. Delegation of Responsibility ....................................................................45 
16.3. Institutional Review Board ...................................................................................45 
16.4. Sponsor Responsibilities .......................................................................................45 
16.4.1. Role of Boston Scientific Representatives ...............................................46 
16.5. Insurance ................................................................................................................46 
17. MONITORING ....................................................................................................................46 
18. POTENTIAL RISKS AND BENEFITS ...................................................................................47 
18.1. Risks Associated with Participation in the Clinical Study ................................47 
18.2. Risks Related to the Systems Used in the Study according to their Instructions 
For Use Manuals ...................................................................................................47 
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18.2.1 Extended Holter monitor (anticipated adverse events associated with the use 
of adhesive patches) ..................................................................................47 
18.2.2 LUX-Dx ICM system (anticipated adverse events associated with the 
implantation of the LUX-Dx ICM) ...........................................................47 
18.3. Possible Interactions with Concomitant Medical Treatments, if applicable ...48 
18.4. Risk Minimization Actions ...................................................................................48 
18.5. Anticipated Benefits ..............................................................................................48 
18.6. Risk to Benefit Rationale, if Applicable ..............................................................48 
19. SAFETY REPORTING .........................................................................................................48 
19.1. Reportable Events by Study Site to Boston Scientific ........................................48 
19.2. Definitions and Classification ...............................................................................49 
19.3. Relationship to Device(s) ......................................................................................51 
19.4. Investigator Reporting Requirements .................................................................53 
19.5. Boston Scientific Device Deficiencies ...................................................................55 
19.6. Reporting to Regulatory Authorities/ IRBs/ ECs/ REBs/ Investigators ..........55 
19.7. Subject Death Reporting ......................................................................................55 
20. INFORMED CONSENT ........................................................................................................56 
21. COMMITTEES ...................................................................................................................57 
21.1. Safety Monitoring Process ....................................................................................57 
21.2. Steering Committee ...............................................................................................58 
21.3. Independent Medical Reviewers – Arrhythmia Episodes .................................58 
21.4. Independent Medical Reviewers – Safety Endpoints .........................................58 
22. SUSPENSION OR TERMINATION ........................................................................................58 
22.1. Premature Termination of the Study ..................................................................58 
22.1.1 
Criteria for Premature Termination of the Study ......................................59 
22.2. Termination of Study Participation by the Investigator or Withdrawal of 
IRB/EC Approval ..................................................................................................59 
22.3. Requirements for Documentation and Subject Follow-up ................................59 
22.4. Criteria for Suspending/Terminating a Study Site ............................................59 
23. STUDY REGISTRATION AND RESULTS .............................................................................60 
23.1. Study Registration .................................................................................................60 
23.2. Clinical Investigation Report ...............................................................................60 
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23.3. Publication Policy ..................................................................................................60 
24. BIBLIOGRAPHY .................................................................................................................61 
25. ABBREVIATIONS AND DEFINITIONS .................................................................................63 
25.1. Abbreviations .........................................................................................................63 
25.2. Definitions ..............................................................................................................64 
26. APPENDICES .....................................................................................................................65 
26.1. Appendix A: Preliminary Data Collection Items ...............................................65 
 
 
3.1. Table of Figures 
Figure 5-1: LUX-Dx ICM System Diagram ........................................................................... 21 
Figure 7-1: Study Design, Subject Cohort, and Flow Diagram .............................................. 24 
 
3.2. Table of Tables 
Table 5-1: BSC LUX-Dx ICM Device and Associated Components ..................................... 22 
Table 8-1: Inclusion Criteria ................................................................................................... 26 
Table 8-2: Exclusion Criteria .................................................................................................. 27 
Table 10-1: Data Collection Schedule (Pre-implant Subject) ................................................. 30 
Table 10-3: Enrollment Visit Source Documentation ............................................................ 31 
Table 10-4: ICM Implant Procedure Source Documentation ................................................. 32 
Table 10-5: ICM Reprogramming Source Documentation .................................................... 33 
Table 10-6: 2-Month Holter Visit Source Documentation ..................................................... 34 
Table 10-7: 6- and 12-Month EMR Review Source Documentation ..................................... 34 
Table 10-8: Device Not in Service, Disabling, and Explant Source Documentation ............. 35 
Table 19-1: Safety Definitions ................................................................................................ 49 
Table 19-2: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 52 
Table 19-3: Investigator Reporting Requirements .................................................................. 53 
Table 25-1: Abbreviations ...................................................................................................... 63 
Table 25-2: Definitions ........................................................................................................... 64 
 
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4. Introduction 
4.1. Background 
Cardiac arrhythmias, especially atrial fibrillation (AF), affect millions of people worldwide. 
Standard of care methodologies to detect and diagnose these arrhythmias include 
electrocardiogram (ECG), ambulatory rhythm monitoring (e.g. Holter monitor), mobile 
cardiac outpatient telemetry (MCOT), and cardiac implantable electronic devices (CIED) 
with arrhythmia detection and therapeutic capabilities such as pacemakers and 
defibrillators.1,2  Non-invasive diagnostic techniques have drawbacks including patient 
compliance and limited duration of monitoring, while pacemakers and defibrillators are 
restricted to only those patients meeting indications for therapy (bradycardia and/or 
tachycardia) once the diagnosis has already been established in most cases.3-7   
To fill this gap and to aid clinicians in determining the cause of symptoms such as 
unexplained syncope and palpitations, insertable cardiac monitors (ICMs) that allow for 
long-term cardiac rhythm monitoring and require a simple subcutaneous implant procedure 
with a low complication rate have been developed.8-11 This approach has shown promising 
results in patients who are at increased risk of cardiac arrhythmias.12-16 
Boston Scientific (BSC) has developed an ICM system, LUX-DxTM, which is indicated for 
use in patients that have a known heart condition, are at risk of developing an abnormal heart 
rhythm, or have symptoms that may suggest a cardiac arrhythmia (e.g. dizziness, 
palpitations, syncope, chest pain, and/or shortness of breath). The LUX-Dx ICM uses a data 
management system, LATITUDE Clarity™, which allows clinicians to remotely monitor and 
program the ICM. In order to transfer the ICM device data to LATITUDE Clarity, the system 
utilizes the myLUX™ mobile patient app. This allows clinicians to access the device data for 
analysis to support their evaluation of the clinical status and to adjust the diagnostic 
programmable features as needed. 
4.2. Study Rationale 
Real-world clinical data for patients implanted due to cryptogenic stroke, suspected AF, 
syncope, AF management, or post-AF ablation are necessary to understand the usage of 
remote programming, the performance of arrhythmia detection algorithms of the LUX-Dx 
ICM, and the safety of the ICM system. This trial’s patient population is representative of the 
majority of the intended recipients of the LUX-Dx ICM. The data collection in the LUX-
DxTM Insertable Cardiac Monitor Remote Programming and Performance Study (LUX-Dx 
PERFORM) may also be used by BSC for future product enhancements and support future 
regulatory submissions. 
5. LUX-Dx ICM Device/System Description  
Refer to Table 5-1 for a summary of the LUX-Dx ICM system components used in the study. 
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5.1. LUX-Dx ICM  
The LUX-Dx ICM is a small, leadless electronic device implanted under the skin in the left 
anterior chest wall. Its primary functions are to monitor, record, and store data related to 
cardiac arrhythmias. Two electrodes on the body of the device are used to monitor and record 
the patient’s subcutaneous ECG (S-ECG) data when specific arrhythmias (according to the 
device-programmed settings) are detected, which include pause, bradycardia, tachycardia, 
AF, and atrial tachyarrhythmias (AT). In addition, the device will record S-ECG data when 
the patient triggers the device to record via the myLUX patient app. The ICM’s memory can 
store up to 60 minutes of S-ECG recordings. Initial default arrhythmia detection parameters 
are provided by LATITUDE Clarity according to the Reason for Monitoring. However, these 
can be configured and adjusted by the clinician according to the subject’s clinical indication.  
5.2. Mobile Applications 
There are two mobile applications used to interrogate the LUX-Dx ICM and transmit data 
from the device to the LATITUDETM server: a patient-specific app called myLUX, and a 
clinic-specific app called LUX-Dx Clinic Assistant. The patient app also allows patients to 
record and send S-ECGs of symptomatic events to the LATITUDE server. Both apps 
communicate with the device using Bluetooth Low Energy (BLE) technology, and with the 
LATITUDE server using a Wi-Fi or cellular connection. Refer to Figure 5-1 for a diagram of 
the LUX-Dx ICM System. 
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7. Study Design 
The LUX-Dx PERFORM Study is a multicenter, prospective, single-arm, post-market, 
observational study.  
7.1. Scale and Duration 
The LUX-Dx PERFORM Study is planned to be conducted at approximately 25 to 35 sites in 
the US and will enroll approximately 600 to 827 subjects. The final enrollment number is 
driven by the number of subjects participating in the Holter study. It is possible that study 
sites from Europe or Asia Pacific may participate upon product approval in those 
geographies. The number of sites may go up to 35 sites if it is required to sufficiently support 
the study enrollment completion. Sites may continue to enroll subjects until notified by BSC 
of enrollment completion. Additional provisions for each site’s enrollment are specified in 
Section 11.2.3. 
The first 227 subjects belong to the “Safety Cohort”, and must be enrolled to satisfy the 
sample size required for the safety endpoint analysis. See Section 11.1.5. for detailed 
discussion on sample size requirements. 
The ICM implant procedure must be performed within 30 days following the subject consent. 
Relevant study data including implant procedure-related data, reportable adverse events, and 
ICM device data from the LATITUDE Clarity will be collected during the subject’s study 
participation period. Specifically, participating sites will review each enrolled subject’s 
electronic medical record (EMR) and communicate with the subject via telephone 
calls/virtual health visit or in-office visit that might be part of the standard of care at two 
primary time points (6 months and 12 months after implant) for relevant adverse events. For 
the purpose of this study, these follow-up visits do not require subjects’ physical presence at 
the study site. Each subject’s study participation period will be approximately one year from 
the point of device implant or until BSC notifies all sites that data collection is complete.  
Defined as the “Holter Cohort”, a subset of approximately 600 subjects will wear an 
extended Holter monitor for a monitoring period of approximately 14 days. This will be 
performed at the 2-month in-office visit or remotely by telephone call/virtual health visit. The 
purpose of the Holter cohort is for calculating diagnostic performance of the ICM.  
Refer to Figure 7-1 for a diagram of the study design, subject cohort, and flowchart.  
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Figure 7-1: Study Design, Subject Cohort, and Flow Diagram 
Enrollment is expected to be completed in approximately 30 months; therefore, the total 
study duration is estimated to be approximately 3-4 years. The total study duration for each 
implanted subject is approximately 12 months.  
7.2. Treatment Assignment 
Patients who have an indication to be implanted with a LUX-Dx ICM based on the product’s 
labelled indications, and who meet study-specific eligibility criteria will be considered for 
enrollment. To be enrolled in the study, subjects must meet all study -specific eligibility 
criteria and sign the study-specific Informed Consent Form (ICF). 
There is no randomized treatment assignment in this study. The study is considered “all 
comers” for patients who are eligible. 
7.3. Justification for the Study Design 
The objective of the LUX-Dx PERFORM Study is to collect data in a clinical setting 
reflecting real-world usage of the LUX-Dx ICM. Therefore, a prospectively enrolled, 
observational, post-market study design was determined to be appropriate. Subject 
enrollment requirements are supported by the following: 
• A sample size of 227 subjects will be required to power the first primary safety 
endpoint analysis (acute endpoint), and 226 subjects will be required to power the 
second primary safety endpoint (chronic endpoint). 
• The Holter study group is expected to enroll approximately 600 subjects, including 
approximately 300 subjects from the “AF management, Post-AF ablation, or 
Suspected AF” subgroup, and approximately 300 subjects from the other 2 subgroups 
(“Syncope” and “Cryptogenic stroke”). The distribution of the device indications is 
desired to generate at least 100 subjects with a detected AF episode during the Holter 
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monitoring period. Refer to Section 11.1.2.2 for rationales of the sample size 
requirement in the Holter study.  
Refer to Section 11 for details of overall study sample size discussion. 
8. Subject Selection  
8.1. Study Population and Eligibility  
Subjects should be selected from the general patient population indicated for ICM 
implantation per BSC labeled indication and are accessible to the Investigators. The LUX-Dx 
ICM System is indicated to monitor and record S-ECG for the clinical evaluation and 
diagnosis of cardiac arrhythmias in patients who have: 1) a known heart condition, 2) are at 
risk of developing an abnormal heart rhythm, or 3) have symptoms that may suggest a 
cardiac arrhythmia (e.g. dizziness, palpitations, syncope, chest pain, and/or shortness of 
breath). The Investigators are responsible for screening all potential subjects and selecting 
those who meet the eligibility for the study as described in Section 8.2 and 8.3 below.  
8.2. Inclusion Criteria 
Patients who meet all of the following criteria (see Table 8-1) may be given consideration for 
inclusion in this clinical investigation, provided no exclusion criteria (see Section 8.3) are 
met.  
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Table 8-1: Inclusion Criteria 
Inclusion 
Criteria 
• Patient is indicated to be implanted with the LUX-Dx ICM for one of 
the following reasons (grouped in three “Reason for Monitoring” 
subgroups): 
o Cryptogenic stroke 
o Syncope 
o AF management, Post-AF ablation, or Suspected AF 
• Patient is willing to enroll and be monitored in LATITUDE Clarity.  
• Patient is willing and able to be followed remotely via the ICM patient 
mobile app. 
• Patient is willing and capable of providing informed consent (which is 
not to include the use of a legally authorized representative (LAR) for 
documentation of informed consent) and agrees to participate in all 
protocol required activities.  
• Patient is age 18 years or above, or of legal age to give informed 
consent specific to state and national law. 
The following inclusion criterion is applicable for patients participating in 
the Holter study:  
• Patient can tolerate the adhesive used in the Holter monitoring for an 
extended period of time. 
 
8.3. Exclusion Criteria 
Patients who meet any one of the following criteria (Table 8-2) may not take part in this 
clinical study. 
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Table 8-2: Exclusion Criteria 
Exclusion 
Criteria 
• Patient is indicated for implantation of, or is currently implanted with an 
active implantable cardiac device (e.g., LVAD, ICD, CRT-D, PPM*). 
• Patient cannot tolerate a subcutaneous, chronically-inserted device due 
to medical condition. 
• Patient has a documented life expectancy of less than 12 months (per 
investigator’s discretion). 
• Patient is known to be pregnant at the time of study enrollment (method 
of assessment upon investigator’s discretion). 
• Patient is currently enrolled in another clinical study including 
observational studies/registries, unless prior written approval from BSC 
is obtained. Mandatory governmental registries are accepted for co-
enrollment without approval by BSC. 
The following exclusion criteria are applicable for patients participating in 
the Holter study:  
• Patient has known allergies to the adhesive materials or hydrogel used 
in the extended Holter monitoring. 
• Patient has broken, damaged, or irritated skin over the chest area where 
the extended Holter monitor will be attached. 
*LVAD: Left Ventricular Assist Device; ICD: Implantable Cardioverter Defibrillator; 
CRT-D: Cardiac Resynchronization Therapy-Defibrillator; PPM: Permanent Pacemaker 
 
9. Subject Accountability 
9.1. Point of Enrollment 
Subjects will be considered enrolled into the study at the time of study-specific ICF 
execution. All subject enrollments will be counted against the enrollment ceiling for the 
study.  
9.2. Enrollment Control 
Approximately 600 to 827 subjects will be enrolled.   
9.2.1. Enrollment Control of the “Safety Cohort” Subjects 
The first 227 subjects are required to meet the sample size requirement set for the study’s 
primary safety endpoint - acute. These subjects will be asked to participate in the Holter 
study, but will not be required to join if subject declines. 
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9.2.2. Enrollment Control of the Holter Study 
Enrollment in the Holter study will also be controlled to ensure approximately 300 subjects 
are from the “AF management, Post-AF ablation, and Suspected AF” subgroup. This sample 
size is required to satisfy the data requirement for this objective.  
It is expected that a total of approximately 600 subjects will be required to participate in the 
Holter study. BSC may determine that additional subjects will be needed to meet the 
requirement if data collected are deemed inadequate. In this case, site will continue to enroll 
Holter subjects until BSC communicates to all sites to stop enrollment.  
9.2.3. Enrollment Control at Each Site 
No single site may enroll greater than 90 subjects in the study without prior approval from 
BSC. Additionally, no single site may enroll greater than 34 subjects in the Safety Cohort 
(the first 227 subjects in the study) without prior approval from BSC. 
9.3. Withdrawal 
All subjects enrolled in the study shall be accounted for and documented including those 
subjects who withdraw prior to the 12-month electronic medical record (EMR) review. The 
reason(s) for withdrawal shall be reported on the End of Study Case Report Form (CRF). 
Reason(s) for withdrawal may include, but are not limited to: 
• Subject found not meeting study’s eligibility criteria 
• Lost to follow-up 
• Not able to re-establish device transmission after 90 days despite subject contact 
• Subject choice to withdraw consent 
• Investigator decision to withdraw the subject 
• Subject is classified as Intent or Attempt as per Section 9.5 
• The ICM is explanted or permanently disabled with all features programmed off  
• Subject implanted with active therapy device (e.g. LVAD, ICD, CRT-D, PPM) even 
if the ICM remains implanted 
9.4. Lost to Follow-Up 
Any subject without a LATITUDE Clarity device transmission within 90 days prior to each 
required data collection point may indicate a potential lost to follow-up subject. The 
investigator or designee shall make efforts to contact the subject in order to re-establish 
successful LATITUDE Clarity device transmission. Subjects will be classified as lost to 
follow-up on the End of Study CRF after three documented failed attempts (by either 
telephone call or certified letter) to contact them are documented in the study file. Note: the 
end of study date should be on or after last documented contact attempt. 
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9.5. Subject Status and Classification 
Enrolled subjects will be classified as follows: 
Intent refers to a subject who has been enrolled in the study but then does not have local 
anesthetic administered in preparation for a LUX-Dx ICM implant procedure. The original 
ICF and enrollment documentation for intent subjects should be maintained in the study file. 
The Intent subjects must be withdrawn from the study and the End of Study CRF completed. 
If the Intent subject is withdrawn due to reason of eligibility violation, a protocol deviation is 
required. There are no follow-up requirements for intent subjects. 
Attempt refers to a subject who has been enrolled in the study, has had local anesthetic 
administered in preparation for the implant procedure of a LUX-Dx ICM, but is not 
successfully implanted with the LUX-Dx ICM. Attempt subjects must be followed at least 30 
days post implant attempt and all reportable adverse events associated with the LUX-Dx 
ICM or attempted implant procedure must be reported and followed to resolution, or closure 
of the event with ongoing or chronic status. The safety check attempts must be made between 
30 days and 60 days after the attempted implant procedure. These subjects must be 
withdrawn from the study and the End of Study CRF completed after the resolution of all 
reportable adverse events and the completion of the safety check. 
Implant refers to a subject who has been enrolled in the study and is successfully implanted 
with the LUX-Dx ICM. These subjects are followed in accordance with the protocol and 
included in all applicable analyses. 
9.6. End-of-Study Definition  
End of Study occurs when all subjects have been enrolled, implanted, and followed for 12 
months. Upon completion of participation in the study, subjects will be followed according to 
the site’s standard of care.  
10. Study Methods 
10.1. Data Collection 
The study data collection and follow-up schedule are shown in Table 10-1. Study data 
collection time-points are initiated from the date of the LUX-Dx ICM implant for each 
subject. Note: the 6-month and 12-month EMR reviews do not require in-office visits but 
instead require the study sites to review a subject’s electronic medical record (EMR) and 
reach the subject by phone/virtual health visit or in-office visit that might be standard of care 
for applicable study data. A preliminary list of data collection items is provided in Appendix 
26.1.  
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Table 10-1: Data Collection Schedule (Pre-implant Subject) 
Procedure/Assessment 
Enrollment 
Implant Procedure 
(day=0) 
(within 30 days 
after enrollment) 
Data Collection Points/Follow-up Visits 
2-Month 
(±30 Days) 
6-Month (±30 Days), 
12-Month ((±30 Days), 
End of Study 
Informed consent  
X 
-- 
-- 
-- 
Inclusion/ exclusion criteria 
X 
-- 
-- 
-- 
Assessment of pregnancy for women of 
childbearing potential 
X 
-- 
-- 
-- 
Demographics / physical assessment 
X 
-- 
-- 
-- 
Medical history 
X 
-- 
-- 
-- 
Implant procedure data 
-- 
X 
-- 
-- 
Holter study 
-- 
-- 
X* 
-- 
ICM reprogramming 
-- 
Collect for each occurrence† 
EMR review and phone/virtual health visit 
or in-office visit per standard of care 
-- 
-- 
-- 
X 
Ongoing AE assessment1 and protocol 
deviation 
Collect as it occurs 
X=Required; X*=Required for approximately 600 subjects; --=Not required; †=Only the first 5 are required to be entered in 
the database 
1 Reportable adverse events are defined in Section 19.1. 
 
10.2. Study Candidate Screening and Recruitment  
After the study site receives IRB/EC approval for the LUX-Dx PERFORM Study protocol 
and ICF, as well as the ATE by BSC, the Investigators may screen patients for inclusion in 
the study. Study recruitment will rely upon the general pool of ICM -indicated patients.  
10.3. Informed Consent 
The investigator and the designated site staff are responsible for obtaining eligible subject’s 
written informed consent before any study-required procedure and data collection take place.  
10.4. Enrollment Visit 
All subjects who sign the IRB/EC-approved ICF will be considered enrolled in the study. 
The study site will collect baseline data from the subject’s medical record and subject 
interview as outlined in Table 10-2. The “Reason for Monitoring” at the time of the 
enrollment will be used to determine which indications subgroup the subject belongs to.  
Print any applicable Technical Source Form (TSF) for this visit. Data and source 
documentation requirements are summarized below in Table 10-2.  
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11.2.3. Number of Subjects per Investigative Site 
To avoid any study site effect and bias, no single site will enroll more than 90 subjects of the 
total enrollments in the study and 34 subjects for the safety endpoint, without prior approval 
from BSC. 
11.3. Data Analyses 
11.3.1. Interim Analyses  
There are no formal interim analyses. Interim analyses may be performed to support 
publications or regulatory product approval in geographies outside of US. The number of 
subjects required for the Holter study will be re-estimated during the study using an observed 
AF incidence rate and data loss rate to obtain approximately 100 subjects with a true AF 
episode. 
11.3.2. Subgroup Analyses 
Objectives may be performed in various subgroups including but not limited to: 
• Reason for monitoring 
• Sex (Male vs. Female) 
• Age (< 65 years vs. > 65 years) 
• BMI (Obese vs. Overweight vs. Normal) 
• History of atrial arrhythmia (All types vs. None) 
• Programming Parameters 
Further details will be outlined in the Statistical Analysis Plan.  
11.3.3. Justification of Pooling 
The poolability of data by center will be assessed to determine if there is heterogeneity of 
data among the different centers. Further details of poolability testing will be outlined in the 
Statistical Analysis Plan. 
11.3.4. Multivariable Analyses 
Multivariable analyses will be detailed in the statistical analysis plan. 
11.3.5. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan approved prior to performing the 
analyses. Changes from the planned statistical methods after performing the analyses will be 
documented in the clinical study report along with a reason for the deviation. 
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12. Health Economics Outcomes 
A formal health economics analysis may be completed as part of the LUX-Dx PERFORM 
Study. This will take into consideration any differences in complication rates and resource 
utilization. These inputs may be used in health economics analyses performed. 
13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data collected on the Case Report Form (CRF) will be recorded in a limited access 
secure electronic data capture (EDC) system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the CRF 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 Medidata EDC system 
and will be issued to the site for appropriate response. Site staff will be responsible for 
resolving all queries in the database. 
All access to the clinical database will be changed to “Read only” after all data is either 
“Hard Locked” or “Entry Locked”. Once acceptance of the final report or finalization of 
publications (as applicable) is received, final database storage and archiving activities can 
begin. Once all of the closeout activities are completed a request to IT is submitted to have 
the “Database Locked” or Decommissioned and all database access revoked. 
In addition, electronic device data from the ICM system will be recorded using the 
LATITUDE Clarity data management system. This system was designed to be in compliance 
with federal regulations pertaining to electronic data. The LATITUDE Clarity Data 
Management System is secured with access limited to appropriately trained personnel and its 
data resides on Boston Scientific servers which perform regular backups. 
13.2. Data Retention 
The Principal Investigator (PI) or his/her designee or Investigational site will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements.   
The PI or his/her designee will take measures to prevent accidental or premature destruction 
of these documents. If for any reason the PI or his/her designee withdraws responsibility for 
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maintaining these essential documents, custody must be transferred to an individual who will 
assume responsibility and BSC must receive written notification of this custodial change. 
Sites are required to inform Boston Scientific in writing where paper or electronic files are 
maintained in case files are stored off site and are not readily available. 
13.3. Technical Source Forms (TSF) 
A TSF is developed by BSC 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 BSC representative may complete the TSF at the 
request of the Principal Investigator. The TSF will be reviewed and signed for approval by 
the Principal Investigator or his/her designee at the end of each procedure.  
13.4. Core Laboratories 
Independent Core lab(s) will be used to provide the extended Holter monitoring product, 
service, and data analysis. Separate instruction on working with the Core lab and applicable 
training will be provided. 
14. 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, the reviewing IRB/EC, and the regulatory authority, if applicable 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 using the relevant CRF. Sites 
may also be required to report deviations to the IRB/EC, and the regulatory authority, per 
local guidelines and national/government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/EC/Regulatory Authority notification, site 
re-training, or site discontinuation/termination) will be put into place by the sponsor. 
The sponsor will not approve protocol waivers.  
15. Device Accountability 
The devices and equipment used in this study will be commercially approved in all 
geographies where the study is being conducted. Any device tracking and accountability will 
occur per the required local regulations for commercial devices.   
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16. Compliance 
16.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site 
can be “Authorized to Enroll,” the investigational site must enter into a Clinical Study 
Agreement with the sponsor that details the financing of the study as well as the rights and 
obligations of the investigational site and the investigator. This study will be conducted in 
accordance with post market clinical follow-up guidelines and will follow the applicable 
sections of ISO 14155 (Clinical Investigation of Medical Devices for Human Subjects – 
Good Clinical Practice), the relevant parts of the ICH Guidelines for Good Clinical Practices, 
ethical principles that have their origins in the Declaration of Helsinki, and applicable 
individual country laws and regulations. The study shall not begin until the required 
approval/favorable opinion from the IRB/EC and/or regulatory authority has been obtained, 
if appropriate. Also, the study shall not begin prior to issuance of the site ATE, as provided 
by the sponsor. Any additional requirements imposed by the IRB/EC or regulatory authority 
shall be followed, if appropriate.  
16.2. Investigator Responsibilities 
The PI of an investigational site is responsible for ensuring that the study is conducted in 
accordance with the Clinical Study Agreement, the Clinical Investigation Plan, the spirit of 
ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB/EC, and prevailing local and/or 
country laws and/or regulations, whichever affords the greater protection to the subject. 
The PI’s responsibilities include, but are not limited to, the following:  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study 
or interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any 
deviation from the approved protocol that occurred during the course of the clinical 
investigation. 
• 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 that data reported to the sponsor in the CRFs and in all required reports are 
attributable, legible, timely, original, accurate, and complete. 
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• 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 reportable events. 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE and potential/USADE or UADE, if required by 
applicable laws or regulations or this protocol or by the IRB/EC, and supply BSC 
with any additional requested information related to the safety reporting of a 
particular event. 
• Maintain records and control of the device, ensuring that the study device is used only 
by authorized/designated users and in accordance with this protocol and Instructions 
For Use. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to 
the clinical research monitor or auditor and respond to questions during monitoring 
visits or audit(s). 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained and documented in accordance with 
applicable laws, this protocol and local IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation 
in a clinical study in the case of adverse events, as described in the ICF. 
• Inform the subject of the nature and possible cause of any adverse events 
experienced. 
• As applicable, provide the subject with necessary instructions on proper use, 
handling, storage, and return of the device when it is used/operated by the subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, 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. 
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• 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. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks 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. 
16.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the PI is responsible for providing appropriate training to 
ensure study staff are competent to perform the tasks they have been delegated. Adequate 
supervision of the study staff by an investigator is required. Where there is a sub-investigator 
at a site, the sub-investigator should not be delegated the primary supervisory responsibility 
for the site. The PI is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  
16.3. Institutional Review Board 
The investigational site will obtain the written and dated approval/favorable opinion of the 
Institutional Review Board (IRB)/Ethics Committee (EC) for the clinical investigation before 
recruiting subjects and implementing all subsequent amendments. 
A copy of the written IRB/EC approval of the protocol (or permission to conduct the study) 
and ICF, must be received by the sponsor before recruitment of subjects into the study. Prior 
approval must also be obtained for other materials related to subject recruitment or which 
will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB/EC before the 
changes are implemented to the study. All changes to the ICF will be BSC and IRB/EC 
approved; a determination will be made regarding whether a new ICF needs to be obtained 
from participants who provided consent, using a previously approved ICF.  
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by applicable local/country laws or regulations or IRB/EC requirements. Copies 
of the study reports and the IRB/EC continuance of approval must be provided to the 
sponsor.  
16.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
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purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects. Subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
16.4.1. Role of Boston Scientific Representatives 
BSC personnel can provide technical support to the investigator and other health care 
personnel (collectively HCP) as needed during implant, testing required by the protocol, and 
follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices. 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during implant or follow-up, assist with the conduct of testing 
specified in the protocol, and interact with the subject to accomplish requested activities.  
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 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  
• Independently collect critical study data 
• Enter data in electronic data capture systems or on paper case report forms 
16.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
17. Monitoring 
Monitoring 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 PI continues to have sufficient 
staff and facilities to conduct the study safely and effectively. The Principal 
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Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements.  
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 PI and relevant study 
personnel are available during on-site or remote monitoring visits or audits and that sufficient 
time is devoted to the process. 
18. Potential Risks and Benefits 
18.1. Risks Associated with Participation in the Clinical Study 
This study will enroll patients who are already indicated to receive an ICM per standard of 
care and meet the study’s eligibility criteria. It involves the collection of data via CRF 
completion and via LATITUDE Clarity, as well as related clinical event data. There are no 
specific required treatments or therapeutic interventions in this study. There are no other, 
additional risks of participating beyond what would be expected with standard of care.  
A subgroup of subjects (~600) will wear an extended Holter monitor as required by this 
study. This device is commercially approved in the US and, despite not being mandatory for 
patients who receive an ICM, is part of the tools available for clinicians to support medical 
diagnosis and treatment.  
18.2. Risks Related to the Systems Used in the Study according to their Instructions 
For Use Manuals 
18.2.1 Extended Holter monitor (anticipated adverse events associated with the use of 
adhesive patches)  
• Minor discomfort, skin irritation, reddening, itching, or rash. 
18.2.2 LUX-Dx ICM system (anticipated adverse events associated with the 
implantation of the LUX-Dx ICM) 
• Device migration 
• Erosion 
• Foreign body rejection phenomena 
• Formation of hematomas or seromas 
• Infection 
• Local tissue reaction 
• Tissue damage   
Refer to the currently available LUX-Dx ICM User’s Manual for an updated list of potential 
adverse events. 
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18.3. Possible Interactions with Concomitant Medical Treatments, if applicable 
There are no concomitant medical treatments.  
18.4. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups, and by promptly supplying BSC with all pertinent information 
required by this protocol. 
18.5. Anticipated Benefits 
Subject who participates in the Holter study may receive additional arrhythmia monitoring in 
the 14-day monitoring period by wearing the Holter monitor. 
There may be no additional benefit to the subject. However, medical science and future 
patients may benefit from their participation in this post-market study. 
18.6. Risk to Benefit Rationale, if Applicable 
The implantable device systems and accessories used for this clinical study will be 
commercially available and are considered to be standard of care for patients indicated for 
the LUX-Dx ICM implants. The risks involved with subject participation in this study are 
essentially the same as those to the patients not participating in the study. 
19. Safety Reporting 
19.1. Reportable Events by Study Site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of the following categories: 
• Serious Adverse Events 
• Serious Adverse Device Effects 
• Device Related Adverse Events  
• Study Procedure Related Adverse Events 
• Cardiac Related Adverse Events  
• ICM Related Device Deficiencies 
• Unanticipated Adverse Device Effects 
• Unanticipated Serious Adverse Device Effects 
• New findings/updates in relation to already reported events 
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When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether 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. 
Any reportable events, experienced by the study subject after informed consent, whether 
prior to, during, or subsequent to the implant procedure, must be recorded on the CRF. 
Underlying diseases and chronic conditions are not reported as AEs unless there is an 
increase in severity or frequency during the course of the investigation. Death should not be 
recorded as an AE, but should only be reflected as an outcome of one (1) specific SAE (see 
Table 19-1 for AE definitions). 
Refer to Instructions For Use for the known risks associated with the commercial device(s). 
19.2. Definitions and Classification 
Adverse event definitions are provided in Table 19-1 . Administrative edits were made on the 
safety definitions from ISO 14155 and EU 2017/745 for clarification purposes. 
 
Table 19-1: 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, in the context of a clinical investigation, 
whether or not related to the study medical device and whether anticipated 
or unanticipated.  
NOTE 1: This includes events related to the study 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 study medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of the study medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the implantation, 
the installation, the operation, or any malfunction of the study medical 
device. 
NOTE 2: This definition includes any event resulting from use error or 
from intentional misuse of the study medical device. 
NOTE 3: This includes ‘comparator’ if the comparator is a medical 
device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons 
as defined by either: 
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Table 19-1: Safety Definitions 
Term 
Definition 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases, or  
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) foetal distress, foetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
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 risk assessment. 
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 assessment. 
Serious Health Threat 
 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an  
imminent risk of death or a serious deterioration in the health in subjects, 
users or other persons, and that requires prompt remedial action 
for other subjects, users or other persons. 
Note 1 to entry: This would include events that are of significant and 
unexpected nature such that they become alarming as a potential serious 
health hazard or possibility of multiple deaths occurring at short intervals. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
An inadequacy of a medical device related to its identity, quality, 
durability, reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and 
inadequacy in the information supplied by the manufacturer including 
labelling. 
NOTE 2: This definition includes device deficiencies related to the 
investigational medical device or the comparator. 
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Table 19-1: Safety Definitions 
Term 
Definition 
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• 
emergency room visit that does not result in in-patient admission  
Note: although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria 
(e.g. medical or surgical intervention to prevent permanent 
impairment or damage) 
• 
elective and pre-planned treatment/surgery for a pre-existing 
condition that is documented in the subject’s record at the time of 
consent/enrollment 
• 
admission for social reasons and/or respite care in the absence of 
any deterioration in the subject’s general condition (e.g. subject is 
homeless, caregiver relief) 
• 
pre-planned, protocol-specified admission related to the clinical 
study (e.g. procedure required by protocol) 
Prolongation of hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
Note: new adverse events occurring during the hospitalization are 
evaluated to determine if they prolonged hospitalization or meet another 
SAE criteria. 
 
19.3. Relationship to Device(s) 
An Investigator must assess the relationship of the reportable AE to the device and/or implant 
procedure. See criteria in Table 19-2:  
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Table 19-2: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Ref: MEDDEV 2.7/3 
Relationship to the device, comparator, or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the study device or the 
procedures; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the 
device or procedure;  
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the study device used for 
diagnosis, when applicable; harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Possibly Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device or comparator, or the relationship 
with procedures is weak but cannot be ruled out completely. Alternative causes are 
also possible (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
Probably Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device or comparator, or the relationship 
with procedures seems relevant and/or the event cannot be reasonably explained by 
another cause, but additional information may be obtained. 
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Table 19-2: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Causal Relationship 
Ref: MEDDEV 2.7/3 
The serious event is associated with the study device, comparator, or with 
procedures beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, 
when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 
 
19.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 19-3. Adverse 
events must always be reported through the EDC system whenever possible. However, in the 
case of any issues where alternative methods of reporting is necessary (i.e. the EDC system is 
not available), the investigator should contact Boston Scientific and provide the relevant 
adverse event information in a timely manner by using the study-specific safety mailbox: 
LUXDXPERFORM.safety@bsci.com.  
Table 19-3: Investigator Reporting Requirements 
 
Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Serious Health Threat 
Complete applicable 
eCRF/paper form 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. 
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Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Provide all relevant source 
documentation 
(de-identified/ 
pseudonymized) for 
reported event. 
• 
Upon request of sponsor. 
Unanticipated Adverse 
Device Effect / Unanticipated 
Serious Adverse Device 
Effect  
 
Complete AE CRF page 
with all available new and 
updated information.  
• Within 1 business day of first becoming 
aware of the event 
• Reporting required through end of study 
 
Provide all relevant source 
documentation 
(de-identified/ 
pseudonymized) for 
reported event.  
• Upon request of sponsor.  
Serious Adverse Event  
Complete AE CRF page 
with all available new and 
updated information.  
• Within 3 calendar days after becoming 
aware of the event or as per local/regional 
regulations.  
• Reporting required through end of study 
Provide all relevant source 
documentation 
(de-identified/ 
pseudonymized) for 
reported event.  
• When documentation is available  
• Upon request of sponsor. 
Serious Adverse Device 
Effects 
Complete AE CRF page 
with all available new and 
updated information. 
• Within 3 calendar days of first becoming 
aware of the event or as per local/regional 
regulations. 
• Reporting required through end of study 
Provide all relevant source 
documentation 
(de-identified/ 
pseudonymized) for 
reported event.  
• When documentation is available  
• Upon request of sponsor. 
Device Deficiencies 
(including but not limited to 
failures, malfunctions, and 
product nonconformities) 
Note:  Any Device Deficiency 
that might have led to a 
serious adverse event if a) 
suitable action had not been 
taken or b) intervention had 
not been made or c) if 
circumstances had been less 
fortunate is considered a 
reportable event. 
Complete Device 
Deficiency CRF with all 
available new and updated 
information.  
• Within 3 calendar days of first becoming 
aware of the event.  
• Reporting required through end of study 
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Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
 
Provide all relevant source 
documentation 
(de-identified/ 
pseudonymized) for 
reported event. 
• Upon request of sponsor 
Adverse Event including 
Adverse Device Effects 
Complete AE CRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• Within 10 business days after becoming 
aware of the information. 
• Reporting required through end of study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• Upon request of sponsor  
 
19.5. Boston Scientific Device Deficiencies 
Device deficiencies will be documented and reported to BSC. If possible, the device(s) 
should be returned to BSC for analysis. Instructions for returning the device(s) will be 
provided to the study site in the event of an ICM explant during study participation. Device 
deficiencies should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency, would be recorded as an adverse event on the appropriate CRF. 
19.6. Reporting to Regulatory Authorities/ IRBs/ ECs/ REBs/ Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs/ECs and regulatory authorities, as applicable.  
The PI is responsible for informing the IRB/EC and regulatory authorities of UADEs and 
SAEs as required by local/regional regulations. 
19.7. Subject Death Reporting  
A subject death during the study must be reported to Boston Scientific as soon as possible 
and, in any event, within three (3) calendar days of center aware date. The center’s IRB/EC 
must be notified of any deaths in accordance with that center’s IRB/EC policies and 
procedures. Whenever possible, the device should be interrogated and BSC system 
components (e.g., the device) should be removed intact and returned promptly to BSC RM 
for analysis.  
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A detailed narrative (death letter) that provides detailed information describing the 
circumstances surrounding the death may be requested. 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 or not the death was witnessed; 
• 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 sub-Investigator signature and date. 
Other Source documents may be requested by BSC. BSC Safety representatives will review, 
at minimum, information regarding subject deaths that are related to ICM system or implant 
procedure. 
20. Informed Consent 
Subject participation in this clinical study is voluntary. Informed Consent is required from 
each subject. The Investigator is responsible for ensuring that Informed Consent is obtained 
prior to the use of any study devices, study-required procedures and/or testing, or data 
collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority, as applicable. The ICF must be accepted 
by BSC or its delegate (e.g. CRO) and approved by the site’s IRB/EC, or central IRB/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 IRB/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 IRB/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 PI or designee authorized to conduct the process,  
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• include a description of all aspects of the clinical study that are relevant to the 
subject’s decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects 
throughout the clinical study.  
The ICF shall always be signed and personally dated by the subject and by the investigator 
and/or an authorized designee responsible for conducting the informed consent process. 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 subject.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), 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 IRB/EC. The new version of the ICF must be approved by 
the IRB/EC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB/EC. The IRB/EC will determine the subject population to be 
re-consented. 
21. Committees 
21.1. Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operation group review safety 
data as it is reported by the sites throughout the duration of the study. During scheduled 
monitoring activities, clinical research monitors further support this review through their 
review of source documents and other data information.The BSC Medical Safety and Safety 
Trial Operations team include medical professionals with expertise in electrophysiology and 
with the necessary therapeutic and subject matter expertise to evaluate and classify the events 
into the categories outlined above. 
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21.2. Steering Committee 
A Steering Committee composed of study’s Coordinating Principal Investigator(s) and 
physicians with expertise in ICM technology will be convened. Responsibilities may include 
oversight of the overall conduct of the study with regard to protocol development, study 
progress, subject safety, overall data quality and integrity, and first line review and final 
decision making of independent medical reviewer recommendations, as well as 
disseminating any study results through appropriate scientific sessions and publications.  
Steering Committee members may participate in the review and approval of all requests for 
data analysis, abstract and manuscript preparation, and submission. 
21.3. Independent Medical Reviewers – Arrhythmia Episodes 
An independent group of physician(s) with pertinent expertise will be established for the 
study. Their responsibility includes reviewing and adjudicating the arrhythmia episodes 
detected and recorded by the LUX-Dx ICM. 
The group will include practitioners of electrophysiology (EP), cardiac device implant, as 
well as experts with the necessary therapeutic and subject matter expertise to adjudicate the 
arrhythmia episodes outlined above. Responsibilities, qualifications and procedures are 
outlined in a charter. 
21.4. Independent Medical Reviewers – Safety Endpoints 
An independent medical review, performed by at least one individual with pertinent 
expertise, will be performed to review serious adverse events reported by study investigators 
for adjudication of LUX-Dx ICM system-related complications. The independent medical 
review will consist of a review of a safety event dossier, which may include copies of subject 
source documents provided by study sites, for all reported subject death from any cause. 
An independent medical reviewer may be a practitioner of EP and/or cardiology or an expert 
with the necessary therapeutic and subject matter expertise to adjudicate the ICM 
system-related complications. Responsibilities, qualifications and procedures are outlined in 
a charter. 
22. Suspension or Termination 
22.1. Premature Termination of the Study 
BSC reserves the right to terminate the study at any stage but intends to exercise this right 
only for valid scientific or business reasons and reasons related to protection of subjects.  
Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, will be notified 
in writing in the event of study termination. 
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22.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IRB/EC or regulatory authorities to suspend or terminate the 
clinical investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of BSC to suspend or discontinue development/marketing of 
the device. 
22.2. Termination of Study Participation by the Investigator or Withdrawal of 
IRB/EC Approval 
Any investigator or associated IRB/EC or regulatory authority may discontinue participation 
in the study or withdraw approval of the study, respectively, with suitable written notice to 
BSC. Investigators, associated IRB/EC, and regulatory authorities, as applicable, will be 
notified in writing in the event of these occurrences. 
22.3. 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 
IRB/EC and regulatory authorities, as applicable, will also be notified. Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB/EC terminates participation in the study, participating investigators, 
associated IRB/EC, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by BSC. 
In the event a PI terminates participation in the study, study responsibility will be transferred 
to another investigator, if possible. In the event there are no opportunities to transfer PI 
responsibility; detailed information on how enrolled subjects will be managed thereafter will 
be provided by BSC. 
The PI or his/her designee must return all study-related documents and devices, if supplied 
by BSC, unless this action would jeopardize the rights, safety, or welfare of the subjects. 
22.4. Criteria for Suspending/Terminating a Study Site 
BSC reserves the right to stop the inclusion of subjects at a study site at any time after the 
study initiation visit if the enrollment rate is significantly less than projected and the 
investigator has been given appropriate time to screen and enroll subjects, or if the site has 
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multiple or severe protocol violations/noncompliance without justification and/or fails to 
follow remedial actions. 
In the event of termination of site participation, the IRB/EC and regulatory authorities, as 
applicable, will be notified. Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
23. Study Registration and Results 
23.1. Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
23.2. Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the BSC Policy. A Clinical Investigation 
Report will be made available to all investigators, IRB/EC, and regulatory authorities, as 
applicable in accordance with the BSC Policy and local requirements.  
23.3. 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 may submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific adheres to the Contributorship Criteria set forth in the 
Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed:  
• All authorship and contributorship requirements as described above must be 
followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy 
should be discussed with the Coordinating Principal Investigator(s) and/or 
Executive/Steering Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the BSC Data Sharing Policy 
(https://www.bostonscientific.com/).  
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24. Bibliography 
1. Feinberg WM, Cornell ES, Nightingale SD, Pearce LA, Tracy RP, Hart RG, Bovill EG: 
Relationship between prothrombin activation fragment f1.2 and international normalized 
ratio in patients with atrial fibrillation. Stroke prevention in atrial fibrillation 
investigators. Stroke 1997;28:1101-1106. 
2. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland Jr JC, Conti JB, 
Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, 
Tracy CM, Yancy CW: 2014 HA/ACC/HRS guideline for the management of patients 
with atrial fibrillation: A report of the American College of Cardiology/American Heart 
Association Task force on Practice Guidelines and the Heart Rhythm Society. J Am Coll 
Cardiol 2014;64:e1-e76. 
3. Vasamreddy CR, Dalal D, Dong J, Cheng A, Spragg D, Lamiy SZ, Meininger G, 
Henrikson CA, Marine JE, Berger R, Calkins H: Symptomatic and asymptomatic atrial 
fibrillation in patients undergoing radiofrequency catheter ablation. J Cardiovasc 
Electrophysiol 2006;17:134-139. 
4. Glotzer TV, Hellkamp AS, Zimmerman J, Sweeney MO, Yee R, Marinchak R, Cook J, 
Paraschos A, Love J, Radoslovich G, Lee KL, Lamas GA; MOST Investigators: Atrial 
high rate episodes detected by pacemaker diagnostics predict death and stroke: Report of 
the atrial diagnostics ancillary study of the mode selection trial (most). Circulation 
2003;107:1614-1619. 
5. de Voogt WG, van Hemel NM, van de Bos AA, Koistinen J, Fast JH: Verification of 
pacemaker automatic mode switching for the detection of atrial fibrillation and atrial 
tachycardia with Holter recording. Europace 2006;8:950-961. 
6. Passman RS, Weinberg KM, Freher M, Denes P, Schaechter A, Goldberger JJ, Kadish 
AH: Accuracy of mode switch algorithms for detection of atrial tachyarrhythmias. J 
Cardiovasc Electrophysiol 2004;15:773-777 
7. Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, Lau CP, Fain 
E, Yang S, Bailleul C, Morillo CA, Carlson M, Themeles E, Kaufman ES, Hohnloser SH: 
Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012;366:120-129. 
8. Beinart SC, Natale A, Verma A, Amin A, Kasner S, Diener HC, Del Greco M, Wilkoff 
BL, Pouliot E, Franco N, Mittal S. Real-world comparison of in-hospital Reveal LINQ 
insertable cardiac monitor insertion inside and outside of the cardiac catheterization or 
electrophysiology laboratory. Am Heart J. 2019 Jan;207:76-82. 
9. Diederichsen SZ, Haugan KJ, Højberg S, Holst AG, Køber L, Pedersen KB, Graff C, 
Krieger D, Brandes A, Svendsen JH. Complications after implantation of a 
new-generation insertable cardiac monitor: Results from the LOOP study. Int J Cardiol. 
2017 Aug 15;241:229-234. 
10. Rogers JD, Sanders P, Piorkowski C, et al. In-office insertion of a miniaturized insertable 
cardiac monitor: Results from the Reveal LINQ In-Office 2 randomized study. Heart 
Rhythm. 2017;14(2):218‐224.  
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11. Sanders P, Piorkowski C, Kragten JA, et al. Safety of in-hospital insertable cardiac 
monitor procedures performed outside the traditional settings: results from the Reveal 
LINQ in-office 2 international study. BMC Cardiovasc Disord. 2019;19(1):132. 
12. Krahn AD, Klein GJ, Skanes AC, Yee R: Use of the implantable loop recorder in 
evaluation of patients with unexplained syncope. J Cardiovasc Electrophysiol 
2003;14:S70-73. 
13. Brignole M, Vardas P, Hoffman E, Huikuri H, Moya A, Ricci R, Sulke N, Wieling W, 
Auricchio A, Lip GY, Almendral J, Kirchhof P, Aliot E, Gasparini M, Braunschweig F, 
Botto GL: Indications for the use of diagnostic implantable and external ECG loop 
recorders. Europace 2009;11:671-687. 
14. Sanna T, Diener H-C, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, Rymer 
MM, Thijs V, Rogers T, Beckers F, Lindborg K, Brachmann J: Cryptogenic stroke and 
underlying atrial fibrillation. N Engl J Med 2014;370:2478-2486. 
15. Eitel C, Husser D, Hindricks G, Fruhauf M, Hilbert S, Arya A, Gaspar T, Wetzel U, 
Bollmann A, Piorkowski C: Performance of an implantable automatic atrial fibrillation 
detection device: Impact of software adjustments and relevance of manual episode 
analysis. Europace 2011;13:480-485. 
16. Hindricks G, Pokushalov E, Urban L, Taborsky M, Kuck K-H, Lebedev D, Rieger G, 
P¨urerfellner H; XPECT Trial Investigators: Performance of a new leadless implantable 
cardiac monitor in detecting and quantifying atrial fibrillation results of the XPECT trial. 
Circ Arrhyth Electrophysiol 2010;3:141-147 
17. Sanders P, Pürerfellner H, Pokushalov E, et al. Performance of a new atrial fibrillation 
detection algorithm in a miniaturized insertable cardiac monitor: Results from the Reveal 
LINQ Usability Study. Heart Rhythm. 2016;13(7):1425‐1430.  
18. Turakhia MP, Hoang DD, Zimetbaum P, et al. Diagnostic utility of a novel leadless 
arrhythmia monitoring device. Am J Cardiol. 2013;112(4):520‐524.  
19. Boston Scientific internal data on file. 2020. 
20. Brachmann J, Morillo CA, Sanna T, Di Lazzaro V, Diener HC, Bernstein RA, Rymer M, 
Ziegler PD, Liu S, Passman RS. Uncovering Atrial Fibrillation Beyond Short-Term 
Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic 
Stroke and Underlying Atrial Fibrillation Trial. Circ Arrhythm Electrophysiol. 2016 
Jan;9(1):e003333.   
21. J. S. Healey, M. Alings, A. C. Ha, P. Leong-Sit, D. H. Birnie, J. J. de Graaf, M. Freericks, 
A. Verma, J. Wang, D. Leong, H. Dokainish, F. Philippon, W. Barake, W. F. McIntyre, 
K. D. Simek, M. D. Hill, S. R. Mehta, M. Carlson, F. Smeele, A. S. Pandey, S. J. 
Connolly and A.-. Investigators, 2017. Subclinical Atrial Fibrillation in Older Patients. 
Circulation. 14, 1276-1283.  
22. F. J. Lacunza-Ruiz, A. Moya-Mitjans, J. Martinez-Alday, G. Baron-Esquivias, R. Ruiz-
Granell, N. Rivas-Gandara, S. Gonzalez-Enriquez, J. Leal-del-Ojo, M. F. Arcocha-
Torres, J. Perez-Villacastin, N. Garcia-Heil and A. Garcia-Alberola, 2013. Implantable 
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loop recorder allows an etiologic diagnosis in one-third of patients. Results of the Spanish 
reveal registry. Circ J. 10, 2535-41.  
23. J. Lauschke, M. Busch, W. Haverkamp, A. Bulava, R. Schneider, D. Andresen, H. 
Nagele, C. Israel, G. Hindricks and D. Bansch, 2017. New implantable cardiac monitor 
with three-lead ECG and active noise detection. Herz. 6, 585-592.  
24. P. M. Magnusson, M. Olszowka, M. Wallhagen and H. Koyi, 2017. Outcome of 
implantable loop recorder evaluation. Cardiol J. 3, 363-370.  
25. S. Mittal, P. Sanders, E. Pokushalov, L. Dekker, D. Kereiakes, E. J. Schloss, E. Pouliot, 
N. Franco, Y. Zhong, D. I. B. M and H. Purerfellner, 2015. Safety Profile of a 
Miniaturized Insertable Cardiac Monitor: Results from Two Prospective Trials. Pacing 
Clin Electrophysiol. 12, 1464-9.  
26. J. M. Nasir, W. Pomeroy, A. Marler, M. Hann, T. Baykaner, R. Jones, R. Stoll, K. 
Hursey, A. Meadows, J. Walker and S. Kindsvater, 2017. Predicting Determinants of 
Atrial Fibrillation or Flutter for Therapy Elucidation in Patients at Risk for 
Thromboembolic Events (PREDATE AF) Study. Heart Rhythm. 7, 955-961.  
27. C. Tondo, M. Tritto, M. Landolina, D. E. G. P, G. Bencardino, M. Moltrasio, A. Dello 
Russo, P. Della Bella, E. Bertaglia, A. Proclemer, D. E. S. V and M. Mantica, 2014. 
Rhythm-symptom correlation in patients on continuous monitoring after catheter ablation 
of atrial fibrillation. J Cardiovasc Electrophysiol. 2, 154-60.  
28. S. Wechselberger, M. Kronborg, Y. Huo, J. Piorkowski, S. Neudeck, E. Passler, A. El-
Armouche, U. Richter, J. Mayer, S. Ulbrich, L. Pu, B. Kirstein, T. Gaspar and C. 
Piorkowski, 2018. Continuous monitoring after atrial fibrillation ablation: the LINQ AF 
study. Europace.  
29. Medicines and Healthcare products Regulatory Agency (MHRA). Leadless cardiac 
pacemaker therapy: design of pre- and post-market clinical studies. Initial 
recommendations from MHRA Expert Advisory Group. March 2017. 
25. Abbreviations and Definitions  
25.1. Abbreviations 
Abbreviations are shown in Table 25-1.   
Table 25-1: Abbreviations 
Abbreviation/Acronym 
Term 
AE 
Adverse Event 
App 
Application 
ASADE 
Anticipated serious adverse device effect 
BSC 
Boston Scientific Corporation 
CHF 
Congestive Heart Failure 
CMS 
Center for Medicare and Medicaid Services 
CRF 
Case Report Form 
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Table 25-1: Abbreviations 
Abbreviation/Acronym 
Term 
CRT-D 
Cardiac Resynchronization Therapy-Defibrillator 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
HF 
Heart Failure 
ICD 
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
ICM 
Insertable Cardiac Monitor 
ID 
Identification 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
IV 
Intravenous 
LVAD 
Left Ventricular Assist Device 
PA 
Pulmonary Artery 
PPM 
Permanent Pacemaker 
PRM 
Programmer 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
UADE 
Unanticipated Adverse Device Effects 
USADE 
Unanticipated Serious Adverse Device Effects 
US 
United States 
VF 
Ventricular Fibrillation 
VT 
Ventricular Tachycardia 
WIRB 
Western IRB 
25.2. Definitions 
Terms used in this protocol are defined in Table 25-2.  
Table 25-2: Definitions 
Term 
Definition 
Source Data 
Ref: ISO 14155 
All information in original records, certified copies of original records of 
clinical findings, observations, or other activities in a clinical 
investigation, necessary for the reconstruction and evaluation of the 
clinical investigation 
Note 1 to entry: This includes source data initially recorded in an 
electronic format. 
Source Document 
Ref: ISO 14155 
Original or certified copy of printed, optical or electronic document 
containing source data. 
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26. Appendices 
26.1. Appendix A: Preliminary Data Collection Items  
Enrollment 
Informed consent signed date 
Holter study consent signed date 
Inclusion criteria 
Exclusion criteria 
Indications 
Pregnancy assessment 
Subject Classification Status 
Subject classification status 
Baseline - Demographics 
Age 
Sex 
Ethnicity 
Baseline - Physical 
Assessment 
Weight 
Height 
Baseline - Cardiac Disease 
History 
Heart failure  
NHYA Class, if available 
LVEF value, if available 
Ischemic cardiomyopathy 
Dilated cardiomyopathy 
Idiopathic cardiomyopathy 
Valvular disease 
Valvular surgery 
Thoracic surgery 
Myocardial infarction 
Coronary artery bypass grafting (CABG) 
Atrial arrhythmia: Atrial fibrillation/ Atrial flutter/ Atrial 
tachycardia 
Ventricular arrhythmia 
Bradyarrhythmia 
Baseline - Comorbidities 
Hypertension 
Hyperlipidemia 
Diabetes 
Anemia 
Chronic obstructive pulmonary disease 
Hepatic disease 
Cerebrovascular disease 
Peripheral vascular disease 
Pulmonary hypertension 
Renal dysfunction 
Sleep apnea 
Implant Procedure Data 
Date of implant procedure 
ICM device information  
Mobile application information 
Implant tools and accessories information 
Released
92557593 C.3
LUX-Dx PERFORM Study Protocol
E.D: 04/Nov/2020
Boston Scientific Confidential. Unauthorized use is prohibited.
Page 65 of 66

Form/Template 92120219_Rev/Ver D 
          Confidential 
 
 
   LUX-Dx PERFORM Protocol, 92557593, Rev/Ver C 
Page 66 of 66 
  
Procedure times 
Suturing technique 
ICM implanting facility 
Confirmation of LATITUDE Clarity enrollment and device 
registration 
ICM programming information 
Reason for unsuccessful implant 
Device Tracking 
Information on ICM repositioning  
Information on device Out of Service (explant, disabling, or 
permanent programmed off) 
ICM Reprogramming 
Initial programmed value 
Reason for reprogramming 
Method of reprogramming (in-office or remote) 
New programmed value 
Confirmation of completion of the reprogramming 
Extended Holter Monitoring 
(Holter Study) 
Holter monitor distribution and return information 
Holter monitor data download and transmission to Core lab 
information 
6-Month and 12-Month EMR 
Review  
Adverse event assessment in EMR 
Adverse event assessment by phone call/virtual health 
visit/in-office visit to subjects  
Arrhythmia diagnoses and treatment information 
Device transmission information 
End of Study 
Subject status  
If withdrawn, reason 
Device transmission information 
If lost to follow-up, information on attempts to locate subject 
Death information 
Ongoing Data Collection 
Reporting of adverse event/device deficiency 
Reporting of protocol deviation 
 
Released
92557593 C.3
LUX-Dx PERFORM Study Protocol
E.D: 04/Nov/2020
Boston Scientific Confidential. Unauthorized use is prohibited.
Page 66 of 66