INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study
Conditions: Bradycardia
Sponsor: Boston Scientific Corporation

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INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study  
C1730 
CLINICAL INVESTIGATION PLAN 
 
 
 
Sponsored By 
Boston Scientific Corporation  
4100 Hamline Ave. N. 
St. Paul, MN 55112 
 
 
 
 
 
 
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 
Boston Scientific, Rhythm Management (RM) 
Gena Kantor 
4100 Hamline Avenue North 
St. Paul, MN 55112 
Phone: 1-800-CARDIAC  
Coordinating Principal 
Investigator(s) 
Devi G. Nair, MD 
Nair Associates, LLC 
3878 Ridgewood Cove 
Jonesboro, AR 72404 
Phone: (870) 935-6729 
 
 
 

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Original Release: 10 September 2019  
Current Version: 12 May 2020  
 
Revision 
Version 
Protocol Date 
Template 
number 
and version 
Protocol 
Section 
Modified 
Summary of Changes 
Justification for Modification 
A 
10 September 2019 
92120219 
Rev/Ver C 
N/A 
Initial version 
N/A 
B 
12 May 2020 
92120219 
Rev/Ver C 
2.0, 7.1, 10.1, 
10.6, 10.7, 10.8, 
10.10, 10.12, 
11.1.2, 11.4.2, 
17.4, 19.2 
Contact Information: Added Study PI 
name and contact information. 
2.0: Synopsis updated to reflect Protocol 
changes.  
7.1: Added clarification that the planned 
enrollment of 105 subjects only includes 
successfully implanted subjects, and does 
not include intent/attempt/partial attempt 
subjects.  Enrollment and study duration 
updated to reflect current expectations.  
10.1, 10.6, 10.7, 10.8, 10.10, 10.12: 
Language was added to the Protocol to 
allow for telephone/telehealth visits with 
LATITUDE transmission of lead 
measurements at the 1 and 3 month 
follow-up visits if it is not possible for a 
subject to complete an in-clinic follow-up 
visit.  The requirement for three 
consecutive threshold measurements was 
also removed from the 3-month follow-up 
visit because it is not possible to obtain 
this from LATITUDE transmission of 
lead measurements.  
11.1.2: Section focus was changed from 
subjects to leads. 
Contact Information:  Study PI 
selected since Rev. A of Protocol. 
2.0: Synopsis updated to reflect 
Protocol changes. 
7.1: To address the foreseen 
attrition rate and slower than 
previously anticipated enrollment 
due to uncertainty during the 
COVID-19 pandemic.   
10.1, 10.6, 10.7,  10.8, 10.10, 
10.12:  The global COVID-19 
pandemic has caused significant 
changes in the administration of 
healthcare and local restrictions at 
sites may exist for in-person 
clinic visits.   
11.1.2: This is more consistent 
with the language elsewhere in 
Section 11. 
11.4.2: Analyses to assess if 
LATITUDE measurements vs in-
clinic measurements had any 
impact on lead data. 
17.4: To provide direction to sites 
on how to report events under 

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                      INGEVITY+ Clinical Study Protocol, 92424682, Rev/Ver B 
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Revision 
Version 
Protocol Date 
Template 
number 
and version 
Protocol 
Section 
Modified 
Summary of Changes 
Justification for Modification 
11.4.2: Added a sub-group analysis to 
compare pacing capture threshold test 
type (In-office vs. Auto-threshold). 
17.4:  Language was added to clarify how 
to report events.  
19.2: CEC adjudication of lead related 
complications was removed. 
usual circumstances, and when 
the EDC is not available.  
19.2: The INGEVITY+ Study’s 
Safety Endpoint was designed for 
comparability to other pace/sense 
lead studies, especially to the 
INGEVITY Study. The 
INGEVITY Study performed 
both BSC and CEC classifications 
of lead-related complications.  
BSC classifications were used for 
the Safety Endpoint evaluations 
and the CEC adjudications were 
used as a confirmation of BSC’s 
classifications (as detailed in the 
PMA report).  Though the CEC 
adjudications would provide a 
confirmation of the BSC 
classifications, the adjudications 
are not critical for the fulfillment 
of the study objectives.  In an 
effort to achieve the ‘least 
burdensome’ means of assuring 
the safety and effectiveness of the 
INGEVITY+ Lead Family, 
especially during the COVID-19 
pandemic this requirement was 
removed. 

 
 
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2. Protocol Synopsis 
INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study 
Study 
Objective(s) 
The objective of this study is it to confirm the safety and effectiveness 
of the INGEVITY+ Active Fixation Pace/Sense Lead. 
Indication(s) for 
Use  
The INGEVITY+ lead is intended for chronic pacing and sensing in the 
right atrium and/or right ventricle when used with a compatible pulse 
generator. 
Commercial 
Device/System 
applied as 
Standard of 
Care and sizes, 
if applicable 
 
INGEVITY+ Lead 
Active fixation models 
Model # 
Lead length 
7840 
45 cm 
7841 
52 cm 
7842 
59 cm 
 
Study Design 
The INGEVITY+ Clinical Study is a prospective, non-randomized, 
multi-center, post-market study. 
 
Planned 
Number of 
Subjects 
At least 105 subjects will be enrolled in the study to achieve 200 
implanted or attempted leads. 
Enrollment 
(N=105 subjects)
Implant Procedure
(N=200 leads)
Pre-Discharge
(N=195 leads)
1-Month Vist
(N=190 leads)
3-Month Visit
(N=185 leads)

 
 
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INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study 
Planned 
Number of Sites 
/ Countries 
This study will include approximately 20 sites in North America. 
Primary Safety 
Endpoint 
Lead-related Complication-Free Rate from Implant through 3-Months 
Post-Implant 
Primary 
Effectiveness 
Endpoint 
Pacing Capture Threshold at 3-Months Post-Implant 
Secondary 
Effectiveness 
Endpoint 
Sensed Amplitude and Pacing Impedance at 3-Months Post-Implant 
Additional 
Analysis 
Implant turn count, lead handling, lead maneuverability, lead-related 
device deficiencies, including extension/retraction and accessories used   
Method of 
Assigning 
Patients to 
Treatment 
This is a one-armed study where every subject is assigned to treatment, 
where treatment means implanted, or attempted implant of INGEVITY+ 
leads in the right atrium and ventricle.  
Follow-up 
Schedule 
Study procedures and clinic visits will occur at the following time 
periods. The study will be considered complete after all subjects have 
completed their 3-Month Clinic Visit and exited the study. 
- Enrollment Visit (less than or equal to 30 days before the 
implant procedure) 
- Implant Procedure (Day 0; all future follow-ups based on 
this date) 
- Pre-Discharge Clinic Visit (3 – 72 hours) 
- 1-Month Clinic Visit (30 ± 7 days) 
- 3-Month Clinic Visit (91 + 31 days) 
Study Duration 
Enrollment is expected to be completed in approximately 12 months; 
therefore, the total study duration is estimated to be approximately 16 
months. 
Participant 
Duration 
The study duration for each subject is expected to be approximately 3 
months. Subjects will be exited from the study after their 3 month visit.  

 
 
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INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study 
Inclusion 
Criteria 
1. Subject is willing and capable of providing informed consent 
2. Subject is intended to undergo initial (de novo) pacing system 
implant using INGEVITY+ Leads in the Right Atrium (RA) and 
Right Ventricle (RV) and a Boston Scientific pulse generator  
3. Subject meets an indication for a Boston Scientific Pacemaker or 
CRT-P device per product labeling (Physician’s Technical Manual): 
o Pacemaker: 
▪ Symptomatic paroxysmal or permanent second- or 
third-degree AV block 
▪ Symptomatic bilateral bundle branch block 
▪ Symptomatic paroxysmal or transient sinus node 
dysfunction with or without associated AV 
conduction disorders (i.e., sinus bradycardia, sinus 
arrest, sinoatrial [SA] block) 
▪ Bradycardia-tachycardia syndrome, to prevent 
symptomatic bradycardia or some forms of 
symptomatic tachyarrhythmias 
▪ Neurovascular (vaso-vagal) syndromes or 
hypersensitive carotid sinus syndromes  
▪ Adaptive-rate pacing for patients exhibiting 
chronotropic incompetence and who may benefit 
from increased pacing rates concurrent with increases 
in minute ventilation and/or level of physical activity 
▪ Dual-chamber and atrial tracking modes for patients 
who may benefit from maintenance of AV synchrony 
▪ Dual chamber modes are specifically indicated for 
treatment of the following: 
• Conduction disorders that require restoration 
of AV synchrony, including varying degrees 
of AV block 
• VVI intolerance (i.e., pacemaker syndrome) in 
the presence of persistent sinus rhythm 
• Low cardiac output or congestive heart failure 
secondary to bradycardia 
o CRT-P: 
▪ Moderate to severe heart failure (NYHA Class III/IV) 
including left ventricular dysfunction (EF ≤ 35%) and 
QRS duration ≥ 120 ms and remain symptomatic 
despite stable optimal pharmacologic therapy for 
heart failure 

 
 
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INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study 
▪ Atrial tracking modes for patients who may benefit 
from maintenance of AV synchrony 
▪ Adaptive-rate pacing for a patient exhibiting 
chronotropic incompetence and who would benefit 
from increased pacing rates concurrent with increases 
in minute ventilation and/or physical activity 
4. Willing and capable of participating in all testing/visits associated 
with this clinical study at an approved clinical study center and at the 
intervals defined by this protocol 
5. Age 18 or above, or of legal age to give informed consent specific to 
state and national law 
Exclusion 
Criteria 
1. Known or suspected sensitivity to dexamethasone acetate (DXA) 
2. Has a mechanical tricuspid heart valve 
3. Women of childbearing potential who are or might be pregnant at 
the time of study enrollment or INGEVITY+ Lead implant (method 
of assessment upon physician’s discretion) 
4. Currently requiring hemo- or peritoneal dialysis  
5. Subject has or has had implanted any pacing or ICD system, 
including subcutaneous, transvenous or leadless systems  
6. Intended to receive a single chamber device 
7. Documented history of permanent or persistent AF  
8. Currently on an active organ transplant list 
9. Documented life expectancy of less than 12 months 
10. Enrolled in any other concurrent study unless prior approval is 
received from the Sponsor 
Statistical Methods  
Primary Safety 
Endpoint 
Statistical 
Hypothesis 
H0:  Lead-Related Complication-Free rate at 3 months ≤ 93% 
HA:  Lead-Related Complication-Free rate at 3 months > 93% 
Performance goal = 93%, if the lower confidence limit exceeds 93%, the 
null hypothesis will be rejected 
Selected to ensure INGEVITY+ has similar rate to other market-
approved pacing leads 
To account for variability in estimate of rate (i.e., confidence limit), 5% 
was subtracted from industry average rate of 98% to determine 
performance goal 

 
 
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INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study 
Primary Safety 
Endpoint 
Statistical Test 
Method 
The 97.5% one-sided lower confidence limit of the rate will be 
compared to performance goal. The complimentary log-log confidence 
limit of the 3-month Kaplan-Meier rate will be calculated. 
Data from RA and RV leads will be combined for the analysis. 
Primary 
Effectiveness 
Endpoint 
Statistical 
Hypothesis 
H0:  Pacing Capture Threshold Responders at 3 months ≤ 80% 
HA:  Pacing Capture Threshold Responders at 3 months > 80% 
Performance goal = 80%, if the lower confidence limit exceeds 80%, the 
null hypothesis will be rejected 
Primary 
Effectiveness 
Endpoint 
Statistical Test 
Method 
The 97.5% one-sided lower confidence limit of the responder rate will 
be compared to performance goal. A Clopper-Pearson (exact) 
confidence interval will be calculated. 
Data from RA and RV leads will be combined for the analysis. 
Study Sample 
Size Parameters 
A sample size of 185 leads with endpoint data is required to provide at 
least 90% power for all endpoints.  Assuming ~7.5% attrition (due to 
attempted implant, death, withdrawal), at least 105 subjects will be 
enrolled to yield 185 leads with endpoint data.  The sample size is 
driven by the primary safety endpoint.  
 
 
 

 
 
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3. Table of Contents  
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................5 
3. 
TABLE OF CONTENTS .......................................................................................................10 
3.1. Table of Figures .....................................................................................................14 
3.2. Table of Tables ......................................................................................................14 
4. 
INTRODUCTION ................................................................................................................15 
4.1. Background ............................................................................................................15 
4.2. Study Rationale .....................................................................................................16 
5. 
COMMERCIAL DEVICE DESCRIPTION .............................................................................16 
5.1. Commercial Device ...............................................................................................16 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................17 
7. 
STUDY DESIGN .................................................................................................................18 
7.1. Scale and Duration ................................................................................................18 
7.2. Treatment Assignment..........................................................................................18 
7.3. Justification for the Study Design ........................................................................18 
8. 
SUBJECT SELECTION ........................................................................................................19 
8.1. Study Population and Eligibility ..........................................................................19 
8.2. Inclusion Criteria ..................................................................................................19 
8.3. Exclusion Criteria .................................................................................................20 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................21 
9.1. Point of Enrollment ...............................................................................................21 
9.2. Withdrawal ............................................................................................................21 
9.3. Lost to Follow-Up ..................................................................................................22 
9.4. Subject Status and Classification .........................................................................22 
9.5. End-of-Study Definition .......................................................................................23 
10. STUDY METHODS .............................................................................................................23 
10.1. Data Collection ......................................................................................................23 

 
 
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10.2. Study Candidate Screening ..................................................................................25 
10.3. Informed Consent .................................................................................................25 
10.4. Enrollment Visit [≤ 30 days prior to Implant]....................................................25 
10.5. Implant Visit [Day 0] ............................................................................................25 
10.5.1. Baseline Lead Measurements with PSA ...................................................26 
10.5.2. Fluoroscopic Image/Chest x-ray ...............................................................26 
10.5.3. Lead Measurements with IPG ..................................................................26 
10.5.4. Implant Questionnaire ..............................................................................27 
10.5.5. AEs/ /Device Deficiencies/ Deviations ....................................................27 
10.5.6. Source Documentation Requirements ......................................................27 
10.6. Pre-Discharge [3-72 hrs] .......................................................................................27 
10.6.1. Lead Measurements with IPG ..................................................................27 
10.6.2. Fluoroscopic Image/Chest x-ray ...............................................................28 
10.6.1. AEs/ Device Deficiencies/ Deviations ......................................................28 
10.6.2. Source Documentation Requirements ......................................................28 
10.7. 1-Month follow-up visit [30 ±7 days] ...................................................................28 
10.7.1. Lead Measurements with IPG ..................................................................28 
10.7.1. AEs /Device Deficiencies/Deviations .......................................................29 
10.7.2. Source Documentation Requirements ......................................................29 
10.8. 3-Month follow-up visit [91 + 31 days] ................................................................29 
10.8.1. Lead Measurements with IPG ..................................................................29 
10.8.2. Cardiovascular Meds/AEs /Device Deficiencies/Deviations ...................30 
10.8.3. Source Documentation Requirements ......................................................30 
10.9. Additional follow-up visits ....................................................................................30 
10.9.1. Source Documentation Requirements ......................................................30 
10.10. 
Remote Follow-up ...................................................................................30 
10.11. 
Study Completion ...................................................................................31 
10.12. 
Source Documents ..................................................................................32 
11. STATISTICAL CONSIDERATIONS ......................................................................................34 
11.1. Endpoints ...............................................................................................................34 
11.1.1. Primary Safety Endpoint: Lead-related Complication-Free Rate from 0 to 
3 Months ...................................................................................................34 
11.1.1.1. Hypotheses ...............................................................................34 
11.1.1.2. Sample Size ..............................................................................35 
11.1.1.3. Statistical Methods ...................................................................35 
11.1.2. Primary Efficacy Endpoint .......................................................................36 

 
 
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11.1.2.1. Hypotheses ...............................................................................36 
11.1.2.2. Sample Size ..............................................................................36 
11.1.2.3. Statistical Methods ...................................................................36 
11.1.3. Secondary Efficacy Endpoint 1: Sensed Amplitude in the RA and RV ...37 
11.1.3.1. Hypotheses ...............................................................................37 
11.1.3.2. Sample Size for Secondary Effectiveness Endpoint 1 .............37 
11.1.3.3. Statistical Methods for Secondary Efficacy Endpoint 1 ..........37 
11.1.4. Secondary Efficacy Endpoint 2: Pacing Impedance .................................38 
11.1.4.1. Hypotheses ...............................................................................38 
11.1.4.2. Sample Size for Secondary Effectiveness Endpoint 2 .............38 
11.1.4.3. Statistical Methods for Secondary Effectiveness Endpoint 2 ..38 
11.2. Ancillary Analysis .................................................................................................38 
11.3. General Statistical Methods .................................................................................39 
11.3.1. Analysis Sets .............................................................................................39 
11.3.2. Control of Systematic Error/Bias ..............................................................39 
11.3.3. Number of Subjects per Investigative Site ...............................................39 
11.4. Data Analyses ........................................................................................................39 
11.4.1. Interim Analyses .......................................................................................39 
11.4.2. Subgroup Analyses ...................................................................................40 
11.4.3. Pooling Analysis .......................................................................................40 
11.4.4. Multivariable Analyses .............................................................................40 
11.4.5. Impact of Repeated Measures ...................................................................40 
11.4.6. Changes to Planned Analyses ...................................................................41 
12. DATA MANAGEMENT .......................................................................................................41 
12.1. Data Collection, Processing, and Review ............................................................41 
12.2. Data Retention .......................................................................................................41 
13. DEVIATIONS .....................................................................................................................42 
14. COMPLIANCE ....................................................................................................................42 
14.1. Statement of Compliance ......................................................................................42 
14.2. Investigator Responsibilities ................................................................................42 
14.2.1. Delegation of Responsibility ....................................................................44 
14.3. Institutional Review Board ..................................................................................44 
14.4. Sponsor Responsibilities .......................................................................................44 
14.4.1. Role of Boston Scientific Representatives ...............................................45 
15. MONITORING ....................................................................................................................46 

 
 
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16. POTENTIAL RISKS AND BENEFITS ...................................................................................46 
16.1. Directions for Use ..................................................................................................46 
16.2. Risks associated with Participation in the Clinical Study .................................46 
16.3. Risk Minimization Actions ...................................................................................48 
16.4. Anticipated Benefits ..............................................................................................48 
17. SAFETY REPORTING .........................................................................................................48 
17.1. Reportable Events by investigational site to Boston Scientific .........................48 
17.2. Definitions and Classification ..............................................................................49 
17.3. Relationship to Device(s) ......................................................................................50 
17.4. Investigator Reporting Requirements .................................................................52 
17.5. Boston Scientific Device Deficiencies ...................................................................53 
17.6. Reporting to Regulatory Authorities / IRBs /Investigators...............................53 
17.7. Subject Death Reporting ......................................................................................54 
18. INFORMED CONSENT........................................................................................................55 
19. COMMITTEES ...................................................................................................................56 
19.1. Safety Monitoring Process ....................................................................................56 
19.2. INGEVITY+ Clinical Events Committee (CEC) ...............................................56 
20. SUSPENSION OR TERMINATION .......................................................................................56 
22.1 Premature Termination of the Study ..................................................................56 
22.1.1 
Criteria for Premature Termination of the Study ......................................57 
22.2 Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval ................................................................................................................57 
22.3 Requirements for Documentation and Subject Follow-up ................................57 
22.4 Criteria for Suspending/Terminating a Study Site ............................................57 
21. PUBLICATION POLICY ......................................................................................................58 
22. ABBREVIATIONS AND DEFINITIONS .................................................................................58 
22.1. Abbreviations ........................................................................................................58 
22.2. Definitions ..............................................................................................................59 
23. BIBLIOGRAPHY .................................................................................................................61 
 
 

 
 
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3.1. Table of Figures 
Figure 7-1: INGEVITY+ Study Design .................................................................................. 18 
 
3.2. Table of Tables 
Table 5-1: INGEVITY+ Lead Models & Lengths .................................................................. 17 
Table 6-1: Overview of objectives and endpoints .................................................................. 17 
Table 8-1: Inclusion Criteria ................................................................................................... 19 
Table 8-2: Exclusion Criteria .................................................................................................. 21 
Table 10-1: Data Collection Schedule .................................................................................... 24 
Table 10-2: Recommended Threshold and Sensing Measurements at Implant with PSA ..... 26 
Table 10-3: Source Documentation Requirements ................................................................. 33 
Table 17-1: Safety Definitions ................................................................................................ 49 
Table 17-2: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 50 
Table 17-3: Investigator Reporting Requirements .................................................................. 52 
Table 22-1: Abbreviations ...................................................................................................... 58 
Table 22-2: Definitions ........................................................................................................... 60 
 

 
 
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4. Introduction 
4.1. Background 
Pacemaker leads are an essential component of a pacemaker system. A pacemaker lead is the 
insulated electrical conductor between the implantable pulse generator (IPG) and the cardiac 
tissue. The lead is a complex mechanical structure that has to withstand biodegradation in the 
environment of the body, repetitive flexural cycles of the heart, and compressive and tensile 
forces in the extravascular space. Design requirements may include requirements related to 
ease of implant handling, fluoroscopic visualization, the diameter of the lead body, durability 
to last beyond the replacement of several IPGs, performance to stimulate the cardiac tissue 
with low energy, ability to reliably sense intrinsic cardiac activity, and design with 
consideration of future lead extraction.  
The INGEVITY lead family, including models labeled as MR Conditional and corresponding 
models without MR Conditional labeling, has demonstrated outstanding clinical and 
commercial performance and safety. Although the implant performance experience is 
positive overall, physicians have provided feedback on the active fixation models regarding 
difficulty in extending and/or retracting the helix; this occurs during implantation when the 
lead is subjected to challenging bends due to tortuous vasculature based on patient anatomy 
and/or when combined with various physician techniques. To address physicians’ feedback, 
Boston Scientific Corporation (BSC) initiated a project to improve the extension/retraction 
performance of the active fixation lead, and has developed, bench tested, and animal-tested 
three new models of the INGEVITY lead family called the INGEVITY+ lead. 
Three design changes were implemented in the INGEVITY+ lead to achieve the goal of 
improving extension/retraction performance as part of the physician’s handling experience 
without compromising the features and functionality of the original INGEVITY active 
fixation lead: 
• Change 1: The inner coil was modified from a uni-filar coil with an Ethylene 
tetrafluoroethylene (ETFE) covering to a tri-filar coil with no ETFE covering to 
improve the consistency of helix extension/retraction performance.  
• Change 2: To accommodate the inner coil change, the design of inner coil 
connections at the terminal pin (proximal end of coil) and the coupler (distal end of 
the coil) were revised to incorporate a counter-bore that allows the inner coil to be 
positioned within these two components. 
• Change 3: The outer diameter of the distal seal is being increased by 0.001 inch to 
align with the design changes to the inner coil. 
All other design specifications and other aspects of lead performance remain unchanged.   
The INGEVITY+ Active Fixation Pace/Sense Lead Clinical Study will gather data to 
confirm the safety, performance, and effectiveness of the INGEVITY+ Lead. 

 
 
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4.2. Study Rationale 
Boston Scientific Rhythm Management is conducting this study to fulfill post-approval 
regulatory requirements.   
5.  Commercial Device Description 
5.1. Commercial Device  
This lead family has the following characteristics: 
• Endocardial pace/sense lead—intended for chronic bipolar pacing and sensing in the 
atrium and/or ventricle. 
• IS-1 bipolar connectori—the industry standard connector to be used in conjunction 
with a compatible cardiac device that accepts the IS-1 connector. 
• MR Conditional—leads can be used as part of the ImageReady MR Conditional 
Pacing System or the ImageReady MR Conditional Defibrillation System when 
connected to Boston Scientific MR Conditional pulse generators ("MR Conditional 
System Information" on page 2 of the Physicians Lead Manual (PLM)). 
• Iridium Oxide (IROX)-coated electrodes—the electrodes are coated with IROX to 
increase the microscopic surface area. 
• Steroid-eluting—upon exposure to body fluids, the steroid elutes from the lead to 
help reduce tissue inflammation response at the distal electrode. The steroid 
suppresses the inflammatory response believed to cause threshold rises typically 
associated with implanted pacing electrodes. Lower thresholds are desirable because 
they can increase pacing safety margins and reduce pacing energy requirements, 
potentially increasing pulse generator longevity. The nominal dose and structure of 
the steroid are listed in the specifications (Table 5 Specifications on page 30 of the 
PLM). 
• Radiopaque suture sleeve—the radiopaque suture sleeve is visible under fluoroscopy 
and is used to secure, immobilize, and protect the lead at the venous entry site after 
lead placement. The window feature is designed to aid compression of the sleeve onto 
the lead during suturing. 
• Extendable/Retractable fixation—the extendable/retractable helix design anchors the 
distal tip electrode to the endocardial surface without support of trabecular structures, 
offering various lead placement possibilities for the tip electrode in the right atrium 
and/or right ventricle. The helix serves as the cathode for endocardial pacing and 
sensing. The helix is extended and retracted using the fixation tool. 
• Fluoroscopic markers—radiopaque markers near the distal tip can be seen under 
fluoroscopy. These markers show when the helix is fully retracted or fully extended. 
• 
Lead body—the isodiametric lead body consists of a coaxial design that includes a 
tri-filar inner coil and a single-filar outer coil. Both the inner and outer coils are 
designed for MR Conditional use in the MRI environment and provide robust flexural 
fatigue performance. In addition, the tri-filar inner coil provides consistent helix 
deployment performance. The conductors are separated by both a silicone rubber and 
 
i IS-1 refers to the international standard ISO 5841-3:2013. 

 
 
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Polytetrafluoroethylene (PTFE) lining. The outer coil is covered in Ethylene 
tetrafluoroethylene (ETFE) for extra insulation protection. The entire lead body is 
encompassed in a polyurethane outer insulation. 
• Stylet delivery method—the design consists of an open-lumen conductor coil to 
enable lead delivery using a stylet. Refer to the stylet information ("Stylets" on page 
12 of the PLM). 
 
The INGEVITY+ lead is indicated for chronic pacing and sensing in the right atrium and/or 
right ventricle when used with a compatible pulse generator. 
Table 5-1 contains the model numbers, and lead lengths of the INGEVITY+ Leads used in 
this study.   
Table 5-1: INGEVITY+ Lead Models & Lengths 
Model Number 
Lead Length 
7840 
45 cm 
7841 
52 cm 
7842 
59 cm 
6. Study Objectives and Endpoints 
See Table 6-1 below for a summary of the primary objectives and endpoints for the 
INGEVITY+ Study. 
Table 6-1: Overview of objectives and endpoints 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR ENDPOINTS 
Primary 
Confirm the safety of the 
INGEVITY+ Lead 
Lead-related Complication-Free 
Rate from Implant through 3-
Months Post-Implant 
Similar endpoints have 
been used to evaluate 
outcomes in other 
pace/sense lead studies   
Confirm the effectiveness of the 
INGEVITY+ Lead 
Pacing Capture Threshold at 3-
Months Post-Implant 
Secondary 
Confirm the effectiveness of the 
INGEVITY+ Lead 
Sensed Amplitude and Pacing 
Impedance at 3-Months Post-
Implant 
Similar endpoints have 
been used to evaluate 
outcomes in other 
pace/sense lead studies   
Additional 
Confirm the device design 
changes of the INGEVITY+ Lead 
Implant turn count, lead handling, 
lead maneuverability, lead-related 
device deficiencies, including 
extension/retraction, and accessories 
used 
Confirm design 
changes had intended 
effects 

 
 
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7. Study Design 
The INGEVITY+ Study is a prospective, non-randomized, multi-center, post-approval study 
utilizing performance goals to confirm the safety, performance, and effectiveness of the 
INGEVITY+ Lead. 
7.1. Scale and Duration 
The INGEVITY+ study will enroll at least 105 subjects at approximately 20 sites in the 
United States to achieve 200 implanted or attempted INGEVITY+ leads. The enrollment 
ceiling of 105 will not include attempt, partial attempt or intent subjects; see section 9.4 for 
subject status and classification definitions.   A maximum of 21 subjects may be enrolled per 
site unless prior approval from the Sponsor is obtained. Enrollment is expected to be 
completed in approximately 12 months; therefore, the total study duration is estimated to be 
approximately 16 months.  Follow up will be required at pre-discharge, 1-month, and 3-
months post-implant. 
 
Figure 7-1: INGEVITY+ Study Design 
7.2. Treatment Assignment 
This is a one-armed study where every subject is assigned to treatment, where treatment 
means implanted, or attempted implant of INGEVITY+ leads in the right atrium and 
ventricle. 
7.3. Justification for the Study Design 
The potential clinical effect or impact of the design changes associated with the INGEVITY+ 
lead would be seen in the short-term use of the lead, which BSC will study in the post-
approval study (PAS) plan outlined in this protocol. In addition, industry-average short-term 
evaluation period for establishing short-term safety and effectiveness of a pace/sense lead 
Enrollment 
(N=105 subjects)
Implant Procedure
(N=200 leads)
Pre-Discharge
(N=195 leads)
1-Month Vist
(N=190 leads)
3-Month Visit
(N=185 leads)

 
 
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equals three months and is slightly longer than the acute (i.e., short-term) period of ≤30 days 
established in the Industry Guidance for Uniform Reporting of Clinical Performance of 
Cardiac Rhythm Management Pulse Generators and Leads.1 
8. Subject Selection  
8.1. Study Population and Eligibility  
Subjects included in the INGEVITY+ Study will be selected from the investigator’s general 
patient population indicated for dual-chamber pacemaker or CRT-P implantation. 
Investigators are responsible for screening all potential subjects and selecting those who meet 
the eligibility criteria for the study as described in sections 8.2 and 8.3. 
8.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8-1) may be considered for 
inclusion in this clinical investigation, provided no exclusion criterion (see Section 8.3) is 
met.  
Table 8-1: Inclusion Criteria 
Inclusion 
Criteria 
1. Subject is willing and capable of providing informed consent 
2. Subject is intended to undergo initial (de novo) pacing system 
implant using INGEVITY+ Leads in the Right Atrium (RA) and 
Right Ventricle (RV) and a Boston Scientific pulse generator  
3. Subject meets an indication for a Boston Scientific Pacemaker or 
CRT-P device per product labeling (Physician’s Technical 
Manual): 
o Pacemaker: 
▪ Symptomatic paroxysmal or permanent second- or 
third-degree AV block 
▪ Symptomatic bilateral bundle branch block 
▪ Symptomatic paroxysmal or transient sinus node 
dysfunction with or without associated AV conduction 
disorders (i.e., sinus bradycardia, sinus arrest, 
sinoatrial [SA] block) 
▪ Bradycardia-tachycardia syndrome, to prevent 
symptomatic bradycardia or some forms of 
symptomatic tachyarrhythmias 
▪ Neurovascular (vaso-vagal) syndromes or 
hypersensitive carotid sinus syndromes  
▪ Adaptive-rate pacing for patients exhibiting 
chronotropic incompetence and who may benefit from 

 
 
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increased pacing rates concurrent with increases in 
minute ventilation and/or level of physical activity 
▪ Dual-chamber and atrial tracking modes for patients 
who may benefit from maintenance of AV synchrony 
▪ Dual chamber modes are specifically indicated for 
treatment of the following: 
• Conduction disorders that require restoration of 
AV synchrony, including varying degrees of 
AV block 
• VVI intolerance (i.e., pacemaker syndrome) in 
the presence of persistent sinus rhythm 
• Low cardiac output or congestive heart failure 
secondary to bradycardia 
o CRT-P: 
▪ Moderate to severe heart failure (NYHA Class III/IV) 
including left ventricular dysfunction (EF ≤ 35%) and 
QRS duration ≥ 120 ms and remain symptomatic 
despite stable optimal pharmacologic therapy for heart 
failure 
▪ Atrial tracking modes for patients who may benefit 
from maintenance of AV synchrony 
▪ Adaptive-rate pacing for a patient exhibiting 
chronotropic incompetence and who would benefit 
from increased pacing rates concurrent with increases 
in minute ventilation and/or physical activity 
4. Willing and capable of participating in all testing/visits associated 
with this clinical study at an approved clinical study center and at 
the intervals defined by this protocol 
5. Age 18 or above, or of legal age to give informed consent specific 
to state and national law  
8.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 8-2) are not eligible for study 
participation. 

 
 
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Table 8-2: Exclusion Criteria 
Exclusion 
Criteria 
1. Known or suspected sensitivity to dexamethasone acetate (DXA) 
2. Has a mechanical tricuspid heart valve 
3. Women of childbearing potential who are or might be pregnant at the time 
of study enrollment or INGEVITY+ Lead implant (method of assessment 
upon physician’s discretion) 
4. Currently requiring hemo- or peritoneal dialysis  
5. Subject has or has had implanted any pacing or ICD system, including 
subcutaneous, transvenous or leadless systems  
6. Intended to receive a single chamber device 
7. Documented history of permanent or persistent AF  
8. Currently on an active organ transplant list 
9. Documented life expectancy of less than 12 months 
10. Enrolled in any other concurrent study unless prior approval is received 
from the Sponsor 
9. Subject Accountability 
9.1. Point of Enrollment 
Subjects will be considered enrolled in the INGEVITY+ Study at the time of informed 
consent form (ICF) execution. All subject enrollments will be counted against the enrollment 
ceiling for the study. 
9.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the clinical 
investigation, the reason(s) shall be reported. If such withdrawal is due to problems related to 
device safety or performance, the investigator shall ask for the subject’s permission to follow 
his/her status/condition outside of the clinical study.  
If the INGEVITY+ lead(s) of a study subject is explanted, the subject must be followed for 
30 ± 7 days after the explant of the INGEVITY+ lead(s); any open adverse events must be 
closed or documented as chronic. Thirty days after the explant of the INGEVITY+ lead(s), a 
30-day Follow-up eCRF must be completed, and the subject can be withdrawn from the 
study. An End of Study eCRF must be completed. 

 
 
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Reasons for withdrawal may include but are not limited to: 
• Physician discretion 
• Subject choice to withdraw consent 
• Explant of all INGEVITY+ lead(s) 
• Loss to follow-up 
• Death 
 
While study withdrawal is discouraged, subjects may withdraw from the study at any time, 
with or without reason, and without prejudice to further treatment.  All applicable electronic 
case report form (eCRFs) up to the point of subject withdrawal and an End of Study eCRF 
must be completed. Additional data may no longer be collected after the point at which a 
subject has been withdrawn from the study or withdraws his/her consent, for whatever 
reason. All open adverse events should be closed or documented as chronic. Data collected 
up to the point of subject withdrawal may be used. 
9.3. Lost to Follow-Up 
For subjects who are “lost-to-follow-up,” the investigator/ center should have at least three 
documented attempts to contact the subject prior to completion of the End of Study eCRF.  
The end of study date for “lost-to-follow-up” subjects should be on or after the last 
documented contact attempt. 
9.4. Subject Status and Classification 
Intent - refers to a subject who has been enrolled, but then does not undergo an implant 
procedure. The original Informed Consent form and screening documentation for intent 
subjects must be maintained in the Center’s files. There are no follow-up requirements for 
intent subjects. The subject can be withdrawn from the study, and an End of Study eCRF 
must be completed. 
Partial Attempt – refers to a subject who has been enrolled and has had anesthesia 
administered in preparation for the surgical implant procedure but does not have the 
INGEVITY+ lead introduced into their vasculature. There are no follow-up requirements for 
partial attempt subjects. The subject can be withdrawn from the study, and an End of Study 
eCRF must be completed. 
Attempt - refers to a subject who has been enrolled in the INGEVITY+ Study and has had 
anesthesia administered in preparation for the surgical implant procedure and has had the 
INGEVITY+ lead introduced into the subject’s vasculature, but is not successfully implanted 
with an INGEVITY+ lead. 
Attempt subjects must be followed 30 ± 7 days post-attempted INGEVITY+ lead implant to 
assure there are no associated adverse events, or to assure the resolution of any adverse 
events associated with the attempted INGEVITY+ lead implant. Thirty days after the attempt 
of the INGEVITY+ lead(s), a 30-day Follow-up eCRF must be completed, and the subject 
can be withdrawn from the study.  An End of Study eCRF must be completed. 

 
 
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Implant - refers to a subject who is successfully implanted and/or tested with the 
INGEVITY+ Lead(s) per the study protocol. These subjects are followed in accordance with 
the follow-up schedule and included in all analyses of safety and performance. 
9.5. End-of-Study Definition  
A clinical trial is considered completed when participants are no longer being examined, and 
the last participant has exited the study, all data is reported, and the database is locked.  
10. Study Methods 
10.1. Data Collection 
Data will be collected from each subject at enrollment, implant, pre-discharge, 1-month and 
3-months post-implant and results recorded on the appropriate eCRF.  Additional follow-up 
visits must be collected as defined in Section 10.9.  All study-related visit windows are 
calculated from the date of initial INGEVITY+ lead implant. 
The data collection schedule is shown in Table 10-1. 
 
 

 
 
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Table 10-1: Data Collection Schedule 
Procedure/Assessment* 
Enrollment 
≤ 30 days 
prior to 
Implant 
Index 
Procedure 
Day 01 
Post- 
procedure/ 
Prehospital 
Discharge 
3-72 hours1 
Follow-up Visits 
1 Month  
(30 ± 7 Days)1 
Clinic Visit 
3 Month 
(91+31 Days)1 
Clinic Visit 
Additional  
Visit  
Informed consent process, 
including informed consent 
signature date 
X 
- 
- 
- 
- 
- 
Demographics 
X 
- 
- 
- 
- 
- 
Physical assessment, including 
weight and height 
X 
- 
- 
- 
- 
- 
Medical history 
X 
- 
- 
- 
- 
- 
Implant Questionnaire 
- 
X 
- 
- 
- 
- 
PSA measurements for all 
leads  
- 
X 
- 
- 
- 
- 
PA and lateral chest X-ray 
and/or fluoroscopic image of 
lead distal tip fixation 
- 
X 
- 
- 
- 
Cardiovascular Medications 
X 
- 
- 
- 
X 
- 
IPG lead measurements for all 
leads  
- 
X 
X 
X 
X 
O / X** 
Adverse events 
assessment/reporting 
X 
X 
X 
X 
X 
X 
Device deficiency 
assessment/reporting 
 
X 
X 
X 
X 
X 
Protocol deviation 
X 
X 
X 
X 
X 
X 
X = Required; - = Not required/Not Applicable; O = Optional 
1 Clock starts after end of implant procedure, day of implant is day 0, and pocket closure is hour 0 
* See Table 10-3 in Section 10.12 for full source requirements 
**Required if there is a lead-related AE or device deficiency, otherwise optional 

 
 
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10.2. Study Candidate Screening 
For the INGEVITY+ Study, physician investigators are responsible for screening all potential 
patients and selecting those who are appropriate for study inclusion. The patients selected for 
participation should be from the investigator’s general patient population with an indication 
for implantation of a Boston Scientific dual-chamber pacemaker or CRT-P system according 
to the product labeling (Physician’s Technical Manual). 
10.3. Informed Consent 
Patients who appear to meet all of the inclusion criteria and none of the exclusion criteria and 
agree to participate in the INGEVITY+ Study must give written informed consent in a form 
approved by the investigational center’s IRB prior to study participation and data collection. 
The Investigator is responsible for ensuring that Informed Consent is obtained prior to any 
study-required procedure and/or testing, or data collection. Patients who complete the 
informed consent process and sign and date the informed consent for the INGEVITY+ Study 
will be considered enrolled in the study at the point of executing an ICF. 
10.4. Enrollment Visit [≤ 30 days prior to Implant] 
The data to be collected during enrollment into the INGEVITY+ Study includes subject 
demographic data, a physical assessment of the subject, including height and weight, 
arrhythmia history, cardiac disease history, and current cardiovascular medications. 
Implant or attempted implant of the INGEVITY+ Leads must occur ≤ 30 days of the subject 
signing informed consent. 
10.5. Implant Visit [Day 0] 
The IPG and INGEVITY+ leads should be implanted and tested in accordance with the 
Physician’s Manuals. The implant procedure, peri-implant management, and post-operative 
care of the INGEVITY+ leads are standard of care for cardiac pacemaker and CRT-P 
implants. There are no special tools or procedures required to implant INGEVITY+ leads.  
Subjects in this clinical study will be required to be attempted with INGEVITY+ Leads in 
their RA and RV. The data to be collected from the implant procedure includes: 
• IPG: 
o Type 
o Manufacture 
o Model 
o Serial number 
o Pocket location 
o Device location in pocket 
o Time of pocket closure 
• Leads (all attempted and successfully implanted): 
o Lead location 
o Model 

 
 
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o Serial number  
o Anatomical space 
o Number of turns to fully extend the helix 
o Number of turns to fully retract the helix, for repositioning if applicable 
o Voltage threshold, sensed amplitude(s), and pacing impedance of the leads 
measured with a pacing system analyzer (PSA) 
o Voltage threshold, sensed amplitude(s), and pacing impedance of the leads 
measured with the implanted IPG 
• Implant accessories used: 
o Vein pick 
o Stylet 
o Stylet guide 
o Fixation tool 
o Slit Suture Sleeve 
10.5.1. Baseline Lead Measurements with PSA  
The voltage threshold, sensed amplitude(s), and pacing impedance of the leads measured 
with a pacing system analyzer (PSA) will be obtained to verify adequate signals. Electrical 
performance of the leads will be verified before attaching the leads to the pulse generator. 
Baseline measurements will be performed after allowing sufficient time for the effect of local 
tissue trauma to subside (approximately 10 minutes). 
If the baseline measurements do not meet clinically acceptable values, it is recommended the 
Investigator reposition the lead system. Table 10-2 includes the recommended baseline 
measurements from the INGEVITY+ Physician’s Lead Manual. 
Table 10-2: Recommended Threshold and Sensing Measurements at Implant with PSA 
Measurements 
Atrial Data 
Ventricular Data 
Voltage Threshold  
(pulse width setting at 0.5ms) 
≤ 1.5 V 
≤ 1.0 V 
P-wave/ R-wave 
≥ 2.0 mV 
≥ 5.0 mV 
Impedance 
200-2000 Ω 
200-2000 Ω 
10.5.2. Fluoroscopic Image/Chest x-ray 
Either a fluoroscopic image or PA and lateral chest X-ray of the lead distal tip fixation must 
be obtained at implant or pre-discharge.   
10.5.3. Lead Measurements with IPG 
Lead measurements, including pacing thresholds, sensed amplitudes, and pacing impedances 
are required post-implant for all implanted leads. After the implant procedure is complete, 
pacing and sensing evaluation of the leads using the IPG (either pacemaker or CRT-P) must 
be performed. Lead baseline measurements are required unless the testing is inhibited by a 
subject condition (subject has no intrinsic rhythm or subject is in atrial fibrillation).  

 
 
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During the INGEVITY+ Study, pacing threshold measurements will be collected in a 
standard manual fashion in bipolar electrode configuration. At least two (2) cardiac cycles at 
a given voltage level shall be obtained before stepping down to the next voltage level. A 
count of two (2) non-capture beats is required at a given voltage level to declare a loss of 
capture (LOC) for any of these tests. The threshold is defined as one voltage level above the 
level where two (2) non-captured beats are observed.  
The following baseline measurements must be taken utilizing the IPG to ensure adequate 
sensing and pacing function of all leads: 
• 
Intrinsic amplitude (mV) 
• 
Voltage pacing capture threshold in the bipolar mode lead configuration (V, at 0.4 ms 
pulse width) 
• 
Lead impedance () 
10.5.4. Implant Questionnaire 
An implant questionnaire is included as a part of the implant procedure. It includes questions 
regarding the implanting physicians’ experience with this new lead, including overall 
handling of the lead, as well as other related questions. 
10.5.5. AEs/ /Device Deficiencies/ Deviations 
Document any applicable adverse events, device deficiencies, and deviations that have 
occurred. 
10.5.6. Source Documentation Requirements 
See Table 10-3 in Section 10.12 for required source documentation for the implant 
procedure.  
10.6. Pre-Discharge [3-72 hrs] 
Subjects will have a lead evaluation prior to leaving the hospital.  
The pre-discharge follow-up must be performed between 3 hours and 72 hours after implant. 
If the subject needs to stay more than 72 hours in the hospital after implant for any reason, 
the pre-discharge procedure should be performed prior to the end of 72 hours even if the 
subject is still in the hospital. Any reasons for prolonged or ongoing hospitalization need to 
be appropriately documented (i.e., Adverse Event eCRF, if applicable).  If the subject will be 
followed on the LATITUDE system, the automatic threshold or automatic capture (TREND 
or Auto) feature must be turned on prior to discharge for all chambers in which INGEVITY + 
leads are implanted. 
10.6.1. Lead Measurements with IPG 
Lead measurements, including pacing thresholds, sensed amplitudes, and pacing impedances 
are required at the pre-discharge visit for all implanted leads. Pacing and sensing evaluation 
using the IPG (either pacemaker or CRT-P) must be performed. Lead measurements are 

 
 
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required unless the testing is inhibited by a subject condition (subject has no intrinsic rhythm 
or subject is in atrial fibrillation).  
During the INGEVITY+ Study, pacing threshold measurements will be collected in a 
standard manual fashion in bipolar electrode configuration. At least two (2) cardiac cycles at 
a given voltage level shall be obtained before stepping down to the next voltage level. A 
count of two (2) non-capture beats is required at a given voltage level to declare a loss of 
capture (LOC) for any of these tests. The threshold is defined as one voltage level above the 
level where two (2) non-captured beats are observed.  
The following measurements are to be taken utilizing the IPG to ensure adequate sensing and 
pacing function of all leads: 
• 
Intrinsic amplitude (mV) 
• 
Voltage pacing capture threshold in the bipolar mode lead configuration (V, at 0.4 ms pulse 
width) 
• 
Lead impedance () 
10.6.2. Fluoroscopic Image/Chest x-ray 
Either a fluoroscopic image or PA and lateral chest X-ray of the lead distal tip fixation must 
be obtained at implant or pre-discharge.   
10.6.1. AEs/ Device Deficiencies/ Deviations 
Document any applicable adverse events, device deficiencies, and deviations that have 
occurred. 
10.6.2. Source Documentation Requirements 
See Table 10-3 in Section 10.12 for required source documentation for the pre-discharge 
visit.  
10.7. 1-Month follow-up visit [30 ±7 days] 
Study follow-up visits shall be completed in-clinic; however, if it is not possible to complete 
an in-clinic follow-up visit (e.g., local restrictions due to global health crisis) a telephone or 
telehealth visit with LATITUDE remote transmission of lead measurement can be 
substituted.   
10.7.1. Lead Measurements with IPG 
Lead measurements, including pacing thresholds, sensed amplitudes, and pacing impedances 
are required at the one-month visit for all implanted leads. Pacing and sensing evaluation 
using the IPG (either pacemaker or CRT-P) must be performed. Lead measurements are 
required unless the testing is inhibited by a subject condition (subject has no intrinsic rhythm 
or subject is in atrial fibrillation).  

 
 
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If the visit is performed in-clinic during the INGEVITY+ Study, pacing threshold 
measurements will be collected in a standard manual fashion in bipolar electrode 
configuration. At least two (2) cardiac cycles at a given voltage level shall be obtained before 
stepping down to the next voltage level. A count of two (2) non-capture beats is required at a 
given voltage level to declare a loss of capture (LOC) for any of these tests. The threshold is 
defined as one voltage level above the level where two (2) non-captured beats are observed.  
The following measurements are to be taken utilizing the IPG to ensure adequate sensing and 
pacing function of all leads: 
• 
Intrinsic amplitude (mV) 
• 
Voltage pacing capture threshold in the bipolar mode lead configuration (V, at 0.4 ms pulse 
width) 
• 
Lead impedance () 
 
If a remote visit with LATITUDE lead measurements is performed see section 10.10 
10.7.1. AEs /Device Deficiencies/Deviations 
Document any applicable adverse events, device deficiencies, and deviations that have 
occurred. 
10.7.2. Source Documentation Requirements 
See Table 10-3 in Section 10.12 for required source documentation for the 1-month follow-
up. 
10.8. 3-Month follow-up visit [91 + 31 days] 
Study follow-up visits shall be completed in-clinic; however, if it is not possible to complete 
an in-clinic follow-up visit (e.g., local restrictions due to global health crisis) a telephone or 
telehealth visit with LATITUDE remote transmission of lead measurement can be 
substituted. 
10.8.1. Lead Measurements with IPG 
Lead measurements, including pacing thresholds, sensed amplitudes, and pacing impedances 
are required at the 3-month visit for all implanted leads. Pacing and sensing evaluation using 
the IPG (either pacemaker or CRT-P) must be performed. Lead measurements are required 
unless the testing is inhibited by a subject condition (subject has no intrinsic rhythm or 
subject is in atrial fibrillation).  
If the visit is performed in-clinic during the INGEVITY+ Study, pacing threshold 
measurements will be collected in a standard manual fashion in bipolar electrode 
configuration. At least two (2) cardiac cycles at a given voltage level shall be obtained before 
stepping down to the next voltage level. A count of two (2) non-capture beats is required at a 
given voltage level to declare a loss of capture (LOC) for any of these tests. The threshold is 
defined as one voltage level above the level where two (2) non-captured beats are observed.  

 
 
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The following measurements are to be taken utilizing the IPG to ensure adequate sensing and 
pacing function of all leads: 
• 
Intrinsic amplitude (mV) 
• 
Voltage pacing capture threshold in the bipolar mode lead configuration (V, at 0.4 ms pulse 
width).  
• 
Lead impedance () 
 
If a remote visit with LATITUDE lead measurements is performed see section 10.10 
10.8.2. Cardiovascular Meds/AEs /Device Deficiencies/Deviations 
The subject’s cardiovascular medications must be assessed for any updates or changes.  Any 
changes to the subject’s cardiovascular medication must be documented.  
Document any applicable adverse events, device deficiencies, and deviations that have 
occurred. 
10.8.3. Source Documentation Requirements 
See Table 10-3 in Section 10.12 for required source documentation for the 3-month follow-
up.  
10.9. Additional follow-up visits 
All follow-ups outside of the designated follow-up windows or multiple visits inside any 
follow-up window need to be reported on an Additional Follow-up eCRF if associated with a 
reportable adverse event or device deficiency.  Routinely scheduled office visits for purposes 
other than these events do not require an Additional Follow-up eCRFs to be completed.  
Document any applicable adverse events, device deficiencies, and deviations that have 
occurred. 
Device evaluation is optional at these visits unless an adverse event is related to the 
INGEVITY+ lead(s) or there is a device deficiency, then an evaluation of the device is 
required. 
10.9.1. Source Documentation Requirements 
See Table 10-3 in Section 10.12 for required source documentation for additional follow-ups. 
10.10. 
 Remote Follow-up  
Study follow-up visits shall be completed in-clinic; however, if it is not possible to complete 
an in-clinic follow-up visit (e.g., local restrictions due to global health crisis) a telephone or 
telehealth visit with LATITUDE remote transmission of lead measurements can be 
substituted.  The reason for the remote follow-up visit must be documented.  Subjects may be 
followed on the LATITUDE system from the time they are implanted.  If a patient is 
followed on the LATITUDE system, the automatic threshold or automatic capture (TREND 

 
 
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or Auto) feature must be turned on for all chambers in which INGEVITY+ leads are 
implanted.    
The subject will be contacted for a telephone or telehealth visit, within the applicable follow-
up window. Any applicable adverse events, device deficiencies, and deviations that have 
occurred will be documented.  If it is the subject’s 3-month follow-up, cardiovascular 
medications must be assessed for any updates or changes.  Any changes to the subject’s 
cardiovascular medication must be documented. 
When a LATITUDE remote transmission is performed to obtain lead measurement data for 
the 1-Month and/or 3-Month Follow-up visits, the following measurements of all leads are to 
be entered in the case report forms: 
• Intrinsic amplitude (mV)  
• Voltage pacing capture threshold from automatic threshold or automatic capture test 
(V, at 0.4 ms pulse width).  Automatic threshold or automatic capture tests in the right 
atrium are performed in the unipolar mode lead configuration.  Automatic threshold 
or automatic capture tests in the right ventricle and left ventricle are performed in the 
programmed configuration.   
• Lead impedance () 
 
The available lead measurements closest to the target visit date should be entered into the 
case report forms. For the 1-Month Follow-up Visit, if complete data from the 30th day post-
implant are available, these data should be used.  If complete data from the 30th day post-
implant are not available, then complete data from the first of the following days post-
implant are to be used: 29th, 31st, 28th, 32nd, 27th, 33rd, 26th, 34th, 25th, 35th,  24th, 36th, 23rd, 
37th day post-implant. The alternating pattern is outlined for consistency in which data is 
entered in the case report form and to obtain data from the closest available date in the +/- 
visit window.  If complete data is not available from any day within the follow-up visit 
window, data from the target visit date will be entered.  
For the 3-Month Follow-up Visit, if complete data from the 91st day post-implant are 
available, these data should be used.  If complete data from the 91st day are not available, 
then complete data from the first available date in the follow-up window are to be used (e.g., 
92nd, 93rd, 94th, 95th, etc.).   If complete data is not available from any day within the follow-
up visit window, data from the target visit date will be entered.  
See Table 10-3 in Section 10.12 for required source documentation for remote follow-ups. 
10.11. 
Study Completion 
Each subject will be followed per the defined follow-up schedule or until they withdraw from 
the study. An End of Study eCRF must be completed when a subject completes or withdraws 
from the study. Subjects should be followed as standard of care by their physician after their 
study participation is completed. 

 
 
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10.12. 
Source Documents 
Table 10-3 below summarizes the source data requirements for this study. It is preferable that 
original source documents are maintained, when available. In lieu of original source 
documents, certified copies are required to be maintained.  A certified copy is a copy 
(irrespective of the type of media used) of the original record that has been verified (i.e., by a 
dated signature or by generation through a validated process) to have the same information, 
including data that describe the context, content, and structure, as the original. Source 
documentation includes but is not limited to those items noted in Table 10-3. 

 
 
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Table 10-3: Source Documentation Requirements 
Requirement 
Disposition 
Informed consent documentation process 
Retain at site 
Assessment of pregnancy for women of childbearing 
potential: method of assessment per physician 
discretion  
Retain at site 
Documentation of: 
• 
Demographics: age at implant, gender, race, 
ethnicity 
• 
Indication for implant 
• 
Cardiovascular medications 
• 
Subject’s height and weight 
• 
Arrhythmia history 
• 
Cardiac disease history 
Retain at site 
Implant details regarding IPG, leads, and accessories 
used or signed Implant Technical Source Form 
Retain at site 
Printout of PSA measurements and ECG strip showing 
loss of capture or signed Implant Technical Source 
Form 
Retain at site 
Implant questionnaire  
Retain at site 
For in-clinic visits: Printout of IPG measurements and 
threshold results (device follow-up report and ECG 
programmer strip documenting LOC), for all lead 
pacing threshold tests 
Retain at site 
For remote visits: Appropriate LATITUDE report or 
page print of LATITUDE data or signed Technical 
Source Form for IPG measurements and threshold 
results 
Retain at site 
Time of pocket closure, to document time 0 
Retain at site 
Time of pre-discharge visit to document visit window 
Retain at site 
PA and lateral chest X-ray or fluoroscopic image of 
lead distal tip fixation, either from Implant or Pre-
Discharge 
Retain at site 
Reportable Adverse Events, Device Deficiencies, and 
Protocol Deviations, if applicable 
Retain at site 
In the event of subject death:  
• 
Death narrative 
• 
Relevant medical records 
• 
Death certificate 
• 
Autopsy report 
Submit one copy to Boston Scientific RM 
At ingevityplus.safety@bsci.com 
or uploaded to the Rave Database  
Retain at site 
Note: If thermal paper from the device programmer is used for source documentation, signed and dated 
photocopies or printed pdfs should be used instead, or the strips should be electronically saved. 
 
 
 
 
 

 
 
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11. Statistical Considerations 
11.1. Endpoints 
For an INGEVITY+ lead to be eligible to contribute to endpoint analyses, it must be the final 
lead implanted or attempted per chamber during the initial procedure.  Therefore, each 
subject may contribute up to two total INGEVITY+ leads to the endpoint analyses – one each 
for the right atrium and right ventricle.  See section 11.3.1 for specifics on the analysis sets 
used for each endpoint analysis. 
11.1.1. Primary Safety Endpoint: Lead-related Complication-Free Rate from 0 
to 3 Months 
Safety of the INGEVITY+ Leads will be confirmed by the lead-related complication-free rate 
(CFR) from lead implant through the three-month follow-up, based on complications that are 
related to the INGEVITY+ Lead. Lead-related complications are defined as lead-related 
adverse events resulting in permanent loss of pacing therapy, invasive intervention, injury, or 
death. Lead-related adverse events include, but are not limited to the following, based on the 
Advamed Industry Guidance for Uniform Reporting of Clinical Performance of Cardiac 
Rhythm Management of Pulse Generators and Leads1, and in accordance with the FDA 
Guidance2: 
• Cardiac perforation requiring surgical intervention 
• Cardiac perforation not requiring surgical intervention 
• Conductor fracture/ helix damage 
• Lead dislodgment 
• Failure to capture 
• Oversensing 
• Failure to sense (undersensing) 
• Insulation breach 
• Abnormal pacing impedance 
• Extracardiac stimulation 
 
Lead-related complications associated with attempted INGEVITY+ Lead implants will count 
toward this safety endpoint. Lead-related adverse events that are not a complication will be 
counted as a complication if intravenous (IV) drug therapy is necessary to treat the event. IV 
drug therapy that occurs concomitant but unrelated to the lead-related adverse event will not 
be counted as a lead-related complication. Complications involving an INGEVITY+ lead that 
occur as a result of a procedure unrelated to that INGEVITY+ lead will not count toward this 
safety endpoint. Two examples of this scenario are 1) an INGEVITY+ lead dislodgement 
resulting from an ablation procedure and 2) an RV INGEVITY+ lead dislodgement resulting 
from a repositioning of an RA lead (INGEVITY+ or other market-released). 
11.1.1.1. Hypotheses 
The following hypotheses will be used to evaluate Primary Safety Endpoint: 
H0:  The lead-related complication-free rate from 0 to 3 months  93% 

 
 
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Ha:  The lead-related complication-free rate from 0 to 3 months > 93% 
The performance goal was selected to ensure that the INGEVITY+ Lead has a similar safety 
profile in the implant through 3-month post-implant period as other market-approved 
pace/sense leads in the same period. The average of the complication-free rates observed in 
studies used to support market approval of various pace/sense leads was used to establish 
average market-approved lead safety. A clinically acceptable delta of 5% was then subtracted 
from this average of 98% to establish the performance goal of 93%. 
11.1.1.2. Sample Size  
A sample size of 200 leads (185 required for analysis plus 15 for attrition) is required to 
evaluate Primary Safety Endpoint. This sample size was calculated using the normal 
approximation to the binomial and confirmed via Monte Carlo simulations employing 
Kaplan-Meier methodology, using SAS version 9.4 with the following assumptions: 
• Expected performance = 98% 
• Performance goal = 93% 
• Expected attrition/missing data = 7.5% 
• One-sided significance level = 2.5% 
• Power = 90% 
The sample size for the INGEVITY+ Study is determined by this endpoint.  
11.1.1.3. Statistical Methods 
Data from all implanted or attempted leads at the time of endpoint analysis will be eligible 
for inclusion in the endpoint analysis.  
The lead-related complication-free rate from date of implant (or date of attempt, for leads 
attempted but not implanted) through 91 days post-implant will be calculated using Kaplan-
Meier methodology. The 97.5% one-sided lower pointwise confidence limit of the 
complication-free rate will be calculated via log-log methodology for all eligible leads 
contributing to the analysis and compared to the performance goal of 93%. If the lower 
confidence limit exceeds 93%, the null hypothesis will be rejected. 
Each lead’s exact follow-up time in the 91-day post-implant period will be included in the 
analysis via Kaplan-Meier methodology. The leads that fail to reach 91 days of follow-up 
(without experiencing an endpoint event prior to their end of follow-up in the period) will be 
censored at the time of their end of follow-up in the period. Because non-informative 
censoring cannot be assumed for these leads, a tipping point analysis will be performed to 
determine the potential effects these censored leads could have on the results if full 
information on each lead was present. The tipping point analysis will assign each lead that 
was censored prior to 91 days as either having or not having an endpoint event. All possible 
combinations of these leads’ data will be evaluated along with the actual observed data to 
find the point, if any, at which the endpoint is failed. An exact binomial test will be 
performed for the tipping point analysis. 

 
 
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11.1.2. Primary Efficacy Endpoint 
The Primary Efficacy Endpoint will confirm the percent of leads with an adequate mean 
INGEVITY+ Pacing Capture Threshold (PCT) measurement. A lead with an adequate mean 
INGEVITY+ PCT measurement will be referred to as a Pacing Capture Threshold 
Responder. 
11.1.2.1. Hypotheses 
H0: Pacing Capture Threshold Responders at 3-month visit ≤ 80% 
HA: Pacing Capture Threshold Responders at 3-month visit > 80%, 
where a Responder is defined by a mean PCT at 3-month visit ≤ 2 V. 
The PCT measurements will be taken using a 0.4 ms pulse width.  The performance goal of 
80% aligns with current performance goals accepted by the FDA for leadless pacemakers and 
responder rates from previous RV lead studies.  
11.1.2.2. Sample Size  
A total of 57 measurements (3-month PCT@0.4 ms) are required to sufficiently power the 
Primary Efficacy Endpoint. The following assumptions were used to calculate the sample 
size: 
• Performance goal = 80% 
• Expected rate = 95% 
• One-sided significance level = 2.5% 
• Power = 90% 
The sample size for this study was not determined by this endpoint. 
11.1.2.3. Statistical Methods 
All INGEVITY+ leads with a PCT measurement taken at the 3-month visit (with a 0.4 ms 
pulse width) will be included in the endpoint evaluation.  The number of responders (PCT at 
3-month visit ≤ 2 V) divided by the total number of INGEVITY+ leads included in the 
endpoint evaluation will be calculated.  The one-sided 2.5% binomial exact lower confidence 
limit will be calculated and compared to the performance goal of 80%. If the lower 
confidence limit exceeds 80%, the null hypothesis will be rejected. 
To assess the potential impact missing data could have had on the analysis results, a tipping 
point analysis will be conducted that will include all implanted INGEVITY+ leads. The 
tipping point analysis will assign each lead with missing data as either being a PCT 
responder or a PCT non-responder. All possible combinations of these leads’ data will be 
evaluated along with the actual observed data to find the point, if any, at which the endpoint 
is failed.   

 
 
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11.1.3. Secondary Efficacy Endpoint 1: Sensed Amplitude in the RA and RV  
The efficacy of the INGEVITY+ Leads will be further be established by demonstrating that 
the leads provide clinically acceptable sensing amplitudes at three months post-implant.  
11.1.3.1. Hypotheses 
The following hypotheses will be used to evaluate Secondary Efficacy Endpoint 1 for each of 
the right-sided chambers: 
 
Atrial leads 
H0:  P-wave sensed amplitude at three months post-implant ≤ 1.5 mV 
Ha:  P-wave sensed amplitude at three months post-implant > 1.5 mV 
Ventricular leads 
H0:  R-wave sensed amplitude at three months post-implant ≤ 5 mV 
Ha:  R-wave sensed amplitude at three months post-implant > 5 mV 
11.1.3.2. Sample Size for Secondary Effectiveness Endpoint 1 
This endpoint will be evaluated separately for each of the two heart chambers. A sample size 
of 13 atrial leads (11 required for analysis plus 2 for attrition) and 9 ventricular leads (8 
required for analysis plus 1 for attrition) is required for Secondary Effectiveness Endpoint 1. 
This sample size was calculated using a one-sample t-test, using SAS version 9.4 with the 
following assumptions: 
Atrial leads: 
• Expected performance = 3.5 ± 2.0 mV 
• Performance goal = 1.5 mV 
• Expected attrition/missing data = 10% 
• One-sided significance level = 5% 
• Power = 90% 
Ventricular leads: 
• Expected performance = 12 ± 6 mV 
• Performance goal = 5 mV 
• Expected attrition/missing data = 10% 
• One-sided significance level = 5% 
• Power = 90% 
Note that the sample size for the study is not determined by this endpoint.  
11.1.3.3. Statistical Methods for Secondary Efficacy Endpoint 1 
All sensed amplitude data collected at the three-month follow-up visit that is available at the 
time of analysis will be included in the endpoint analyses.  

 
 
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Endpoint analysis will be performed separately for each heart chamber. A one-sided one-
sample t-test will be performed, using an alpha equal to 5%. If the t-test is deemed to be 
inappropriate based on the data, then a data transformation or a non-parametric test will be 
performed. If the p-value for the one-sided test is less than 0.05, the null hypothesis will be 
rejected.  
11.1.4. Secondary Efficacy Endpoint 2: Pacing Impedance 
The efficacy of the INGEVITY Leads will further be established by demonstrating that the 
leads provide clinically acceptable pacing impedance at three months post-implant.  
11.1.4.1. Hypotheses 
The following hypotheses will be used to evaluate Effectiveness Endpoint 3 for each of the 
lead fixation types: 
H0:  Pacing impedance ≤ 300 Ω, or Pacing impedance ≥ 1300 Ω 
Ha:  300 Ω < Pacing impedance < 1300 Ω 
11.1.4.2. Sample Size for Secondary Effectiveness Endpoint 2 
A sample size of 15 leads (13 required for analysis plus 2 for attrition) is required for 
Effectiveness Endpoint 3. This sample size was calculated using a one-sample t-test, using 
SAS version 9.4 with the following assumptions: 
• Expected performance = 650 ± 400 Ω 
• Performance goals = 300 Ω and 1300 Ω 
• Expected attrition/missing data = 10% 
• One-sided significance level = 5% 
• Power = 90% 
Note that the sample size for the study is not determined by this endpoint.  
11.1.4.3. Statistical Methods for Secondary Effectiveness Endpoint 2 
All pacing impedance data collected at the three-month follow-up visit that is available at the 
time of analysis will be included in the endpoint analysis.  
Two one-sided t-tests (TOST) will be performed, using an alpha equal to 5% for each test. If 
the TOST is deemed to be inappropriate based on the data, a data transformation or a non-
parametric test will be performed. If both of the p-values for the two one-sided tests are less 
than 0.05, the null hypothesis will be rejected. 
11.2. Ancillary Analysis 
• Summary of turn count for all implanted and attempted leads 
• Summary of the implant questionnaire including: 
o Lead handling 
o Lead maneuverability 
• Summary of accessories used 

 
 
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• Summary of lead-related Adverse Events 
• Summary of lead-related device deficiencies, including extension/retraction issues 
11.3. General Statistical Methods 
11.3.1. Analysis Sets 
For an INGEVITY+ lead to be eligible to contribute to endpoint analyses, it must be the final 
lead implanted or attempted per chamber during the initial procedure.  Therefore, each 
subject may contribute up to two total INGEVITY+ leads to the endpoint analyses – one each 
for the right atrium and right ventricle.  These leads will be called ‘endpoint leads’ in this 
section.  The following analysis sets will be used for each endpoint.  
Endpoint  
Analysis Sets 
Primary Safety Endpoint 
All endpoint leads 
Primary Efficacy Endpoint 
All endpoint leads with 3-month visit PCT data  
Secondary Efficacy Endpoint 1 
All implanted endpoint leads with 3-month visit sensed 
amplitude measurements 
Secondary Efficacy Endpoint 2 
All implanted endpoint leads with 3-month visit pacing 
impedance measurements 
11.3.2. Control of Systematic Error/Bias 
Selection of subjects will be made from the investigator’s usual patient load. All patients 
meeting the eligibility criteria and having signed the ICF will be eligible for enrollment in the 
study.  
11.3.3. Number of Subjects per Investigative Site 
To avoid any center effect and bias, one center will not be authorized to implant or attempt 
more than 20% of the maximum number of subjects, without approval from BSC.   
11.4. Data Analyses 
11.4.1. Interim Analyses  
Analyses of adverse events and device deficiencies will occur at frequent intervals during the 
course of the study. Results of these analyses will be reviewed by the BSC Medical Safety 
Group to evaluate the safety of the subjects under study. 
No formal interim analyses are planned for the purpose of stopping the study early for 
declaring safety or effectiveness. The hypothesis test for each endpoint will be performed 
when all applicable data for that endpoint has been collected.  
 

 
 
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11.4.2. Subgroup Analyses 
Analyses will be performed for each endpoint to determine whether significant differences 
exist in primary endpoint results between subgroups. The list of subgroups (with applicable 
definitions in parentheses) includes, but is not necessarily limited to: 
• Sex (Female vs. Male) 
• BMI (Obese vs. Non-Obese) 
• Age (< 65 years vs. ≥ 65 years) 
• Race (Black or African heritage vs. other races) 
• Lead Chamber (Right Atrium vs. Right Ventricle) 
• Pulse generator type (pacemaker vs. CRT-P) 
• Pacing Capture Threshold Test Type (In-office vs. Auto-threshold) – applicable to 
Primary Efficacy Endpoint only 
Female sex and minority races are considered under-represented group in most 
cardiovascular device clinical studies. Any efforts to maximize subject retention would be 
targeted to the under-represented group as well. The study’s inclusion and exclusion criteria 
are not expected to have a negative effect on the recruitment or retention of the said 
populations. 
A log-rank test will be performed to assess differences in Primary Safety endpoint results by 
subgroup.  A Pearson’s chi-square test will be performed to assess the differences in Primary 
Effectiveness endpoint results by subgroup.  A test for significance at the 15% level will be 
performed. For each subgroup variable in which a significant difference exists, the results for 
each subgroup will be presented separately. BSC does not plan to seek labeling for these 
subgroups based on these analyses.  
11.4.3. Pooling Analysis 
For both primary endpoints, data from the right atrial and right ventricular leads will be 
pooled for analysis, based on the expected similarity in results across chambers.  The 
assumption of poolability across chambers will be assessed through the subgroup analysis 
described in Section 11.4.2. 
11.4.4. Multivariable Analyses 
Univariable analyses of various baseline covariates and their relationship to each endpoint 
are outlined in Section 11.4.2. For each endpoint, all baseline characteristics found to be 
significantly associated with the outcome will be included as covariates in a multivariable 
regression model. The impact of each baseline characteristic’s subgroups will be presented 
along with the multivariable model results. 
11.4.5. Impact of Repeated Measures 
As stated in Section 11.3.1, each subject in the study can contribute up to two leads to the 
endpoint analyses. To investigate the potential impact of repeated measures on the endpoint 

 
 
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results, analyses will be performed for each primary endpoint comparing a model adjusted 
for repeated measures to one unadjusted for repeated measures.  Results from both models – 
accounting and not accounting for repeated measures – will be presented. 
11.4.6. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in the SAP 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.  
12. Data Management 
12.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited-access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the site for appropriate response. Site staff will be responsible for 
resolving all queries in the database. 
12.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform Boston Scientific in 
writing where paper or electronic files are maintained in case files are stored off-site and are 
not readily available. 

 
 
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13. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB 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 an eCRF. Sites may also 
be required to report deviations to the IRB, per local guidelines and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
14. Compliance 
14.1. Statement of Compliance 
This study will be conducted in accordance with the requirements of this protocol, US Title 
21 CFR Part 11, Part 50, Part 54, Part 56, Part 814.82(a)(2) and ISO14155, Clinical 
Investigation of Medical Devices for Human Subjects – Good Clinical Practice, ethical 
principles that have their origins in the Declaration of Helsinki, and applicable country laws 
and regulations. The study shall not begin until the required approval/favorable opinion from 
the IRB, and the US FDA (regulatory authority) has been obtained, as appropriate. Also, the 
study shall not begin prior to issuance of the site Authorization to Enroll, as provided by the 
sponsor. Any additional requirements imposed by the IRB or regulatory authority shall be 
followed, as appropriate.  
14.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan, ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB, and prevailing local and/or country 
laws and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 

 
 
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interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to sponsor, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
• Report to the IRB 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, and supply BSC with any additional requested 
information related to the safety reporting of a particular event. 
• Allow the sponsor to perform monitoring and auditing activities and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the device when it is used/operated by the subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 

 
 
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• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
14.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated and 
adequate supervision of those to whom tasks are delegated. Where there is a sub-investigator 
at a site, the sub-investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  
14.3. Institutional Review Board 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB for the clinical investigation before recruiting subjects and implementing all subsequent 
amendments if required. 
A copy of the written IRB approval of the protocol (or permission to conduct the study) and 
ICF, must be received by the sponsor before recruitment of subjects into the INGEVITY+ 
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 before the 
changes are implemented to the study.  All changes to the ICF will be IRB 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 approval and renewals will be obtained throughout the duration of the study as 
required by applicable local laws or regulations or IRB requirements. Copies of the study 
reports and the IRB continuance of approval must be provided to the sponsor.  
14.4. 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 

 
 
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information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
14.4.1. Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during 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 (including 
programmers, analyzers, and other support equipment). 
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.  
Typical tasks may include the following: 
• Interrogating the device or programming device parameters to investigator-requested 
settings as well as operating study equipment 
• Performing lead diagnostic testing using a Pacing System Analyzer or programmer to 
obtain pacing and sensing thresholds and impedance measurements 
• Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
• Assisting with the collection of study data from Pacing System Analyzers, programmers, 
and other equipment 
• Entering technical data on technical source form as long as the responsible investigator 
verifies and signs the completed form  
• Print out/download programming reports/parameters directly from the programmer and 
provide original printouts or electronic data reports to clinical site as source 
documentation 
• Provide technical expertise/support to subjects during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or their 
delegated site staff and the subject.  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following: 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 

 
 
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• 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 (defined as primary or secondary endpoint data) 
• Enter data in electronic data capture systems or on paper case report forms 
15. Monitoring 
Monitoring will be performed by BSC or delegate during the study per the study monitoring 
plan to assess continued compliance with the protocol and applicable regulations. In addition, 
the clinical research monitor verifies that study records are adequately maintained, that data 
are reported in a satisfactory manner with respect to timeliness, adequacy, and accuracy, and 
that the Principal Investigator continues to have sufficient staff and facilities to conduct the 
study safely and effectively. The Principal Investigator/institution guarantees direct access to 
original source documents by BSC personnel, their delegate, and appropriate regulatory 
authorities. 
The study may also be subject to a quality assurance audit(s) by BSC Clinical Quality 
Assurance (CQA) or its designees, as well as inspection(s) by appropriate regulatory 
authorities. It is important that the Principal Investigator and relevant study personnel are 
available during on-site, central and remote monitoring visits, audits and inspections and that 
sufficient time is devoted to the process. 
16. Potential Risks and Benefits 
16.1. Directions for Use 
Please refer to the INGEVITY+ lead and BSC pacemaker, or CRT-P Physician’s Manual for 
an overview of anticipated adverse (device) effects, and risks associated to the commercial 
device(s).   
16.2. Risks associated with Participation in the Clinical Study 
This clinical study does not involve additional risks to study subjects since it is an 
observational study collecting data that is consistent with approved device labeling and 
standard of care.  The risks associated with participation in this study are the same as those 
associated with all standard device system procedures.  Please see the INGEVITY+ lead and 
BSC pacemaker, or CRT-P Physician’s Manual for reference. 

 
 
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As described in the INGEVITY+ Physician’s Lead Manual, possible adverse events 
associated with pulse generator and/or lead implant include: 
• 
Air embolism 
• 
Allergic reaction 
• 
Arterial damage with subsequent stenosis 
• 
Bleeding 
• 
Bradycardia 
• 
Breakage/failure of the implant instruments 
• 
Cardiac perforation 
• 
Cardiac tamponade 
• 
Chronic nerve damage 
• 
Component failure 
• 
Conductor coil fracture 
• 
Death 
• 
Electrolyte imbalance/dehydration 
• 
Elevated thresholds 
• 
Erosion 
• 
Excessive fibrotic tissue growth 
• 
Extracardiac stimulation (muscle/nerve stimulation) 
• 
Fluid accumulation 
• 
Foreign body rejection phenomena 
• 
Formation of hematomas or seromas 
• 
Heart block 
• 
Hemorrhage 
• 
Hemothorax 
• 
Inability to pace 
• 
Inappropriate therapy (e.g., shocks and antitachycardia pacing [ATP] where applicable, 
pacing) 
• 
Incisional pain 
• 
Incomplete lead connection with pulse generator 
• 
Infection including endocarditis 
• 
Lead dislodgment 
• 
Lead fracture 
• 
Lead insulation breakage or abrasion 
• 
Lead tip deformation and/or breakage 
• 
Malignancy or skin burn due to fluoroscopic radiation 
• 
Myocardial trauma (e.g., tissue damage, valve damage) 
• 
Myopotential sensing 
• 
Oversensing/undersensing 
• 
Pericardial rub, effusion 
• 
Pneumothorax 
• 
Pulse generator and/or lead migration 
• 
Syncope 
• 
Tachyarrhythmias, which include acceleration of arrhythmias and early, recurrent atrial 
fibrillation 
• 
Thrombosis/thromboemboli 
• 
Valve damage 

 
 
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• 
Vasovagal response 
• 
Venous occlusion 
• 
Venous trauma (e.g., perforation, dissection, erosion) 
 
For a list of potential adverse events associated with MRI scanning, refer to the appropriate 
ImageReady MR Conditional Pacing System or Defibrillation System MRI Technical Guide. 
16.3. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
16.4. Anticipated Benefits 
Subjects enrolled in this clinical study may not receive any direct benefit from their 
participation; however, medical science and future patients may benefit from their 
participation in this clinical study. 
The potential benefits the subject may receive from the INGEVITY+ Lead would be the 
same if they did not enroll in this study.   
17. Safety Reporting 
17.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All Serious Adverse Events 
• All Device Deficiencies  
• Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
• All INGEVITY+ Lead Related Adverse Events 
• All Cardiac Related Adverse Events 
• All INGEVITY+ Lead Procedure Related Adverse Events 
 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any AE event required by the protocol, experienced by the study subject after informed 
consent and once considered enrolled in the study (as defined in study subject classification 
section), whether during or subsequent to the procedure, must be recorded in the eCRF. 

 
 
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Underlying diseases 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 17-1 for AE 
definitions). 
Refer to Directions for Use for the known risks associated with the commercial device(s). 
17.2. Definitions and Classification 
Adverse event definitions are provided in Table 17-1. Administrative edits were made on the 
safety definitions from ISO 14155 and MEDDEV 2.7/3 for clarification purposes. 
 
Table 17-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
 
 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the study 
medical device.  
NOTE 1: This includes events related to the study medical device or 
comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the study medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event related to the use of the study medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
study medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the study medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Note: This definition meets the reporting objectives and requirements of 
ISO 14155 and MEDDEV 2.7/3. 
Adverse event that: 
a) Led to death, 
b) Led to serious deterioration in the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 

 
 
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Table 17-1: Safety Definitions 
Term 
Definition 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or 
welfare of subjects.   
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk analysis report. 
Device Deficiency 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
An inadequacy of the study medical device related to its identity, quality, 
durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 
 
17.3. Relationship to Device(s) 
The Investigator must assess the relationship of the reportable AE to the device, 
therapy/stimulation or procedure. See criteria in Table 17-2:  
Table 17-2: 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 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; 

 
 
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Table 17-2: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event 
Classification 
Description 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the 
device or procedure;  
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the study device used for 
diagnosis, when applicable; harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Unlikely Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). 
Cases were relatedness cannot be assessed or no information has been obtained 
should also be classified as possible. 
Probably Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device seems relevant and/or the event 
cannot be reasonably explained by another cause, but additional information may 
be obtained. 
Causal Relationship 
Ref: MEDDEV 2.7/3 
The serious event is associated with the study device or with procedures beyond 
reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, 
when applicable; 

 
 
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Table 17-2: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event 
Classification 
Description 
- 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. 
 
17.4. Investigator Reporting Requirements 
The communication requirements for reporting adverse events and device deficiencies to 
BSC are as shown in Table 17-3. 
Adverse events must always be reported through the EDC system for INGEVITY+. 
However, in the case of any issues where an alternative method of reporting is necessary 
(i.e., the EDC system is not available), please report the adverse event to Boston Scientific by 
sending the Event Notification Form via email to the following email address: 
Ingevityplus.safety@bsci.com 
 
Table 17-3: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Unanticipated Adverse 
Device Effect / Unanticipated 
Serious Adverse Device 
Effect  
 
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 1 business day of first becoming 
aware of the event. 
• 
Terminating at the end of the study. 
 
 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
Upon request of sponsor.  
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 10 business days after becoming 
aware of the event or as per local/regional 
regulations.  
• 
Reporting required through the end of 
study  
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
When documentation is available 
Serious Adverse Device 
Effects 
Complete AE eCRF page 
with all available new and 
updated information. 
• 
Within 2 business days of first becoming 
aware of the event or as per local/regional 
regulations. 
• 
Reporting required through the end of the 
study 

 
 
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Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/2 :  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
When documentation is available 
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 Product 
Deficiency section of the 
Adverse Event eCRF with 
all available new and 
updated information.  
• 
Within 2 business days of first becoming 
aware of the event. Reporting required 
through the end of the study 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event. 
• 
At request of sponsor  
Adverse Event including 
Adverse Device Effects 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• 
In a timely manner  (e.g. recommend 
within 30 business days) after becoming 
aware of the information 
• 
Reporting required through the end of the 
study  
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
 
17.5. Boston Scientific Device Deficiencies 
All lead deficiencies (including but not limited to failures, malfunctions, use errors, product 
nonconformities, and inadequacy in the information supplied by the manufacturer) will be 
documented and reported to BSC. The device(s) should be returned to BSC for analysis. 
Instructions for returning the device(s) will be provided in the site initiation visit slides. 
Device deficiencies should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency, would be recorded as an adverse event on the appropriate eCRF. 
17.6. Reporting to Regulatory Authorities / IRBs /Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs and regulatory authorities, as applicable.  

 
 
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The Principal Investigator is responsible for informing the IRB and regulatory authorities of 
UADEs and SAEs as required by local regulations. 
17.7. Subject Death Reporting  
A subject death during the study should be reported to Boston Scientific RM as soon as 
possible, preferably within three (3) calendar days of center notification. The center’s IRB 
must be notified of any deaths in accordance with that center’s IRB policies and procedures. 
Notification of death must include a detailed narrative (death letter) that provides detailed 
information describing the circumstances surrounding the death and is signed by the principal 
Investigator or authorized co-Investigator. The details listed below should be addressed in the 
death narrative, in order for BSC to understand the circumstance surrounding the death: A 
death narrative in the local language is acceptable, if accompanied by a translation in English 
(signed by a translator. The death narrative must include all of the following, if available: 
• Date and time of death 
• Place death occurred 
• Immediate cause of death 
• Rhythm at the time of death, if known (include any available documentation) 
• Whether the death was related to the pulse generator, lead/catheter, clinical 
investigation, procedure, or patient condition 
• Whether or not the death was witnessed 
• Device status and/or activity at the time of death (device recipients only – pacing 
and defibrillation, active or inactive) 
• Whether the patient had worsening heart failure 
• Any other circumstances surrounding the death 
• Approximate time interval from the initiating event to death (temporal course) 
• Investigator or sub-investigator signature and date 
Any information listed above that is unavailable or unknown must be specified as 
unavailable or unknown, as applicable, in the narrative. Also submit the following 
documentation: 
If the subject expired in the hospital: 
• A copy of the medical records for that admission (e.g., H & P, consults, test 
results, operative reports, and/or progress notes from the hospital chart) 
• Death certificate (if available) 
• Autopsy report (if applicable) 
If the subject expired outside of the hospital (e.g., home): 
• A copy of the most recent clinic visit (if not already submitted to Boston 
Scientific RM) 
• Death certificate (if available) 
Whenever possible, the IPG should be interrogated. Leads and related Boston Scientific RM 
system components (e.g., IPGs) should be removed intact and returned promptly to Boston 
Scientific RM for analysis. 

 
 
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The INGEVITY+ Clinical Events Committee (CEC) must review information regarding 
subject deaths (see Section 19.2). 
18. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any study devices, study-
required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
Regulatory authority, as applicable. The ICF must be accepted by BSC or its delegate (e.g. 
CRO) and approved by the site’s IRB, or central IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB.  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 may 
assist the site in obtaining a written consent translation. Translated consent forms must also 
have IRB approval prior to their use.  Privacy language shall be included in the body of the 
form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 

 
 
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learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local IRB , 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. The new version of the ICF must be approved by the 
IRB. Acceptance by Boston Scientific is required if changes to the revised ICF are requested 
by the site’s IRB. The IRB will determine the subject population to be re-consented. 
19. Committees 
19.1. Safety Monitoring Process 
The BSC Medical Safety group reviews unmonitored data as soon as the event is reported, on 
a continuous basis. During scheduled monitoring activities, clinical research monitors will 
support this continuous review through their review of source document and other data 
information. The BSC Medical Safety group includes healthcare professionals with expertise in 
Cardiology and with the necessary therapeutic and subject matter expertise to evaluate and 
classify the events into the categories outlined above. 
19.2. INGEVITY+ Clinical Events Committee (CEC) 
A CEC is an independent group of individuals with pertinent expertise that reviews and 
adjudicates important endpoints and relevant adverse events reported by study investigators. 
The CEC will review a safety event dossier, which may include copies of subject source 
documents provided by study sites, for all reported subject death from any cause. 
Committee members will include practitioners of Electrophysiology (EP), and/ or 
Cardiology, as well as other experts with the necessary therapeutic and subject matter 
expertise to adjudicate the event categories outlined above. CEC responsibilities, 
qualifications, membership, and committee procedures are outlined in the CEC charter. 
20. Suspension or Termination 
22.1 Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs, 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: 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue 
development/marketing of the device. 
22.2 Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval 
Any investigator, or associated IRB or regulatory authority may discontinue participation in 
the study or withdraw approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated IRB, 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 and regulatory authorities, as applicable, will be notified. Detailed information on how 
enrolled subjects will be managed thereafter will be provided.  
In the event an IRB terminates participation in the study, participating investigators, 
associated IRBs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. Boston Scientific 
should be notified as soon as possible for any changes related to the  Principal Investigator 
status to ensure no gaps in study oversight.  
The Principal Investigator or his/her designee must return all study-related documents and 
devices, if supplied by Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
22.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time 
after the study initiation visit if no subjects have been enrolled  for a period beyond 2 months 
after site initiation, or if the site has multiple or severe protocol violations/noncompliance 
without justification and/or fails to follow remedial actions. 

 
 
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In the event of termination of site participation, all devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB and regulatory authorities, as applicable, will be notified. 
Study participants will be contacted, as applicable, and be informed of changes to study visit 
schedule. 
21. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC will submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study. Boston Scientific adheres to the Contributorship Criteria set forth in the 
Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed:  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/).  
22. Abbreviations and Definitions  
22.1. Abbreviations 
Abbreviations are shown in Table 22-1.   
Table 22-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse Device Effect 
AE  
Adverse Event 
AF 
Atrial Fibrillation 
AV 
Atrioventricular 
BSC 
Boston Scientific 
CEC 
Clinical Events Committee 
CFR 
Complication Free Rate 
CRO 
Contract Research Organization 
CRT-P 
Cardiac Resynchronization Therapy - Pacemaker 

 
 
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Table 22-1: Abbreviations 
Abbreviation/Acronym 
Term 
DXA 
Dexamethasone Acetate 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
EP 
Electrophysiology 
ETFE 
Ethylene tetrafluoroethylene 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCP 
Health Care Professional 
ICD  
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IPG 
Implantable Pulse Generator 
IRB 
Institutional Review Board 
IS-1 
International Standard-1 
IROX 
Iridium Oxide 
ISO 
International Standard Organization 
LOC 
Loss of Capture 
MR 
Magnetic Resonance 
MRI 
Magnetic Resonance Imaging 
mV 
Millivolts 
Ω 
Ohms 
PA 
Posterior-Anterior 
PAS 
Post-Approval Study 
PLM 
Physician’s Lead Manual 
PSA 
Pacing System Analyzer 
PTFE 
Polytetrafluoroethylene 
RA 
Right atrium/ atrial 
RM 
Rhythm Management 
RV 
Right ventricle/ ventricular 
SA 
Sinoatrial 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
TOST 
Two one-sided t-tests  
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
V 
Volts 
22.2. Definitions 
Terms are defined in Table 22-2.  

 
 
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Table 22-2: Definitions 
Term 
Definition 
Lead-related adverse 
event 
Lead-related adverse events include, but are not limited to the following, 
based on the Advamed Industry Guidance for Uniform Reporting of 
Clinical Performance of Cardiac Rhythm Management of Pulse 
Generators and Leads1 and in accordance with the FDA Guidance2: 
• 
Cardiac perforation requiring surgical intervention 
• 
Cardiac perforation not requiring surgical intervention 
• 
Conductor fracture/ helix damage 
• 
Lead dislodgment 
• 
Failure to capture 
• 
Oversensing 
• 
Failure to sense (undersensing) 
• 
Insulation breach 
• 
Abnormal pacing impedance 
• 
Extracardiac stimulation 
Lead-related 
complication 
Lead-related complications are defined as lead-related adverse events 
resulting in permanent loss of pacing therapy, invasive intervention, 
injury or death.  
Observation 
An adverse event that was transient or reversible and corrected with 
non-invasive interventions, such as reprogramming or oral medications, 
or else resolved with no intervention or monitoring. 
Pacing impedance 
An assessment of the opposition to the flow of current by the pacing 
system; measured in ohms (Ω). 
Pacing threshold 
An assessment of the minimum electrical stimulation required to 
consistently initiate cardiac depolarization; measured in Volts (V). 
Permanent Atrial 
Fibrillation (AF)3 
When a patient and clinician make a joint decision to stop further 
attempts to restore and/or maintain sinus rhythm.  
Persistent AF3 
Continuous AF that is sustained > 7 days. 
Sensed amplitude 
An assessment of how well the lead senses the heart’s intrinsic electrical 
activity; measured in millivolts (mV). 
Source Data 
All information in original records of clinical findings, observations, or 
other activities in a clinical investigation, necessary for the 
reconstruction and evaluation of the clinical study.  
Source Document 
Printed, optical or electronic document containing source data. 
Examples: Hospital records, laboratory notes, device accountability 
records, radiographs, records kept at the investigation site, and at the 
laboratories involved in the clinical study.   
 
 

 
 
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23. Bibliography 
 
1 Industry Guidance for Uniform Reporting of Clinical Performance of Cardiac Rhythm Management of Pulse 
Generators and Leads, (21 May 2009). 
https://www.advamed.org/sites/default/files/resource/081709_advamedfinalguidanceforuniformreportingleadsa
ndpgs21may09.pdf.  Visited 07 August 2019. 
2 Guidance for Industry: Guidance for the Submission of Research and Marketing Applications for Permanent 
Pacemaker Leads and for Pacemaker Lead Adaptor 510(k) Submissions. November 1, 2000. 
3 January, CT, Wann LS, Alpert JS, et al.  2014 AHA/ACC/HRS Guideline for the Management of Patients with 
Atrial Fibrillation: Executive Summary.  Journal of the American College of Cardiology. 2014; 64(21): 2246-
2280.