Extravascular ICD Pivotal Study (EV ICD)
Phase: NA
Conditions: Tachycardia, Ventricular Arrythmia
Sponsor: Medtronic Cardiac Rhythm and Heart Failure

ExtraVascular Implantable Cardioverter Defibrillator (EV ICD) Pivotal Study 
NCT04060680 
Clinical Investigation Plan, 02-JUL-2019 

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  ExtraVascular Implantable Cardioverter Defibrillator 
(EV ICD) Pivotal Study 
Clinical Investigation Plan Identifier 
MDT16028 
Study Product Name 
EV ICD System 
Sponsor/Local Sponsor 
Sponsor: 
Medtronic, Inc. 
8200 Coral Sea Street NE 
Mounds View, MN USA 
55112 
+1-800-328-2518 
 
Local Sponsors: 
Australia 
Medtronic Australasia Pty Ltd 
2 Alma Road 
Macquarie Park 
NSW, 2113 
Australia 
+61 2 9857 9000 
 
Canada 
Medtronic of Canada, Ltd. 
99 Hereford Street Brampton 
Ontario, L6Y 0R3 Canada 
+1-905-460-3800 
 
Europe, Middle East, Africa 
Medtronic, Bakken Research Center B.V. 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
+31-43-35-66-566 
 
Hong Kong 
Medtronic Hong Kong Medical Ltd. 
1104-11, 11/F, Tower 1, 
The Gateway, Harbour City, Kowloon 
Hong Kong SAR, China 
+852-2919-1300 
 
 

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Japan 
Medtronic Japan Co., Ltd. 
1-2-70 Konan, Minato-ku, 
Tokyo Japan 108-0075 
Shinagawa Season Terrace 22F 
Phone: (+81) 3-6774-4611 
Fax: (+81) 3-6774-4605 
 
New Zealand 
Medtronic New Zealand Limited  
Level 3, Building 5  
666 Great South Road  
Penrose  
Auckland 1051 
New Zealand  
+64 9 634-1049 
 
Document Version 
1.0, 02-JUL-2019 
Lead Principal Investigator/Coordinating Investigator 
Dr. Paul Friedman  
Mayo Clinic Rochester 
  
 
 
 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. Any 
distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly prohibited. 
Persons to whom the information is disclosed must know that it is confidential and that it may not be further 
disclosed by them. 

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Table of Contents  
 
 
Table of Contents ...................................................................................................................... 3 
1. 
Contact Information and Glossary ................................................................................... 10 
1.1. Steering Committee ............................................................................................................. 10 
1.2. Sponsor Contact Information ................................................................................................ 10 
1.3. CROs and Core Labs ............................................................................................................ 11 
1.4. Glossary .............................................................................................................................. 12 
2. 
Synopsis ........................................................................................................................... 14 
3. 
Introduction ..................................................................................................................... 22 
3.1. Background ......................................................................................................................... 22 
3.2. Purpose .............................................................................................................................. 24 
4. 
Objectives and/or Endpoints ........................................................................................... 24 
4.1. Objectives ........................................................................................................................... 24 
 Primary Objectives .................................................................................................................... 24 
 Ancillary Objectives ................................................................................................................... 25 
5. 
Study Design .................................................................................................................... 26 
5.1. Duration ............................................................................................................................. 28 
5.2. Rationale ............................................................................................................................ 28 
5.3. Minimization of Bias ............................................................................................................. 29 
6. 
Product Description.......................................................................................................... 30 
6.1. General ............................................................................................................................... 30 
 EV ICD (Model DVEX3E4) .......................................................................................................... 31 
 EV ICD Lead (Model EV2401) .................................................................................................... 32 
 Sternal Tunneling tool (Model EAZ101) .................................................................................... 33 
 Transverse Tunneling tool (Model EAZ201) .............................................................................. 34 
 Oscor SafeSheath® II Model SSCL9 ............................................................................................ 34 
 EV ICD Programmer Software (Model SW041), Medtronic CareLink 2090 Programmer with 
Analyzer and Medtronic CareLink Encore 29901 Programmer .......................................................... 35 
 MyCareLink Patient Monitor (Model 24952) ............................................................................ 35 
6.2. Manufacturer ....................................................................................................................... 36 

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6.3. Packaging ........................................................................................................................... 36 
6.4. Intended Population ............................................................................................................. 37 
6.5. Equipment .......................................................................................................................... 37 
6.6. Product Use......................................................................................................................... 37 
6.7. Product Training Requirements ............................................................................................. 37 
6.8. Product Receipt, Tracking, and Accountability ......................................................................... 38 
6.9. Product Storage ................................................................................................................... 39 
6.10. Product Return .................................................................................................................. 39 
7. 
Selection of Subjects ........................................................................................................ 40 
7.1. Study Population .................................................................................................................. 40 
7.2. Subject Enrollment ............................................................................................................... 40 
7.3. Inclusion Criteria .................................................................................................................. 40 
7.4. Exclusion Criteria ................................................................................................................. 41 
8. 
Study Procedures ............................................................................................................. 43 
8.1. Schedule of Events .............................................................................................................. 44 
8.2. Medications ......................................................................................................................... 46 
 Prior and Concomitant Medications ......................................................................................... 46 
8.3. Subject Consent .................................................................................................................. 46 
8.4. Enrollment / Baseline ........................................................................................................... 48 
 Subject Pre-implant Anatomy Evaluation ................................................................................. 49 
8.5. Implant Visit ........................................................................................................................ 49 
 Antibiotic and Infection Control Strategies .............................................................................. 49 
 Anticoagulation ......................................................................................................................... 50 
 Dual antiplatelet therapy .......................................................................................................... 50 
 Fluoroscopy and Photography .................................................................................................. 50 
 Implant Procedure Steps ........................................................................................................... 51 
 Implant Testing – EV ICD System .............................................................................................. 56 
 Induction and Defibrillation Testing ......................................................................................... 57 
 Subject Exit for Incomplete Implant Visit ................................................................................. 64 
8.6. Pre-Hospital Discharge ......................................................................................................... 65 
 Sensing Testing.......................................................................................................................... 66 

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 Impedance Testing .................................................................................................................... 66 
 Pacing Testing ........................................................................................................................... 67 
 Imaging ...................................................................................................................................... 67 
8.7. Scheduled Follow-up Visits .................................................................................................... 67 
 2-Week Follow-up Visit ............................................................................................................. 68 
 3-Month Follow-up Visit ........................................................................................................... 69 
 6-Month Follow-up Visit ........................................................................................................... 69 
 Long-term follow-up Visits ........................................................................................................ 70 
 Device Troubleshooting ............................................................................................................ 71 
 Electrical Testing ....................................................................................................................... 71 
8.8. Unscheduled Visits ............................................................................................................... 72 
8.9. Images and recordings ......................................................................................................... 72 
8.10. Save-to-Media Files ............................................................................................................ 72 
8.11. CareLink Transmissions ...................................................................................................... 72 
8.12. Healthcare Utilizations ........................................................................................................ 72 
8.13. System Modification ........................................................................................................... 73 
8.14. Role of the Sponsor Representatives .................................................................................... 74 
8.15. Assessment of Efficacy ....................................................................................................... 74 
8.16. Assessment of Safety ......................................................................................................... 74 
8.17. Recording Data .................................................................................................................. 74 
8.18. Deviation Handling ............................................................................................................. 75 
8.19. Subject Withdrawal or Discontinuation ................................................................................. 76 
9. 
Risks and Benefits ............................................................................................................ 77 
9.1. Potential Risks ..................................................................................................................... 77 
9.2. Potential Benefits ................................................................................................................. 83 
9.3. Risk-Benefit Rationale .......................................................................................................... 84 
10. 
Adverse Events and Device Deficiencies ....................................................................... 84 
10.1. Assessment ....................................................................................................................... 85 
 Adverse Events Assessment .................................................................................................... 85 
 Device Deficiencies Assessment ............................................................................................. 85 
10.2. Processing Updates and Resolution ...................................................................................... 86 
10.3. Adverse Events and Device Deficiency Definitions ................................................................. 86 

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10.4. Adverse Event and Deficiency Classification .......................................................................... 92 
10.5. Reporting of Adverse Events ............................................................................................... 94 
10.6. Subject Death .................................................................................................................... 99 
10.7. Death Classification and Reporting ....................................................................................... 99 
10.8. Product Complaint Reporting ............................................................................................. 100 
11. 
Data Review Committees ............................................................................................ 100 
11.1. Clinical Events Committee ................................................................................................. 100 
11.2. Data Monitoring Committee .............................................................................................. 101 
11.3. Episode Review Committee ............................................................................................... 102 
12. 
Statistical Design and Methods ................................................................................... 102 
12.1. General Considerations ..................................................................................................... 102 
12.2. Analysis for market approval outside the US ....................................................................... 102 
12.3. Sample Size ..................................................................................................................... 103 
 Primary Objective #1: Safety ................................................................................................. 103 
 Primary Objective #2: Efficacy .............................................................................................. 104 
12.4. Primary Objective #1: Safety ............................................................................................ 104 
 Hypothesis............................................................................................................................. 105 
 Performance Requirements .................................................................................................. 105 
 Rationale for Performance Criteria ....................................................................................... 105 
 Analysis Methods .................................................................................................................. 108 
 Determination of Subjects/Data for Analysis ....................................................................... 108 
12.5. Primary Objective #2: Efficacy .......................................................................................... 108 
 Hypothesis............................................................................................................................. 108 
 Performance Requirements .................................................................................................. 109 
 Rationale for Performance Criteria ....................................................................................... 109 
 Analysis Methods .................................................................................................................. 111 
 Determination of Subjects/Data for Analysis ....................................................................... 111 
12.6. Ancillary Objective #1 ...................................................................................................... 112 
 Hypothesis............................................................................................................................. 112 
 Performance Requirements .................................................................................................. 112 
 Rationale for Performance Criteria ....................................................................................... 112 

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 Analysis Methods .................................................................................................................. 112 
 Determination of Subjects/Data for Analysis ....................................................................... 112 
12.7. Ancillary Objective #2 ...................................................................................................... 113 
 Hypothesis............................................................................................................................. 113 
 Performance Requirements .................................................................................................. 113 
 Rationale for Performance Criteria ....................................................................................... 113 
 Analysis Methods .................................................................................................................. 113 
 Determination of Subjects/Data for Analysis ....................................................................... 113 
12.8. Ancillary Objective #3 ...................................................................................................... 113 
 Hypothesis............................................................................................................................. 114 
 Performance Requirements .................................................................................................. 114 
 Rationale for Performance Criteria ....................................................................................... 114 
 Analysis Methods .................................................................................................................. 114 
 Determination of Subjects/Data for Analysis ....................................................................... 114 
12.9. Ancillary Objective #4 ...................................................................................................... 114 
 Hypothesis............................................................................................................................. 114 
 Performance Requirements .................................................................................................. 114 
 Rationale for Performance Criteria ....................................................................................... 115 
 Analysis Methods .................................................................................................................. 115 
 Determination of Subjects/Data for Analysis ....................................................................... 115 
12.10. Ancillary Objective #5 ..................................................................................................... 115 
 Hypothesis........................................................................................................................... 115 
 Performance Requirements ................................................................................................ 115 
 Rationale for Performance Criteria ..................................................................................... 115 
 Analysis Methods ................................................................................................................ 116 
 Determination of Subjects/Data for Analysis ..................................................................... 116 
12.11. Ancillary Objective #6 ..................................................................................................... 116 
 Hypothesis........................................................................................................................... 116 
 Performance Requirements ................................................................................................ 116 
 Rationale for Performance Criteria ..................................................................................... 116 

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 Analysis Methods ................................................................................................................ 117 
 Determination of Subjects/Data for Analysis ..................................................................... 117 
12.12. Ancillary Objective #7 ..................................................................................................... 117 
 Hypothesis........................................................................................................................... 117 
 Performance Requirements ................................................................................................ 117 
 Sample Size ......................................................................................................................... 117 
 Rationale for Performance Criteria ..................................................................................... 118 
 Analysis Methods ................................................................................................................ 118 
 Determination of Subjects/Data for Analysis ..................................................................... 118 
12.13. Supplemental Analysis .................................................................................................... 118 
13. 
Ethics ........................................................................................................................... 118 
13.1. Statement(s) of Compliance .............................................................................................. 118 
14. 
Study Administration ................................................................................................... 121 
14.1. Monitoring ....................................................................................................................... 121 
14.2. Data Management ............................................................................................................ 122 
14.3. Direct Access to Source Data/Documents ........................................................................... 123 
14.4. Confidentiality .................................................................................................................. 123 
14.5. Liability ........................................................................................................................... 123 
14.6. CIP Amendments ............................................................................................................. 124 
14.7. Required Records and Reports .......................................................................................... 124 
 Investigator Records ............................................................................................................. 124 
 Investigator Reports .............................................................................................................. 125 
 Sponsor Records ................................................................................................................... 129 
 Sponsor Reports .................................................................................................................... 130 
14.8. Suspension or Early Termination ....................................................................................... 134 
 Study-wide Suspension or Early Termination ....................................................................... 135 
 Investigator/Site Suspension or Early Termination .............................................................. 135 
 Procedures for Suspension or Early Termination ................................................................. 135 
15. 
References ................................................................................................................... 138 
16. 
Appendices .................................................................................................................. 140 
Appendix A: Draft Data Collection Elements (Case Report Forms) ........................................... 141 

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Appendix B: Preliminary Publication Plan ............................................................................... 142 
Appendix C: Instructions for Use ............................................................................................ 145 
Appendix D: Informed Consent Templates............................................................................... 146 
Appendix E: Foreseeable Adverse Event List .......................................................................... 147 
Appendix F: Participating Investigators and Institutions .......................................................... 157 
Appendix G: Ethics Committee and Competent Authority List ................................................. 158 
Appendix H: Previous Clinical Investigations .......................................................................... 159 
Appendix I: Chronic Defibrillation Testing Protocol ................................................................. 160 
Appendix J: Applicability to CMS Beneficiaries ....................................................................... 162 
Appendix K: Investigator Statement (where applicable) ........................................................... 163 
17. 
Version History ............................................................................................................ 165 
 
 
 

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1. Contact Information and Glossary 
1.1. Steering Committee 
The Steering Committee (SC) is responsible for the scientific content of the study and provides input for 
its execution. The SC will also serve as the sponsor’s Medical Experts for the trial. The members and 
contact details of the SC will be provided under separate cover. 
1.2. Sponsor Contact Information 
Medtronic contact information is provided below. This information is subject to change during the 
course of the clinical study. Periodic updates to study contact information will be sent to the sites as 
needed. Other sponsor contact information, such as name and address of local monitors, etc. will be 
provided under a separate cover to the sites as needed. 
Table 1: Study sponsor contact information 
Study sponsor and contacts 
Program Manager 
Sarah Willey, Program Manager  
Direct Phone: +1 763 526 2813 
Email: sarah.a.willey@medtronic.com   
Worldwide Clinical Study Leader  
Jo Krueger, Prin. Clinical Research Specialist 
Direct Phone: +1 612 271 2848 
Email: jo.krueger@medtronic.com 
Australia and New Zealand  
Samuel Liang, Sr. Clinical Research Specialist  
Direct Phone: +61-2 9857 9391 
Email: samuel.liang@medtronic.com  
Canada 
Aarthi Kamath, Sr. Clinical Research Specialist  
Direct Phone: +1 905 460 3722 
Email: aarthi.kamath@medtronic.com  
Europe, Middle East, and Africa (EMEA) 
Katrien Vandersteegen, Sr. Clinical Research 
Specialist 
Direct Phone: +31 433566728 
Email: katrien.vandersteegen@medtronic.com  
Hong Kong 
Tina Ling, Clinical Research Specialist 
Direct Phone: +85 229191300 
Email: tina.ling@medtronic.com  
Japan 
Naohiro Masumoto, PhD, Pr. Clinical Research 
Specialist  
Direct Phone: +81 367760056 
Email: naohiro.masumoto@medtronic.com 
United States of America (US) 
Diedre Ribbens, Sr. Clinical Research Specialist 
Direct Phone: +1 763 526 3075 
Email: diedre.j.ribbens@medtronic.com 

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Monitoring contacts 
US/Canada 
Taryn Randall, Sr. Clinical Monitoring Manager 
Direct Phone: +1 763 250 0785 
Email: taryn.randall@medtronic.com 
EMEA/Asia Pacific/Hong Kong/Japan 
Anja Hesse, Monitoring Portfolio Specialist CRHF 
Direct Phone: +49 1702266577 
Email: anja.hesse@medtronic.com 
1.3. CROs and Core Labs 
No core labs will be used in this study. At the time of finalization of this clinical investigation plan (CIP), 
there is only one contract research organization (CRO) planned: 
Cognizant Technology Solutions 
500 Frank W. Burr Blvd. 
Teaneck, NJ 07666 
United States of America 
Direct Phone: +1 201 801 0233 
Direct Fax: +1 201 801 0243 
Duties performed: 
• 
Development of study electronic case report forms, edit checks, and study management reports 
• 
Review of electronic case report forms and management of discrepancies. 
 
 

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1.4. Glossary 
Term 
Definition 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
ALARA 
As Low as Reasonably Achievable 
ANZ 
Australia and New Zealand 
AP 
Anterior-Posterior  
ATP 
Antitachycardia Pacing 
BMI 
Body Mass Index 
“can” 
Used to indicate that something is possible, for example, that an organization or individual is able to 
do something 
CEC 
Clinical Events Committee 
CIP 
Clinical Investigation Plan 
CMS 
Centers for Medicare & Medicaid Services 
CFR 
(US) Code of Federal Regulations 
DD 
Device Deficiency 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
Ethics 
Committee 
Term that will be used collectively in reference to an Institutional Review Board (IRB)/Medical Ethics 
Committee (MEC)/Human Research Ethics Committee (HREC)/Research Ethics Board (REB)/Head of 
Medical Institution (HOMI) unless otherwise stated 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EGM 
Electrogram 
EMEA 
Europe, Middle East, and Africa 
EP 
Electrophysiologist/Electrophysiology 
ERC 
Episode Review Committee 
EV ICD 
Extravascular Implantable Cardioverter Defibrillator 
FDA 
(US) Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 
FPAS 
Florida Patient Acceptance Survey 
GCP 
Good Clinical Practice 
HCU 
Health Care Utilization 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HOMI 
Head of Medical Institution 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
ICD 
Implantable Cardioverter Defibrillator 
ICF 
Informed Consent Form 
ID 
Identification 
IFU 
Instructions for Use 

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Term 
Definition 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
LA 
Left Atrium 
LAT 
Lateral 
LV 
Left Ventricular 
LVEF 
Left Ventricular Ejection Fraction 
LVEDD 
Left Ventricular End Diastolic Diameter 
“may” 
Used to indicate that something is permitted 
MedDRA 
Medical Dictionary for Regulatory Activities 
NHMRC 
The National Health and Medical Research Council 
NOAC 
Novel Oral Anticoagulant 
PA 
Posterior-Anterior  
PHD 
Pre-Hospital Discharge  
OPC 
Objective Performance Criterion 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SC 
Steering Committee 
SDN 
Software Distribution Network 
“shall” 
Indicates a requirement 
“should” 
Indicates a recommendation 
SF-12 
Short Form, 12-question (Quality of Life Survey) 
SSI 
Significant Safety Issue 
SSVA 
Sustained Shockable Ventricular Arrhythmia  
TEE 
Transesophageal Echocardiogram 
TV 
Transvenous 
US 
United States of America 
USM 
Urgent Safety Measure 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
VF 
Ventricular Fibrillation 
VT 
Ventricular Tachycardia 
Zone 1 
Tunnelling and deployment of the lead in the substernal space 
Zone 2 
Tunnelling of the lead from the sternum to the device pocket 
 
 
 

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2. Synopsis 
Title 
Extravascular Implantable Cardioverter Defibrillator (EV ICD) 
Pivotal Study 
Clinical Study Type 
Prospective, multi-center, single-arm, non-randomized, pre-
market clinical study  
Product Name and Status 
Investigational System Components: 
• 
Medtronic Model DVEX3E4 EV ICD 
• 
Medtronic Model EV2401 EV ICD Lead 
 
Investigational Accessory Components: 
• 
Medtronic Model EAZ101 Sternal Tunneling Tool 
• 
Medtronic Model EAZ201 Transverse Tunneling Tool 
• 
Oscor SafeSheath® II, model number SSCL9 introducer 
(market-released in US) 
• 
EV ICD SW041 Programmer Software Version 8.1 (or 
greater) 
• 
MyCareLink Patient Monitor Model 24952 (may become 
available during the course of the study) 
 
Market Released Components: 
• 
Medtronic 2090 CareLink Programmer with analyzer (or 
CareLink Encore 29901 Programmer)  
Sponsor  
Medtronic, Inc. 
8200 Coral Sea Street NE 
Mounds View, MN 55112 
United States of America 
+1 800 328 2518 
Local Sponsor 
Local Sponsors: 
Australia 
Medtronic Australasia Pty Ltd 
2 Alma Road 
Macquarie Park 
NSW, 2113 

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Australia 
+61 2 9857 9000 
 
Canada 
Medtronic of Canada, Ltd. 
99 Hereford Street Brampton 
Ontario, L6Y 0R3  
Canada 
+1 905 460 3800 
 
Europe, Middle East, Africa 
Medtronic, Bakken Research Center B.V. 
Endepolsdomein 5 
6229 GW Maastricht 
Netherlands 
+31 433566566 
 
Hong Kong 
Medtronic Hong Kong Medical Ltd. 
1104-11, 11/F, Tower 1, 
The Gateway, Harbour City, Kowloon 
Hong Kong SAR, China 
+852 29191300 
 
Japan 
Medtronic Japan Co., Ltd. 
1-2-70 Konan, Minato-ku, 
Tokyo Japan 108-0075 
Shinagawa Season Terrace 22F 
Phone: +81 3 6774 4611 
 
New Zealand 
Medtronic New Zealand Limited  
Level 3, Building 5  
666 Great South Road  
Penrose  
Auckland 1051 
New Zealand  
+64 9 634 1049 
Indication under investigation  
The Medtronic EV ICD System (defibrillator and lead) is 
indicated for the automated treatment of patients who have 

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experienced, or are at significant risk of developing, life-
threatening ventricular tachyarrhythmias.   
Investigation Purpose 
The main purpose of the EV ICD Pivotal study is to 
demonstrate safety and efficacy of the EV ICD System. 
Primary Objective(s) 
Primary Safety Objective:  Demonstrate the freedom from 
major complications related to the EV ICD System and/or 
procedure at 6 months post-implant exceeds 79% Objective 
Performance Criterion (OPC). 
 
The endpoint is defined as a subject’s first occurrence of a 
major complication related to the EV ICD System and/or 
procedure, as determined by an independent Clinical Events 
Committee (CEC), that occurs on or prior to 6 months (182 
days) post-implant. 
 
Primary Efficacy Objective: Demonstrate the EV ICD 
defibrillation testing success rate at implant is greater than 
88% OPC. 
 
The endpoint, defibrillation testing success, is defined as: 
• 
Single SSVA conversion at 20J, or  
• 
Conversion of two successive episodes of SSVA at 30J in 
final system configuration. 
Ancillary Objective(s) 
• 
Characterize appropriate and inappropriate shocks  
• 
Characterize electrical performance (pacing capture 
thresholds, pacing impedance, sensing amplitudes) over 
time  
• 
Characterize extracardiac pacing sensation 
• 
Characterize asystole pacing 
• 
Summarize ATP performance with spontaneous 
arrhythmias 
• 
Summarize adverse events 
• 
Characterize the EV ICD defibrillation testing success rate 
at 6 months post-implant. 
Sample Size 
Up to 400 enrollments at up to 60 sites worldwide, to allow at 
least 292 subjects to, in the case of the safety objective, 
undergo an implant attempt of the EV ICD System, and in the 

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case of the efficacy objective, complete the pre-specified 
defibrillation testing protocol.  
 
Maximum number of subjects enrolled at each site will be 
capped at 35, which is approximately 10% of the total number 
of subjects enrolled. 
Inclusion/Exclusion Criteria 
Inclusion Criteria 
1. Patient has a Class I or IIa indication for implantation of an 
ICD according to the ACC/AHA/HRS Guidelinesi, or ESC 
guidelinesii. 
2. Patient is at least 18 years of age and meets age 
requirements per local law. 
3. Patient is geographically stable and willing and able to 
complete the study procedures and visits for the duration 
of the follow-up. 
Exclusion Criteria 
1. Patient is unwilling or unable to personally provide 
Informed Consent. 
2. Patient has indications for bradycardia pacing iii or Cardiac 
Resynchronization Therapy (CRT) iv (Class I, IIa, or IIb 
indication). 
3. Patient with an existing pacemaker, ICD, or CRT device 
implant or leads. 
4. Patients with these medical interventions are excluded 
from participation in the study: 
• 
Prior sternotomy 
                                                            
i Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis 
AM, Hlatky MA, Granger CB, Hammill SC, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline 
for management of patients with ventricular arrhythmias. 
ii Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliot PM, Fitzsimons D, Hatala R, Hindricks G, 
Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ. 2015 ESC 
guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European 
Heart Journal 2015 36:41 (2793-2867). https://doi.org/10.1093/eurheartj/ehv316 
iii 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator 
programming and testing). 
iv ACC/AHA/HRS guidelines for Cardiac Resynchronization Therapy 

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• 
Any prior medical condition or procedure that leads to 
adhesions in the anterior mediastinal space (i.e., prior 
mediastinal instrumentation, mediastinitis) 
• 
Prior abdominal surgery in the epigastric region 
• 
Planned sternotomy 
• 
Prior chest radiotherapy 
Or any other prior/planned medical intervention not listed 
that precludes their participation in the opinion of the 
Investigator. 
5. Patient has previous pericarditis that: 
• 
Was chronic and recurrent, or  
• 
Resulted in pericardial effusion v, or 
• 
Resulted in pericardial thickening or calcification. vi 
6. Patients with these medical conditions or anatomies are 
excluded from participation in the study: 
• 
Hiatal hernia that distorts mediastinal anatomy 
• 
Marked sternal abnormality (e.g., pectus excavatum) 
• 
Decompensated heart failure 
• 
COPD with oxygen dependence 
• 
Gross hepatosplenomegaly 
Or any other known medical condition or anatomy type 
not listed that precludes their participation in the opinion 
of the Investigator. 
7. Patients with a medical condition that precludes them 
from undergoing defibrillation testing:  
• 
Severe aortic stenosis 
• 
Intracardiac LA or LV thrombus 
• 
Severe proximal three-vessel or left main coronary 
artery disease without revascularization 
• 
Hemodynamic instability 
• 
Unstable angina 
                                                            
v As documented on echo or MRI 
vi As documented on CT scan or MRI  

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• 
Recent stroke or transient ischemic attack (within the 
last 6 months) 
• 
Known inadequate external defibrillation 
• 
LVEF <20% 
• 
LVEDD >70 mm 
Or any other known medical condition not listed that 
precludes their participation in the opinion of the 
Investigator. 
8. Patient with any evidence of active infection or 
undergoing treatment for an infection. 
9. Patient is contraindicated from temporary suspension of 
oral/systemic anticoagulation   
10. Patient with current implantation of neurostimulator or 
any other chronically implanted device that delivers 
current in the body. 
11. Patient meets ACC/AHA/HRS or ESC clinical guideline Class 
III criteria for an ICD (e.g., life expectancy of less than 12 
months). 
12. Patient is enrolled or planning to enroll in a concurrent 
clinical study that may confound the results of this study, 
without documented pre-approval from a Medtronic 
study manager. 
13. Patient with any exclusion criteria as required by local law 
(e.g., age or other). 
14. Pregnant women or breastfeeding women, or women of 
child bearing potential and who are not on a reliable form 
of birth regulation method or abstinence. vii 
Study Procedures and Assessments 
Subjects indicated for single-chamber ICD therapy will be 
recruited and implanted with the Medtronic EV ICD System. 
Once enrolled, a subject will be assessed at the following 
visits: 
• 
Baseline  
                                                            
vii if required by local law, women of child-bearing potential must undergo a pregnancy test within seven days 
prior to EV ICD Pivotal Study procedures 

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• 
Implant  
• 
Pre-Hospital Discharge (PHD) 
• 
2 Weeks (2WK) 
• 
3 Months (3M) 
• 
6 Months (6M) 
• 
Long-term: Every 6 months thereafter until study closure 
(12, 18, 24… Months) 
• 
Unscheduled (as they occur) 
• 
System Modifications (as they occur) 
• 
Exit 
 
Study procedures are outlined in the table below. 
 
Study procedure 
Baseline 
Implant 
PHD 
2WK 
3M 
6M 
Long 
Term 
Unscheduled 
Sys 
Mod 
Exit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
 
 
 
 
 
 
Physical Exam, Demographics, 
Cardiovascular Medical History, 
Surgical History 
X 
 
 
 
 
 
 
 
 
 
SF-12 quality of life survey 
X 
 
 
 
 
X 
 
 
 
 
Florida Patient Acceptance 
Survey (FPAS)1 
 
 
 
 
 
X 
 
 
 
 
System and procedure 
information 
 
X 
 
 
 
 
 
 
X 
 
Pre-procedure Transesophageal 
Echocardiogram (TEE)2 
 
X2 
 
 
 
 
 
 
 
 
CT-Scan or MRI 
X3 
 
 
 
 
 
 
 
 
 
Fluoroscopy recordings during 
tunneling procedure 
 
X 
 
 
 
 
 
 
X6 
 
Fluoroscopy (AP and Lateral 
cine) of final ICD generator and 
lead position 
 
X 
 
 
 
 
 
 
X6 
 
Sensing, Impedance, & Pacing 
tests 
 
X 
X 
X 
X 
X 
X 
X5 
X6 
 
Defibrillation testing 
 
X 
 
 
 
X4 
 
 
X6 
 
Chest Radiographs (PA/Lateral) 
X 
 
X 
 
 
X 
 
 
 
 
Echocardiographic data within 
the last 6 months 
X 
 
 
 
 
 
 
 
 
 
Save-to-media files 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications (for subjects 
implanted with any device) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Adverse Events7 (including AEs 
with fatal outcome), Device 
Deficiencies, HCUs, Study 
Deviations, and Other cardiac 
imaging 
As they occur 
1 Only for subjects who complete their ICF in English. 
2 Required for subjects presenting in persistent atrial fibrillation to confirm the absence of LA or LV thrombus.  
3 Taken within the last year. Recommended for first 3 subjects at minimum, for each implanter. If collected/reviewed, send CT-scan and/or 
MRI to Medtronic. 
4 Only for subjects participating in chronic defibrillation testing, see CIP Addendum for 6-Month Defibrillation Testing.  
5 Optional. If electrical testing conducted, print the Testing Reports to PDR or paper and send a copy of the reports to Medtronic. 
6 System modification where a subject leaves the procedure with an EV ICD System. 
7 Recommended to collect incision photographs if an infection related to the EV ICD System is suspected. 
Safety Assessments 
All Adverse Events that occur from the time of enrollment 
through study exit will be collected and reported to Medtronic 
and regulatory agencies (per local requirement) during the 
study. Additionally, any device deficiency related to the EV ICD 
System or accessory will be collected.   
 Statistics 
The efficacy primary objective will be evaluated using a 
binomial confidence interval compared against a pre-specified 
threshold. To evaluate the safety primary objective, the 95% 
confidence interval for the 6-month system/procedure major 
complication-free rate will be generated and compared 
against a pre-specified threshold. A Kaplan-Meier survival 
curve will also be generated to provide incidence of EV ICD 
System/procedure-related major complications over time. 
Descriptive statistics will be used to summarize remaining 
endpoints. For some endpoints such as pacing testing, 
multiple measurements per subject will be assessed and 
compared.  
 
 
 

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3. Introduction  
3.1. Background  
Today, implantable cardioverter defibrillator (ICD) therapy is the treatment of choice for patients who 
are at risk for sudden cardiac death due to life-threatening ventricular arrhythmias. Traditional ICD 
systems with transvenous leads are considered standard of care for primary or secondary prevention of 
tachyarrhythmic death. However, these systems have limitations. Short- and long-term complications 
arising from ICD systems with transvenous leads, such as infection, pneumothorax, venous thrombosis, 
lead dislodgement, lead malfunction, and lead perforation, have persisted for decades as impediments 
to ICD usage1,2,3,4,5. As a result, there is demand for novel ICD systems that circumvent the potential 
disadvantages of transvenous ICD systems by preserving the heart and vasculature6,7. 
Non-transvenous ICD systems may represent a means of providing life-saving therapy to patients in 
whom it is not possible or desired to enter the venous system or heart chambers; for example, patients 
with anatomical anomalies, high infection risk, limited vascular access, or juvenile patients where the 
venous anatomy is preferably avoided8,9,10,11.  
Currently, there are non-transvenous subcutaneous and epicardial leads that are used with standard 
ICDs. Cameron Health developed the SQ-RX SubQ ICD system, which was market released in 2009. 
Boston Scientific acquired the Cameron Health device, and market released their Emblem Subcutaneous 
(SubQ) ICD system in 2015. During clinical studies for both of these devices, patients were implanted 
with a non-transvenous ICD system and a subcutaneous lead. Perioperative results from the S-ICD post 
approval study indicate acceptable short-term complication rates12, and first year post-implant results 
from the EFFORTLESS study confirm the safety demonstrated in the IDE S-ICD trial, and indicate 
performance rates for S-ICD complications, inappropriate shocks, and conversion efficacy similar to 
those observed in transvenous systems13. 
Medtronic has developed an extravascular ICD system which uses a substernal lead rather than a 
transvenous or a subcutaneous lead. The EV ICD System has similar capabilities to a single-chamber 
transvenous system while avoiding leads in the heart or vasculature. Compared to current market-
released non-transvenous subcutaneous ICDs, the EV ICD System includes a smaller device that uses less 
defibrillation energy which may result in longer battery life and has the additional capabilities to deliver 
pacing therapies such as ATP and backup asystole pacing from a single device. 
Previously published case studies indicate defibrillation from non-endocardial locations is possible and 
shock energies similar to those of transvenous devices can successfully defibrillate if the defibrillation 
coil is placed in an epicardial or mediastinal location8,9,10,14,15,16,17,18,19,20. The EV ICD System is of similar 
size and energy outputs as current transvenous systems (e.g., approximately 33cc and 40 Joules).  

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The first human experience of acute and chronic defibrillation lead placement in the substernal extra-
cardiac space was reported by Tung et al. in 2007 using a minimally invasive approach via the 
manubrium10. In three patients (two patients having ipsilateral venous occlusion and one patient 
wishing to avoid additional transvenous hardware placement), either a Medtronic Model 6996SQ or 
Model 6937 coil was tunneled to the substernal extra-cardiac space anterior to the right ventricle (RV). 
All implants were successful without complication. Ventricular Fibrillation (VF) was induced with T-wave 
shock. In each patient, the safety margin was determined to be at least 10 Joules (J) by two successful VF 
terminations. 
Later, Guenther et al. reported the results of failed subcutaneous defibrillation lead implantation in one 
human patient for whom defibrillation threshold testing (DFT) at 65 Joules and 80 Joules failed to 
terminate VF six times17. As a result of failed subcutaneous DFT, the lead was instead positioned 
substernally using an 11-French peel-away insertion sheath and the tunneling tool of the manufacturer. 
After making a small incision at the xiphoid process, fluoroscopy and “direct bone contact” were used to 
guide lead placement. Substernal DFT was successful and substernal sensing quality was acceptable. 
There were no complications, including no damage to the pericardium. The patient reported no chronic 
pain and there were no other findings at follow-up of four weeks. Guenther et al. concluded that 
“substernal lead positioning is easy to achieve” and provides an effective means of extravascular lead 
implantation17. 
In order to develop and evaluate a newly designed system for the substernal space, Medtronic 
completed pre-clinical research evaluations of substernal defibrillation, pacing, and sensing, and 
subsequently initiated three acute human clinical research feasibility studies with combined 121 
implants to explore the potential development of a future chronic implantable extravascular 
defibrillation system with a lead implanted in the substernal space. Both pre-clinical and clinical data are 
described in further detail within the Investigator’s Brochure. 
The first human clinical feasibility study, Acute Substernal Defibrillation (ASD), showed substernal 
defibrillation is feasible with energy available in current transvenous ICDs, with defibrillation successful 
in 13 of 14 subjects (93%) at 35J (95% CI: 74.7% - 99.8%). One failure was associated with high and 
lateral shock coil placement21. The second human clinical feasibility study, Substernal Pacing Acute 
Clinical Evaluation (SPACE), in which 26 subjects underwent pacing evaluation, showed that pacing is 
possible in nearly all patients from the extravascular substernal location22. The third human clinical 
feasibility study, Acute Extravascular Defibrillation, Pacing and Electrogram (ASD2), was designed to 
further assess study pacing thresholds and defibrillation efficacy via substernal therapy delivery in a 
larger cohort as well as collect additional data, mainly multi-vector substernal electrograms during 
induced VF/VT and intrinsic rhythms directly from an investigational lead placed in the substernal space. 
The substernal lead was implanted in 79 patients, with a median implantation time of 12.0 ± 9.0 min. 
Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), and 72 of 78 (92.3%) 
patients had capture in ≥1 vector with no extracardiac stimulation. A 30-J shock successfully terminated 

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104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. The ASD2 study demonstrated the 
ability to pace, sense, and defibrillate using a lead designed specifically for the substernal space23. 
Acute feasibility data from 121 patients provided assurance to initiate a pilot study with first-in-human 
chronic device implant of the EV ICD System. The main benefits of conducting a pilot study included (1) 
facilitating optimization of device settings, (2) providing additional recommendations and best practices 
during the implant procedure, and (3) providing an avenue for more robust data collection leading up to 
a pivotal trial. A pilot study was initiated to allow for characterization of the EV ICD System in a limited 
number of subjects before launching into this large-scale, global, pivotal study. 
The EV ICD Pilot Study is a prospective, non-randomized, chronic first-in-human study conducted in four 
sites in Australia and New Zealand. In this pilot study, 21 patients underwent the EV ICD implant 
procedure. Patients were evaluated at implant, two weeks, four to six weeks, and three months after 
device implant, and continue to be followed. Study investigators characterized the safety of the system 
and implant procedure, defibrillation effectiveness, and sensing and pacing. At the time of implant, 
defibrillation testing was completed on 20 patients. The system successfully terminated induced 
ventricular arrhythmias in 18 patients (90.0%), which is consistent with prior clinical studies of existing 
ICDs24,25. Pacing capture was achieved in more than 95% of study patients. One patient experienced 
ventricular tachycardia outside the hospital setting, which was successfully detected and treated by the 
EV ICD system. This first-in-human chronic study demonstrated that the EV ICD system can be implanted 
with no major complications, and can sense, pace and defibrillate the heart26.   
In summary, the acute feasibility and pilot studies contributed to the advancement of the EV ICD 
program, including refinement of the device, algorithm and implant procedure.  
3.2. Purpose 
The purpose of the clinical study is to demonstrate the safety and efficacy of the EV ICD System: a 
complete single-chamber extravascular ICD system with the lead implanted substernally.    
4. Objectives and/or Endpoints 
4.1. Objectives 
 Primary Objectives  
The first primary objective is to demonstrate the freedom from major complications related to the EV 
ICD System and/or procedure at 6 months post-implant exceeds 79% Objective Performance Criterion 
(OPC). The endpoint is defined as a subject’s first occurrence of a major complication related to the EV 

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ICD System and/or procedure, as determined by an independent Clinical Events Committee (CEC), that 
occurs on or prior to 6 months (182 days) post-implant.  
For an adverse event to meet the endpoint, the event must have occurred within 182 days (inclusive) of 
the EV ICD System implant and be adjudicated by the CEC as being a major complication related (causal 
relationship) to the EV ICD System and/or procedure. Major complications are those complications 
resulting in: 
• 
Death 
• 
Permanent loss of defibrillation function (specifically shock) due to mechanical or electrical 
dysfunction of the device  
• 
Hospitalization 
• 
Prolongation of an existing hospitalization by at least 48 hours 
• 
System revision (reposition, replacement, explant) 
The second primary objective is to demonstrate the defibrillation efficacy at implant of the EV ICD 
System exceeds 88% (OPC). The endpoint, defibrillation testing success, is defined as: 
• 
Single sustained shockable ventricular arrhythmia (SSVA) conversion at 20J, or  
• 
Conversion of two consecutive episodes of SSVA at 30J in final system configuration. 
Notes: 
• 
In one of the two consecutive SSVA episodes, up to two 30J shocks are permitted. 
• 
To achieve final system configuration, changing the position of the ICD generator and/or the 
lead, or changing shock polarity is permitted. 
• 
Subjects can return for testing on another day if testing is not fully completed on the day of 
implant. 
• 
If SSVA cannot be induced, the EV ICD System must be removed (refer to section 8.5.8). 
• 
For more information on the rationale behind these objectives, refer to section 12. 
 Ancillary Objectives  
• 
Characterize appropriate and inappropriate shocks  
• 
Characterize electrical performance (pacing capture thresholds, pacing impedance, sensing 
amplitudes) over time  
• 
Characterize extracardiac pacing sensation 
• 
Characterize asystole pacing 
• 
Summarize ATP performance with spontaneous arrhythmias 
• 
Summarize adverse events 
• 
Characterize the EV ICD defibrillation testing success rate at 6 months post-implant. 

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5. Study Design  
The EV ICD Pivotal Study is a prospective, multi-center, single-arm, non-randomized, pre-market clinical 
study. Enrollment will include up to 400 subjects at up to 60 sites worldwide.  
Participating geographies are expected to include but are not limited to: ANZ (Australia and New 
Zealand), Canada, EMEA (Europe, Middle East, and Africa), Hong Kong, Japan, and the United States. 
Participating sites that enroll faster than others will be allowed to do so to maintain an adequate 
enrollment rate. However, to ensure a reasonable distribution of experience and minimize site bias in 
study results, the maximum number of subjects enrolled at each site will be capped at 35 
(approximately 10% of total enrollments). 

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Figure 1: Overview of the EV ICD Pivotal Study  
 

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5.1. Duration 
The expected study duration is approximately 3 years from the study’s first enrollment. The enrollment 
period is expected to take approximately 15 months. Individual subjects may be participating in the 
study for a period of minimum 2 to approximately 3.5 years. The duration of individual subject 
participation will vary based on timing of site activation, timing of enrollment and enrollment rate. 
Subjects will undergo assessments at Baseline, Pre-Hospital Discharge, 2 Weeks, 3 Months, 6 Months, 
and every 6 months thereafter until official study closure. Official study closure is defined as when 
Medtronic and/or applicable regulatory authority agency or governing body requirements have been 
satisfied per the CIP and/or by a decision by Medtronic or regulatory authority to stop or close the 
study. Official study closure is expected to occur after the EV ICD System is approved by the FDA, 
anticipated in 2022.  
5.2. Rationale  
The main purpose of the EV ICD Pivotal Study is to demonstrate safety and efficacy of the EV ICD 
System.  
Prior to this study, three acute human feasibility studies were performed: 
• 
The ASD study demonstrated that substernal defibrillation is feasible with energy available in 
current transvenous (TV)-ICDs21 
• 
The SPACE study demonstrated that pacing is possible in nearly all patients with detection 
comparable to TV-ICD22 
• 
The ASD2 study demonstrated that pacing, sensing, and defibrillation is feasible with a lead designed 
specifically for the substernal space23 
EV ICD device features were designed and developed using data collected from these studies and 
supplemented with animal and bench evaluations.  
In addition to the acute feasibility studies, the EV ICD Pilot study was initiated to allow for chronic 
characterization of the EV ICD System in a limited number of subjects before launching into a large-
scale, global, pivotal study. At this time, the EV ICD Pilot study long-term follow-up is ongoing, and will 
continue through the duration of the EV ICD Pivotal Study in order to continue collecting long-term 
follow-up data.  
 

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5.3. Minimization of Bias 
Selection of subjects, treatment of subjects, and evaluation of study data are potential sources of bias. 
Methods incorporated in the study design to minimize potential bias include (but are not limited to): 
• 
Subject demographics and comorbidities will be collected at baseline to later assess possible 
characteristics that may influence endpoints 
• 
Data collection requirements and study procedures will be standardized across all geographies 
• 
To ensure a reasonable distribution of data among sites, the maximum number of enrollments 
per site will be 35 subjects. Additionally, sites will be encouraged to enroll at least 3 subjects.  
• 
A statistical analysis plan will be developed prior to analyzing data which will document all pre-
specified analyses and analysis methods 
• 
All study clinicians will be trained on and required to follow the CIP 
• 
All study clinicians and Medtronic personnel will be trained on their respective aspects of the 
study using standardized training materials 
• 
An independent Clinical Events Committee (CEC) will be utilized to regularly review and 
adjudicate reported adverse events 
• 
An Episode Review Committee (ERC) containing independent reviewers will be utilized to 
review and adjudicate device-treated episodes to determine appropriateness of therapy 
(shocks and ATP) delivered to subjects 
• 
An independent Data Monitoring Committee (DMC) will be utilized to review accumulating 
data and interim analyses, help safeguard the interests of study subjects, and monitor the 
overall conduct of the study 
• 
All sites will use the same version of the CIP and standardized case report forms when possible 
• 
All study investigators will be required to meet 21 CFR Part 54, Financial Disclosure by Clinical 
Investigators  
• 
Monitoring visits will be conducted to verify adherence to the CIP and source data. 
In summary, potential sources of bias that may be encountered in this clinical study have been 
considered and minimized by careful study design. 
 
 

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6. Product Description 
6.1. General 
The EV ICD System consists of market-released and investigational components. 
 Table 2: EV ICD System Components 
Model Number 
Component 
Investigational or Commercially 
Available at study start 
System Components 
DVEX3E4 
Extravascular Implantable Cardioverter 
Defibrillator (EV ICD) 
Investigational in all geographies 
EV2401 
Extravascular quadripolar lead with shaped 
passive fixation 
Investigational in all geographies 
Accessory Components 
EAZ101 
Sternal Tunneling Tool 
Investigational in all geographies 
EAZ201 
Transverse Tunneling Tool  
Investigational in all geographies 
SSCL9 
Oscor SafeSheath® II Hemostatic Tear-away 
Introducer System with Infusion Side Port 
Investigational in all geographies 
SW041 
Medtronic EV ICD SW041 Programmer 
Software Version 8.1 or greater 
Investigational in all geographies 
2090 
 
or 
29901 
Medtronic CareLink Programmer with 
analyzer  
or 
Medtronic CareLink Encore Programmer 
Commercially available in all 
geographies  
Investigational EV ICD SW041 
software is downloaded onto 
programmer, and programmer is 
subsequently labeled as containing 
investigational software  
24952 
Medtronic MyCareLink Patient Monitor (may 
become available during the course of the 
study) 
Commercially available in all 
geographies, but investigational 
when used with EV ICD 
 
The CIP permits up to 400 enrollments to allow at least 292 subjects undergoing system implant and 
defibrillation testing to be included in the study. Under the assumption that one system is used per 
subject, as well as a 15% increase to account for system revisions, dropped product, etc., it is expected 
that up to approximately 460 of the following investigational devices may be used during the trial: EV 
ICD, lead, sternal tunneling tool, transverse tunneling tool, introducer, and MyCareLink monitor. Each 
site (up to 60 sites) will have access to at least one programmer with software.  

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  EV ICD (Model DVEX3E4) 
The Medtronic Model DVEX3E4 is an investigational single-chamber, MR-conditional, extravascular 
implantable cardioverter defibrillator (EV ICD). It consists of a titanium generator and a connector port 
housing made from polyurethane and silicone rubber. This multiprogrammable cardiac device monitors 
and regulates the subject’s heart rate. It provides asystole detection and therapy (Pause Prevention), 
ventricular tachyarrhythmia detection and therapy including ATP, and post-shock pacing. The EV ICD 
also provides diagnostic and monitoring features to assist with system evaluation and patient care.  
 
Figure 2: The Medtronic EV ICD Model DVEX3E4 
The DVEX3E4 EV ICD contains an EV4 connector, which is compatible with an EV4-LLHH quadripolar lead. 

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  EV ICD Lead (Model EV2401) 
The Medtronic Model EV2401 extravascular lead is an investigational, pre-shaped, MR-conditional lead 
with passive fixation, designed for sensing, cardioversion, defibrillation and pacing therapies. The lead is 
8.7 Fr and available in both 52 cm or 63 cm lengths. The body of the lead is made from polyurethane, 
with ring electrodes made from titanium nitride coated platinum iridium, and coil electrodes from 
platinum iridium and tantalum. The lead has two ring electrodes and two coil electrodes: Ring 2 
(proximal ring), Coil 2 (proximal coil), Ring 1 (distal ring), Coil 1 (distal coil). The configuration of these 
electrodes is shown in Figure 3. The lead has the ability to pace and sense between the ring and coil 
electrodes. In addition, the Coil 1 and Coil 2 electrodes deliver cardioversion and defibrillation therapy. 
Figure 3: The EV2401 lead 
The proximal end of the lead features an EV4-LLHH quadripolar connector, which is compatible with an 
EV4 connector on an EV ICD.  
 

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  Sternal Tunneling tool (Model EAZ101)  
The Medtronic Model EAZ101 sternal tunneling tool is an investigational tool designed to deliver an 
introducer and an extravascular lead into the anterior mediastinum during implant of an extravascular 
implantable device system.  This is referred to as Zone 1 in Table 5: Outline of the proposed implant 
procedure steps. 
The sternal tunneling tool, shown in Figure 4  below, consists of the following components: 
• 
Handle 
• 
 tunneling rod that delivers a 
 introducer to the anterior mediastinum. The 
tunneling rod is malleable to accommodate patient anatomy 
• 
External guide that remains above the skin and indicates the distance and direction of the 
tunneling rod. The external guide is hinged and removable to accommodate physician preference 
and patient anatomy 
• 
Thumb tab used to raise and lower the external guide 
 
 
Figure 4: EAZ101 sternal tunneling tool 
 
 
 The Oscor 
SafeSheath® II (Model SSCL9) introducer (section 6.1.5)  is to be used with the sternal tunneling tool.   
 
 

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  Transverse Tunneling tool (Model EAZ201) 
The Medtronic Model EAZ201 transverse tunneling tool, shown in Figure 5, is an investigational tool 
designed to deliver the proximal portion of an extravascular lead to the device pocket during implant of 
an extravascular implantable device system. This is referred to as Zone 2 in Table 5: Outline of the 
proposed implant procedure steps. 
 
Figure 5: EAZ201 transverse tunneling tool 
 
 
 
 
   
If additional tunneling tools are used to tunnel the lead subcutaneously, this shall be discussed with 
Medtronic clinical study personnel prior to use and the tools used will be documented. Use of additional 
tools will be considered a study deviation.  
  Oscor SafeSheath® II Model SSCL9 
The Oscor (Palm Harbor, FL) SafeSheath® II Model SSCL9 introducer is a hemostatic tear-away 
introducer. 
  A 10cc 
plastic syringe will be packaged with the introducer sheath. The introducer sheath and hemostatic valve 
are indicated for the introduction of various types of pacing leads and catheters. The infusion side port is 
used to inject or aspirate through the sheath. 

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In this study, the SSCL9 introducer is used over the tunneling rod of the EAZ101 sternal tunneling tool to 
create a tunnel and facilitate insertion of the EV2401 extravascular lead into the mediastinum with a 
saline-filled syringe connected to the infusion sideport.  
 
Figure 6: The Oscor SafeSheath® II Model SSCL9 
The Oscor SafeSheath® II Model SSCL9 introducer is considered investigational in all geographies but 
may become commercially available during the course of the study. 
 EV ICD Programmer Software (Model SW041), Medtronic CareLink 
2090 Programmer with Analyzer and Medtronic CareLink 
Encore 29901 Programmer  
The investigational Medtronic Model SW041 programmer software, Version 8.1 (or greater) runs on the 
commercially available Medtronic CareLink 2090 Programmer or the commercially available Medtronic 
CareLink Encore 29901 Programmer, both with Conexus telemetry, and communicates with an 
implanted EV ICD Model DVEX3E4. Following software download, the Medtronic Programmer 2090 or 
29901 will be labeled per local requirements to indicate that it contains investigational software.  
Within its intended use, the programmer and programmer software will be used to provide a user 
interface with which the user can interrogate the device, control induction, shocking, sensing and pacing 
features and their parameters, and display diagnostic information. At implant, the 2090 analyzer (which 
is part of the 2090 programmer) will be used to test the lead electrical signals before the device is 
implanted.  
 MyCareLink Patient Monitor (Model 24952) 
The commercially available Model 24952 MyCareLink Patient Monitor may be made available to 
subjects during this study when CareLink is made available for use with EV ICD. The MyCareLink Patient 

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Monitor communicates with an implanted EV ICD Model DVEX3E4 device to transmit data about device 
episodes to the subject’s clinic using the CareLink network. In this study, the CareLink monitor will be 
used within its intended use, but will be considered investigational when used with EV ICD until the 
firmware is approved for use with the EV ICD system.  
6.2. Manufacturer 
All of the EV ICD System and accessory components are manufactured by Medtronic, with the exception 
of the SSCL9 introducer sheath, manufactured by Oscor, Inc. 
Manufacturer Name 
Manufacturer Address 
Medtronic 
710 Medtronic Parkway 
Minneapolis, MN 55432 
USA 
www.medtronic.com 
+1 763 514 4000 
6.3. Packaging 
For investigational products, the device labeling and clinical manuals will be translated into the local 
language. The Clinical Manuals or Instructions for Use (IFU) will accompany each investigational 
component. Investigational products will be clearly labeled, e.g., “Exclusively for clinical investigations” 
and with the study identifier “Protocol #: MDT16028” per local requirements. In some geographies, the 
IFUs may be delivered via an alternate format (e.g., CD-ROM format, USB, or electronic format) if 
allowed within local requirements. 
The investigational Medtronic Model SW041 programmer software application may be installed onto 
the Medtronic CareLink 2090 or Medtronic CareLink Encore 29901 programmers using USB drives with 
SW041 or Software Distribution Network (SDN) (if available); media packaging requirements are not 
applicable for distribution via the SDN. USB drives containing SW041, will be clearly labeled with 
identifier, version, and marked as “Exclusively for clinical investigations”. 
When investigational Medtronic Model SW041 software is installed on the 2090 or 29901 Medtronic 
Programmers, the Medtronic Programmers will be labeled to indicate they contain investigational 
software per local requirements. 
Packaging and labeling for all other market approved system components can be found with each 
package insert. Manuals for market approved Medtronic devices can be found on 
http://manuals.medtronic.com. For CE marked devices and market devices in Japan, the labeling is in 
the appropriate local language.  

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The labeling for all components may include but is not limited to the following: 
• 
Device Name 
• 
Model number 
• 
Serial or Lot number, as applicable 
• 
Date of manufacture  
• 
Expiration date 
6.4.  Intended Population 
The Medtronic EV ICD System is indicated for the automated treatment of patients who have 
experienced, or are at significant risk of developing, life-threatening ventricular tachyarrhythmias. The 
intended population to receive the EV ICD System includes patients who are indicated for implantation 
of a single chamber ICD according to current ACC/AHA/HRS or ESC guidelines, and who do not have a 
bradycardia pacing or cardiac resynchronization therapy indication.  
6.5.  Equipment 
Sites are responsible for maintaining and calibrating site equipment used in the course of this study 
(e.g., radiograph machine and fluoroscope) as applicable in accordance with established site practice 
and local regulation. Records shall be kept and available to be provided during monitoring visits and 
upon request by the Sponsor or regulatory agency.  
6.6. Product Use 
Instructions for installation and use for the components of the EV ICD System and accessories are 
located in the accompanying IFU for each component. Additionally, trained and experienced Medtronic 
personnel will provide support at implant.  
6.7.  Product Training Requirements 
The EV ICD implant procedure is to be performed by an investigator who has received training on all 
aspects of the implant procedure, including but not limited to:  
• 
Access into the anterior mediastinum, 
• 
Substernal tunneling (Zone 1),  
• 
Lead anchoring technique 
• 
Transverse tunneling to the device pocket (Zone 2),  
• 
Device pocket creation, and  
• 
Implant device testing 
All implant training will be documented in the Investigator Site File (ISF). 

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During the implant procedure, the investigator will be placing the lead utilizing a tunneling procedure. It 
is imperative that methods are utilized to ensure safe access to the anterior mediastinum via a sub-
xiphoid approach. As cardiothoracic surgeons routinely perform midline sternotomy procedures, 
Medtronic intends to use a team approach during the EV ICD implant to ensure the knowledge and skills 
are transferred to a non-surgical physician specialty (EP/Cardiologist). A Cardiac Surgeon/Cardiothoracic 
Surgeon trained on relevant components of the study procedure will attend, at minimum, the first five 
implant procedures attempted by each implanting physician to partner on safe blunt dissection 
technique for tunneling into the anterior mediastinum and support the implant procedure. The Cardiac 
Surgeon/Cardiothoracic Surgeon can also add context to specific subject anatomy. It is required that the 
Cardiac Surgeon/Cardiothoracic Surgeon will also provide emergency support during all clinical study 
implant procedures.  
For sites that participated in the EV ICD Pilot study, implanting physicians with previous proctored 
implant procedures from the EV ICD Pilot study may be counted towards the requirement for the 
Cardiac Surgeon/Cardiothoracic Surgeon to attend the first five EV ICD Pivotal Study implant procedures. 
If the implanting physician is also trained and currently performing activities similar to a cardiothoracic 
surgeon, there may be instances where a separate CT surgeon is not required. If this occurs, this shall be 
discussed ahead of time with the Medtronic clinical study team, and Medtronic approval must be 
documented prior to the procedure taking place. 
6.8.  Product Receipt, Tracking, and Accountability 
The EV ICD System components (EV ICD, lead) and accessory components (sternal tunneling tool, 
transverse tunneling tool, SafeSheath introducer, software, and MyCareLink Patient Monitor), will be 
considered investigational in geographies in which the product is not available commercially and will be 
labeled for exclusive use in clinical investigations. Investigational system components will be distributed 
to a site only when Medtronic has received all required documentation (not limited to, Ethics 
Committee or Competent Authority approval, a signed Clinical Trial Agreement, and documentation of 
training) and has notified the site of site readiness.  
Distribution of the investigational product to study sites will be managed by Medtronic and 
investigational products may only be ordered by Medtronic personnel. Sites with these clinically labeled 
EV ICD System components will track disposition upon receipt or return of the components, as well as 
upon implant or explant of the components. 
Product accountability will be documented on the Device Accountability electronic Case Report Form 
(eCRF), which will be maintained in the Electronic Data Capture (EDC) system.  
This eCRF will track, at a minimum, the following information:  
• 
Date of receipt 

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• 
Identification of the investigational components, if applicable (Lot or serial number or 
unique code) 
• 
Expiration date, if applicable 
• 
Date used or installed 
• 
Subject identification (ID) Number, if applicable 
• 
Date and reason for return or disposal, if applicable 
• 
Name of person responsible for receipt, return or destruction/disposal, if applicable 
• 
Uninstallation or explant date of the investigational components and software, if applicable 
Medtronic will perform internal final study product reconciliation per the applicable study-specific 
document or per local requirements, to ensure all study product has been accounted for either by 
physical return to Medtronic or documented disposal at the site or vendor (including method of 
disposal). Periodic reconciliation of investigational product will be performed to ensure traceability.  
6.9.  Product Storage 
All investigational products must be stored in accordance with their labelling in a secure location at the 
site with access limited only to authorized personnel. It is the responsibility of the investigator to 
correctly handle, store, and track the investigational products. If allowed per local regulations, the 
programmer installed with the investigational software may be used for commercial use as the software 
can only communicate with investigational EV ICD devices. 
6.10.  Product Return 
All explanted, open but unused and potentially defective products (device, leads, tools, etc.) should be 
returned to Medtronic for analysis whenever possible and when permissible by local laws and 
regulations. If the products are explanted but not returned, a justification is required to be reported on 
the appropriate eCRF(s) (note that this is not considered a study deviation). The Device Accountability 
eCRF must be updated in the event of an explant. Local Medtronic field personnel or representative can 
be contacted to receive a Return Mailer Kit. All unused investigational products must be returned to 
Medtronic upon study closure at the site.  
The SW041 software may remain installed on specific 2090 programmers for the purposes of providing 
support for subject’s EV ICD System after the study is closed. If SW041 software is no longer required 
(e.g., replaced by updated market-released software), the SW041 software will be removed from the 
2090 or 29901 programmers manually. 

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7. Selection of Subjects 
7.1. Study Population 
The study population will consist of subjects who have class I or IIa indication for implantation of a single 
chamber Implantable Cardioverter Defibrillator (ICD) according to current ACC/AHA/HRS or ESC 
guidelines, and who do not have a bradycardia pacing or cardiac resynchronization therapy indication.  
7.2. Subject Enrollment 
Patients will be screened to ensure they meet all the inclusion and none of the exclusion criteria.  
Subjects are considered enrolled in the study upon signing the Informed Consent Form. Informed 
Consent must be obtained prior to performing any study-related procedures. 
7.3. Inclusion Criteria 
 
Inclusion Criteria 
Rationale 
1. 
Patient has a Class I or IIa indication for implantation of 
an ICD according to the ACC/AHA/HRS Guidelinesviii, or 
ESC guidelinesix. 
Study will be evaluated in the standard patient 
population that is indicated for the device 
under evaluation. 
2. 
Patient is at least 18 years of age and meets age 
requirements per local law. 
Ensure age is appropriate to provide Informed 
Consent. 
3. 
Patient is geographically stable and willing and able to 
complete the study procedures and visits for the 
duration of the follow-up. 
Ensure ascertainment of data required for 
clinical evaluation. 
 
                                                            
viii Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, 
Gillis AM, Hlatky MA, Granger CB, Hammill SC, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS 
guideline for management of patients with ventricular arrhythmias. 
ix Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliot PM, Fitzsimons D, Hatala R, Hindricks G, 
Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ. 2015 ESC 
guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European 
Heart Journal 2015 36:41 (2793-2867). https://doi.org/10.1093/eurheartj/ehv316 
 

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7.4. Exclusion Criteria 
 
Exclusion Criteria 
Rationale 
1. 
Patient is unwilling or unable to personally provide 
Informed Consent. 
Not allowing legally authorized 
representatives. 
2. 
Patient has indications for bradycardia pacing x or 
Cardiac Resynchronization Therapy (CRT) xi (Class I, IIa, 
or IIb indication).  
First generation of system does not include 
chronic bradycardia pacing support and does 
not include a left ventricular lead. 
3. 
Patients with an existing pacemaker, ICD, or CRT device 
or leads. 
Avoid possible confounding factors (e.g., 
complications due to changeout procedure). 
Subjects who have recently had a system 
removal may be considered if the physician 
feels procedure complications and/or 
infections are resolved.  
4. 
Patients with these medical interventions are excluded 
from participation in the study: 
• 
Prior sternotomy 
• 
Any prior medical condition or procedure that 
leads to adhesions in the anterior mediastinal 
space (i.e., prior mediastinal instrumentation, 
mediastinitis) 
• 
Prior abdominal surgery in the epigastric region 
• 
Planned sternotomy 
• 
Prior chest radiotherapy 
Or any other prior/planned medical intervention not 
listed that precludes their participation in the opinion 
of the Investigator. 
Avoid possible surgical risks during the 
tunneling procedure due to fibrosis or 
scarring in the mediastinal tissue. 
5. 
Patient has previous pericarditis that: 
• 
Was chronic and recurrent, or  
• 
Resulted in pericardial effusion xii, or 
• 
Resulted in pericardial thickening or 
calcification. xiii 
Avoid possible surgical risks related to the 
tunneling procedure arising from clinically 
significant pericarditis. 
                                                            
x 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming 
and testing). 
xi ACC/AHA/HRS guidelines for Cardiac Resynchronization Therapy 
xii As documented on echo or MRI 
xiii As documented on CT scan or MRI 

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Exclusion Criteria 
Rationale 
6. 
Patients with these medical conditions or anatomies 
are excluded from participation in the study: 
• 
Hiatal hernia that distorts mediastinal anatomy 
• 
Marked sternal abnormality (e.g., pectus 
excavatum) 
• 
Decompensated heart failure 
• 
COPD with oxygen dependence 
• 
Gross hepatosplenomegaly 
Or any other known medical condition or anatomy type 
not listed that precludes their participation in the 
opinion of the Investigator. 
Excluded due to anatomical abnormalities 
that increase procedure risk, increased risk of 
infection, or risk of potential comorbidities 
that impact evaluation of the system during a 
clinical study. 
7. 
Patients with a medical condition that precludes them 
from undergoing defibrillation testing:  
• 
Severe aortic stenosis 
• 
Current Intracardiac LA or LV thrombus 
• 
Severe proximal three-vessel or left main coronary 
artery disease without revascularization 
• 
Hemodynamic instability 
• 
Unstable angina 
• 
Recent stroke or transient ischemic attack (within 
the last 6 months) 
• 
Known inadequate external defibrillation 
• 
LVEF < 20% 
• 
LVEDD >70 mm 
Or any other known medical condition not listed that 
precludes their participation in the opinion of the 
Investigator. 
Exclude patients who may be more 
vulnerable to potential increased risk during 
the evaluation of the clinical study 
defibrillation protocol.  
8. 
Patient with any evidence of active infection or 
undergoing treatment for an infection. 
Standard exclusion criterion for device 
implant, emphasized due to importance. 
9. 
Patient is contraindicated from temporary suspension 
of oral/systemic anticoagulation   
To reduce risk of bleeding/hematoma 
intraprocedurally or in the event that an 
urgent sternotomy/thoracotomy is required 
10. 
Patient with current implantation of neurostimulator or 
any other chronically implanted device that delivers 
current in the body. 
For the purposes of clinical data collection 
and interpretation it is preferable to avoid 
any possible electrical interference with the 
EV ICD System. 

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Exclusion Criteria 
Rationale 
11. 
Patient meets ACC/AHA/HRS or ESC clinical guideline 
Class III criteria for an ICD (e.g., life expectancy of less 
than 12 months). 
 
Standard exclusion criterion to ensure study 
cohort is expected to survive to the time of 
endpoint evaluation and to ensure the study 
only includes patients with current clinical 
indications for an ICD. 
12. 
Patient is enrolled or planning to enroll in a concurrent 
clinical study that may confound the results of this 
study, without documented pre-approval from a 
Medtronic study manager. 
Standard exclusion criterion to avoid 
confounding procedural requirements due to 
multiple experimental studies. 
13. 
Patient with any exclusion criteria as required by local 
law (e.g., age or other).  
Standard exclusion criterion to comply with 
any additional local requirements which may 
apply.  
14. 
Pregnant women or breastfeeding women, or women 
of child bearing potential and who are not on a reliable 
form of birth regulation method or abstinence. xiv  
Pregnant women are excluded to avoid harm 
to the fetus caused by fluoroscopy 
requirements. 
 
 
8. Study Procedures  
The following criteria were considered when selecting sites for the EV ICD Pivotal Study: 
• 
Investigator/site is qualified by training, education, and relevant experience appropriate to the 
use of the product and associated procedures 
• 
Investigator/site expects to have adequate time and resources to conduct the study 
throughout the duration of the study 
• 
Investigator/site has access to an adequate number of eligible subjects 
• 
Ability to comply with applicable Ethics Committee and regulatory requirements 
• 
Investigator is not debarred, disqualified, or working under sanctions in applicable regions 
• 
Site has demonstrated experience working (well) with Medtronic clinical research in the last 3 
years 
• 
Site can support timely data entry (e.g., coordinator) 
• 
Site has the ability to do full (90°) lateral fluoroscopy (biplane preferred), anesthesia, and the 
ability to treat AEs that require surgical intervention in the location where they plan to perform 
the procedure 
                                                            
xiv If required by local law, women of child-bearing potential must undergo a pregnancy test within seven days prior to EV ICD 
Pivotal Study procedures 

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• 
Investigator(s) is willing and able to attend hands on implant training as outlined in section 6.7 
(1-2 implanting investigators per site) 
• 
Site has a robust emergency protocol - site can react to need for major cardiac surgery within 
10 minutes 
Medtronic contracts with participating institutions/investigators through a Clinical Trial Agreement that 
defines the scope and responsibilities and associated compensation related to carrying out the 
obligations under a clinical study sponsored by Medtronic.  
During the activation process (prior to subject enrollment), Medtronic will train site personnel on, but 
not limited to, the current version of the CIP, relevant standards and regulations, Informed Consent 
process, data collection and reporting tools. In addition, site personnel must be delegated by the 
Principal Investigator to perform study-related activities. If new members join the site team, required 
documentation will be obtained and they will receive training on the applicable clinical investigation 
requirements relevant to their role before contributing to the clinical investigation. Medtronic will 
provide each study site with written documentation of study site/investigator readiness. In order to 
receive written documentation of study site/investigator readiness, the following documentation must 
be available: 
• 
Regulatory authority approval 
• 
Ethics Committee approval and voting list 
• 
Signed Clinical Trial Agreement 
• 
Current CVs for investigators and authorized designees, signed and dated 
• 
Confirmation of receipt of IB, if available 
• 
Financial disclosure for investigators 
Prior to performing study-related procedures, all sites must have Ethics Committee and associated 
regulatory authority approval if applicable (e.g., Competent Authority approval) as well as 
documentation from Medtronic of site readiness.  
8.1. Schedule of Events 
Visit schedule and data collection requirements are summarized below in Table 3.  

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Table 3: EV ICD Pivotal Study schedule of events 
Study procedure 
Baseline 
Implant 
PHD 
2 Weeks  
3 Months 
6 Months 
Long-Term (12, 18, 
24…months)  
Unsched. 
Sys. Mod. 
Exit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Assessment 
X 
 
 
 
 
 
 
 
 
 
Physical Exam, Demographics, Cardiovascular Medical 
History, Surgical History 
X 
 
 
 
 
 
 
 
 
 
SF-12 quality of life survey 
X 
 
 
 
 
X 
 
 
 
 
Florida Patient Acceptance Survey (FPAS)1 
 
 
 
 
 
X 
 
 
 
 
System and procedure information 
 
X 
 
 
 
 
 
 
X 
 
Pre-procedure Transesophageal Echocardiogram (TEE)2 
 
X2 
 
 
 
 
 
 
 
 
CT or MRI scan  
X3 
 
 
 
 
 
 
 
 
 
Fluoroscopy recordings during tunneling procedure 
 
X 
 
 
 
 
 
 
X6 
 
Fluoroscopy (AP and Lateral cine) of final ICD generator and 
lead position 
 
X 
 
 
 
 
 
 
X6 
 
Sensing, Impedance & Pacing Tests 
 
X 
X 
X 
X 
X 
X 
X5 
X6 
 
Defibrillation Testing 
 
X 
 
 
 
Subset4 
 
 
X6 
 
Chest Radiographs – (PA/Lateral) 
X 
 
X 
 
 
X 
 
 
 
 
Echocardiographic data within the last 6 months 
X 
 
 
 
 
 
 
 
 
 
Save-to-media files  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications (for subjects implanted with any device) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events7 (including AEs with fatal outcome), Device 
Deficiencies, HCUs, Study Deviations, and Other Cardiac 
Imaging 
As they occur 
1 Only for subjects who complete their ICF in English.  
2 Required for subjects presenting in persistent atrial fibrillation to confirm the absence of LA or LV thrombus. 
3 Taken within the last year. Recommended for first 3 subjects at minimum, for each implanter. If collected/reviewed, send CT-scan and/or MRI to Medtronic. 
4 Only for subjects participating in chronic defibrillation testing, see CIP Addendum for 6-Month Defibrillation Testing. 
5 Optional. If electrical testing conducted, print the Testing Reports to PDF or paper and send a copy of the reports to Medtronic 
6 System modification where a subject leaves the procedure with an EV ICD System. 
7 Recommended to collect incision photographs if an infection related to the EV ICD System is suspected.   

 
 
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8.2. Medications 
Medication details will be collected via electronic case report forms (eCRFs) on a rolling basis 
throughout the study. Document all oral and intravenous medications prescribed to the subject at the time 
of the Baseline visit on the eCRFs and continue to document medication changes (when medications are 
stopped or started) throughout the subject’s participation in the study. In addition, medications administered or 
adjusted to treat a reported adverse event shall be reported. If the subject is not implanted or attempted to be 
implanted, medication collection is not required. 
 Prior and Concomitant Medications 
There are no restrictions regarding prior or concomitant medications, with the exception of 
oral/systemic anticoagulants per study exclusion criteria (section 7.4).  
8.3. Subject Consent 
Informed Consent (IC) is defined as a legally effective documented confirmation of a subject’s voluntary 
agreement to participate in a particular clinical study. This confirmation occurs after information has 
been given to the subject on all aspects of the clinical study that are relevant to the subject’s decision 
to participate (ISO 14155:2011). This process includes obtaining an Informed Consent Form (ICF) and an 
Authorization to Use and Disclose Personal Health Information/Research Authorization/other privacy 
language as required by law. The ICF and Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other privacy language as required by law shall be approved by 
Medtronic and each study site’s Ethics Committee (EC) prior to enrolling subjects. These shall be signed 
and personally dated by the subject and the Principal Investigator or authorized designee as required.  
Subjects of centers that agree with and obtain approval from their EC and associated regulatory 
authority, if applicable, will be invited to participate in the optional 6-month defibrillation testing. 
Subjects are free to decline this testing with no penalty.  
An ICF, either part of the initial ICF or a stand-alone document, will be provided to potential 
participants, outlining the procedure, potential risks, and benefits. Subjects will be considered enrolled 
for the 6-month defibrillation testing at the time they sign the ICF.  
The document(s) must be controlled (i.e., versioned and dated) to ensure it is clear which version(s) 
was/were approved by Medtronic and the EC. Any adaptation of the previously approved ICF must be 
reviewed and approved by Medtronic and the EC prior to being used to consent or re-consent a study 
subject. 

 
 
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The investigator must notify the subject of any significant new findings about the study that become 
available during the course of the study which are pertinent to the safety and well-being of the subject, 
as this could impact a subject’s willingness to participate in the study. If relevant, subjects must be 
requested to confirm their continued participation in writing.  
Prior to initiation of any study-specific procedures, IC must be obtained from the subject. Subjects in 
the US will be required to sign a HIPAA authorization form before participating sites can collect, use 
and submit subject information to the study sponsor.   
The process of obtaining Informed Consent shall: 
• 
Ensure that the Principal Investigator or an authorized designee conducts the IC process. 
• 
Include all aspects of the EV ICD Pivotal Study that are relevant to the subject's decision to 
participate throughout the clinical study. 
• 
Avoid any coercion or undue improper influence on, or inducement of the subject to 
participate. 
• 
Not waive or appear to waive the subject’s legal rights. 
• 
Ensure the ICF and Authorization to Use and Disclose Personal Health Information/Research 
Authorization/HIPAA/other privacy language, as required by law, are given to the subject in a 
non-technical language the subject is able to read and understand. 
• 
Provide ample time and opportunity for the subject to read and understand the ICF to inquire 
about details of the study, and to consider participation. All questions about the study should 
be answered to the satisfaction of the subject. 
• 
Include a personally dated signature of the subject acknowledging that their participation in 
the study is voluntary. 
• 
Include a personally dated signature of the Principal Investigator or authorized designee 
responsible for conducting the IC process, as required by local law. 
• 
Include any other locally required signatories, such as witnesses, as indicated by country-
specific legislations. 
• 
Provide the subject with a copy of the ICF and Authorization to Use and Disclose Personal 
Health Information/Research Authorization/HIPAA/other privacy language as required by law, 
and any other written information, signed and dated if required by local law.   
• 
Ensure subject is notified of any significant new findings about the study that become available 
during the course of the study which are pertinent to the safety and well-being of the subject, 
as this could impact a subject’s willingness to participate in the study. 
If the IC is obtained the same day the subject begins participating in study-related procedures, it must 
be documented in the subject’s case history that consent was obtained prior to participation in any 
study-related procedures. The IC process shall be documented in the subject’s case history, regardless 
of circumstance. 

 
 
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In the event the subject cannot read and/or write, and if allowed by local law, the IC shall be obtained 
through a supervised oral process. An independent witness (if applicable as per local regulation) must 
be present during this process. The ICF and any other information must be read aloud and explained to 
the prospective subject, and whenever possible, either the witness or prospective subject shall sign and 
personally date the ICF attesting that the information was accurately explained, and that IC was freely 
given. The source documentation shall provide the method used for communication with the 
prospective subject and the specific means by which the prospective subject communicated agreement 
to participate in the study. 
The original signed ICF must be filed in the hospital/clinical chart and/or with the subject’s study 
documents. 
The ICF and Authorization to Use and Disclose Personal Health Information/Research 
Authorization/HIPAA/other privacy language shall be available for monitoring and auditing if required 
by law. Any Medtronic personnel who support the study procedure must be able to review the 
subject’s signed and dated ICF and verify its completeness prior to proceeding with the study 
procedure. In the event the Medtronic personnel identify the ICF as being incomplete, the study 
procedure will not be allowed to occur until the consent of the subject can be adequately and 
appropriately obtained. 
8.4. Enrollment / Baseline 
When a patient and the Principal Investigator or authorized designee (if applicable) signs and dates the 
ICF, the patient is considered a subject enrolled in the study. The date the subject signed the ICF must 
be documented in the subject’s medical records. Enrollment can be a stand-alone visit or can occur on 
the same day as the baseline visit. Medtronic shall be notified (via Enrollment eCRF) as soon as possible 
to aid in enrollment tracking. Once consent is obtained, report adverse events, device deficiencies, 
study deviations, system modifications, and subject exits or deaths as they occur. 
The following information is required to be collected at the baseline visit: 
• 
Confirmation of Inclusion/Exclusion Criteria 
o It is recommended to perform a pre-implant anatomy evaluation (see section 8.4.1) 
• 
Demographics 
• 
Physical exam: A basic physical exam will be performed, including height and weight  
• 
Relevant medication and relevant cardiovascular medical history 
• 
Relevant surgical history 
• 
Primary indication for ICD implant 
• 
Echocardiographic data within the last 6 months 

 
 
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• 
SF-12 quality of life survey 
• 
Chest radiograph, standing tidal inhalation breath hold (see Table 4) 
o Radiographs shall be sent to Medtronic (see section 8.9) 
Table 4: Chest Radiograph collection during Baseline Visit 
Visit 
Image Collection 
Baseline 
• 
Standing PA  Tidal inhalation breath hold 
• 
Standing LAT  Tidal inhalation breath hold 
 
 Subject Pre-implant Anatomy Evaluation  
Assess the subject in a supine position to evaluate potential abdominal interference to safely access 
substernal space and operator’s ability to palpate xiphoid process, costal-rib margins and left sternal 
border to confirm the subject does not meet exclusion criterion 6.  
Review the baseline chest radiographs. It is also recommended to review a CT-scan (cardiac gated 
preferred) or MRI (taken within the last year) for the first 3 subjects at minimum, for each implanter. 
Imaging may help with pre-procedure planning and assessment of the subject’s anatomy. If the 
implanter feels the subject has unfavorable mediastinal anatomy, the procedure shall not be 
attempted, and the subject shall be exited from the study (see section 8.19 Subject Withdrawal or 
Discontinuation).  
If collected/reviewed, send CT-scan and/or MRI to Medtronic (see section 8.9). This information will be 
used to further characterize clinical results and anatomical considerations. 
8.5. Implant Visit 
It is recommended that the implant visit occurs within 30 days of study enrollment.   
 Antibiotic and Infection Control Strategies  
Prophylactic antibiotic administration per standard of care (e.g., as specified by the site policies) is 
required. Standard hospital procedures shall be followed regarding antibiotic therapy for ICD 
implantation.  
 

 
 
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 Anticoagulation 
It is required that subjects on anticoagulants have oral and/or systemic anticoagulants withheld peri-
procedurally in order to reduce risk of bleeding/hematoma, as follows: 
Pre-procedure: 
• 
Withhold anticoagulants per local protocol.  
• 
Follow the treatment procedures suggested by the drug manufacturer for timing of temporary 
discontinuation. 
• 
Recommendations by anticoagulant type include: 
o Suspension of novel oral anticoagulants (NOACs) ≥24 hours pre-procedure 
o Suspension of heparin ≥6 hours pre-procedure 
o Suspension of low molecular weight heparin ≥72 hours pre-procedure 
o Suspension of warfarin ≥48 hours pre-procedure 
 
Post-procedure: 
• 
It is recommended to resume oral anticoagulation as soon as possible post-procedurally unless 
clinically contraindicated (e.g. effusion observed).  
 
• 
Post-procedure anticoagulation should be resumed as soon as possible unless clinically 
contraindicated in patients who have had AF for ≥ 48 hours in duration prior to the implant 
procedure and who convert to sinus rhythm during defibrillation testing to diminish the risk of peri-
procedural stroke. 
 
Document all medication changes on the Medications eCRF. 
 Dual antiplatelet therapy 
Patients on dual antiplatelet therapy will be treated per standard of care, at physician discretion. 
 Fluoroscopy and Photography 
Prior to inserting the sternal tunneling tool into the mediastinal space, the investigator is required to 
review AP and Lateral fluoroscopy to determine the best incision location and angle of entry. The 
investigator should consider the subject’s BMI and abdomen when in the supine position, as it may 
challenge safe tool utilization. If the investigator does not believe he/she can maintain close proximity 

 
 
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to, or contact with, the posterior of the sternum with the tip of tunneling tool, the investigator should 
not proceed with the EV ICD implant procedure.  
In the event that the investigator does not proceed with the implant procedure: 
• 
AP and lateral fluoroscopic images or videos must be sent to Medtronic. These data will help 
further the understanding of anatomic variances for future procedure development considerations.  
In cases where the investigator does proceed with the implant procedure: 
• 
Collect fluoroscopy cine recordings during the substernal tunneling with the sternal tunneling tool 
and introducer as well as during EV ICD lead placement.  
• 
Two fluoroscopy cine images (AP and Lateral) are required of the final EV ICD lead placement and 
device placement for one full respiration cycle.   
• 
Fluoroscopy cine recordings and cine images will be will be sent to Medtronic (see section 8.9).  
 
Photography/ Videography 
If allowed per local regulations and accepted by the subject in the Informed Consent Form, Medtronic 
personnel attending the Implant Visit may take pictures of and/or videotape the implant procedure for 
training, education, and/or research purposes. These photographs and/or video recordings will not 
display any identifiable features of the subject. The original files will be kept at the hospital and copies 
will be sent to Medtronic.  
 Implant Procedure Steps 
Prior to performing the implant procedure, it is important that implanting investigators read and 
understand the Instructions for Use (IFU) that accompanies each device and undergo documented 
training by Medtronic.  
It is strongly recommended to use general anesthesia with cardiac monitoring during the implant 
procedure to prevent subject movement and minimize the likelihood of adverse events during 
procedure. Additionally, general anesthesia will afford a greater level of cardiac monitoring compared 
to what is practiced when patients are under conscious sedation. 
If the procedure is aborted at any point, refer to section 8.19 for additional instructions. 
The proposed procedure steps are listed in Table 5. The steps are strongly recommended unless 
otherwise noted as required steps.  

 
 
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Table 5: Outline of the proposed implant procedure steps 
Implant Step 
Procedure + Imaging 
1. Subject Assessment  
• 
Review pre-procedure chest imaging.  
• 
Required: Pre-procedural fluoroscopy in both Lateral and AP views is 
required prior to starting the implant procedure to assist in 
determining sub-xiphoid incision location for the patient anatomy, to 
determine whether the sternal tunneling tool tunnel rod curvature 
needs adjustment based on subject anatomy, to assist in sternal 
tunneling tool entry into the substernal space to inform the angle of 
insertion, and identification of appropriate device pocket location. 
• 
If the implanter cannot find a way to achieve or maintain consistent 
contact or close proximity between the distal tip of the tunneling rod 
and the sternum during insertion or advancement, the procedure 
should be stopped. 
• 
Required: If subject presents in atrial fibrillation, perform a pre-
procedure TEE to ensure the absence of LA or LV thrombus. 
2. Subject Preparation 
and Drape 
• 
Place 1 set of External Defibrillation Patches in locations that will not 
compromise the implanted system defibrillation vector or sterile 
operating field. 
• 
Position left arm to allow full lateral fluoroscopy and pocket incision 
access on left mid-axillary chest. 
• 
Determine ICD pocket location using fluoroscopy (AP & Lateral 
views) and the cardiac silhouette as guidance with demonstration 
lead and ICD.   
• 
Draw surface landmarks on chest, including sternal midline, left 
sternal border, xiphoid process, costal margins, top of cardiac 
silhouette and incision location and device pocket location. 
• 
Perform sterile preparation of the chest for implant per Standard of 
Care. 
• 
Drape patient chest to provide sterile operating field to access the 
sub-xiphoid and device pocket incisions. 

 
 
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Implant Step 
Procedure + Imaging 
3. Sternal Tool and 
Introducer Preparation 
• 
If needed, manually bend the tunneling rod of the sternal tunneling 
tool to a curvature suitable for the patient’s anatomy. The angle 
should allow for the tunneling rod tip to remain in contact with (or 
as close as possible to) the posterior of the sternum during 
tunneling.  
• 
Prepare introducer sheath according to manufacturer’s instructions 
for use and load onto the tunneling rod of sternal tool. 
• 
Attach a pre-filled saline syringe (10 cc) to hemostasis valve side-port 
on introducer with valve open for the implant procedure. 
4. Sub-Xiphoid Access 
• 
Make an incision below the xiphoid process and left of sternal 
midline.  Anatomical variation adjustments may be necessary: 
o Consider the margins of the left costal rib and xiphoid 
process.  A lower incision may be required in larger patients 
to allow for shallow blunt dissection and <30-degree angle of 
a medical instrument or tunneling rod insertion. 
5. Blunt Dissection of 
Diaphragmatic 
Attachments 
• 
Use a fingertip and/or curved Kelly hemostat to dissect through 
diaphragmatic attachments and confirm the tissue plane using 
lateral fluoroscopy for visualization.  
• 
Once the implanter has completed blunt dissection and has entered 
the mediastinal tissue plane, if resistance is felt (e.g., fibrotic 
attachments between heart and sternum), abort procedure. 
• 
Pre-lay 2 sutures into the rectus fascia (to later secure lead 
anchoring sleeve). 
6. Substernal Tunneling 
Procedure (Zone 1) 
• 
Insert prepared sternal tunneling rod using full Lateral fluoroscopy 
into anterior mediastinum. Keep tip of tunneling rod in contact or 
close to xiphisternal junction and sternum during insertion. 
• 
Tunnel approximately midline or just left of sternal midline and no 
further than the top of cardiac silhouette, as determined by AP 
Fluoroscopy and surface landmarks.  Keep tunneling rod in contact 
with or close to the posterior of sternum. If any resistance is felt, 
stop and confirm tunneling tool location in alternate fluoroscopic 
view. Redirect tunneling rod under the sternum. If patient has COPD 
or lungs crossing midline are suspected, consider tunneling during 

 
 
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Implant Step 
Procedure + Imaging 
end-expiration apnea. 
• 
Confirm the pre-filled saline syringe (10 cc) is connected to 
hemostasis valve side-port on introducer sheath with valve open. 
• 
Retain the sheath in position, then slowly remove the sternal 
tunneling tool from the sheath and incision. 
7. EV ICD Lead 
Insertion and 
Deployment 
• 
Use AP fluoroscopy to insert the lead to the distal tip of the 
introducer sheath. 
• 
Required Lead Orientation: Defibrillation Coils toward subject’s right 
chest; Pace/Sense Rings toward patient’s left chest.  
• 
Position the lead with respect to the cardiac silhouette and intended 
ICD location. 
• 
Deploy the lead by withdrawing the sheath out of the incision to 
expose the electrodes over cardiac silhouette for achieving adequate 
sensing, pacing and defibrillation. Retain the sheath until completion 
of Step 8.  
• 
In the event of the lead deployment in the opposite orientation (Coil 
1 and Coil 2 electrodes toward patient’s left lateral border), it is 
recommended to re-advance the introducer over the lead body to 
the distal tip. 
• 
Next, withdraw the lead and reinsert in the required orientation 
prior to acute testing.  
• 
Do not reinsert the lead through the introducer valve more than 
three times during the procedure. If this occurs, use a new lead. 
 

 
 
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Implant Step 
Procedure + Imaging 
8. Assessment of EV 
ICD Lead 
• 
Evaluate R-wave signal amplitude for Ring1-Ring2 configuration, 
through one full respiration cycle, using Medtronic CareLink 
Programmer Model 2090 Analyzer. 
o Set up the 2090 Analyzer to new R-wave filter, ODO mode.  
Set sensitivity to appropriate setting. 
o Record the measured sensing values. 
• 
If R-wave amplitude is < 1mV for the Ring1-Ring2 configuration, or P-
wave or T-wave oversensing is suspected, attempt repositioning or 
re-tunneling the lead. If R-wave amplitude remains < 1mV, the 
implant shall be abandoned, and the implant of an alternative ICD 
system should be considered.  
• 
Remove introducer sheath prior to sub-xiphoid suture sleeve 
fixation. 
9. Sub-Xiphoid Suture 
Sleeve and Lead 
Fixation 
• 
Required: Use a minimum of three non-absorbable sutures with high 
tension force to fixate anchoring sleeve to lead body in sub-xiphoid 
incision using each of the three grooves.  
• 
Required: Tie two non-necrosing sutures to the fascia, then tie to 
lead anchoring sleeve grooves. Next, tie one suture onto the lead 
anchoring sleeve to secure to the lead body. 
10. Create EV ICD 
device pocket 
• 
Use fluoroscopy to confirm defibrillation vector based on final lead 
placement and cardiac silhouette for EV ICD device location. 
• 
Create device pocket incision near the left mid-axillary chest to form 
an optimized vector with the implanted lead. 
11. Transverse 
Subcutaneous 
Tunneling Procedure 
(Zone 2) 
• 
Insert distal tip of transverse subcutaneous tunneling rod in sub-
xiphoid incision, above/anterior to the costal rib margin and advance 
into the device pocket incision. 
• 
Remove handle to expose lead channel and insert lead connector pin 
into channel. 
• 
Pull tunneling rod with lead inserted in the channel into the device 
pocket incision.  Remove the transverse subcutaneous tunneling rod 
through the pocket incision. 

 
 
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Implant Step 
Procedure + Imaging 
12. Device Pocket and 
Sub-Xiphoid Incision 
Closure 
• 
Fixate device header against fascial plane using non-absorbable 
suture in the holes provided. 
• 
If the TYRXTM Envelope is used, this shall be documented. 
• 
Remove air from incision and close the pocket and sub-xiphoid 
incisions, at least one layer, prior to device testing.  
• 
Final closure of incisions shall be in at least three layers, and wound 
dressings shall be applied per standard of care. 
13. Required Cine of 
final lead and device 
placement 
• 
Required: Cine, both AP & Lateral views during a full respiration 
cycle, to document final lead and EV ICD position. 
 
14. EV ICD Device 
Testing 
• 
Interrogate the EV ICD device and perform electrical testing (sensing, 
pacing, impedance), as described in section 8.5.6. 
• 
Perform defibrillation testing protocol, as described in section 8.5.7. 
 
 Implant Testing – EV ICD System 
Perform the following tests of the EV ICD System after the EV2401 lead is connected to the EV ICD 
device and the device is placed into the pocket.  
8.5.6.1. Sensing Testing 
Perform an RV sensing test. Set ICD RV sensing vector to Ring1-Ring2. Adjust sensing parameters to 
avoid T-wave oversensing, P-wave oversensing, or other oversensing. Once configured, perform the 
Sensing Test. Print the Sensing Test Report on the programmer to PDF or paper and store at site. 
Evaluate alternate sensing vectors as necessary. Program determined sensing settings. 
The R-wave amplitude for sensing shall be greater than or equal to 1mV for the Ring1-Ring2 
configuration. 
If the R-wave amplitude is less than 1mV for the Ring1-Ring2 configuration after all troubleshooting 
attempts have been exhausted (refer to step 8 in Table 5), the EV ICD implant shall be abandoned and 
the implant of an alternative ICD system should be considered. 

 
 
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8.5.6.2. Impedance Testing 
Subthreshold impedance will be measured for the following electrode pairs:  
• 
Ring1 to Ring2 
• 
Ring1 to Coil2 
• 
High Voltage 
Print the Lead Impedance Test Report to PDF or paper and send to Medtronic. 
8.5.6.3. Pacing Testing  
Pacing capture threshold testing will be performed, potentially in multiple vectors: Ring1-Coil2, Ring1-
Ring2, Coil2-Coil1.  Pacing capture is defined as at least three consecutive captured beats. 
At the conclusion of pacing capture threshold testing, it is recommended to leave pacing settings at the 
shipped nominal values until pre-hospital discharge.  
Print final capture threshold report to PDF or paper and send to Medtronic. 
  Induction and Defibrillation Testing 
To ensure subject safety in an ambulatory setting, sustained shockable ventricular arrhythmia (SSVA) 
induction and defibrillation testing is required at implant. Adjust device programming to ensure 
adequate safety margins for sensing and defibrillation during SSVA induction testing.  
The testing protocol may require up to six successful SSVA episodes induced and up to 10 EV ICD 
shocks delivered (Figure 7).  
8.5.7.1. General Requirements 
Induction of SSVA will be achieved using one of the following methods: 
• 
Burst Induction (Coil2-Coil1, 40V). 
• 
T-shock (up to 20J). 
If a subject cannot be induced using these methods, other methods may be employed at the discretion 
of the investigator (e.g., EP catheter). The investigator may choose to attempt induction on another 
day prior to discharge. If the investigator determines the subject cannot be induced, the EV ICD System 
must be removed (refer to section 8.5.8).  
Ensure a Wavelet template is collected and EV ICD detection is enabled prior to induction. If the 
subject's health is at risk, defibrillation testing should be suspended or terminated. 

 
 
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Ensure an external transthoracic defibrillation system is present and ready to deliver rescue shocks 
during defibrillation testing, and at least one set of rescue patches are in place in locations that will not 
compromise the implanted system defibrillation vector or sterile operating field. 
It is recommended to wait five minutes between the end of an SSVA episode and subsequent induction 
to ensure that the patient is hemodynamically stable. Waiting period after failed induction attempts is 
at the investigator's discretion. 
Defibrillation testing may continue on a future day if episodes remain within the testing protocol, but 
lead revision is not permitted on a future day if the subject has resumed anticoagulation.   
Anticoagulation should be resumed as soon as possible post-procedurally unless clinically 
contraindicated (e.g. effusion observed) in subjects who have presented in atrial fibrillation for ≥ 48 
hours in duration prior to the implant procedure and who convert to sinus rhythm during defibrillation 
testing to diminish the risk of peri-procedural stroke. 
Reminder:  After each induced SSVA episode, save-to-media files shall be collected (see section 8.10). 
Print the live strip for the duration of each SSVA episode. Retain a copy of the live strip for each 
episode not recorded by the ICD. If requested, send a copy of the live strip to Medtronic (e.g., a scan). 
Print the VT/VF episode report to PDF or paper and store at the site.  
Record shock outcome and shock impedance (if available) for each EV ICD and rescue shock.  A shock 
will be considered successful if it results in termination of the induced SSVA episode, with termination 
defined as a return to normal intrinsic rhythm or to a supraventricular tachycardia before the next 
shock is given. Additional processing of the VF sensing data may be performed after implant data 
collection. 
8.5.7.2. Testing and Programming Defibrillation Therapy 
Defibrillation testing success is defined as meeting one of the following criteria: 
a. Single SSVA conversion at 20J, or  
b. Conversion of two consecutive episodes of SSVA at 30J in final system configuration. 
Follow the defibrillation testing as outlined in Figure 7, beginning at Episode 1 (20J). The following 
requirements shall be observed while conducting defibrillation testing: 
• 
Defibrillation at a given energy will be deemed successful if SSVA is terminated, regardless of 
whether the shock is delivered manually or automatically by device.  
• 
In one of the two consecutive SSVA episodes, up to two 30J shocks are permitted. 

 
 
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• 
To achieve final system configuration, changing the position of the ICD generator and/or the 
lead, or changing shock polarity is permitted. 
• 
If the device or lead position are altered (e.g., position changed as part of troubleshooting), 
defibrillation success must be demonstrated with the new system configuration. 
• 
If defibrillation protocol episodes are not exhausted, remaining episodes may be used on a 
subsequent day (e.g., next day or during the admission) to complete the defibrillation testing 
protocol 
• 
For the first episode following the 20J therapy or the first 30J episode following a 
“Troubleshoot System” step in Figure 7, program Rx1 polarity to either STD or REV, and 
program Rx2 polarity the opposite of Rx1 polarity. 
• 
If the episode follows a defibrillation success at 30J, and the previous episode had a 
defibrillation success with Rx1, program Rx1 and Rx2 to the polarity of Rx1 in the previous 
episode. 
• 
If the episode follows a defibrillation success at 30J, and the previous episode had a 
defibrillation success with Rx2, program Rx1 to the same polarity as Rx2 in the previous 
episode and program Rx2 off. 

 
 
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Figure 7: Diagram outlining the process of SSVA induction and defibrillation testing 

 
 
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8.5.7.3. Testing and Programming VF Detection 
VF detection success at implant is defined as successful VF detection in a single SSVA episode in the 
Ring1-Ring2 configuration at a value greater than or equal to 0.2 mV (e.g., 0.2, 0.45, or 0.6 mV). VF 
detection and defibrillation success do not need to be demonstrated on the same episode(s), but each 
must be demonstrated in the final system configuration. 
Follow the VF detection testing as outlined in Figure 8, beginning at Episode 1. This aligns with Episode 
1 for Defibrillation Testing outlined in Figure 7. The following requirements shall be observed while 
conducting VF detection testing: 
• 
The VF detection shall be demonstrated in the Ring1-Ring2 vector with a Number of Intervals to 
Detect (NID) setting of 30/40. 
o If VF detection is demonstrated in the Ring1-Ring2 vector, the remaining induction 
attempts may be programmed with a NID setting of 18/24. 
o Redetect NID shall be programmed to 9/12 when Rx2 is enabled. 
• 
Begin testing with VF Sensitivity programmed to Ring1-Ring2, 0.45 mV.  
o Use this setting when restarting testing to evaluate a new lead position. 
• 
If the first programmed setting is unsuccessful, program VF Sensitivity to Ring1-Ring2, 0.2 mV. 
• 
If the second programmed setting is unsuccessful, reposition the lead and test again with the first 
programmed VF Sensitivity setting of Ring1-Ring2, 0.45 mV. 
• 
If VF detection is demonstrated in the Ring1-Ring2 vector, program VF Sensitivity to Ring1-Can, 
0.45 mV. 
• 
Once VF detection is demonstrated in Ring1-Ring2 and attempted in Ring1-Can, VF detection shall 
be programmed to the Ring1-Ring2 vector for remaining induction attempts.  
o If desired, additional margin can be assessed by programming VF Sensitivity to 0.6 mV, 
otherwise it is recommended to complete the remaining induction attempts with 
Sensitivity programmed to 0.15 mV.xv 
• 
Additional inductions beyond those specified in Figure 7 are allowed if needed per medical 
judgment (e.g., to program sensitivity or to obtain supplementary information on an alternate 
vector). 
• 
If the VF detection success is demonstrated in the Ring1-Ring2 vector, and the lead position is 
preserved, it is not necessary to re-demonstrate VF detection in the Ring1-Ring2 configuration, 
even if the device position is altered (e.g., as part of troubleshooting). 
                                                            
xv In instances where detection has been demonstrated in the Ring1-Ring2 vector at 0.45 mV and the lead is not repositioned, 
subsequent episodes may be programmed Ring1-Ring2 at 0.15 mV, Ring1-Can at 0.45 mV, or Ring1-Ring2 at 0.6 mV to check 
for additional margin. Programming VF Sensitivity to 0.6 mV increases the likelihood that VF Detection will not occur, and 
delivery of a manual shock will be necessary.  

 
 
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• 
If the lead position is altered (e.g., as part of troubleshooting), previously demonstrated VF 
detection success is invalidated and success must be demonstrated with the new system 
configuration with an NID setting of 30/40. 

 
 
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Figure 8: Diagram outlining the process of VF sensing margin testing 
 
1 In instances where detection has been demonstrated in the Ring1-Ring2 vector at 0.45 mV and the lead is not repositioned, VF Sensitivity for subsequent episodes may be 
programmed to Ring1-Ring2 at 0.15 mV, Ring1-Can at 0.45 mV, or Ring1-Ring2 at 0.6 mV to check for additional margin. Programming VF Sensitivity to 0.6 mV increases the likelihood 
that VF detection will not occur, and delivery of a manual shock will be necessary. 
2 Ring1-Ring2 equal to or more sensitive than 0.20 mV programming option is only available if Ring1-Ring2 was tested successfully at 0.6 mV; Ring1-Ring2 equal to or more sensitive 
than 0.15 mV programming should be used if 0.6 mV was not successfully tested. 

 
 
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8.5.7.4. Implant Defibrillation Troubleshooting Recommendations 
Prior to inducing and throughout the defibrillation protocol, it is recommended to consider the 
following to improve defibrillation outcome or troubleshooting in the event of failure of first 
episode(s):  
• 
Check for/resolve pneumothorax 
• 
Check for/resolve high impedance values 
• 
Check for/resolve air in tunnel (e.g., fluoroscopy) 
• 
Check for/resolve air in pocket (e.g., flush with saline or antibiotic wash, massage air out of 
pocket) 
• 
Check for/resolve gastric bubbles (gas) 
• 
Press on device pocket during testing 
• 
Perform defibrillation during held end tidal expiration (end expiration apnea) 
• 
If all of the above measures are exhausted, evaluate the position of the EV ICD device and the EV 
ICD Lead. If required, consider repositioning of EV ICD generator or EV ICD lead.xvi 
• 
Allow time (e.g., next day or during the admission) to minimize transient factors affecting 
defibrillation success 
Note: Troubleshooting attempts after Episode 5 (Figure 7) may not leave enough remaining episodes to 
confirm both Defibrillation and VF detection success.  
8.5.7.5. Programming Requirements at End of Implant Procedure 
At the end of the procedure, VF Detection shall be ON and VF Therapies and Pacing therapies shall be 
programmed OFF until Pre-Hospital Discharge evaluation to prevent oversensing/undersensing prior to 
proper evaluation of threshold once the subject is ambulatory. While VF Therapies are OFF, the subject 
shall have cardiac monitoring.  
 Subject Exit for Incomplete Implant Visit 
The subject shall be exited if any of the following occur during the implant visit: 
                                                            
xvi Lead revision is not permitted if the subject has resumed anticoagulation. Post-procedure anticoagulation should be 
resumed as soon as possible unless clinically contraindicated (e.g. effusion observed) in subjects who have had atrial 
fibrillation for ≥ 48 hours in duration prior to the implant procedure and who convert to sinus rhythm during defibrillation 
testing to diminish the risk of peri-procedural stroke. 

 
 
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• 
Incomplete Placement of Lead and/or Device – The EV ICD System is not fully implanted. 
• 
Incomplete Defibrillation Testing Protocol – The subject cannot complete the entire defibrillation 
testing protocol because they were not inducible or failed to induce a sufficient number of 
episodes. 
o 
Note: If the subject completes the initial implant procedure without completing the 
defibrillation testing protocol, the subject may be brought back prior to hospital 
discharge to complete the remainder of the defibrillation testing protocol, as outlined in 
Figure 7. 
• 
Failure of Defibrillation Testing Protocol – The subject completes the defibrillation testing protocol 
but does not meet the criteria for success for defibrillation testing. 
• 
Inadequate Sensing – The subject cannot achieve an R-wave ≥ 1 mV for the Ring1-Ring2 sensing 
vector after troubleshooting methods are exhausted. 
• 
Inadequate SSVA Detection – The subject cannot achieve successful VF detection in a single SSVA 
episode in the Ring1-Ring2 configuration at a value greater than or equal to 0.2 mV after 
troubleshooting methods are exhausted. 
If the subject does not complete the implant visit due to any of the reasons specified above, the EV ICD 
System shall be explanted, and the subject shall be followed and assessed for AEs through 30 days or 
until procedure or system related AEs have been resolved, at which point the subject can be exited (see 
section 8.19). If the subject receives an alternative system (e.g., S-ICD or TV ICD), any AEs related to the 
alternate system will be recorded during the course of subject participation, but will not be considered 
related to the EV ICD System. 
Incomplete placement of the lead and/or device, and incomplete or failed electrical or defibrillation 
testing (including prolongation of hospital stay by allowing time to minimize transient factors affecting 
defibrillation) are not considered adverse events; however, any adverse events occurring during an 
unsuccessful implant attempt (e.g., subject allergy to electrodes used during implant) must be recorded 
and classified on an AE eCRF. Unsuccessful EV ICD system implants and/or failed defibrillation testing 
shall be evaluated for reporting as a device deficiency. 
If the EV ICD System is explanted or repositioned after initial implant procedure but prior to pre-
hospital discharge, this shall be captured on a System Modification eCRF.  
8.6. Pre-Hospital Discharge 
Perform the following pre-hospital discharge tests of the EV ICD System at any time after implant, but 
prior to discharge. Prior to the subject being discharged, VF Therapies shall be programmed ON and 
pacing therapies, as appropriate, should be programmed ON.  

 
 
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Programming requirements and recommendations at PHD are outlined in Table 6. 
Table 6: PHD Programming Requirements and Recommendations 
Required Programming 
Recommended Programming 
Initial NID for VF 
Therapies  
Minimum 30/40 
VF Sensing 
Per implant testing 
results (most 
sensitive setting) 
All Rx 
40 J 
VF Sensing if PHD 
Troubleshooting is 
required 
Per PHD testing 
results (most 
sensitive setting) 
Pause Prevention 
Monitor, 5 s 
Post Shock Pacing 
Per physician 
recommendation; 4 V 
margin minimum 
 
 
ATP 
At physician 
discretion; 4 V margin 
minimum 
 
An initial interrogation save-to-media file shall be collected at the beginning of the visit, and a final 
(interrogate all) save-to-media file shall be collected at the end of the visit (see section 8.10). 
 Sensing Testing 
At the Pre-Hospital Discharge visit, perform the Sensing Test in the following postures: 
• 
Sitting 
• 
Supine 
• 
Lying on left 
• 
Lying on right 
Print the Sensing Test Report to PDF or paper and send a copy of the report to Medtronic. 
 Impedance Testing 
Perform the Impedance Test in a sitting posture. If necessary, impedance testing in additional postures 
may be performed. Print the Impedance Test Report to PDF or paper and send a copy of the report to 
Medtronic.  

 
 
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 Pacing Testing 
Perform pacing testing in a supine posture. If necessary, pacing testing in additional postures may be 
performed. The following configurations may be evaluated: Ring1-Coil2, Ring1-Ring2, Coil2-Coil1. 
Pacing capture is defined as at least three consecutive captured beats. 
The clinician will evaluate for pacing sensation during testing. Note: Pacing sensation or discomfort 
observed during testing will not be considered a reportable adverse event.  
If post pace oversensing is observed, sensing parameters should be adjusted to eliminate or minimize 
oversensing. Print the final capture threshold report to PDF or paper and send a copy to Medtronic. 
  Imaging  
Collect the chest radiographs at Prehospital Discharge (PHD) per Table 7 and send to Medtronic (see 
section 8.9). Additional radiographs may be collected at the discretion of the physician at any post-
implant time point if electrical testing at follow-up reveals deterioration in sensing or pacing 
performance.  
Table 7: Chest Radiograph collection during Pre-Hospital Discharge Visit 
Visit 
Image Collection 
Pre-hospital Discharge Visit 
• 
Standing PA  Tidal inhalation breath hold 
• 
Standing LAT  Tidal inhalation breath hold 
Collection of echocardiogram at pre-hospital discharge may be performed per physician discretion, for 
example, if suspicion of potential pericardial effusion exists. 
If additional images (CT scans, radiographs, TEE, MRI or other imaging modalities) are collected at 
physician discretion throughout the duration of the study, it is requested that a copy of the images be 
sent to Medtronic (see section 8.9).  
8.7. Scheduled Follow-up Visits 
Subjects will undergo assessments at scheduled follow-up visits to characterize the safety and efficacy 
of the EV ICD System.  
Medtronic will provide the target dates and windows for each follow-up visit to the implanting site. 
Follow-up visit windows open on the Window Start date and remain open as defined in Table 8. It is 
recommended that subjects are scheduled as close as possible to the target date for a given follow-up 
visit. 

 
 
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Table 8: Scheduled visit windows 
Study Follow-up Visit 
Window 
(Calculated days post-implant procedure) 
Window Start (days 
post-procedure) 
Target (days post-
procedure) 
Window End (days 
post-procedure) 
2 Week 
7 
14 
50 
3 Month 
90 
90 
120 
6 Month 
182 
182 
210 
12 Month (1 Year) 
335 
365 
395 
18 Month 
518 
548 
578 
24 Month (2 Year) 
701 
730 
760 
30 Month 
883 
913 
943 
36 Month (3 Year) 
1066 
1096 
1126 
42 Month 
1248 
1278 
1308 
48 Month (4 Year) 
1431 
1461 
1491 
 
All subjects with an implanted EV ICD System will remain in the study and be followed at pre-defined 
study visits until official study closure. After their study participation ends, the EV ICD System will 
remain implanted and the subject will be provided with standard medical care by their physician. 
At all follow-up visits, photographs of the device pocket and sternal incision are recommended in case 
an infection related to the EV ICD System is suspected or diagnosed. These photographs will not display 
any identifiable features of the subject. The original files will be kept at the hospital and copies will be 
sent to Medtronic. Report any adverse events, including infections, per section 10.5.  
  2-Week Follow-up Visit 
The following data will be collected at the 2-week follow-up visit: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests (see section 8.7.6) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 

 
 
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• 
Medication Log updates 
 3-Month Follow-up Visit 
The following data will be collected at the 3-month follow-up visit: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests (see section 8.7.6)) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 
• 
Medication Log updates 
 6-Month Follow-up Visit 
The following data will be collected at the 6-month follow-up visit: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests (see section 8.7.6)) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 
• 
Medication Log updates 
• 
SF-12 quality of life survey 
• 
Florida Patient Acceptance Survey (FPAS) (only for subjects who complete their ICF in English) 
• 
Chest Radiographs per Table 9 (required for subjects participating in chronic defibrillation 
testing, for other subjects this is recommended) (see section 8.9) 

 
 
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• 
Chronic Defibrillation Testing, for those subjects who consent to this testing (see CIP 
Addendum for 6-Month Defibrillation Testing and Appendix I: Chronic Defibrillation Testing 
Protocol) 
Table 9: Chest Radiograph collection during 6-Month Follow-up Visit. 
Visit 
Image Collection 
6-Month Visit 
• 
Standing PA  Tidal inhalation breath hold 
• 
Standing LAT  Tidal inhalation breath hold 
Chest radiographs should be reviewed by the physician for lead stability at the six-month visit. Chest 
radiographs for subjects participating in chronic defibrillation testing shall be sent to Medtronic (see 
section 8.9), and for all other subjects shall be retained at the site and may be sent to Medtronic upon 
request.  
Prior to chronic defibrillation testing, both chest radiographs  and the EV ICD System’s electrical 
performance should be considered to decide whether or not to proceed with chronic defibrillation 
testing. If there is evidence for deterioration of electrical performance or  significant movement of the 
lead, the clinician may consider either changing the device programming or moving the lead (Note: lead 
repositioning involves a system modification and overall subject health and safety should be 
considered before proceeding) to ensure adequate functioning of the EV ICD System.  
 Long-term follow-up Visits 
Subjects will be followed up at 12 months post-implant and every 6 months thereafter until the study is 
closed. The following data will be collected at these visits: 
• 
Electrical Testing (Sensing, Impedance, and Pacing tests; see section 8.7.6) 
• 
Initial (interrogation) and final (interrogate all) save-to-media files (see section 8.10) 
• 
Adverse Event assessment 
• 
Device Deficiencies assessment 
• 
Healthcare Utilizations 
• 
Study Deviations 
• 
Other Cardiac Imaging 
• 
Medication Log updates 

 
 
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 Device Troubleshooting 
Device troubleshooting is generally required per standard of care for ICD systems and may require 
additional testing. Additional imaging or data collection may be necessary, and a DR220 Digital Holter 
Recorder (North East Monitoring, Inc.; investigational in Australia, Canada, New Zealand, and Japan) 
may be used for up to 24 hours of Holter monitoring. If additional data are collected, data shall be 
submitted to Medtronic.  
If troubleshooting includes a chronic defibrillation test, it is recommended to follow the steps outlined 
in Appendix I: Chronic Defibrillation Testing Protocol. After conducting a chronic defibrillation test, it is 
required to complete a Chronic Defibrillation Testing eCRF.  
 Electrical Testing 
Subjects’ medical records shall be made available prior to performing electrical testing. An initial 
interrogation save-to-media file shall be collected at the beginning of the visit, and a final (interrogate 
all) save-to-media file shall be collected at the end of the visit (see section 8.10).    
8.7.6.1. Sensing Testing 
At the 2-Week, 3-Month, 6-Month, and Long-Term follow up visits, perform the Sensing Test in a sitting 
posture. If necessary, sensing testing in additional postures may be performed. Print the Sensing Test 
Report to PDF or paper and send a copy of the report to Medtronic.  
8.7.6.2. Impedance Testing 
At the 2-Week, 3-Month, 6-Month, and Long-Term follow up visits, perform the Impedance Test in a 
sitting posture. If necessary, impedance testing in additional postures may be performed. Print the 
Impedance Test Report to PDF or paper and send a copy of the report to Medtronic.  
8.7.6.3. Pacing Testing  
At the 2-Week, 3-Month, 6-Month, and Long-Term follow up visits, perform pacing testing in a sitting 
posture. If necessary, pacing testing in additional postures may be performed. The following 
configurations may be evaluated: Ring 1-Coil2, Ring1-Ring2, Coil2-Coil1. Pacing capture is defined as at 
least three consecutive captured beats. If post pace oversensing is observed, sensing parameters 
should be adjusted to eliminate or minimize oversensing. Print the final capture threshold report to 
PDF or paper and send a copy to Medtronic. 

 
 
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8.8. Unscheduled Visits 
An Unscheduled follow-up visit is defined as any non-standard of care visit by the subject to the 
investigative study site due to the EV ICD System between CIP-required visits.  
If an Unscheduled Visit occurs: 
• 
Document any adverse events and/or device deficiencies on the associated eCRFs, as applicable.  
• 
Where possible, initial (beginning of the visit) and final (end of the visit) device interrogation data 
should be collected via a save-to-media file (see section 8.10).  
• 
If electrical testing is conducted, print the Testing Reports to PDF or paper and send a copy of the 
reports to Medtronic. 
8.9. Images and recordings 
All images and recordings shall be retained in the subject’s file. Copies of images sent to Medtronic 
shall be transferred in DICOM format.  
8.10. Save-to-Media Files  
When a save-to-media file/save-to-media files should be collected, a device interrogation (full 
summary interrogation/interrogate all is best practice) must be performed and saved in a digital format 
(.pdd) on a USB or other removable electronic media. Save-to-media files shall be sent to Medtronic, 
with a copy being maintained at the site in the subject’s file. It is recommended that data are not 
cleared during any interrogation. 
8.11. CareLink Transmissions 
At the time of CIP approval, CareLink will not be available for subjects implanted with the EV ICD 
System. In the event it becomes available, it is acceptable to collect and utilize data via CareLink 
transmissions. A CareLink file collected within a visit window will be considered equivalent to an in-
office save-to-media file, but a save-to-media file for in-office visits is preferred. If review of a CareLink 
transmission results in a subject visit to the study center between scheduled visit windows, an 
Unscheduled Visit eCRF shall be completed. 
8.12. Healthcare Utilizations 
Health Care Utilization (HCU) information will be collected when the utilizations are related to the 
following characteristics of the EV ICD System: 

 
 
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• 
All procedure, system, and accessory related adverse events  
• 
Shocks delivered by the EV ICD System (inclusive of inappropriate shocks and appropriate shocks 
delivered to treat ventricular arrhythmias) 
• 
Cardiovascular syncope  
All inpatient hospitalizations, outpatient hospital encounters, emergency department visits, clinic visits, 
urgent care, or rehab center utilizations associated with the characteristics listed above are considered 
reportable HCUs for this study. CIP-required utilizations (except unscheduled visits) should not be 
reported on HCU eCRFs. 
8.13. System Modification 
A System Modification eCRF form shall be completed in the event the EV ICD System requires an 
invasive modification after the subject has been transported out of the procedure room from their 
initial implant (e.g., explant, replacement, repositioning).  
Prior to a system revision a save-to-media file (initial, see section 8.10) shall be collected and the 
physician should consider the following actions: 
• 
Evaluate electrical performance 
• 
Reprogramming 
• 
Imaging (e.g., chest radiographs), images reviewed by the physician shall be sent to Medtronic 
(see section 8.9). 
• 
Chronic defibrillation test, it is recommended to follow the steps outlined in Appendix I: Chronic 
Defibrillation Testing Protocol. After conducting a chronic defibrillation test, it is required to 
complete a Chronic Defibrillation Testing eCRF. 
• 
Risk-benefit to subject   
Unless urgent, the physician should consult with a member of the steering committee for questions 
about moving forward with a system modification. 
In the event of a system modification where an EV ICD System remains in the body, the follow up 
schedule for the subject will remain unchanged. In cases where an EV ICD System is explanted and not 
replaced with an EV ICD System, the subject will be exited according to section 8.19.  
If the system modification involves replacing or repositioning the lead, the procedure shall be 
completed by a physician who has undergone EV ICD implant procedure training as specified by 
Medtronic. It is recommended to demonstrate at least a 10J safety margin. Repeat all data collection 
from the PHD visit (see section 8.6), including a final save-to-media file (see section 8.10).     

 
 
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8.14. Role of the Sponsor Representatives 
Sponsor representatives will provide support as required for the study under supervision of the 
Principal Investigator, including: 
• 
Provide study training, including but not limited to training on the: CIP, Informed Consent 
process, data collection tools, and regulations 
• 
Technical support in installing/uninstalling the programmer software into/from the 
Programmer manually or via the SDN  
• 
Technical support at all study visits under the supervision of the Principal Investigator, 
including device programming, but no data entry on eCRFs shall be performed by Medtronic 
personnel or their representatives at sites 
• 
A trained Medtronic representative may support a study investigator at the Implant Visit by 
proactively providing support and feedback during the implant procedure. 
• 
Sponsor representatives may conduct monitoring and auditing activities for this study. 
8.15.  Assessment of Efficacy  
Efficacy of the EV ICD System with regards to defibrillation testing success will be assessed per the 
primary efficacy objective at the implant visit (see section 12.5). In addition, efficacy of ATP and shock 
for termination of spontaneous ventricular arrhythmias will be characterized as part of the ancillary 
objectives (see sections 12.6 and 12.10). 
8.16.  Assessment of Safety 
Safety of the EV ICD System with regard to major complications related to the system or procedure will 
be assessed by way of the primary safety objective (see section 12.4). All Adverse Events will be 
collected throughout the study duration, starting at the time of signing the Informed Consent Form. 
The prevalence of these adverse events will further be summarized by MedDRA key terms (see section 
12.11). Additionally, any device deficiencies related to the EV ICD system or accessory will be collected. 
Further information on the collection of Adverse Events is discussed in section 10. 
8.17.  Recording Data 
This study will be conducted using an electronic data capture system (e.g., Oracle Clinical Remote Data 
Capture system, or OC RDC). The electronic data capture system, which allows the study sites to enter 
study data into the sponsor’s database over a secure internet connection, will be used to capture study 

 
 
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required eCRF information. The Principal Investigator or an individual delegated by the Principal 
Investigator is responsible for entering data for the study on the eCRFs. The Principal Investigator or 
Sub-Investigator designee (if allowed by local regulation) is required to approve all data on eCRFs via 
electronic signature. The data reported on the eCRFs shall be derived from source documents, and any 
discrepancies shall be explained in writing.  
Save-to-media files will be collected and stored at the site. Copies submitted to Medtronic should be 
sent via secure and compliant electronic file transfer services (e.g., Box) and/or secure mail. 
Programmer printouts will be collected in hard or electronic copy and stored at the site. Copies 
submitted to Medtronic shall be sent via secure and compliant electronic file transfer services (e.g., 
Box) and/or secure mail. 
Fluoroscopy /radiograph/ CT images, if collected, shall be stored on a CD/DVD or USB flash drive at the 
site. Copies submitted to Medtronic shall be sent via secure and compliant electronic file transfer 
services (e.g., Box) and/or secure mail.  
8.18. Deviation Handling 
A study deviation is defined as an event within a study that did not occur according to the Clinical 
Investigation Plan or the Clinical Trial Agreement. 
Prior approval by Medtronic is expected in situations where the investigator anticipates, contemplates, 
or makes a conscious decision to deviate. Prior approval is not required when a deviation is necessary 
to protect the safety, rights or well-being of a subject in an emergency or in unforeseen situations 
beyond the investigator’s control (e.g., subject failure to attend scheduled follow-up visit, inadvertent 
loss of data due to computer malfunction, inability to perform required procedures due to subject 
illness). 
For medically justifiable conditions which preempt a subject’s ability to complete a study-required 
procedure, it may be permitted to report only one deviation which will apply to all visits going forward. 
This may also apply for other unforeseen situations (e.g., the subject permanently refuses to complete 
a study required procedure and the data will not contribute to the primary endpoint analysis). 
However, prior approval from Medtronic is required for such situations. 
All study deviations must be reported on an eCRF regardless of whether medically justifiable, pre-
approved by Medtronic, an inadvertent occurrence, or taken to protect the subject in an emergency. In 
the occurrence of a corrupted device interrogation file, Medtronic may request a deviation to 
document that a readable interrogation file is unavailable. 

 
 
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Refer to section 14.7.2 for deviation reporting requirements and timeframes for reporting to 
Medtronic, Ethics Committee and/or regulatory bodies, as required per local law.  
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions (e.g., amend the Clinical Investigation Plan, conduct 
additional training, terminate the investigation). Repetitive or serious investigator compliance issues 
may result in initiation of a corrective action plan with the investigator and site, and in some cases, 
necessitate suspending enrollment until the problem is resolved or ultimately terminating the 
investigator's participation in the study. Medtronic will provide site-specific reports to investigators 
summarizing information on deviations that occurred at their investigational site on a periodic basis. 
Examples of study deviations include but are not limited to: 
• 
Failure to obtain proper Informed Consent 
• 
Failure to collect required study data (e.g., required imaging) 
• 
Inclusion criteria not met/exclusion criteria met at enrollment 
• 
Missing required save-to-media files 
8.19. Subject Withdrawal or Discontinuation  
Subjects may be exited from the study for reasons such as: 
• 
Subject has completed the study 
• 
Subject lost to follow-up 
• 
Subject death 
• 
Subject did not meet inclusion or met exclusion criteria or meets exclusion due to change since 
initial evaluation 
• 
Subject chooses to withdraw (e.g., consent withdrawal, relocation to another geographic 
location) 
• 
Subject does not have or no longer has EV ICD System implanted 
• 
Subject completes but does not pass defibrillation testing prior to pre-hospital discharge 
• 
Investigator deems withdrawal necessary (e.g., medically justified) 
A withdrawn subject will be treated according to standard of medical care and will not be replaced. 
Subjects will be included in the analyses up to the time that consent was withdrawn, or up to the time 
that the subject is exited.  
Subjects who had undergone an implant attempt and did not have an EV ICD System implanted or had 
their EV ICD System removed without replacement with an EV ICD System may be exited by phone at 

 
 
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the end of 30 days following implant attempt or system removal, or once all system and procedure-
related AEs are resolved.  
The following information is required to be collected at study exit: 
• 
Reason for exit (this shall be documented on the Study Exit eCRF and in the subject’s medical 
record) 
• 
Save-to-media 
In the case that the subject is determined to be lost to follow-up, details of a minimum of two attempts 
and the method of attempt (e.g., one letter and one phone record or two letters) to contact the subject 
must be recorded. In addition, follow the regulations set forth by the governing Ethics Committee. 
Upon withdrawal from the study, no further study data will be collected, and no additional study visits 
will occur for the subject.  
9. Risks and Benefits 
9.1. Potential Risks 
Medtronic follows rigorous Quality Assurance and Control procedures throughout the development 
and clinical study of a research system. The formal Hazard/ Risk Analysis for the EV ICD System is 
performed according to ISO 14971:2012 (Medical Device Risk Management) and is used to ensure that 
the level of risk is acceptable and reduced as low as possible prior to starting the EV ICD Pivotal Study. 
  
The EV ICD System is assessed via a System Hazard Analysis to ensure all potential risks, at individual 
component and at system-levels, are evaluated and minimized via risk controls. The subject risk 
assessment evaluates potential risks associated with: system implant/explant, biological compatibility, 
therapy delivery, diagnostic data integrity and security, and potential failure modes associated with the 
finished devices. Risk control strategies for the EV ICD Pivotal Study risks were developed by a cross-
functional team and in accordance with the Risk Management process. Risk controls are implemented 
via safety design inputs, and acceptable safety performance is demonstrated via system design 
verification and validation activities. During the course of the study, risks will be continuously 
monitored, assessed and documented by the investigators. It is the Principal Investigator’s decision to 
assess whether to continue the study at the respective site, should safety-related concerns arise.   
The risks are reduced as much as possible, with residual risk being documented within the Risk 
Management Report (DSN028279, Version 2.0 or currently approved version) and disclosed in the 
Informed Consent Forms provided to subjects. A summary of the risk analysis and risk assessment will 

 
 
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also be listed in the EV ICD Pivotal Investigator’s Brochure. 
 
A summary of potential risks and risk mitigation strategies associated with the EV ICD System and EV 
ICD Pivotal Study is presented in Table 10. Potential risks associated with the study are further 
minimized by selecting qualified investigators and training site personnel on the CIP and hands-on 
training program. 
Table 10: Potential Risks and Mitigation Strategies 
Risks 
Mitigation Strategies 
Procedural risks such as acute trauma, 
infection, or chronic trauma 
i. Procedural technique instructions intended to optimize 
safety are provided in the CIP 
ii. The CIP requires that the EV ICD implant procedure is to 
be performed by an investigator who has received timely 
hands-on training on all aspects of the implant procedure 
iii. Medtronic intends to use a proctorship strategy during 
the EV ICD implant in order to ensure the knowledge and 
skills are transferred to a non-surgical physician specialty 
(EP/Cardiologist). Cardiothoracic surgeons will also provide 
emergency support during the clinical study. 
Failure to provide effective high 
voltage shock therapy when needed 
by the subject 
i. An external defibrillation system(s) is required to be 
present and ready at all times during the implant 
defibrillation testing procedure. The external defibrillator(s) 
is to be prepared to be used in case of emergency. 
ii. Exclusion of subjects with current implantation of a 
pacemaker, ICD, neurostimulator or any other chronically 
implanted device which delivers current in the body, that 
may interfere with therapy delivery 
iii. Testing during the implant procedure to ensure proper 
system set-up connections and lead integrity  
iv. Defibrillation therapy configuration instructions 
provided in the protocol which help promote optimal 
tachyarrhythmia detection and therapy  
v. EV ICD System design verification and end-to-end system 
design validation ensuring defibrillation therapy as 
specified  
Inappropriate delivery of high voltage 
i. Exclusion of subjects with current implantation of a 

 
 
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Risks 
Mitigation Strategies 
shock therapy 
pacemaker, ICD, neurostimulator or any other chronically 
implanted device which uses current in the body, that may 
interfere with therapy delivery 
ii. Testing during the implant procedure to ensure proper 
system set-up connections and lead integrity 
iii. Defibrillation therapy configuration instructions 
provided in the protocol and training which help avoid 
oversensing and resulting inappropriate therapy delivery 
iv. EV ICD System design verification and end-to-end system 
design validation ensuring defibrillation therapy as 
specified 
Failure to provide effective 
bradycardia pacing therapy when 
needed by the subject 
i. Exclusion of subjects with current implantation of a 
pacemaker, ICD, neurostimulator or any other chronically 
implanted device which delivers current in the body, that 
may interfere with therapy delivery 
ii. Testing during the implant procedure to ensure proper 
system set-up connections and lead integrity 
iii. Pacing therapy configuration instructions provided in the 
CIP and training which help avoid oversensing and resulting 
failure to deliver pacing therapy when needed (e.g., post-
shock) 
iv. EV ICD System design verification and end-to-end system 
design validation ensuring pacing therapy as specified 
Delivery of bradycardia pacing therapy 
at an excessive rate causing symptoms 
i. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
Arrhythmia induction (pacing during 
vulnerable period, proarrhythmic 
pauses, electrical/mechanical 
stimulus) 
i. An external defibrillation system(s) is required to be 
present and ready at all times during the implant 
defibrillation testing procedure. The external defibrillator(s) 
is to be prepared to be used in case of emergency. 
ii. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
Acceleration of an existing 
tachyarrhythmia 
i. Defibrillation therapy configuration instructions provided 
in the protocol and training which help avoid ineffective 
shock therapy and resulting arrhythmia acceleration 
ii. EV ICD System design verification and end-to-end system 

 
 
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Risks 
Mitigation Strategies 
design validation ensuring defibrillation therapy as 
specified 
Extracardiac stimulation 
i. Clinician training and CIP procedures for preventive 
measures regarding pain/ stimulation thresholds, including 
the use of general anesthesia, for the potential discomfort 
or pain associated with the pacing stimulation outputs and 
shocks 
ii. Pacing therapy configuration instructions provided in the 
CIP and training which help avoid unnecessary therapy 
energy delivery such that extracardiac stimulation can be 
minimized/avoided 
iii. EV ICD System design verification and end-to-end system 
design validation ensuring pacing therapy as specified 
Thermal/electrical injury to subject 
tissues 
i. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
Subject exposure to toxic materials 
i. EV ICD System design utilizes materials that have 
sufficient biological compatibility and performance as 
demonstrated by a biocompatibility assessment 
Subject exposure to allergic materials 
i. EV ICD System design utilizes materials that have 
sufficient biological compatibility and performance as 
demonstrated by a biocompatibility assessment 
Product degradation due to bio 
instability 
i. EV ICD System design utilizes materials that have 
sufficient biological compatibility and performance as 
demonstrated by years of successful field performance in 
products using equivalent materials 
Missing or misleading data pertaining 
to diagnostic data or system integrity 
is presented to user 
i. EV ICD System design verification and end-to-end system 
design validation ensuring data corruption monitoring as 
specified 
Catastrophic failure of implanted 
product necessitating procedural 
revision of implanted components 
i. EV ICD System reliability analysis ensuring freedom from 
failures as specified 
ii. EV ICD System design verification and end-to-end system 
design validation ensuring system integrity monitoring 
mechanisms as specified 
Exposure to radiation energy via 
diagnostic imaging modalities 
i. Expected medical practice includes shielding the subject 
against unnecessary radiation exposure during diagnostic 
imaging. 

 
 
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Risks 
Mitigation Strategies 
ii. Practicing as low as reasonably achievable (ALARA) 
principles during the device implantation. 
During travel, subjects may not have 
immediate access to programmers 
with applicable software 
i. Subjects will be provided with subject ID cards. Software 
may be downloaded upon request by contacting subject’s 
doctor or Medtronic. 
 
If a subject becomes pregnant during the study, there may be risks that are not yet known. Radiation 
exposure may cause miscarriage, birth defects or other unforeseen medical conditions. 
There may be other discomforts and risks related to the EV ICD System and/or this study that are not 
foreseen at this time. 
The potential adverse events related to the EV ICD System and procedure and the EV ICD Pivotal Study 
procedures identified from the risk assessment are listed in Table 11. The additional procedural steps 
beyond traditional ICD implant such as increased radiation due to additional required radiographs and 
the substernal placement of the lead were considered in the creation of this list. In addition, the risks 
associated with the optional 6-month defibrillation testing (see CIP Addendum for 6-Month 
Defibrillation Testing) are the same as for the implant defibrillation testing and therefore also included 
in the list.  
Table 11: EV ICD System/Procedure- and EV ICD Pivotal Study-related Potential Adverse Events 
EV ICD System/Procedure-related Potential Adverse Events 
EV ICD Pivotal Study-related Potential Adverse Events 
Acute tissue trauma 
Acute tissue trauma 
Allergic reaction of local tissues 
Allergic reaction of local tissues 
Bradyarrhythmia 
Cardiac arrest 
Cardiac arrest 
Chronic tissue trauma 
Cardiac perforation 
Discomfort associated with implant 
Cardiac tamponade 
Dizziness 
Chronic tissue trauma 
Dyspnea 
Death 
Hiccups 
Device migration 
Infection 
Discomfort associated with fibrotic growth 
Mental anguish* 
Discomfort associated with implant 
Organ damage (liver, mammary arteries, diaphragmatic arteries) 
Discomfort associated with product migration 
Pain 

 
 
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EV ICD System/Procedure-related Potential Adverse Events 
EV ICD Pivotal Study-related Potential Adverse Events 
Dizziness 
Palpitations 
Dyspnea 
Radiation sickness 
Electrical/thermal tissue damage 
Skeletal muscle twitching 
Erosion 
Syncope 
Extracardiac stimulation 
Tachyarrhythmia 
Failure to provide necessary therapy 
 
Hematoma 
 
Haemorrhage 
 
Hemothorax 
 
Hiccups 
 
Hospitalization 
 
Inappropriate shocks 
 
Infection 
 
Lead abrasion 
 
Lead fracture 
 
Lead insulation failure 
 
Lead migration 
 
Lethargy 
 
Mental anguish* 
 
Organ damage (liver, mammary arteries, diaphragmatic arteries) 
 
Pain 
 
Palpitations 
 
Pericardial effusion 
 
Pericarditis 
 
Pneumothorax 
 
Radiation sickness 
 
Return of cardiac symptoms 
 
Seroma 
 
Skeletal muscle twitching 
 
Syncope 
 
Tachyarrhythmia 
 

 
 
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EV ICD System/Procedure-related Potential Adverse Events 
EV ICD Pivotal Study-related Potential Adverse Events 
Toxic reaction to implant 
 
Twiddler's syndrome 
 
Wound dehiscence 
 
*Subjects susceptible to frequent shocks despite medical management could develop psychological 
intolerance to an ICD system that might include the following conditions: 
• 
Dependency 
• 
Depression 
• 
Fear of premature battery depletion 
• 
Fear of shocking while conscious 
• 
Fear that shocking capability may be lost 
• 
Imagined shocking (phantom shock) 
9.2. Potential Benefits 
The EV ICD Pivotal Study provides access to ICD therapy for patients who are unable to receive a 
transvenous system because they have occluded vessels or anatomical anomalies, and for patients that 
can benefit from preservation of cardiac vasculature. For other patients, there is no proven benefit. 
Furthermore, the EV ICD System introduces additional potential benefits as compared to subcutaneous 
ICD systems currently on the market, specifically: 
• 
Better signal to noise ratio from the substernal space as compared to a subcutaneous 
configuration, resulting in better detection/discrimination algorithms for sensing arrhythmias (and 
potentially fewer inappropriate shocks) 
• 
Reduced defibrillation energy required to defibrillate as compared to a subcutaneous 
configuration, resulting in improved battery longevity 
• 
Longer battery longevity and corresponding reduction in adverse events associated with device 
replacement 
• 
Asystole pacing 
• 
Anti-tachycardia pacing 
• 
Smaller device which increases patient comfort and acceptance 
The information gained from this study could result in the improved management of patients with the 
EV ICD System. Additionally, information collected from this study may assist in the design of new 
product(s)/therapy(ies) and/or instructions for use. 

 
 
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9.3. Risk-Benefit Rationale 
The majority of the risks associated with the EV ICD System are similar to the risks associated with 
existing transvenous and subcutaneous ICD systems on the market. The unique risks introduced by the 
EV ICD System include: unique harms associated with procedural complications (e.g., liver laceration, 
cardiac trauma/ tamponade), unique harms associated with defibrillating from a substernal lead 
position (e.g., tissue heating/necrosis), unique harms from chronic lead implant in the substernal space 
(e.g., dislodgment due to absence of fibrosis), and the general risk that an EV ICD System has not yet 
been chronically implanted in humans for greater than 12 months. The results of the System Hazard 
Analysis confirm that the patient risks are reduced as far as possible and the residual risks are deemed 
acceptable. 
The foreseeable benefits of the EV ICD System for patients with occluded vessels or anatomical 
anomalies and for patients that can benefit from preservation of cardiac vasculature include: a 
reduction in procedural risk as compared to transvenous systems, enhanced tachyarrhythmia therapies 
as compared to subcutaneous systems (i.e., improved signal/noise, reduced shock energy, and offering 
of ATP), and improved patient comfort and acceptance due to the smaller size of device as compared 
to subcutaneous systems. Although there is no proven benefit for patients who are able to receive a 
transvenous system, there may be benefits specific to the novel design of the EV ICD System. As 
compared to a transvenous system, the EV ICD System is expected to result in fewer extraction 
complications. Since the EV ICD System avoids implanting a lead in the heart, risks such as: systemic 
infection, embolism, vascular/SVC tears, and lead extraction injuries are expected to be significantly 
reduced or eliminated. 
10. Adverse Events and Device Deficiencies 
Timely, accurate, and complete reporting and analysis of safety information for clinical studies are 
crucial for the protection of subjects. Reporting and analysis of safety data are mandated by regulatory 
authorities worldwide. Medtronic has established procedures in conformity with worldwide regulatory 
requirements to ensure appropriate reporting of safety information. The study is conducted in 
accordance with these procedures and regulations. 
Since the safety reporting requirements and classification systems vary for each regulatory agency, 
requirements from all geographies are taken into account for the collection and reporting of safety 
information.  

 
 
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10.1.  Assessment 
 Adverse Events Assessment 
Adverse Event (AE) definitions are provided in Table 12.  All AEs will be collected throughout the study 
duration, starting at the time the Informed Consent Form is signed. For purposes of reporting, events 
shall be captured on an AE eCRF. 
All instances of shocks delivered by the EV ICD will be considered associated with a reportable AE. 
Shocks delivered appropriately to treat a ventricular arrhythmia should be noted as treatment 
delivered within the AE for the ventricular arrythmia(s) experienced.  If shocks are delivered 
inappropriately due to an EV ICD issue, the issue should be reported as the underlying system related 
AE. 
Reporting of these events to Medtronic will occur on an Adverse Event eCRF, including a description of 
AE, date of onset of AE, date of awareness of site, treatment, resolution, assessment of both the 
seriousness and the relatedness to the system and/or procedure. Each AE must be recorded on a 
separate AE Form. Subject deaths are also required to be reported. Refer to section 10.7 for Subject 
Death collection and reporting requirements. 
Documented pre-existing conditions are not considered AEs unless the nature or severity of the 
condition has worsened. Worsening may be identified if there is a change in frequency, associated 
symptoms, or the need for new/additional treatment (e.g., ventricular arrhythmias would be 
considered worsened if there are new associated symptoms or treatment/shock is warranted). In all 
geographies, Unavoidable Adverse Events, listed in Table 12 need not be reported unless the adverse 
event worsens or is present outside the stated timeframe post-implant procedure. Adverse events 
impacting users or other persons are also reportable during the course of the study. 
For AEs that require immediate reporting, initial reporting may be done by phone, fax, or on the eCRF 
by completing as much information as possible. The AE eCRF must be completed as soon as possible. 
 Device Deficiencies Assessment 
Device deficiency information will be collected throughout the study and reported to Medtronic. An 
eCRF should be completed for each device deficiency that did not lead to an Adverse Event.   
Note that device deficiencies that result in an adverse device effect (ADE) to the subject should be 
captured as an AE only. Device deficiencies that did not lead to an AE but could have led to a Serious 

 
 
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Adverse Device Effect (SADE) (i.e., if suitable action had not been taken, if intervention had not been 
made, or if the circumstances had been less fortunate) require immediate reporting. 
Examples of instances that may be considered device deficiencies in the absence of an untoward 
clinical occurrence to the subject may include, but are not limited to: 
• 
Damaged components observed out of packaging 
• 
Unsuccessful EV ICD System implant and/or failed defibrillation testing 
• 
Pervasive/persistent sensing issues occurring outside of device testing 
• 
System placement outside of labeling (e.g., lead in pleural space) 
10.2.  Processing Updates and Resolution 
For any changes in status of a previously reported AE (i.e., change in actions taken, change in outcome, 
change in relatedness), information needs to be updated on or added to the original AE form. All AEs 
must be followed until the AE has been resolved, the subject exits the study, or until study closure, 
whichever occurs first.  
All efforts should be made to continue following subjects until all system or procedure related AEs that 
are not resolved, as classified by the investigator, are resolved.  
At the time of study exit, all collected AEs with an outcome of “not recovered/not resolved”, 
“recovering/resolving” or “unknown” must be reviewed and updates provided as applicable. 
10.3.  Adverse Events and Device Deficiency Definitions 
For the purposes of the clinical report, Medtronic will classify each AE according to ISO 14155:2011. 
Where the definition indicates “device”, it refers to any device used in the study. This might be the 
device under investigation, or any market released component of the EV ICD System or accessory. 

 
 
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Table 12: Adverse Event and Device Deficiency definitions 
General 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device. 
Note: This definition includes events related to the investigational medical device or the 
comparator. 
Note: This definition includes events related to the procedures involved. 
Note: For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
(ISO 14155:2011 section 3.2) 
Adverse Device Effect (ADE) 
AE related to the use of an investigational medical device. 
Note: This definition includes AEs resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
Note: This definition includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
(ISO 14155:2011 section 3.1) 
Device Deficiency (DD) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, 
safety or performance.  
 
Note: Device deficiencies include malfunctions, use errors, and inadequate labeling.  
(ISO 14155:2011, 3.15) 
Relatedness 
Procedure Related  
An adverse event that is directly related to the implantation or modification of the EV 
ICD System. 
NOTE: In general, this excludes events that are inherent to any surgical procedure (e.g., 
anesthesia complications, anticoagulation interruption) as well as indirect subsequent 
consequences of the procedure (e.g., reaction to pain medication). 
System Related 
An adverse event that results from the presence or performance of any component of 
the EV ICD System.  
 
Device Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the device. 
 
Lead Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the lead. 

 
 
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Accessory Related 
An adverse event that results from the presence or performance of the EV ICD System 
accessory. 
 
Sternal Tunneling Tool Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the sternal tunneling tool. 
 
Transverse Tunneling Tool Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the transverse tunneling tool. 
 
Safesheath II Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the SafeSheath II. 
 
Programmer Related: An adverse event that results from the presence or performance 
(intended or otherwise) of the programmer. 
 
Programmer Software Related: An adverse event that results from the presence or 
performance (intended or otherwise) of the programmer software. 
 
MyCareLink Patient Monitor Related: An adverse event that results from the presence 
or performance (intended or otherwise) of the patient monitor. 
Not Related 
Relationship to the device or procedures can be excluded when: 
• 
The event is not a known side effect of the product category the device belongs 
to or of similar devices and procedures; 
• 
The event has no temporal relationship with the use of the device or the 
procedures; 
• 
The serious event does not follow a known response pattern to the medical 
device (if the response pattern is previously known) and is biologically 
implausible; 
• 
The discontinuation of medical device application or the reduction of the level of 
activation/exposure – when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure) do not impact 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 device used for 
diagnosis (when applicable); 
• 
Harm 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 
event. 

 
 
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Unlikely 
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. 
Possible 
The relationship with the use of the investigational device is weak but cannot be ruled 
out completely. Alternative causes are also possible (e.g., an underlying or concurrent 
illness/ clinical condition or/and an effect of another device, drug or treatment). Cases 
where relatedness cannot be assessed or no information has been obtained should also 
be classified as possible. 
Probable 
The relationship with the use of the investigational device seems relevant and/or the 
event cannot reasonably be explained by another cause, but additional information may 
be obtained.  
Causal Relationship 
The event is associated with the device or study 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 device use/application or 
procedures; 
• 
The event involves a body-site or organ that the device or procedures are 
applied to or the 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 device used for diagnosis 
(when applicable); 
• 
In order to establish the relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the 
serious event. 
 

 
 
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Seriousness 
Serious Adverse Event (SAE) 
 
Adverse event that 
a) led to death, 
b) led to serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body function, 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect 
 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by 
the CIP, without serious deterioration in health, is not considered a serious adverse 
event. 
(ISO 14155:2011, 3.37) 
 
Serious Adverse Event (SAE) – Germany 
Definition 
A serious adverse event is an event that occurs in a clinical investigation subject to 
approval or occurring in a performance evaluation which led, might have led or could 
lead directly or indirectly to death or serious deterioration of health of the subject, the 
user or a third party, without consideration if the event has been caused by the medical 
device itself; this applies accordingly to serious adverse events occurring in a clinical 
investigation or performance evaluation for which an exemption of the approval 
authorization as per MPG § 20 paragraph 1 sentence 2 has been granted. (MPSV § 2 
Definitions Abs 5) 
 
Serious Adverse Device Effect (SADE) 
ADE that has resulted in any of the consequences characteristic of a SAE. 
(ISO 14155:2011 section 3.36) 
Unanticipated Adverse Device Effect 
(UADE) 
 
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 a 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. (21 CFR 812.3(s)) 
Unanticipated Serious Adverse Device 
Effect (USADE) 
 
SADE which by its nature, incidence, severity or outcome has not been identified in the 
current version of the risk analysis report. 
Note: 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. 
(ISO 14155:2011 section 3.42) 
Significant Safety Issue (SSI) 
A safety issue that could adversely affect the safety of participants or materially impact 
on the continued ethical acceptability or conduct of the trial. 

 
 
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Urgent Safety Measure (USM) 
A measure required to be taken in order to eliminate an immediate hazard to a 
participant’s health or safety. 
 
Note: This type of significant safety issue can be instigated by either the investigator or 
sponsor and can be implemented before seeking approval from HRECs or institutions. 
Complication 
An adverse event that includes the following is considered a complication: 
• 
Results in death,  
• 
Involves any termination of significant device function (i.e., defibrillation 
therapy), or  
• 
Requires an invasive intervention 
Non-invasive (21 CFR 812.3(k)): when applied to a diagnostic device or procedure, 
means one that does not by design or intention: 
Penetrate or pierce the skin or mucous membranes of the body, the ocular cavity, or 
the urethra, or enter the ear beyond the external auditory canal, the nose beyond the 
nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina 
beyond the cervical os 
 
For purposes of this part, blood sampling that involves simple venipuncture is 
considered non-invasive, and the use of surplus samples of body fluids or tissues that 
are left over from samples taken for non-investigational purposes is also considered 
non-invasive. 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Major complication 
A system or procedure-related complication which results in: 
• 
Death 
• 
Permanent loss of defibrillation function due to mechanical or electrical 
dysfunction of the device  
• 
Hospitalization 
• 
Prolongation of an existing hospitalization by at least 48 hours  
• 
System revision (reposition, replacement, explant) 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Minor complication 
Any complication that is not a major complication (e.g., event classified as a 
complication solely based on intravenous drug administration). 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 
Observation 
Any adverse event that is not a complication. 
 
Note: Only system or procedure related AEs will be classified as complication (major, 
minor) or observation. 

 
 
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Timing 
Pre-Implant Procedure 
Occurs after the IC has been signed but before the skin incision during the EV ICD 
implant procedure. 
During Implant Procedure 
Occurs during the EV ICD implant procedure, after skin incision and prior to completion 
of skin closure. 
Post-Implant Procedure 
Occurs after the completion of skin closure for the EV ICD implant procedure. 
Other 
Unavoidable Adverse Event 
An Adverse Event inherent to a surgical procedure that is expected to occur in all 
subjects for a projected duration according to the Investigator’s opinion, including, but 
not limited to:  
Event Description 
Timeframe (hours) 
from the Surgical 
Procedure 
Anesthesia related nausea / vomiting  
24 
Low-grade fever (oral temperature >98.6°F 
(>37°C) but <100.4°F (<38.0°C)) 
48 
Pocket site / Incisional pain 
72 
Mild to moderate bruising / ecchymosis 
168 
Sleep problems (insomnia) 
72 
Back pain related to laying on table 
72 
Shoulder pain/discomfort/stiffness related to 
shoulder immobilization during procedure 
72 
Hospitalization 
A therapeutic inpatient hospitalization (excludes observation unit, emergency room and 
outpatient visits) lasting greater than or equal to 24 hours. 
10.4.  Adverse Event and Deficiency Classification 
All adverse events and device deficiencies will be reviewed by a Medtronic representative. AEs will be 
classified according to the definitions provided in section 10.3.  
Upon receipt of AEs at Medtronic, a Medtronic representative will review the adverse event/device 
deficiency for completeness and accuracy and when necessary will request clarification and/or 
additional information from the Investigator. Medtronic will utilize MedDRA, the Medical Dictionary for 
Regulatory Activities, to assign a MedDRA term for each AE based on the information provided by the 
investigator.  
Regulatory reporting of AEs and device deficiencies that could have led to a SADE will be completed 
according to local regulatory requirements. Refer to section 14.7 for a list of additional required 

 
 
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investigator and Medtronic reporting requirements and timeframes. It is the responsibility of the 
investigator to abide by any additional AE reporting requirements stipulated by the Ethics Committee 
responsible for oversight of the study. 
For a list of Foreseeable Adverse Event List, refer to Appendix E: Foreseeable Adverse Event List. The 
Foreseeable Adverse Event List consists of observed adverse device effects in similar Medtronic 
studies, adverse events reported in published literature and other special considerations. An evaluation 
of potentially anticipated events, adverse device effects observed in previous clinical studies, and 
reported events in literature may be used in combination with device labeling, current event reporting 
information, and other published data to assess if an adverse event is unexpected. 
Adverse Events and Deaths will be classified according to the standard definitions as outlined in Table 
12. 
Table 13: Adverse Event classification responsibilities 
What is classified  Who classifies 
Classification Parameters 
Timing of the Event 
Investigator 
Pre-implant procedure, During implant procedure, Post-
implant procedure 
Relatedness 
 
Investigator 
Procedure, Device, Lead, Sternal Tunneling Tool, 
Transverse Tunneling Tool, SafeSheath II, Programmer, 
Programmer Software, Patient Monitor 
Sponsor 
Procedure, Device, Lead, Sternal Tunneling Tool, 
Transverse Tunneling Tool, SafeSheath II, Programmer, 
Programmer Software, Patient Monitor 
Severity 
Investigator 
SAE, Device Deficiency with SADE potential 
Sponsor 
SAE, UADE/USADE, Device Deficiency with SADE 
potential 
Diagnosis 
Investigator 
Based on presenting signs and symptoms and other 
supporting data 
Sponsor 
MedDRA term assigned based on the data provided by 
Investigator 
Death Classification Investigator 
Sudden Cardiac, Non-sudden Cardiac, Non-Cardiac, 
Unknown 
 
An independent Clinical Events Committee (CEC) will review and adjudicate, at a minimum, all events 
classified by the investigator or Medtronic as procedure or system related to determine relatedness 
and complication (major, minor) or observation classifications. In addition, the CEC will also review and 
adjudicate all Adverse Events resulting in death. 

 
 
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When determining whether a USADE has occurred, where the sponsor’s causality assessment conflicts 
with the assessment made by the site investigator, the site investigator’s assessment cannot be 
downgraded by the sponsor (i.e., altered from ‘related’ to ‘not related’). In this case, if an investigator’s 
judgment triggers the reporting of a USADE, the opinion of both the investigator and the sponsor 
should be provided with any report sent to regulatory reporting as required. 
10.5.  Reporting of Adverse Events 
Adverse events and Device Deficiencies will be reported according to local regulatory requirements. It 
is the responsibility of the investigator to abide by the AE/DD reporting requirements stipulated by 
local law and the Ethics Committee. Reporting requirements in Table 14 have been summarized at the 
time of CIP creation; however, changes may occur during the course of the study. Updates may be 
provided under separate cover and it is the investigator’s responsibility to comply with current local 
regulatory and institutional reporting requirements.  
Refer to section 14.7 for a list of additional required investigator and Medtronic reporting 
requirements and timeframes.  
For AEs/DDs that require immediate reporting, initial reporting may be done by contacting the study 
sponsor per the sponsor contact information provided in this document. For emergency contact 
regarding a UADE/USADE, SAE and/or SADE, contact a clinical study representative immediately (refer 
to the study contact list provided in the site’s study documents binder/investigator site file or refer to 
the contact information provided on the title page).   

 
 
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Table 14: Adverse Event Reporting Requirements 
Serious Adverse Events (SAEs) 
Investigator submit to: 
Medtronic 
Australia: Without unjustified delay. (The National Health and Medical Research Council (NHMRC) 
Safety monitoring and reporting in clinical trials involving therapeutic goods November 2016 section 
C.2.b) 
Europe: To the sponsor in acceptable timely conditions, but not later than within 3 calendar days 
after investigational site study personnel’s awareness of the event, including new information in 
relation to an already reported event (ISO 14155:2011 and local law) 
Japan: Immediately (no later than 72 hours) (Japan GCP Article 68) 
All geographies: Submit per local reporting requirements 
Ethics Committee 
All geographies: Submit per local reporting requirements 
Regulatory authorities 
All geographies: Submit per local reporting requirements 
Head of Medical Institution 
(HOMI) 
Japan: Immediately (Japan GCP Article 68) 
Sponsor submit to: 
Investigators 
Japan: Annually (Japan GCP Article 28) 
All geographies: Submit per local reporting requirements 
Regulatory authorities 
Europe:  No later than 7 calendar days after awareness;  Report immediately, but no later than 2 
calendar days after awareness by sponsor for SAE and/or DD that may have led to a SADE which 
indicates an imminent risk of death, serious injury, or serious illness and that requires prompt 
remedial action for other patients/subjects, users or other persons or a new finding to it (occurred in 
the study under same CIP*)  
Japan: Annually (Enforcement Regulation of the PMDL Article 274- 2) 
All geographies: Submit per local reporting requirements 
Ethics Committee 
All geographies: Submit per local reporting requirements 
HOMI 
Japan: Annually (Japan GCP Article 28) 
Serious Adverse Device Effects (SADEs) 
Investigator submit to: 
Medtronic 
Australia: Without unjustified delay. (NHMRC Safety monitoring and reporting in clinical trials 
involving therapeutic goods November 2016 section C.2.b) 
Canada: SADEs on the patient, the user or any other person must be reported to the regulator and to 
the Sponsor within 72 hours after it comes to the attention of the qualified investigator. 
Japan: Immediately (no later than 72 hours) (Japan GCP Article 68) 
All geographies: Submit per local reporting requirements 
Ethics Committee 
All geographies: Submit per local reporting requirements 
Regulatory authorities 
Canada: SADEs on the patient, the user or any other person must be reported to the regulator and to 
the Sponsor within 72 hours after it comes to the attention of the qualified investigator. 
All geographies: Submit per local reporting requirements 
HOMI 
Japan: Immediately (Japan GCP Article 68) 
Sponsor submit to: 
Investigators 
Japan: Annually (Japan GCP Article 28) 
All geographies: Submit per local reporting requirements 

 
 
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Regulatory authorities 
Canada: Report within 10 days after the sponsor becomes aware. 
Japan: [Life threatening or death] Individual reporting within 15 calendar days after awareness, and 
[All SADEs] Annually (Enforcement Regulation of the PMDL Article 274- 2) 
Saudi Arabia: Within 15 working days 
All geographies: Submit per local reporting requirements 
Ethics Committee 
All geographies: Submit per local reporting requirements 
HOMI 
Japan: Annually (Japan GCP Article 28) 
Unanticipated Adverse Device Effects (UADEs) and Unanticipated Serious Adverse Device Effects (USADEs) 
Investigator submit to: 
Medtronic 
Canada: USADEs on the patient, the user or any other person must be reported to the regulator and 
to the Sponsor within 72 hours after it comes to the attention of the qualified investigator. 
US: An investigator shall submit to the sponsor and to the reviewing IRB a report of any UADE 
occurring during an investigation as soon as possible, but in no event later than 10 working days after 
the investigator first learns of the effect. (21 CFR 812.150(a)) 
Europe: Immediately after the investigator learns of the event or of new information in relation to an 
already reported event. (ISO 14155:2011 and local law) 
Japan: Immediately (no later than 72 hours) (Japan GCP Article 68) 
All geographies: Submit per local reporting requirements 
Regulatory Authority 
Canada: USADEs on the patient, the user or any other person must be reported to the regulator and 
to the Sponsor within 72 hours after it comes to the attention of the qualified investigator. 
All geographies: Submit per local reporting requirements 
Ethics Committee 
Australia: Report USADE to their institution without undue delay and no later than 72 hours of the 
Principal Investigator becoming aware of the event. (NHMRC Safety monitoring and reporting in 
clinical trials involving therapeutic goods November 2016 section C.2.g) 
US: An investigator shall submit to the sponsor and to the reviewing IRB a report of any UADE 
occurring during an investigation as soon as possible, but in no event later than 10 working days after 
the investigator first learns of the effect. (21 CFR 812.150(a)) 
All geographies: Submit per local reporting requirements 
Institution 
Australia: Report USADE to their institution without undue delay and no later than 72 hours of the 
Principal Investigator becoming aware of the event. (NHMRC Safety monitoring and reporting in 
clinical trials involving therapeutic goods November 2016 section C.2.g) 
HOMI 
Japan: Immediately (Japan GCP Article 68) 
Sponsor submit to: 
Investigator 
US: Notification as soon as possible, but not later than 10 working days after the sponsor first learns 
of the effect. (21 CFR 812.150(b)) 
Japan: Immediately (Japan GCP Article 28) 
All geographies: Submit per local reporting requirements  

 
 
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Regulatory authorities 
Australia: Fatal or life-threatening Australian USADE – No later than 7 calendar days after being made 
aware of the case with any follow up information within a further 8 calendar days. Other Australian 
USADEs- No later than 15 calendar days after being made aware of the case.  (NHMRC Safety 
monitoring and reporting in clinical trials involving therapeutic goods November 2016 section C.1.f) 
Canada: Report within 10 days after the sponsor becomes aware. 
Japan: [Life-threatening or death) Individual reporting within 7 calendar days after awareness, [Non-
life threatening or death) Individual reporting within 15 calendar days after awareness, and [All 
USADE] Annually.  (Enforcement Regulation of PMDL Article 274-2) 
US: Notification as soon as possible to FDA, but not later than 10 working days after the sponsor first 
receives notice of the effect. (21 CFR 812.150(b)) 
All geographies: Submit per local reporting requirements 
Ethics Committee 
US: Notification as soon as possible, but not later than 10 working days after the sponsor first learns 
of the effect. (21 CFR 812.150(b))  
All geographies: Submit per local reporting requirements  
HOMI 
Japan: Immediately (Japan GCP Article 28) 
Significant Safety Issue (SSI): Sponsor reporting in Australia 
Events to Report 
Reporting Requirement and Timeframe 
Significant Safety Issue 
• 
Urgent Safety Measure (USMs): within 24 hours (where possible) to TGA and without undue 
delay to investigators & HREC and in any case, no later than 72 hours of the measure being taken.  
- 
Reasons for the urgent safety measure, Measures taken, Further actions planned 
- 
Reasons for the termination, Measures taken, Further actions planned  
(NHMRC Safety monitoring and reporting in clinical trials involving therapeutic goods November 
2016 section C.1.k) 
Significant Safety Issue 
(continued)  
Submit to TGA 
• 
Other significant safety measures: Without undue delay and no later than 15 calendar days 
of the sponsor being aware of the issue. 
Details of significant safety issue, Further actions planned 
• 
Notification of an amendment: Without undue delay and no later than 15 calendar days  
Note: TGA should receive notification that a SSI has occurred but the amendment revising 
trial documentation should be submitted to the HREC only 
• 
Action taken with respect to safety that has been taken by another country’s regulatory 
agency (relevant to an ongoing clinical trial in Australia): Without undue delay and no later 
than 72 hours of the trial sponsor becoming aware of the action (Australian clinical trial 
handbook version 2.2) 
Significant Safety Issue 
(continued) 
Submit to TGA, any Australian investigator and HREC 
• 
Temporary halt of a trial for safety reasons: Without undue delay and no later than 15 
calendar days of the sponsor’s decision to halt the trial. 
                     Reasons for the halt, the scope of the halt, Measures taken, Further actions planned  
• 
Early termination of a trial for safety reasons: Without undue delay and no later than 15 
calendar days of the sponsor’s decision to termination the trial. 

 
 
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Significant Safety Issue (SSI): Investigator Reporting in Australia 
Events to Report 
Reporting Requirements and Timeframe to submit to Sponsor, HREC and institution 
Significant Safety Issues 
 
 
• Urgent Safety Measure (USMs): Within 24 hours 
(NHMRC Safety monitoring and reporting in clinical trials involving therapeutic goods November 
2016 section C.2.c) 
• All other significant safety issues: without undue delay and no later than 72 hours of the principal 
investigator becoming aware of the event 
(NHMRC Safety monitoring and reporting in clinical trials involving therapeutic goods November 2016 
section C.2.g) 
Device Deficiencies with SADE potential 
Investigator submit to: 
Medtronic 
Australia: Without unjustified delay. (NHMRC Safety monitoring and reporting in clinical trials 
involving therapeutic goods November 2016 section C.2.b) 
Canada: DDs that have resulted in any of the consequences characteristic of an SAE on the patient, 
the user or any other person or could do so were it to reoccur must be reported to the regulator and 
the Sponsor within 72 hours after it comes to the attention of the qualified investigator. 
Europe: To the sponsor in acceptable timely conditions, but not later than within 3 calendar days 
after investigational site study personnel’s awareness of the event , including new information in 
relation to an already reported event (ISO 14155:2011 and local law) 
Japan: Immediately (no later than 72 hours) (Japan GCP Article 68) 
All geographies: Submit per local reporting requirements 
Regulatory authorities 
Canada: DDs that have resulted in any of the consequences characteristic of an SAE on the patient, 
the user or any other person or could do so were it to reoccur must be reported to the regulator and 
the Sponsor within 72 hours after it comes to the attention of the qualified investigator. 
All geographies: Submit per local reporting requirements 
Ethics Committee  
All geographies: Submit per local reporting requirements 
HOMI 
Japan: Immediately (Japan GCP Article 68) 
Sponsor submit to: 
Investigator 
Japan: Immediately per the direction of PMDA and/or annually (Japan GCP Article 28) 
All geographies: Submit per local reporting requirements  
Regulatory authorities 
Canada: Submit to regulatory authorities within 30 calendar days of awareness by Sponsor. 
Japan: Within 30 calendar days after awareness and annually (Enforcement Regulation of PMDL 
Article 274-2) 
Europe:  No later than 7 calendar days after awareness;  Report immediately, but no later than 2 
calendar days after awareness by sponsor for SAE and/or DD that may have led to a SADE which 
indicates an imminent risk of death, serious injury, or serious illness and that requires prompt 
remedial action for other patients/subjects, users or other persons or a new finding to it (occurred in 
the study under same CIP*)  
Saudi Arabia: Within 15 working days 
All geographies: Submit per local reporting requirements 
Ethics Committee 
All geographies: Submit per local reporting requirements  
HOMI 
Japan: Immediately per the direction of PMDA and/or annually (Japan GCP Article 28) 
All other Adverse Events, Device Deficiencies, and new information that may  
adversely affect safety of the subjects or the conduct of the study 
Investigator submit to: 

 
 
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Medtronic 
Europe: Submit in a timely manner after the investigator first learns of the event 
All geographies: Submit per local reporting requirements  
Regulatory Authorities 
All geographies: Submit per local reporting requirements  
Ethics Committee 
All geographies: Submit per local reporting requirements  
Sponsor submit to: 
Investigator 
All geographies: Submit per local reporting requirements  
Regulatory authorities 
All geographies: Submit per local reporting requirements  
Ethics Committee 
All geographies: Submit per local reporting requirements  
 
10.6. Subject Death 
All subject deaths must be reported by the investigator to Medtronic on an AE eCRF (AE with fatal 
outcome) as soon as possible after the investigator first learns of the death. In case of death, there 
should be one SAE with an outcome of fatal. 
A de-identified copy of the death certificate, if available and allowed by state/local law, should be sent 
to the Medtronic clinical study team. When a death occurs in a hospital, a copy of the death summary 
report and all relevant hospital records should be sent to Medtronic, if available. If an autopsy is 
conducted, the autopsy report should also be sent to Medtronic if available and allowed by state/local 
law. When the death occurs at a remote site, it is the investigative site’s responsibility to attempt 
retrieval of information about the death. In summary, the following data will be collected: 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death 
• 
Relatedness to system and/or procedure 
• 
Device interrogation (if available) 
• 
Death summary/hospital records (if available and allowed by state/local law) 
• 
Autopsy report (if available and allowed by state/local law) 
• 
Death certificate (if available and/or allowed by state/local law) 
10.7.  Death Classification and Reporting 
Sufficient information will be required in order to properly classify the subject’s death. The Investigator 
shall classify each subject death per the following definitions: 
Cardiac Death: A death directly related to the electrical or mechanical dysfunction of the heart. 

 
 
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• 
Sudden Cardiac Death (SCD): Natural death due to cardiac causes, indicated by abrupt loss of 
consciousness within one hour of the onset of acute symptoms; preexisting heart disease may 
have been known to be present, but the time and mode of death are unexpected. If time of 
onset cannot be determined, SCD will alternatively be defined as any unexpected cardiac death 
occurring out of the hospital or in the emergency room as dead on arrival. 
• 
Non-sudden Cardiac Death: All cardiac deaths that are not classified as sudden deaths, 
including all cardiac deaths of hospitalized subjects on inotropic support. 
Non-cardiac Death: A death not classified as a cardiac death. 
Unknown Cardiac Classification: Unknown death classification is intended for use only when there is 
insufficient or inadequate information to classify the death. 
The Clinical Events Committee will also review all deaths and provide an adjudication of the death 
classification. See section 11.1 for handling events where the adjudication of the investigator and the 
CEC differ. 
10.8.  Product Complaint Reporting 
The reporting of product complaints is not part of the EV ICD Pivotal Study and should be done in 
addition to the AE/DD reporting requirements.  It is the responsibility of the investigator to report all 
product complaints associated with a medical device distributed by Medtronic, regardless of whether 
they are related to intended use, misuse or abuse of the product. Reporting must be done immediately 
and via the regular channels for market-released products.   
Product Complaint: any written, electronic or oral communication that alleges deficiencies related to 
the identity, quality, durability, reliability, safety, effectiveness or performance of a medical device that 
has been placed on the market. 
11. Data Review Committees  
11.1.  Clinical Events Committee 
The study will utilize an independent Clinical Events Committee (CEC). At regular intervals, an 
independent CEC will review events and adjudicate at a minimum all system and procedure-related 
events. Additionally, the CEC will provide an adjudication of the death classification for all reported 
deaths.  
The CEC will consist of a minimum of three (3) non-Medtronic-employed physicians whose site is not 
participating in the study, including a CEC chairperson.  

 
 
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Medtronic personnel may facilitate and participate in CEC meetings but will be non-voting members. 
For AEs and deaths reviewed by the CEC, Medtronic will provide the CEC with the Investigator’s 
description and supportive documentation (when available). The CEC is responsible for reviewing the 
Investigator’s description and supportive documentation (when available), reviewing applicable 
definitions, and determining final classifications for all adjudication parameters. For AEs, classification 
includes system/procedure relatedness and complication (major, minor) or observation. Additionally, 
the CEC will provide an adjudication for all reported deaths, including system/procedure relatedness 
and cardiac relatedness. 
If the CEC disagrees with the investigator’s classification of the event, the difference will be provided to 
the investigator. If the investigator agrees with the CEC’s adjudication, the eCRF documenting the AE 
will be updated accordingly. 
If the investigator does not agree with the CEC’s adjudication classification, both determinations will be 
provided within the final report; however, the CEC’s adjudication will be used for data analysis. The 
disagreement will also be included in reporting to ethics committees and regulatory authorities, if 
required. 
11.2.  Data Monitoring Committee 
An independent Data Monitoring Committee will be established by Medtronic to periodically review 
the total incidence of adverse events and follow trends of these events in this study, and make 
recommendations to Medtronic and/or the Steering Committee regarding study conduct and subject 
safety. The DMC for this study will consist of a minimum of three and up to seven non-Medtronic 
members with study related backgrounds and not from sites participating in the study. Medtronic will 
appoint members of the Committee and the Chairperson. Up to two additional investigators 
participating in this study may participate in the meetings to offer clarification of events, but none will 
be given voting privileges. Medtronic personnel may facilitate the DMC meeting (e.g., study manager, 
statistician), but they will not be voting members. 
 
A quorum of the committee may review interim analyses in which the results are analyzed against the 
primary objective. A summary of adverse events will be reviewed at this time also. Review and 
consensus by the entire committee is required to recommend to the sponsor that the study should be 
stopped for safety reasons.  
The DMC Member list will be under a separate cover and available upon request. 

 
 
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11.3. Episode Review Committee 
An Episode Review Committee (ERC) will be established to evaluate device-treated ventricular episodes 
according to an ERC Charter. Committee membership, meeting frequency, roles and responsibilities 
and procedures will also be described in the ERC Charter. Device-treated ventricular episodes in the 
device episode log with EGM will be reviewed by the ERC and adjudicated based on appropriateness of 
therapy (shocks and ATP) delivered to subjects and success of the therapy. Inappropriate therapy will 
be identified based on adjudication rhythm truth and device episode log information.  
This committee may include independent physicians and/or Medtronic personnel. The ERC Member list 
will be under a separate cover and available upon request. 
12. Statistical Design and Methods 
12.1.  General Considerations  
Data analysis will be performed by a Medtronic statistician or designee. 
The cohort will include all enrolled subjects who undergo the study procedures unless the subject does 
not complete the required testing, and there are no pre-specified subgroups for assessment. For 
endpoints involving only measurements collected at follow-up visits, only subjects who complete those 
visits will be included in the analysis of those endpoints. 
Any tests of treatment effects will be conducted at a two-sided alpha level of 0.05 unless otherwise 
stated. 
A Statistical Analysis Plan will be developed and kept under separate cover and will include a 
comprehensive description of the statistical methods and reports to be included in the final study 
report, as well as a description of how missing, unused, and spurious data will be accounted. Any 
change to the data analysis methods described in the CIP will require an amendment only if it changes 
a principal feature of the CIP. Any other change to the data analysis methods described in the CIP, and 
the justification for making the change, will be described in the clinical study report. 
12.2. Analysis for market approval outside the US  
Human clinical data may be needed to support marketing applications in CE Mark countries and other 
geographies outside the US. Therefore, Medtronic plans to analyze the accumulated data once 60 
subjects undergoing implant of the EV ICD System have completed their 3 Month follow-up visit. This 
analysis will include characterizing both defibrillation efficacy at implant and incidence of major EV ICD 

 
 
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System/procedure-related complications through at least 3 months. All subjects will continue to be 
followed and the timeline for other marketing applications will not be impacted by this analysis. 
12.3.  Sample Size  
There are two primary objectives (safety and efficacy), and each objective requires 292 subjects to, in 
the case of the safety objective, undergo an implant attempt of the EV ICD System, and in the case of 
the efficacy objective, complete the pre-specified defibrillation testing protocol (see section 8.5.7 for 
details).  Since the defibrillation protocol may not be initiated until an implant attempt occurs, the 
overall sample size requirement will be derived from the efficacy objective; at least 292 subjects will 
undergo the defibrillation testing protocol, which may result in more than 292 subjects undergoing an 
implant attempt to satisfy this requirement.  To further account for subjects who enroll in the study but 
exit prior to an implant attempt (19% of 26 enrolled subjects in the EV ICD Pilot study did not undergo 
an implant attempt), up to 400 subjects may be enrolled.   
 Primary Objective #1: Safety 
An Objective Performance Criterion (OPC) of 79% was chosen based on prior precedent to evaluate the 
primary safety objective metric of the EV ICD System/procedure-related major complication-free rate 
at 6 months.  The estimated EV ICD System/procedure-related major complication-free rates through 6 
months are provided in Figure 9. They are modeled using a Weibull distribution assuming a rate of 90% 
at one month and 86% at 6 months.  A solid line denoting the Objective Performance criterion of 79% is 
also provided.  It is also assumed that attrition (exit or death) will follow a Weibull distribution, with an 
attrition rate of 9% at one month (allowing for unsuccessful implants) and 16% through one-year post-
implant.   
The trial was simulated 10,000 times. Each time a sample size of 292 subjects had a time to safety 
endpoint simulated and a time to attrition simulated using the assumptions above. Using these data, a 
lower confidence bound for the 6-month Kaplan-Meier freedom from safety endpoint rate was 
generated using the log scale for each simulation of the trial. It was determined that based on these 
assumptions and the requirements of a false positive rate (alpha) controlled at 2.5%, a sample size of 
292 subjects undergoing an implant attempt is required to allow for 90% power of assessing this 
objective. 

 
 
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Figure 9: Estimated Freedom from System/Procedure-related Major Complications 
 
 
 Primary Objective #2: Efficacy 
An OPC of 88% was chosen to evaluate the primary efficacy objective metric of implant testing success 
defined as successfully terminating one or more induced ventricular fibrillation episodes (see sections 
8.5.7 and 12.5.2 for more details).  Each subject who completes the defibrillation protocol will be 
counted as a success or failure; it is assumed the true success rate is 93.5%. The required sample size to 
evaluate this objective using a two-sided exact binomial 95% confidence bound and OPC of 88% with 
90% power is 292 subjects completing the defibrillation protocol.  
12.4.  Primary Objective #1: Safety 
Demonstrate the freedom from major complications related to the EV ICD System and/or procedure at 
6 months post-implant exceeds an OPC of 79%.  

 
 
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 Hypothesis 
The hypotheses for this objective are as follows, with π6 denoting the 6-month freedom from major EV 
ICD System/procedure-related complications rate: 
 
HO: π6 ≤ 0.79 
HA: π6 > 0.79 
 Performance Requirements 
Performance requirements for this objective define both the endpoint and the OPC. The endpoint is 
defined as a subject’s first occurrence of a major complication related to the EV ICD System and/or 
procedure as determined by the independent Clinical Event Committee (CEC) that occurs on or prior to 
6 months (182 days) post-implant.  
For an adverse event to meet the endpoint, the event must have occurred within 182 days (inclusive) 
of the EV ICD System implant attempt and be adjudicated by the CEC as being a major complication 
related to the EV ICD System and/or procedure. Major complications are those complications resulting 
in: 
• 
Death 
• 
Permanent loss of defibrillation function due to mechanical or electrical dysfunction of the 
device  
• 
Hospitalization (see Table 12 for Hospitalization definition) 
• 
Prolongation of an existing hospitalization by at least 48 hours 
• 
System revision (reposition, replacement, explant) 
The pre-specified OPC for the major complication free rate at 6 months is 0.79, meaning the 95% lower 
confidence bound for the freedom from EV ICD major complication incidence rate must exceed 0.79. 
 Rationale for Performance Criteria 
The determination of the pre-specified OPC (79%) for the major complication objective was based on 
review of internal Medtronic transvenous ICD trial data as well as literature involving alternative 
devices.  An assessment of comparable major complication-free rates at 6 months for Medtronic 
transvenous devices showed observed rates as low as 85% (Figure 10).  In each such study, only ICD 
subjects with no history of CABG or valve surgery were analyzed, as that subset of subjects was 
considered representative of the possible EV ICD population.   

 
 
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Figure 10: Historical ICD Generator/RV Lead/Procedure-related Major Complication-free Rates 
 
*SCD-HeFT rates may include major and minor complications 
 
The following table provides further detail regarding these trials. 

 
 
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Table 15: Historical Medtronic Transvenous ICD Trial Major System/Procedure Complication-free Rates 
Study 
Study Description 
30-day Freedom 
Rate (95% CI) 
6-Month 
Freedom Rate 
(95% CI) 
Marquis VRxvii 
Medtronic Market Release Study Evaluating 
Marquis VR ICD 
90.2% 
(79.8%, 96.3%) 
N/A, subjects 
not followed to 
6 months 
SCD-HeFTxviii 
Randomized study comparing ICD therapy to 
placebo 
89.8%* 
(87.1%, 92.0%) 
88.5%* 
(85.6%, 90.8%) 
MVPxix 
Post-market study comparing MVP to VVI pacing 
in ICD population without pacing indication 
95.4% 
(93.5%, 96.8%) 
93.2% 
(91.0%, 94.9%) 
BLOCK HFxx 
IDE (G030156) study comparing efficacy of CRT to 
RV pacing in AV block patients 
89.3% 
(83.8%, 95.2%) 
85.3% 
(79.0%, 92.3%) 
REVERSExxi 
IDE (G040004) study comparing efficacy of CRT to 
ICD/OMT therapy in NYHA II patients 
92.6% 
(88.2%, 95.4%) 
89.4% 
(84.5%, 92.8%) 
Evera MRIxxii 
IDE (G140039) study evaluating safety and 
efficacy of the Medtronic Evera MRI ICD System 
94.6% 
(90.5%, 97.0%) 
93.1% 
(88.6%, 95.8%) 
PainFREE SSTxxiii 
Randomized study to evaluate the Medtronic 
Protecta ICD System 
96.7% 
(93.5%, 98.3%) 
93.8% 
(89.9%, 96.2%) 
*Included both major and minor complications 
 
                                                            
xvii Data on file. 
xviii Bardy G, et al.  Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure.  NEJM. 2005; 352:3: 
225-237.  
xix Sweeney M, et al.  Atrial pacing or ventricular backup-only pacing in implantable cardioverter-defibrillator patients.  Heart 
Rhythm.  2010; 7(11); 1552-1560. 
xx Curtis A, et al.  Biventricular Pacing for Atrioventricular Block and Systolic Dysfunction.  NEJM.  2013; 368:17: 1585-1593. 
xxi Linde C, et al.  Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in 
asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms.  JACC.  2008; 52(23): 1834-1843. 
xxii Gold MR, et al.  Full-Body MRI in Patients With an Implantable Cardioverter-Defibrillator: Primary Results of the 
Randomized Study.  JACC.  2015; 65(24):2581-2588. 
xxiii Auricchio A, et al.  Low inappropriate shock rates in patients with single- and dual/triple-chamber implantable 
cardioverter-defibrillators using a novel suite of detection algorithms; PainFree SST trial primary results.  Heart Rhythm.  2015; 
12(5):926-936. 
 

 
 
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Additionally, the OPC threshold of 79% has been used to evaluate only system-related complications in 
a pivotal trial for an alternative subcutaneous defibrillation devicexxiv, and so there is precedent for 79% 
being considered an acceptable criterion for evaluating safety at 6 months for defibrillation products. 
In that S-ICD study the observed 6-month freedom from system-related or procedure-related 
complications was 92.1% with a lower confidence limit of 88.9%.  A pooled analysis of the S-ICD IDE and 
EFFORTLESS Post Market S-ICD Registryxxv reported that 92.3% of subjects were free of a system or 
procedure-related complication through 6 months.  Since Medtronic is evaluating both EV ICD System 
and procedure-related complications, an OPC of 0.79 at 6 months for establishing freedom from such 
complications is appropriate. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. The total number of major 
complications experienced by subjects for whom an implant is attempted will be summarized. Subjects 
not experiencing an event will be censored at their last point of contact.  The 182-day freedom from 
major complication rate will be generated using the Kaplan-Meier method, along with a two-sided 95% 
confidence bound.  If the lower bound is at least 0.79 (79%), the objective will be considered met.   
 Determination of Subjects/Data for Analysis 
All subjects with an implant attempt of the investigational product will be included in the analysis. 
12.5.  Primary Objective #2: Efficacy  
Demonstrate the EV ICD defibrillation testing success rate at implant is greater than an OPC of 88%. 
 Hypothesis 
The hypotheses for this objective are as follows, with PI denoting the probability of EV ICD defibrillation 
success at implant: 
 
HO: PI ≤ 0.88 
HA: PI > 0.88 
                                                            
xxiv Weiss R, et al.  Safety and Efficacy of a Totally Subcutaneous Implantable-Cardioverter Defibrillator.  Circulation.  2013; 
128: 944-953. 
xxv Burke M, et a.  Safety and Efficacy of the Totally Subcutaneous Implantable Defibrillator: 2-Year Results From a Pooled Analysis of the IDE 
Study and EFFORTLESS Registry.  JACC (April 2015); 65 (16).   

 
 
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  Performance Requirements 
Performance requirements for this objective define both the endpoint and the OPC. The endpoint, 
defibrillation testing success, is defined as: 
• 
Single SSVA conversion at 20J, or  
• 
Conversion of two consecutive episodes of SSVA at 30J in final system configuration. 
Notes: 
• 
In one of the two consecutive SSVA episodes, up to two 30J shocks are permitted. 
• 
To achieve final system configuration, changing the position of the ICD generator and/or the lead 
or changing shock polarity is permitted. 
• 
Subjects can return for testing on another day if testing is not fully completed on the day of 
implant. 
The pre-specified OPC for this objective is 0.88 (88%), meaning the 95% lower confidence bound for the 
proportion of EV ICD pts who achieve defibrillation testing success at implant must exceed 0.88.    
 Rationale for Performance Criteria 
Defibrillation implant success for transvenous devices, though no longer routinely performed, has 
historically been shown to be as low as 88% (Table 16). A literature search combined with prior 
Medtronic trial data showed transvenous defibrillation testing rates commonly in the 90-93% range, 
which is in line with the hypothesized defibrillation efficacy of EV ICD.   
Table 16: Historical Transvenous ICD Defibrillation Testing Success Rates 
Reference 
Sample Size 
Defibrillation 
Implant 
Success 
Medtronic 6932 Lead Study  
(MDL #13520, Data on file) 
N=165 Model 6932 leads 
N=166 Model 6936 leads 
87.7% 
83.5% 
Medtronic 6944 Lead Study  
(MDL #24416, Data on file) 
N=112 Model 6944 leads 
N=122 Model 6942 leads 
91.1% 
91.8% 
Leong-Sit AMJ: 2006; 152:1104-8 
N=168 
90.5% 
Pires JCE 2006; 17:1-6 
DFT at implant (N=129) 
Safety Margin Testing at Implant (N=503) 
No Testing at Implant (N=203) 
77% 
93% 
N/A 
Michowitz Europace 2011; 13:683-88 
N=204 
91.7% 
SIMPLE Study Lancet 2015; 385:785-91 
Safety Margin Testing at Implant (N=1218) 
91.8% 

 
 
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Reference 
Sample Size 
Defibrillation 
Implant 
Success 
No Testing at Implant (N=1227) 
N/A 
 
The OPC threshold of 88% has also been used in a pivotal trial for an alternative defibrillation device (S-
ICD), so there is precedent for an OPC of 88% being considered an acceptable criterion for evaluating 
termination of induced ventricular rhythms at implant. The S-ICD literature shows acute defibrillation 
testing results less than 93% when testing at 65J (applying a 15J safety margin).    
 
Defibrillation results in the post market setting support the belief of S-ICD efficacy being 91-94%.  The 
first results from the EFFORTLESS Studyxxvi provided a report on the full patient cohort and study 
endpoint with follow-up ≥1 year.  The pre-defined endpoints of this registry are 30- and 360-day 
complications, and shocks for atrial fibrillation or supraventricular tachycardia.  These results provide 
more data on the efficacy of the S-ICD over time, during both induced and spontaneous arrhythmias.  
In the first 30 days following implantation, 861 patients had at least 1 evaluable acute conversion test, 
with 777 of these tests (91.6%) using a defibrillation energy of ≤65 J, which allows for a safety margin. 
In a retrospective analysis, Friedman et alxxvii reported on trends and in-hospital outcomes associated 
with early adoption of the S-ICD compared to single- and dual-chamber transvenous ICD implants. 
Table 17 provides in-hospital outcomes associated with the S-ICD implants.  Among 2791 patients with 
S-ICD who underwent DFT testing, 2588 (92.7%), 2629 (94.2%), 2635 (94.4%), and 2784 (99.7%) were 
successfully defibrillated (≤65, ≤70, ≤75, and ≤80 J, respectively). The 92.7% defibrillation efficacy at 65J 
is the best comparator, as it offers a 15J safety margin. 
 
Additionally, there have been other studies and sub-analyses that have reported on the defibrillation 
threshold testing performance of the S-ICD device.  Frankel DS et alxxviii evaluated 65J first shock success 
in acute DFT testing in the S-ICD IDE trial among subgroups define by BMI, while Peddareddy L et alxxix 
reported acute DFT testing results at their site only.  These studies show evidence of defibrillation 
                                                            
xxvi    Boersma L, et al.  Implant and Midterm Outcomes of the Subcutaneous Implantable Cardioverter-Defibrillator Registry – The 
EFFORTLESS Study.  JACC (August 2017); 70(7): 830-841. 
xxvii    Friedman D, et al.  Trends and In-Hospital Outcomes Associated with Adoption of the Subcutaneous Implantable Defibrillator in the 
United States.  JAMA Cardiol (November 2016); 1(8): 900-911. 
xxviii     Frankel DS et al.  Impact of Body Mass Index on Safety and Efficacy of the Subcutaneous Implantable Cardioverter-Defibrillator.  JACC:  
Clinical Electrophysiology (May 2018): 4(5): 652-659. 
xxix     Peddareddy L et al.  Effect of Defibrillation Threshold Testing on Effectiveness of the Subcutaneous Implantable Cardioverter 
Defibrillator.  Pacing Clin Electrophysiol (PACE) June 12 2018. doi: 10.1111/pace.13416 [epub] 

 
 
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testing performance of less than the OPC of 88% in subgroups of patients, further justifying the clinical 
relevance of such a threshold. 
Table 17: S-ICD EFFORTLESS Defibrillation Testing Results 
Final Conversion Result 
Without 
Repositioning 
With 
Repositioning 
Total 
EFFORTLESS Trial Results (N=861) 
 
 
 
   Success ≤ 65J (15J Safety Margin) 
777 (90.2%) 
12 (1.4%) 
789 (91.6%) 
   Success at 70-80J (0-10J Safety Margin) 
36 (4.2%) 
2 (0.2%) 
38 (4.4%) 
   Success at Unknown Energy 
29 (3.4%) 
1 (0.1%) 
30 (3.5%) 
   Summary of Success Conversion 
842 (97.8%) 
15 (1.7%) 
857 (99.5%) 
Friedman et al Retrospective Analysis (N=2791) 
 
 
 
   Success ≤ 65J (15J Safety Margin) 
N/A 
N/A 
2588 (92.7%) 
   Success ≤ 70J (10J Safety Margin) 
N/A 
N/A 
2629 (94.2%) 
   Success ≤ 75J (5J Safety Margin) 
N/A 
N/A 
2635 (94.4%) 
   Success ≤ 80J  
N/A 
N/A 
2784 (99.7%) 
Frankel DS et al Assessment of S-ICD IDE by BMI 
(Evaluating 65J First Shock Success) 
 
 
 
   BMI < 25.0 kg/m2 (N=79) 
N/A 
N/A 
75 (94.9%) 
   BMI 25.0-29.9 kg/m2 (N=105) 
N/A 
N/A 
91 (86.7%) 
   BMI ≥ 30.0 kg/m2 (N=137) 
N/A 
N/A 
114 (83.2%) 
Peddareddy L et al Single Site DFT Success (N=135) 
N/A 
N/A 
113 (83.7%) 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. Subjects will be partitioned by the 
results of their defibrillation testing (e.g., no rescue shocks required, one rescue shock required), with 
counts and percentage falling into each subgroup reported. Each subject who completes the 
defibrillation protocol will be determined to either have successfully met the defibrillation endpoint or 
not met the endpoint. A 95% two-sided binomial confidence interval for the proportion of subjects who 
met the endpoint will be generated. If the lower bound exceeds 0.88, the objective will be met.  
Subjects who do not complete the defibrillation protocol will be reported separately and will not be 
included in the calculation of the 95% confidence interval. 
 Determination of Subjects/Data for Analysis 
All subjects who complete the defibrillation protocol will be included in the analysis. 

 
 
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12.6.  Ancillary Objective #1  
Characterize appropriate and inappropriate shocks. 
 Hypothesis 
There are no hypotheses for this objective.  Spontaneous episodes receiving shocks will be 
summarized.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is defined as a shock 
delivered by the EV ICD. Spontaneous arrhythmic episodes resulting in a shock will be adjudicated to 
determine the underlying rhythm.  
 Rationale for Performance Criteria 
Due to the minimal number of appropriate and inappropriate shocks expected for spontaneous 
arrhythmias, this objective is intended to only characterize device performance with regard to sensing 
ventricular arrhythmias and delivering shocks when the episode either does not self-terminate or is not 
terminated by ATP. There are no pre-specified performance criteria. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. All shocks delivered by the device 
for spontaneous arrhythmias will be partitioned by whether the treated rhythm was a VT/VF episode, 
and by the specific rhythm of the episode. Both the number of episodes and the number of subjects 
experiencing such episodes will be reported, as well as the energy delivered.  Kaplan-Meier curves for 
time to first appropriate shock and time to first inappropriate shock may be provided to demonstrate 
shock incidence. 
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD having at least one device interrogation post-implant 
will be included in the analysis. At minimum, all episodes occurring by the date at which all implanted 
subjects have had the opportunity to be followed for 6 months post-implant will be included. 

 
 
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12.7.  Ancillary Objective #2 
Characterize electrical performance (pacing capture thresholds, pacing impedance, sensing amplitudes) 
over time. 
 Hypothesis 
There are no hypotheses for this objective. Pacing capture performance, as well as pacing impedance 
and sensing amplitudes, will be summarized. 
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoints are defined as pacing 
capture threshold, pacing impedance, and sensing amplitude. The pacing testing will be performed at 
pre-hospital discharge, as well as visits at 2 weeks, 3- and 6-months post-implant and every 6 months 
thereafter.  
 Rationale for Performance Criteria 
This objective is for the purpose of characterizing device performance with regard to achieving pacing 
capture and determining sensing performance over time. There are no pre-specified performance 
criteria. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics.  For each follow-up visit, the 
proportion of subjects undergoing pacing testing will be reported, as well as the proportion for whom 
capture is obtained. Mean impedance and R-wave amplitudes will also be reported at each follow-up 
for which the testing occurs (pre-hospital discharge, 2 weeks, 3- and 6-months post-implant, and every 
6 months thereafter). 
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD having relevant data (pacing tests, impedance, 
sensing amplitudes) will be included in the analysis of that endpoint at that timepoint. 
12.8.  Ancillary Objective #3  
Characterize extracardiac pacing sensation. 

 
 
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 Hypothesis 
There are no hypotheses for this objective.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint will be defined as 
whether pacing therapies were programmed OFF due to pacing sensation. 
 Rationale for Performance Criteria 
There are no pre-specified performance criteria; pacing sensation at follow-up will be summarized and 
reported. 
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. Descriptive statistics will be used to 
summarize distribution among the subjects who completed each follow-up visit, and whether pacing 
therapies, specifically ATP, were programmed OFF due to the subject reporting pacing sensation. This 
objective will be analyzed using data from the pre-hospital discharge, 2 weeks, 3- and 6-month, and 
long-term visits. 
 Determination of Subjects/Data for Analysis 
For each visit (e.g., PHD, 2 weeks), all subjects successfully implanted with an EV ICD who complete 
that visit will be included in the analysis.     
12.9.  Ancillary Objective #4 
Characterize asystole pacing.  
 Hypothesis 
There are no hypotheses for this objective, as the purpose of this objective is simply to characterize 
prevalence of asystole pacing in this population.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is the amount of 
pacing for asystole the subject received.  

 
 
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 Rationale for Performance Criteria 
This objective is for the purpose of characterizing prevalence of need for asystole pacing in this 
population. There are no pre-specified performance criteria. 
 Analysis Methods 
Descriptive statistics will be used to summarize the number of subjects and amount of asystole pacing 
experienced during follow-up.   
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD with at least one device interrogation post-implant 
will be eligible for the analysis. At minimum, all instances occurring on or before the date at which all 
implanted subjects have had the opportunity to be followed for 6 months post-implant will be 
included. 
12.10. Ancillary Objective #5 
Summarize ATP performance with spontaneous arrhythmias. 
 Hypothesis 
There are no hypotheses for this objective, as the purpose is to characterize defibrillation performance 
through use of ATP.  
  Performance Requirements 
Performance requirements are not pre-specified for this objective.  The endpoint is defined as whether 
a spontaneous ventricular tachycardia episode for which ATP was delivered by the EV ICD was 
terminated by ATP. Spontaneous arrhythmias will be adjudicated to determine the underlying rhythm 
and whether they were terminated by ATP.  
 Rationale for Performance Criteria 
It is projected that only a small subset of implanted subjects may experience one or more ventricular 
arrhythmias during follow-up. Therefore, device performance regarding such episodes will be 
characterized only.  There are no pre-specified performance criteria. 

 
 
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 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. All monomorphic and polymorphic 
ventricular arrhythmias with EGM will be partitioned by whether the treated rhythm received ATP 
and/or shock, whether it successfully terminated as a result, and by the specific rhythm of the episode 
(monomorphic vs. polymorphic VT/VF). Both the number of episodes and the number of subjects 
experiencing such episodes will be reported. A 95% confidence interval will be provided for the 
percentage of monomorphic VT episodes successfully terminated by ATP. 
 Determination of Subjects/Data for Analysis 
All subjects successfully implanted with an EV ICD having at least one device interrogation post-implant 
will be included in the analysis. At minimum, all VT/VF episodes occurring on or prior to the date by 
which all implanted subjects have had the opportunity to be followed for 6 months post-implant will be 
included in the analysis.  
12.11. Ancillary Objective #6 
Summarize adverse events. 
 Hypothesis 
There are no hypotheses for this objective, as safety of the EV ICD System is being evaluated by Primary 
Objective #1 (see section 12.4).  This objective is to provide a comprehensive summary of adverse 
events experienced during follow-up.  
 Performance Requirements 
Performance requirements are not pre-specified for this objective. The endpoint is an adverse event 
(see Table 12 for definition of adverse event) experienced by a subject post-enrollment and prior to 
exit. Adverse events will be adjudicated by a Clinical Events Committee for relatedness to the EV ICD 
System and procedure.  
 Rationale for Performance Criteria 
This objective is for the purpose of gathering comprehensive data pertaining to subject health over at 
least the first six months post-implant. There are no pre-specified performance criteria. 

 
 
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 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics. Counts and percentages of subjects 
experiencing system and/or procedure-related adverse events will be reported, as well as, in the case 
of system-related events, the specific component of the system to which the event was related. 
Adverse Events will be broken out by MedDRA keyterm, with both counts of events and counts of 
subjects experiencing each type of event reported. 
 Determination of Subjects/Data for Analysis 
All subjects for whom an implant of the investigational product is attempted will be included in the 
analysis. At minimum, all adverse events recorded by the date by which all implanted subjects have 
been followed at least 6 months post-implant will be included. 
12.12. Ancillary Objective #7 
Characterize the EV ICD defibrillation testing success rate at 6 months post-implant. 
 Hypothesis 
No statistical hypotheses will be tested for this objective. 
 Performance Requirements 
The performance requirement for this objective is that the observed proportion of subjects, among 
those with an induced VF episode at their 6-month visit, for whom the episode is successfully 
terminated with a shock is at least 0.88.  The endpoint, defibrillation testing success, is defined as 
successful completion of the chronic defibrillation testing protocol at the 6-month visit. 
 Sample Size 
Consecutive subjects at centers that agree with and obtain approval from their EC and associated 
regulatory authority if applicable will be approached for consent to undergo chronic defibrillation 
testing (see CIP Addendum for 6-Month Defibrillation Testing) until a minimum of 17 and up to 34 
subjects have completed testing. Subjects who have consented to participate in this testing will have 
their chronic defibrillation testing included in the analysis. 

 
 
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 Rationale for Performance Criteria 
Chronic defibrillation testing is rarely done as standard of care, and places burden on the subject.  
Therefore, this trial will gather minimal chronic defibrillation testing data to assess efficacy of the EV 
ICD System in a chronic defib testing, as defined by an observed chronic defibrillation success rate 
meeting the primary efficacy Objective Performance Criterion of 0.88.    
 Analysis Methods 
Results will be summarized in aggregate using descriptive statistics.  Subjects will be partitioned by the 
results of their defibrillation testing (e.g., no rescue shocks required, one rescue shock required), with 
counts and percentage falling into each subgroup reported.  As supplemental data of chronic 
performance, if spontaneous VF episodes treated with a shock by the EV ICD System and occurring at 
least 120 days post-implant are available, they will be summarized separately. Additionally, subjects 
who do not consent to chronic defibrillation testing but who undergo chronic defibrillation testing at 6-
month or later follow-up per physician discretion will be analyzed separately. 
 Determination of Subjects/Data for Analysis 
All subjects for whom defibrillation testing is attempted at 6 months or who experience a spontaneous 
VF episode treated with a shock by the EV ICD System at least 120 days post-implant will be included in 
the analysis. 
12.13. Supplemental Analysis 
Quality of Life/patient acceptance will also be measured through the SF-12 Questionnaire at baseline 
and 6 months and FPAS at 6 months. These tools will be administered so that subject response in this 
study may be compared to response to such tools in other ICD studies. 
13. Ethics 
13.1.  Statement(s) of Compliance  
The study will be conducted according to the Declaration of Helsinki, CIP, Good Clinical Practice (GCP) 
and in accordance to the national and local laws, regulations, standards, and requirements of the 
countries/geographies in which the study is conducted. The principles of the Declaration of Helsinki are 
implemented in this study by means of the Informed Consent process, Ethics Committee approval, study 
training, clinical trial registration, and risk benefit assessment. 

 
 
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The clinical investigation shall not begin until all required approvals and documents from the Ethics 
Committee and regulatory authorities, if needed, have been received. Any additional requirements 
imposed by the Ethics Committee or regulatory authority shall be followed, if appropriate. 
This EV ICD Pivotal Study will be conducted in compliance with international ethical and scientific quality 
standards, known as good clinical practice (GCP). GCP includes review and approval by an independent 
Ethics Committee before initiating a study, continuing review of an ongoing study by an Ethics 
Committee, and obtaining and documenting the freely given Informed Consent of a subject before 
initiating the study. 
The EV ICD Pivotal Study is designed to reflect the GCP principles outlined in ISO 14155:2011 and other 
international clinical requirements outlined below. These include the protection of the rights, safety and 
well-being of human subjects, controls to ensure the scientific conduct and credibility of the clinical 
investigation and the definition of responsibilities of the sponsor and investigators. In accordance with 
ISO 14155:2011, the sponsor shall avoid improper influence on, or inducement of, the subject, monitor, 
any investigator(s) or other parties participating in, or contributing to, the clinical investigation. All 
investigators shall avoid improper influence on or inducement of the subject, sponsor, monitor, other 
investigator(s) or other parties participating in or contributing to the clinical investigation.  Adverse 
Event and Device Deficiency handling in the EV ICD Pivotal Study is ISO 14155:2011 compliant for all 
participating geographies. 
Ultimately, all sites in all geographies will follow and comply with: 
• 
The Clinical Trial Agreement 
• 
The procedures described within this CIP 
• 
Local Ethics Committee Requirements 
In addition to the requirements outlined above, the study will be conducted according to federal, 
national and local laws, regulations, standards, and requirements of the countries/geographies where 
the study is being conducted. These include but are not limited to the following:  
• 
In Australia and New Zealand: local laws will be complied with and below will be followed: 
• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including 
the latest version 2013 
• 
ISO 14155:2011 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
In Canada below will be followed: 
• 
SOR/98-282, Section 59-88 

 
 
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• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including 
the latest version 2013 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
In Europe, Middle East, Africa, the study will be conducted in compliance with: 
• 
ISO 14155:2011  
• 
Active Implantable Medical Device Directive (AIMDD) 
• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including 
the latest version 2013 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
In Hong Kong, the study will be conducted in compliance with: 
• 
ISO 14155:2011 
• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including 
the latest version 2013 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
In Japan, the study will be conducted in compliance with: 
• 
Ministerial Ordinance Concerning Good Clinical Practice for Medical Devices (The 
Ministry of Health, Labour and Welfare (MHLW) Ministerial Ordinance No.36 in 2005 
revised on 26 Oct 2017) 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including 
the latest version 2013 
• 
In the United States, the study will be conducted under an FDA Investigational Device Exemption 
(IDE) in compliance with: 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 50: Protection of Human Subjects 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
21 CFR Part 56: Institutional Review Boards 
• 
21 CFR Part 812: Investigational Device Exemptions 

 
 
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• 
Principles of Declaration of Helsinki and all of its subsequent amendments, including 
the latest version 2013 
The study will be publicly registered prior to first enrollment in accordance with the 2007 Food and Drug 
Administration Amendments Act (FDAAA) and Declaration of Helsinki on http://clinicaltrials.gov (PL 110-
85, section 810(a)). In addition, the study may be registered in local regulatory databases where 
required by local law.  
Approval of the CIP and CIP amendments, if applicable, is required from the following groups prior to 
any study procedures at a study site: 
• 
Medtronic 
• 
Principal Investigators  
• 
Geography-specific regulatory authorities (if regulatory approval is required) 
• 
Ethics Committees 
Similarly, approval of subsequent revisions to the CIP is required from the above-mentioned groups 
prior to implementation of the revised CIP at each study site. 
14. Study Administration 
14.1.  Monitoring 
It is the responsibility of Medtronic to ensure proper monitoring of this clinical study. Trained 
Medtronic personnel or delegates appointed by Medtronic may perform study monitoring at the study 
site to ensure the study is conducted in accordance with the CIP, the Clinical Trial Agreement, and 
applicable regulatory and local requirements. Medtronic, or delegates, must therefore have access to 
the subjects’ case histories (clinic and hospital records, and other source data/documentation) upon 
request as per the Informed Consent Form, Authorization to Use and Disclose Personal Health 
Information/Research Authorization/HIPAA/other privacy language (where applicable) and Clinical Trial 
Agreement. The Principal Investigator should also be available during monitoring visits. 
Frequency of monitoring visits may be based upon subject enrollment, duration of the study, study 
compliance, number of adverse events, number of deviations, findings from previous monitoring visits 
and any suspected inconsistency in data that requires investigation. Monitoring for the study, including 
site initiation visits, interim monitoring visits, and closeout visits, will be done in accordance to the 
study-specific monitoring plan. 

 
 
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Monitoring visits may be conducted periodically in accordance with the study monitoring plan to assess 
site study progress, the investigator’s adherence to the CIP, regulatory compliance including but not 
limited to Ethics Committee approval and review of the study, maintenance of records and reports, 
and review of source documents against eCRFs. Monitors review site regulatory and study compliance 
by identifying findings of non-compliance and communicating those findings along with 
recommendations for preventative/corrective actions to site personnel. Monitors may work with study 
personnel to determine appropriate corrective action recommendations and to identify trends within 
the study or at a particular site. 
14.2.  Data Management 
Data will be collected using an electronic data management system for clinical studies.  Electronic Case 
Report Form (eCRF) data will be stored in a secure, password-protected database which will be backed 
up nightly. Data will be reviewed using programmed and manual data checks. Data queries will be made 
available to sites for resolution. Study management reports may be generated to monitor data quality 
and study progress. At the end of the study, the data will be frozen and will be retained by Medtronic. 
 
The data reported on the eCRFs shall be derived from source documents and be consistent with these 
source documents.  Source documents, which may include patient medical records, device interrogation 
files, programmer printouts, and worksheets, must be created and maintained by site personnel. The 
eCRF may be considered as source for the following data points: 
• 
Adverse Event: date site became aware of event  
• 
Non-Subject Adverse Event: date site became aware of event  
• 
Device Deficiency: date site became aware of deficiency  
• 
Protocol Deviation: reason for deviation 
• 
EV ICD Device Accountability eCRFs: 
o DVEX3E4 EV ICD (except for date used/date explanted) 
o EV2401 EV ICD Lead (except for date used/date explanted) 
o EAZ101 and EAZ201 Tunneling Tools (except for date used) 
o Oscor SafeSheath® II Model SSCL9 introducer (except for date used) 
o SW041 Programmer Software 
o DR220 NorthEast Monitoring Digital Holter Recorder 
Device data from transmissions provided to Medtronic will be uploaded to secure servers and made 
accessible to the study team. Save-to-media files and other non-eCRF data such as Radiographs and 
Fluoroscopies collected via electronic media at office visits may be sent to Medtronic. Upon receipt via 

 
 
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transmission or electronic media, non-eCRF data will be securely maintained, and stored, and retrieved 
for analysis and reporting. 
 
14.3. Direct Access to Source Data/Documents  
The sponsor or a regulatory authority may audit or inspect the study site to evaluate the conduct of the 
study. The clinical investigator(s)/institution(s) shall allow study related monitoring, audits, Ethics 
Committee review, and regulatory inspection(s) by providing direct access to source data/documents. If 
study site’s documents are electronic, these must be made available in their original form (or printouts 
signed and dated with the statement that this is complete and true reproduction of the original source 
document) if requested by the sponsor and/or regulatory authority. Study sites should inform Medtronic 
upon notification of an audit by a regulatory body immediately. 
14.4. Confidentiality 
All records and other information about subjects participating in this study will be treated as 
confidential. Data will be transferred and processed by Medtronic or a third party designated by 
Medtronic in a key coded form, unless it is impossible to make it anonymous, for instance, where the 
subject’s name cannot be removed from the data carrier, such as fluoroscopy images. Participating 
subjects will not be identified by name in any published reports about the study. 
14.5. Liability 
Medtronic Australasia Pty Ltd is a wholly owned subsidiary of Medtronic, Inc., which as the parent 
company of such entity maintains appropriate clinical study liability insurance coverage as required 
under applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. If required, a Clinical Study insurance statement/certificate will be provided 
to the Ethics Committee. 
Medtronic New Zealand Ltd. is a wholly owned subsidiary of Medtronic, Inc., which as the parent 
company of such entity maintains appropriate clinical study liability insurance coverage as required 
under applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. If required, a Clinical Study insurance statement/certificate will be provided 
to the Ethics Committee. 
Medtronic Bakken Research Center B.V. (Europe, Middle East) is a wholly owned subsidiary of 
Medtronic, Inc., which as the parent company of such entity maintains appropriate clinical study liability 

 
 
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insurance coverage as required under applicable laws and regulations and will comply with applicable 
local law and custom concerning specific insurance coverage. If required, a Clinical Trial insurance 
statement/certificate will be provided to the Ethics Committee. 
Medtronic International (Hong Kong), Ltd. is a wholly owned subsidiary of Medtronic, Inc., which as the 
parent company of such entity maintains appropriate clinical trial liability insurance coverage as 
required under applicable laws and regulations and will comply with applicable local law and custom 
concerning specific insurance coverage. If required, a Clinical Trial insurance statement/certificate will 
be provided to the Ethics Committee. 
Medtronic Japan Co., Ltd is a wholly owned subsidiary of Medtronic, which as the parent company of 
such entity maintains appropriate clinical study liability insurance coverage as required under applicable 
laws and regulations and will comply with applicable local law and custom concerning specific insurance 
coverage. If required, a clinical study insurance statement/certificate will be provided to the Institutional 
Review Board. 
14.6. CIP Amendments 
Approval of CIP amendments is required from the following groups prior to any study procedures at 
a study site: 
• 
Medtronic 
• 
Principal Investigators (where required by local law) 
• 
Geography-specific regulatory authorities (if regulatory approval is required) 
• 
An independent Ethics Committee. 
14.7. Required Records and Reports 
 Investigator Records 
The investigator is responsible for the preparation and retention of the records cited below. All of the 
below records, with the exception of case history records and case report forms, should be kept in the 
Investigator Site File (e.g., the study binder provided to the investigator) or Subject Study Binder. 
Electronic CRFs must be maintained and signed electronically within the electronic data capture system 
during the study. The following records are subject to inspection and must be retained: 
• 
All correspondence between the Ethics Committee, sponsor, monitor, regulatory authority and 
the investigator that pertains to the investigation, including required reports.  

 
 
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• 
Subject’s case history records, including:  
o Signed and dated Informed Consent Form.  
o Observations of adverse events/adverse device effects/device deficiencies. 
o Medical history. 
o Implant and follow-up data (if applicable). 
o Documentation of the dates and rationale for any deviation from the CIP. 
• 
Subject identification log. 
• 
List of investigation sites. 
• 
Financial disclosure. 
• 
All approved versions of the CIP, IC, other information given to the subject and Investigator’s 
Brochure. 
• 
Signed and dated Clinical Trial Agreement.  
• 
Current signed and dated curriculum vitae of Principal Investigator and key members of the 
investigation site team (as required by local law). 
• 
Documentation of delegated tasks.  
• 
Ethics Committee approval documentation. Written information that the investigator or other 
study staff, when member of the Ethics Committee, did not participate in the approval process. 
Approval documentation must include the Ethics Committee composition, where required per 
local law.   
• 
Regulatory authority notification, correspondence and approval, where required per local law. 
• 
Study training records for site staff.  
• 
Insurance certificates.  
• 
Shipping records of investigational devices. 
• 
Equipment maintenance records, if applicable. 
• 
Any other records that local regulatory agencies require to be maintained.  
• 
Final Study Report including the statistical analysis. 
 
The above-mentioned documentation shall be kept for a period of at least 15 years after the clinical 
investigation with the device in question has ended, or, in the event that the device is subsequently 
placed on the market, at least 15 years after the last device has been placed on the market or longer as 
local law or hospital administration requires.  
 Investigator Reports  
The investigator is responsible for the preparation (review and signature) and submission to the 
sponsor of all case report forms, including adverse events and adverse device effects (reported per the 

 
 
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country-specific collection requirements), device deficiencies, deaths, and any deviations from the CIP. 
If any action is taken by an Ethics Committee with respect to this clinical study, copies of all pertinent 
documentation must be forwarded to Medtronic in a timely manner. Reports are subject to inspection 
and to the retention requirements as described above for investigator records. 
Safety data investigator reporting requirements are listed in Table 14 of the Adverse Event section 
10.5. The investigator shall prepare and submit in a complete, accurate and timely manner the reports 
listed in this section. 
Table 18: Investigator reports applicable for all geographies per Medtronic requirements 
Report  
Submit to 
Description/Constraints 
Withdrawal of Ethics 
Committee approval 
Sponsor and 
Relevant 
Authorities, where 
applicable per local 
requirements 
The investigator must report a withdrawal of approval by the reviewing Ethics 
Committee of the investigator’s part of the investigation within 5 working days, 
or sooner as required per local requirements. 
Study Deviations  
Sponsor  
Ethics Committee 
and Relevant 
Authorities, where 
applicable per local 
requirements 
Any deviation from the Clinical Investigation Plan shall be reported together with 
the explanation of the deviation as soon as possible upon the site becoming 
aware of the deviation. 
Notice of deviations from the CIP involving a failure to obtain a subject’s consent, 
or is made to protect the life or physical well-being of a subject in an emergency 
shall be given within 5 working days, or sooner if required by local requirements. 
Except in such emergency, prior approval is required for changes in the plan or 
deviations. Reporting of serious breaches as per requirements in Australia must 
be complied with. 
Australia: Report any suspected breaches to the sponsor and confirmed serious 
breaches to their institution (research governance office) within 72 hours of 
becoming aware or notified of the same; provide any follow-up information as 
required and work with the institution or sponsor, as appropriate, to implement 
any corrective and preventative actions. 
Progress report 
Sponsor and 
Ethics Committee 
As required by local requirements. 
Final Report 
Ethics Committees 
and Relevant 
Authorities 
This report must be submitted per local requirements. 
 

 
 
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Table 19: Investigator reports applicable to the United States per FDA regulations 
Report  
Submit to 
Description/Constraints 
Withdrawal of Ethics 
Committee approval (either 
suspension or termination) 
Sponsor 
The investigator must report a withdrawal of approval by the reviewing 
Ethics Committee of the investigator’s part of the investigation within 5 
working days.  (21 CFR 812.150(a)(2)) 
For any action taken by an EC with respect to the investigation 
information will be forwarded to the sponsor. 
Progress report  
Sponsor and 
Ethics Committee 
The investigator must submit this report to the sponsor and Ethics 
Committee at regular intervals, but in no event less than yearly. (21 CFR 
812.150 (a)(3)).   
Study deviations  
Sponsor and 
Ethics Committee 
Notice of deviations from the CIP to protect the life or physical wellbeing 
of a subject in an emergency shall be given as soon as possible, but no 
later than 5 working days after the emergency occurred.  Except in such 
emergency, prior approval is required for changes in the plan or 
deviations.  If the deviation may affect the scientific soundness of the plan 
or the rights, safety and welfare of the subjects, the deviation must be 
approved by Medtronic, the EC, and the FDA/applicable regulatory 
authorities.  If the deviation does not affect these issues then only 
Medtronic must approve it.  (21 CFR 812.150(a)(4)) 
Failure to obtain Informed 
Consent prior to 
investigational device use 
Sponsor and 
Ethics Committee 
If an investigator uses a device without obtaining Informed Consent, the 
investigator shall report such use within 5 working days after device use.  
(21 CFR 812.150(a)(5)) 
Final report 
Sponsor 
Ethics Committee 
Relevant 
Authorities 
This report must be submitted within 3 months of study completion or 
termination of the investigation or the investigator’s part of the 
investigation.  (21 CFR 812.150(a)(6)) 
Other 
Ethics Committee 
and FDA 
An investigator shall, upon request by a reviewing Ethics Committee or 
regulatory agency, provide accurate, complete, and current information 
about any aspect of the investigation. (21 CFR 812.150(a)(7)) 
 
 
 

 
 
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Table 20: Investigator reports applicable to Europe, Middle East and Africa per ISO 14155:2011 
Report  
Submit to 
Description/Constraints 
Progress Report  
Sponsor and 
Ethics Committee 
Provide if required by local law or Ethics Committee.  
Study Deviations  
Sponsor and 
Ethics Committee 
Any deviation from the CIP shall be recorded together with an explanation for the 
deviation.  Deviations shall be reported to the sponsor who is responsible for 
analyzing them and assessing their significance.   
Note: When relevant, Ethics Committees, competent authorities or the appropriate 
regulatory bodies should be informed.  
Failure to obtain 
Informed Consent 
Sponsor and 
Ethics Committee 
Informed Consent shall be obtained in writing and documented before a subject is 
enrolled into the clinical investigation.   
 
Table 21: Investigator reports applicable to Japan 
Report  
Submit to 
Description/Constraints 
Co-Investigator/ 
Clinical Trial 
Collaborator List 
Head of Medical 
Institution (HOMI) 
When the principal Investigator assigns important parts of the clinical trial duties to 
co-Investigators and/or clinical trial collaborators, he or she shall prepare a list of 
the assigned duties and the individual performing the assigned duties, submit the 
list to the HOMI on the list, and receive the appointments of such individuals. 
(MHLW Ordinance 36, 2005 Article 63) 
Study Deviations 
Sponsor and HOMI 
The Investigator may implement a deviation from, or a change in, the CIP to 
eliminate an immediate hazard(s) to study subjects without prior Ethics Board 
approval. In this case, the Investigator shall immediately submit to the sponsor, the 
HOMI, and to the Ethics Board via the HOMI, the description and reason for the 
deviation and the proposed revision to the CIP, if one is necessary, to receive 
agreement. All deviations, regardless of the reason, shall be submitted to the 
sponsor. (MHLW Ordinance 36, 2005 Article 66) 
Summary of the 
Clinical Study Status HOMI 
The principal Investigator shall submit a summary of the clinical study status to the 
HOMI in writing once a year, or more frequently if requested by the Ethics Board, to 
receive the continuation review by the institutional review board. (MHLW 
Ordinance 36, 2005 Article 68) 
Premature 
Termination or 
Suspension of the 
Clinical 
Investigation 
HOMI 
When the principal Investigator discontinues or suspends the clinical study, he or 
she shall promptly notify the HOMI thereof in writing, and explain in detail in writing 
the discontinuation or suspension. (MHLW Ordinance 36, 2005 Article 69) 
Completion of the 
Clinical 
Investigation 
HOMI 
When the clinical study is completed, the principal Investigator shall notify the 
HOMI thereof in writing and report on a summary of the clinical study results in 
writing. (MHLW Ordinance 36, 2005 Article 69) 
 

 
 
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Additional reporting requirements and if stricter timelines of reporting are required per EC and/or local 
regulation, the same should be complied with, including any reporting needs to regulators, when 
required by local law. 
 Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records: 
• 
All correspondence which pertains to the investigation. 
• 
Investigational device traceability records.  
• 
Software traceability records.  
• 
Signed Clinical Trial Agreements, financial disclosure and current signed and dated (Europe, 
ANZ, and Hong Kong only) curriculum vitae of Principal Investigator and key members of the 
investigation site team (as required by local law), delegated task list. 
• 
All approved Informed Consent templates, and other information provided to the subjects, 
including translations. 
• 
Copies of all Ethics Committee approval letters and relevant Ethics Committee correspondence 
and Ethics Committee voting list/roster/letter of assurance. 
• 
Names of the institutions in which the clinical study will be conducted. 
• 
Regulatory authorities’ correspondence, notification and approval as required by national 
legislation. 
• 
Insurance certificates (if applicable per local law). 
• 
Names/contact addresses of monitors. 
• 
Site visit reports and follow-up letters. 
• 
Statistical analyses and underlying supporting data. 
• 
Final report of the clinical study. 
• 
The Clinical Investigation Plan, Investigator’s Brochure and study related reports, and 
revisions. 
• 
eCRFs, including AE and Device Deficiency (DD) forms and eCRF corrections. 
• 
Study training records for site personnel and Medtronic personnel involved in the study. 
• 
Any other records that local regulatory agencies require to be maintained. 

 
 
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 Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports listed in the 
tables below (by geography). In addition to the reports listed below, Medtronic shall, upon request of 
reviewing Ethics Committee or regulatory agency, provide accurate, complete and current information 
about any aspect of the investigation. Safety data Medtronic reporting requirements are listed in Table 
14 of the Adverse Event section 10.5. 
Table 22: Sponsor reports for Australia and New Zealand 
Report  
Submit to 
Description/Constraints 
Premature termination or 
suspension of the clinical 
study 
Investigators, Ethics 
Committee, and 
relevant authorities 
Provide prompt notification of termination or suspension and reason(s).  
Recall and device disposition Investigators, Ethics 
Committee, relevant 
authorities,  
Notification as required per local regulations in country 
Study deviation  
Investigators 
Ensure that all deviations from the Clinical Investigation Plan are reviewed 
with the appropriate clinical investigator(s), are reported on the case report 
forms and the final report of the clinical investigation. Site specific study 
deviations will be submitted to investigators periodically.  Reporting of 
serious breaches to required parties in Australia as per local requirements 
will be done. 
Annual safety reports and 
single case Adverse events 
TGA 
Submit upon request from TGA 
USADEs for Australia and 
international / Safety Report 
/ updated IB / approved 
Product Information 
Investigator and HREC 
Per EC requirements, but at least annually: 
• Annual safety report including; - a summary of the evolving safety 
profile of the trial, a brief description and analysis of new/relevant 
findings, implications of safety data to the risk-benefit ratio for the 
trial, a description of any measures taken or proposed to minimize 
risks  
(NHMRC Safety monitoring and reporting in clinical trials involving 
therapeutic goods November 2016 section C.1.i) 
• An updated/addenda of IB or IFU, if appropriate (e.g., when an IB is 
no longer maintained). 
(NHMRC Safety monitoring and reporting in clinical trials involving 
therapeutic goods November 2016 section C.1.h) 
 

 
 
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Table 23: Sponsor reports for Canada 
Report  
Submit to 
Description/Constraints 
Premature termination or 
suspension of the clinical 
study 
Investigators, 
Ethics Committee, 
Relevant 
authorities, and  
Head of the 
Institution 
Provide prompt notification of termination or suspension and reason(s).  
Recall and device disposition 
Investigators, 
Head of Institution, 
Ethics Committee, 
relevant 
authorities, and  
FDA 
Notification within 30 working days and will include the reasons for any 
request that an investigator return, repair, or otherwise dispose of any 
devices.   
Study deviation  
Investigators 
Ensure that all deviations from the Clinical Investigation Plan are reviewed 
with the appropriate clinical investigator(s), are reported on the case report 
forms and the final report of the clinical study.  
Site specific study deviations will be submitted to investigators periodically.  
Table 24: Sponsor reports for Europe, Middle East, Africa 
Report  
Submit to 
Description/Constraints 
Premature termination or 
suspension of the clinical 
study 
Investigators, 
Ethics Committee, 
Relevant 
authorities and 
Head of the 
Institution 
Provide prompt notification of termination or suspension and reason(s). 
(ISO 14155:2011) 
Withdrawal of Ethics 
Committee approval 
Investigators, 
Head of Institution, 
Ethics Committee 
and  
relevant authorities 
Investigators, Ethics Committee will be notified only if required by local 
laws or by the Ethics Committee. 
Withdrawal of CA approval 
Investigators, 
Head of Institution, 
Ethics Committee, 
and 
relevant authorities 
Investigators, Ethics Committee will be notified only if required by local 
laws or by the Ethics Committee. 

 
 
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Report  
Submit to 
Description/Constraints 
Progress Reports 
Ethics Committee 
and 
regulatory 
authorities 
This will be submitted to the Ethics Committee only if required by the Ethics 
Committee. 
Final report 
Investigators,  
Ethics Committee, 
and 
Regulatory 
authorities upon 
request 
For studies with sites complying to ISO 14155:2011: 
 
• 
The investigator shall have the opportunity to review and 
comment on the final report. 
• 
If a clinical investigator does not agree with the final report, 
his/her comments shall be communicated to the other 
investigator(s).   
• 
The coordinating investigator shall sign the report. If no 
coordinating investigator is appointed, then the signature of the 
Principal Investigator in each site should be obtained.    (ISO 
14155:2011) 
Study deviation  
Investigators 
Ensure that all deviations from the Clinical Investigation Plan are reviewed 
with the appropriate clinical investigator(s), are reported on the case report 
forms and the final report of the clinical investigation.  (ISO 14155:2011) 
Site specific study deviations will be submitted to investigators periodically.  
Table 25: Sponsor reports for Hong Kong 
Report  
Submit to 
Description/Constraints 
Premature termination or 
suspension of the clinical 
study 
Investigators, 
Ethics Committee 
Provide prompt notification of termination or suspension and reason(s).  
Recall and device disposition 
Investigators, 
Ethics Committee, 
relevant authorities 
Notification within 30 working days and will include the reasons for any 
request that an investigator return, repair, or otherwise dispose of any 
devices.   
Study deviation  
Investigators 
Ensure that all deviations from the CIP are reviewed with the appropriate 
clinical investigator(s), are reported on the case report forms and the final 
report of the clinical study.     

 
 
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Table 26: Sponsor reports for the United States 
Report  
Submit to 
Description/Constraints 
Withdrawal of Ethics 
Committee approval 
Investigators, 
Ethics Committee, 
FDA, and relevant 
authorities 
Notification within five working days.  (21 CFR 812.150(b)(2))   
Withdrawal of FDA approval 
Investigators, 
Ethics Committee, 
and relevant 
authorities 
Notification within five working days.  (21 CFR 812.150(b)(3)) 
Investigator List 
FDA 
Submit at 6-month intervals, a current list of the names and addresses of all 
investigators participating in the investigation.  (21 CFR 812.150(b)(4)) 
Progress Reports 
Ethics Committee 
and FDA 
Progress reports will be submitted at least annually.  (21 CFR 812.150(b)(5), 
812.36(f)   
Recall and device disposition 
Investigators, Head 
of Institution, 
Ethics Committee, 
relevant 
authorities, and  
FDA 
Notification within 30 working days and will include the reasons for any 
request that an investigator return, repair, or otherwise dispose of any 
devices.  (21 CFR 812.150(b)(6)) 
Failure to obtain Informed 
Consent  
FDA 
Investigator’s report will be submitted to FDA within five working days of 
notification.  (21 CFR 812.150(b)(8)) 
Final report 
Investigators, 
Ethics Committee, 
Regulatory 
authorities upon 
request, and FDA 
Medtronic will notify FDA within 30 working days of the completion or 
termination of the investigation.  A final report will be submitted to the 
FDA, investigators, and Ethics Committee within six months after 
completion or termination of this study.  (21 CFR 812.150(b)(7)) 
Study deviation  
Investigators 
Ensure that all deviations from the Clinical Investigation Plan are reviewed 
with the appropriate clinical investigator(s), are reported on the case report 
forms and the final report of the clinical study.  
Site specific study deviations will be submitted to investigators periodically.  
Other 
IRB, FDA 
Accurate, complete, and current information about any aspect of the 
investigation. (21 CFR 812.150(b)(10)) 
 
Table 27: Sponsor reports for Japan 
Report  
Submit to 
Description/Constraints 

 
 
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Premature termination or 
suspension of the clinical 
investigation 
HOMI 
PMDA 
When the sponsor suspends or discontinues the clinical trial, he or she 
shall promptly notify the heads of all the medical institutions and 
regulatory authorities thereof and the detailed reason therefor in writing. 
(MHLW Ordinance 36, 2005 Article 32) 
Suspension of development of 
investigational device 
HOMI 
PMDA 
When the sponsor decides not to attach the documents concerning 
clinical trial records collected in the clinical trial to the authorization 
application, he or she shall promptly notify the heads of all the medical 
institutions other facilities engaged in the clinical trial thereof and the 
detailed reason therefor in writing. (MHLW Ordinance 36, 2005 Article 32) 
Investigator List 
HOMI 
PMDA 
The sponsor shall beforehand submit the list of Investigators to PMDA and 
HOMI. (Pharmaceutical and Medical Device Act Enforcement Regulations) 
The sponsor shall submit the list of Investigators to PMDA and HOMI 
when making any changes in the list. (Pharmaceutical and Medical Device 
Act Enforcement Regulations) 
Important information 
concerning the quality, 
effectiveness, and safety of the 
investigational device 
Investigators 
HOMI 
PMDA 
When new, important information is obtained, the sponsor shall revise 
the Investigator’s brochure. In addition, prior to revising the Investigator’s 
brochure, the sponsor shall report the information to the principal 
Investigator, HOMI, and regulatory authorities. (MHLW Ordinance 36, 
2005 Article 28) 
Clinical Trial Report 
PMDA upon 
request 
The sponsor shall prepare, according to the procedure, a clinical study 
report that summarizes the results, etc., of a clinical study when it is 
completed or discontinued. (MHLW Ordinance 36, Article 33) 
Study deviation 
Investigators 
HOMI as 
necessary 
Ensure that all deviations from the Clinical Investigation Plan are reviewed 
with the appropriate clinical Investigator(s), are reported on the case 
report forms and the final report of the clinical investigation. (ISO 
14155:2011) Site specific study deviations will be submitted to 
Investigators periodically. When the monitor confirms deviation as a 
result of monitoring, the monitor shall notify the principal Investigator 
and, as necessary, the HOMI thereof. The monitor shall also request for 
appropriate measures to be taken to prevent such deviation in the future. 
(MHLW Ordinance 36, 2005 Article 30) 
 
Medtronic records and reports will be maintained in a password-protected document management 
system, and paper documents (where applicable) will be stored in secured file cabinets at Medtronic 
during the course of this study. 
After closure of the study, Medtronic will archive records and reports and these will be retained per 
Medtronic standard and applicable regulations. 
14.8. Suspension or Early Termination 
Early Termination is the closure of a clinical study that occurs prior to meeting defined endpoints. This 
is possible for the whole study or a single site. Suspension is a temporary postponement of study 

 
 
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activities related to enrollment and distribution of the product. This is possible for the whole study or a 
single site. 
 Study-wide Suspension or Early Termination 
Possible reasons for considering study suspension or termination of the study include but are not 
limited to: 
• 
Adverse events associated with the system or product under investigation which might 
endanger the safety or welfare of the subject 
• 
Observed/suspected performance different from the product’s design intent 
• 
Decision by Medtronic or regulatory body (where the study is operating under regulatory 
body authority) 
• 
Technical issues during the manufacturing process 
 Investigator/Site Suspension or Early Termination 
Possible reasons for clinical investigator or site termination or suspension include but are not limited to: 
• 
Failure to obtain initial Ethics Committee approval or annual renewal of the study approval 
• 
Persistent non-compliance to the CIP (e.g., failure to adhere to inclusion/exclusion criteria, 
failure to follow subjects per scheduled follow-ups) 
• 
Lack of enrollment 
• 
Noncompliance to regulations and the terms of the Clinical Trial Agreement (e.g., failure to submit 
data in a timely manner, failure to follow-up on data queries and monitoring findings in a timely 
manner) 
• 
Ethics Committee suspension of the site 
• 
Fraud or fraudulent misconduct is discovered (as defined by local law and regulations) 
• 
Investigator request (e.g., no longer able to support the study) 
 Procedures for Suspension or Early Termination 
Below procedures will apply in addition to any other specific requirement per local regulations. 
Medtronic-initiated and regulatory authority-initiated 
• 
Medtronic will promptly inform the clinical investigators of the termination or suspension 
and the reasons and inform the regulatory authority(ies) where required 

 
 
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• 
In the case of study termination or suspension for reasons other than a temporary EC approval 
lapse, the investigator will promptly inform the EC. A detailed written explanation of the 
termination or suspension will be provided, where required per regulatory requirements. 
• 
In the case of study termination, the investigator must inform the subjects and may inform the 
personal physician of the subjects to ensure appropriate care and follow-up is provided 
• 
In the case of a study suspension, subject enrollment must stop until the suspension is 
lifted by Medtronic 
• 
In the case of a study suspension, enrolled subjects should continue to be followed out of 
consideration of their safety, rights and welfare 
 
Investigator-initiated 
• 
The investigator will immediately or promptly inform Medtronic and provide a detailed 
written explanation of the termination or suspension 
• 
The investigator will promptly inform the institution (where required per regulatory 
requirements) 
• 
The investigator will promptly inform the EC, along with a detailed written explanation of the 
termination or suspension (where required per regulatory requirements) 
• 
The investigator will promptly inform the subjects and/or the personal physician of the subjects 
to ensure appropriate care and follow-up is provided 
• 
In the case of a study suspension, subjects enrolled should continue to be followed out of 
consideration of their safety, rights and welfare 
Ethics Committee-initiated 
• 
The investigator will inform Medtronic and provide a detailed written explanation of the 
termination or suspension within 5 business days, or sooner if required per local requirements 
• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance with EC policy or its 
determination that an overriding safety concern or ethical issue is involved 
• 
The investigator will inform his/her institution (where required per local requirements) 
• 
The investigator will promptly inform the subjects and/or the personal physician of the subjects, 
with the rationale for the study termination or suspension to ensure appropriate care and 

 
 
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follow-up is provided 
 
 

 
 
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15. References  
 
1. Weiss R, et al., Safety and efficacy of a totally subcutaneous implantable-cardioverter 
defibrillator, Circulation, 2013;128:944-53 
2. U.S. Food and Drug Administration. (2012). A Patient Guide - Living with your S-ICD 
System. U.S. Food and Drug Administration/Devices@FDA. Retrieved 16-Jan-2018 from: 
http://www.accessdata.fda.gov/cdrh_docs/pdf11/P110042c.pdf. 
3. U.S. Food and Drug Administration. (2012). FDA Circulatory Systems Device Panel 
Transcript for April 26, 2012. U.S. Food and Drug Administration Medical Device 
Advisory Committees. Retrieved 26-Jan-2018 from: 
https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevi
ces/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/ucm124182.ht
m. 
4. Ellenbogen KA, Wood MA, Shepard RK, Clemo HF, Vaughn T, et al. 2003. Detection and 
management of an implantable cardioverter defibrillator lead failure: incidence and 
clinical implications. J Am Coll Cardiol 41:73-80. 
5. Kleemann T, Becker T, Doenges K, Vater M, Senges J, Schneider S, Saggau W, Weisse U, 
Seidl K.  Annual Rate of Transvenous Defibrillation Lead defect in Implantable 
Cardioverter-Defibrillators over a Period of >10 Years. Circulation. 2007;115:2474-2480. 
6. Bardy GH, et al., An entirely subcutaneous implantable cardioverter-defibrillator, N Engl 
J Med., 2010;363:36-44.  
7. Cappato R, Smith WM, Hood MA, Crozier IG, Jordaens L, Spitzer SG, Ardashev AV, 
Boersma L, Lupo P, Grace AA, Bardy GH. Subcutaneous chronic implantable 
defibrillation systems in humans, J Interv Card Electrophysiol., 2012;34:325–332. 
https://doi.org/10.1007/s10840-012-9665-6. 
8. Tomaske M, Prêtre R, Rahn M, Bauersfeld U. Epicardial and pleural lead ICD systems in 
children and adolescents maintain functionality over 5 years. Europace. 2008 
Oct;10(10):1152-6. 
9. Molina JE, Benditt DG. An epicardial subxiphoid implantable defibrillator lead: superior 
effectiveness after failure of standard implants. Pacing Clin Electrophysiol. 2004 
Nov;27(11):1500-6. 
10. Tung SK, Bennett M, Yeung-Lai-wah JA, Ling H.  Minimal invasive extra cardiac 
placement of high voltage defibrillator leads. Heart Rhythm 2007; 4(5, Suppl.):S200 

 
 
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11. Bauersfeld U, Tomaske M, Dodge-Khatami A, Rahn M, Kellenberger CJ, Prêtre R. Initial 
experience with implantable cardioverter defibrillator systems using epicardial and 
pleural electrodes in pediatric patients. Ann Thorac Surg 2007;84:303-5. 
12. Gold, M., Aasbo, J., El-Chami, M. et al., Subcutaneous implantable cardioverter-
defibrillator Post-Approval Study: Clinical characteristics and perioperative results. 
Heart Rhythm. 2017;14:1456–1463. 
13. Boersma L, Barr C, Knops R et al. Implant and Midterm Outcomes of the Subcutaneous 
Implantable Cardioverter-Defibrillator Registry: The EFFORTLESS Study. J Am Coll 
Cardiol 2017;70:830-841. 
14. Jacob S, Lieberman RA. Percutaneous epicardial defibrillation coil implantation: a viable 
technique to manage refractory defibrillation threshold. Circ Arrhythm Electrophysiol. 
2010 Apr;3(2):214-7. 
15. Haydin S, Saygi M, Ergul Y, Ozyilmaz I, Ozturk E, Akdeniz C, Tuzcu V. Subxiphoid 
approach to epicardial implantation of implantable cardioverter defibrillators in 
children. Pacing Clin Electrophysiol. 2013 Aug;36(8):926-30. 
16. Hajj-Chahine J, Houmaida H, Tomasi J, Corbi P. Epicardial defibrillation patch or coil 
lead? Interact Cardiovasc Thorac Surg. 2011 Apr;12(4):630. 
17. Guenther M, Kolschmann S, Knaut M. Letter to the Editors: Substernal lead 
implantation: A Novel Option to Manage DFT failure in S-ICD Patients. Clin Res Cardiol, 
DOI 10.1007/s00392-014-0764-5. 
18. Boyle TA, Cohen J, Carrillo R. Substernal implantation of a subcutaneous implantable 
cardioverter-defibrillator in a patient with preexisting Hemodialysis Reliable Outflow 
graft. HeartRhythm Case Rep 2016;2:412-414. 
19. Bhagwandien RE, Kik C, Yap SC, Szili-Torok T. Substernal ICD lead implantation in a 
patient not suitable for subcutaneous ICD implantation without venous access due to 
superior vena cava syndrome. HeartRhythm Case Rep 2017;3:97-99. 
20. Hata H, Sumitomo N, Nakai T, Amano A. Retrosternal Implantation of the Cardioverter-
Defibrillator Lead in an Infant. Ann Thorac Surg 2017;103:e449-e451. 
21. Chan JYS, Lelakowski J, Murgatroyd FD, Boersma LV, Cao J, Nikolski V, Wouters G, Hall 
MCS. Novel Extravascular Defibrillation Configuration With a Coil in the Substernal 
Space: The ASD Clinical Study, JACC: Clinical Electrophysiology, Volume 3, Issue 8, 2017, 
Pages 905-910, ISSN 2405-500X, https://doi.org/10.1016/j.jacep.2016.12.026. 
22. Sholevar DP, Tung S, Kuriachan V, et al. Feasibility of extravascular pacing with a novel 
substernal electrode configuration: The Substernal Pacing Acute Clinical Evaluation 

 
 
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Study. Heart Rhythm. Published online 29Nov2017. DOI: 
http://dx.doi.org/10.1016/j.hrthm.2017.11.030 
23. Boersma LV, Merkely B, Neuzil P, Crozier IG, Akula DN, Timmers L, Kalarus Z, Sherfesee 
L, DeGroot PJ, Thompson AE, Lexcen DR, Knight BP. Therapy from a Novel Substernal 
Lead: The ASD2 study. JACC: Clinical Electrophysiology, Volume 5, Issue 2, 2019, Pages 
186-196. 
24. Blatt JA, Poole JE, Johnson GW, et al. No benefit from defibrillation threshold testing in 
the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). J Am Coll Cardiol. 2008 Aug 
12;52(7):551-6. 
25. Neuzner J, Hohnloser SH, Kutyifa V, et al. Effectiveness of single- vs. dual-coil 
implantable defibrillator leads: An observational analysis from the SIMPLE study. J 
Cardiovasc Electrophysiol. 2019 Apr 4. doi: 10.1111/jce.13943. 
26. Crozier IG, Haqqani H, Kotschet E, Shaw D, Prabhu A, Roubos N, Alison J, Melton I, 
Denman R, Lin T, Almeida A, Portway B, Sawchuk B, Sherfesee L, Liang S, BENG, 
Thompson AE, Lentz L, DeGroot PJ, O’Donnell D. First-in-human Chronic Implant 
Experience of the Substernal Extravascular Implantable Cardioverter Defibrillator. Heart 
Rhythm 2018 S-LBCT04-01.  
16. Appendices  
 
 

 
 
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Appendix A: Draft Data Collection Elements (Case Report Forms) 
Draft Case Report Forms for the EV ICD Pivotal Study will be provided under separate cover. Final eCRFs 
will be provided to sites via the electronic data management system after the site has fulfilled all 
requirements for database access. 
 

 
 
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Appendix B: Preliminary Publication Plan 
Publications from the EV ICD Pivotal Study will be handled according to the sponsor’s Standard 
Operating Procedures and as indicated in the Clinical Trial Agreement. 
Publication Committee 
The Steering Committee will serve as the Publication Committee as they will play a role in 
disseminating the study outcomes to the broader medical community. Additional members of the 
Publication Committee may include representation from Medtronic study management, statistics, 
marketing, research, etc. This committee will manage study publications with the goal of publishing 
findings from the data. Together with Medtronic representatives, the Publication Committee will 
develop a final Publication Plan as a separate document.  
The Publication Committee’s role is to:  
1) manage elements addressed in the publication plan as outlined in this appendix,  
2) develop the final Publication Plan under separate cover,  
3) finalize the Publication Plan,  
4) oversee the publication of primary and ancillary study results,  
5) review and prioritize publication proposals,  
6) provide input on publication content, and  
7) determine authorship.   
In addition, the committee will apply and reinforce the authorship guidelines set forth in the 
Publication Plan. Membership in the Publication Committee does not guarantee authorship. The 
committee will meet as needed. 
Management of Primary and Ancillary Publications 
The Publication Committee reviews, prioritizes, and manages all publications including primary and 
ancillary publications.  Primary and ancillary publications are those that address analyses of any or all 
primary objectives or ancillary objectives, respectively, as specified in the Clinical Investigation Plan.  
An ancillary publication is any publication that does not address the study objectives identified in the 
Clinical Investigation Plan. They include publications proposed and developed by other Medtronic 
departments or entities, clinicians participating in this clinical study, and clinicians not participating in 
this clinical study. The committee will work with Medtronic to ensure that requests do not present 
conflicts with other proposals, are not duplicative, and to determine which ancillary publication 
proposals, if any, will be supported.   

 
 
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The committee may decide that no publications, including abstracts, will be published prior to the end 
of the study or with individual site data. Requests for publications on study objectives utilizing subset 
data (e.g., regional) will be evaluated for scientific validity and the ability of Medtronic to provide 
resources. 
Criteria for Determining Authorship 
Publications will adhere to authorship criteria defined by the International Committee of Medical 
Journal Editors (ICMJE, Uniform requirements for manuscripts submitted to biomedical journals, 
www.icmje.org). Individual authorship criteria defined by the target journal or conference will be 
followed when it differs from ICMJE criteria. 
Authors, including Medtronic personnel, must at a minimum meet all conditions below: 
• 
Substantial contribution to conception and design, or acquisition of data, or analysis and 
interpretation of data; and 
• 
Drafting the article or revising it critically for important intellectual content; and 
• 
Final approval of the version to be published; and 
• 
Agreement to be accountable for all aspects of the work in ensuring that questions related to the 
accuracy or integrity of any part of the work are appropriately investigated and resolved. 
Decisions regarding authorship and contributor-ship will be made by the committee. The selected 
authors will be responsible for drafting the publication. All selected authors must fulfill the authorship 
conditions stated above to be listed as authors, and all contributors who fulfill the conditions must be 
listed as authors. 
Contributors who make substantial contributions, but do not meet authorship criteria may be 
considered for inclusion in an Acknowledgement section of the publication.  Depending on the degree, 
these contributions might merit contributor-ship in the publication.  
Transparency 
Transparency of study results will be maintained by the following means: 
• 
a final report, describing the results of objectives and analysis, will be distributed to all 
investigators, Ethic Committees and Regulatory Authorities of participating countries when 
required by local law 
• 
registering and posting the study results on ClinicalTrials.gov based on the posting rules stipulated  

 
 
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• 
Medtronic intends to publish the primary study results in a manner that is sensitive to the 
commercial application of the results. Publication may be delayed until closer to the potential 
release of a device feature 
• 
disclosing conflicts of interest (e.g., financial) of the co-authors of publications according to the 
policies set forth by the corresponding journals and conferences  
• 
making an individual site’s study data accessible to the corresponding investigator after the 
completion of the study, if requested. 
 
 

 
 
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Appendix C: Instructions for Use 
Instructions for Use (IFU) for the components of the EV ICD System and accessories, and equipment are 
provided with each component under separate cover. The cover of each IFU will have a clinical 
statement on the cover indicating the device is an investigational device. 
 

 
 
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Appendix D: Informed Consent Templates 
Medtronic legal-approved Informed Consent Templates for each geography where the study will be 
conducted will be distributed under separate cover. 
 
 

 
 
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Appendix E: Foreseeable Adverse Event List 
Potential risks associated with the implantation of the EV ICD System, associated harms and adverse 
events, as well as risk minimization are discussed in more detail within section 9, Risks and Benefits. 
The information provided in this section includes additional reference information and may collectively 
assist in identifying those events for a given device or therapy that are unexpected in nature. The 
foreseeable adverse event information consists of three parts: (1) rates of adverse events reported 
from previous Medtronic studies evaluating transvenous ICD systems, (2) adverse event rates reported 
in published literature for procedures similar to EV ICD, and (3) additional adverse events for 
consideration.  An evaluation of potentially anticipated events, adverse device effects observed in 
previous clinical studies, and reported events in literature may be used in combination with device 
labeling, current event reporting information, and other published data to assess for an unexpected 
occurrence.  
The implantation of the EV ICD System involves surgery; therefore, standard adverse events associated 
with a surgical procedure may be experienced (e.g., anesthesia complications, injury, infections, 
bleeding, exacerbation of pre-existing conditions, healing complications). However, the focus of this 
section is to address in more detail, those events that are foreseeable due to the implantation, use, 
performance, and/or presence of the system under investigation or comparable systems. 
Treatment required for procedure and/or system related adverse events may include medication, 
device reprogramming, device modification (e.g., repositioning, electrical abandonment, surgical 
removal), or other surgical and medical remedies.  
Adverse Events Reported in Previous Clinical Studies of Transvenous ICD 
Systems 
Table 28 provides examples of adverse events associated with the use of transvenous ICD systems 
reported in three previous Medtronic studies. These three predicate studies were selected as a 
reference for EV ICD performance as they were contemporary and used adverse event definitions 
consistent with those utilized in the EV ICD Pivotal Study. The three predicate Medtronic studies 
include BLOCK HF, REVERSE, and Evera MRI. These studies collected adverse event data from 1035 
subjects that underwent an ICD implant. The average follow-up time exceeded 9 months in all three 
trials. Table 28 displays the adverse event rates classified as related to the implanted system and/or 
procedure. To characterize the safety profile of a single lead ICD system, all adverse events related to 
an atrial or left ventricular pacing lead were excluded from consideration. Kaplan-Meier estimates and 
associated 95% confidence intervals of the adverse event rates are provided in the Table below at 30-
days and 12-months (365 days) post-implant to characterize both peri-procedural and long-term 
adverse events related to the procedure or implanted system. 

 
 
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Table 28: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
ACUTE PULMONARY OEDEMA 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
ADVERSE DRUG REACTION 
5 (5, 0.39%) 
0.15% - 1.03% 
5 (5, 0.39%) 
0.15% - 1.03% 
ANGINA UNSTABLE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ANXIETY 
0 (0, 0%) 
-- 
1 (1, 0.13%) 
0.02% - 0.93% 
ARRHYTHMIA SUPRAVENTRICULAR 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (1, 0.10%) 
0.01% - 0.68% 
ATELECTASIS 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
ATRIAL FIBRILLATION 
8 (7, 0.68%) 
0.32% - 1.41% 
8 (7, 0.68%) 
0.32% - 1.41% 
ATRIAL FLUTTER 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ATRIAL THROMBOSIS 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.74% 
ATRIOVENTRICULAR BLOCK COMPLETE 
3 (2, 0.19%) 
0.05% - 0.77% 
3 (2, 0.19%) 
0.05% - 0.77% 
ATRIOVENTRICULAR BLOCK THIRD DEGREE 
6 (6, 0.58%) 
0.26% - 1.29% 
6 (6, 0.58%) 
0.26% - 1.29% 
BACTERAEMIA 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.71% 
BODY TEMPERATURE INCREASED 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
BRADYCARDIA 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
BRONCHITIS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CARDIAC FAILURE 
16 (16, 1.55%) 
0.95% - 2.52% 
16 (16, 1.55%) 
0.95% - 2.52% 
CARDIAC FAILURE CHRONIC 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CARDIAC PERFORATION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CARDIAC PROCEDURE COMPLICATION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CARDIAC TAMPONADE 
2 (2, 0.19%) 
0.05% - 0.77% 
3 (3, 0.29%) 
0.09% - 0.91% 
CEREBROVASCULAR ACCIDENT 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CHEST PAIN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE 
3 (1, 0.10%) 
0.01% - 0.68% 
3 (1, 0.10%) 
0.01% - 0.68% 
COMPLICATION OF DEVICE INSERTION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
CONTRAST MEDIA REACTION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
CORONARY SINUS DISSECTION 
9 (9, 0.87%) 
0.45% - 1.66% 
9 (9, 0.87%) 
0.45% - 1.66% 
DECREASED SENSING 
0 (0, 0%) 
-- 
2 (2, 0.28%) 
0.07% - 1.10% 

 
 
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Table 28: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
DEEP VEIN THROMBOSIS 
2 (2, 0.19%) 
0.05% - 0.77% 
4 (4, 0.40%) 
0.15% - 1.05% 
DEFIBRILLATION THRESHOLD INCREASED 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.20%) 
0.05% - 0.79% 
DEHYDRATION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
DEVICE ELECTRICAL FINDING 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
DEVICE LEAD DAMAGE 
0 (0, 0%) 
-- 
2 (2, 0.23%) 
0.06% - 0.91% 
DEVICE MALFUNCTION 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.74% 
DEVICE MIGRATION 
1 (1, 0.10%) 
0.01% - 0.69% 
2 (2, 0.20%) 
0.05% - 0.78% 
DEVICE RELATED INFECTION 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 
DIZZINESS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
DRUG HYPERSENSITIVITY 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
DYSPNOEA 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
DYSPNOEA EXERTIONAL 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ELECTRICAL RESET OF DEVICE 
0 (0, 0%) 
-- 
2 (2, 0.21%) 
0.05% - 0.82% 
ELECTROMECHANICAL DISSOCIATION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
ELEVATED PACING THRESHOLD 
0 (0, 0%) 
-- 
2 (2, 0.20%) 
0.05% - 0.81% 
ENTERITIS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
EXTRASYSTOLES 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 
FAILURE TO CAPTURE 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.73% 
FLUID RETENTION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HAEMATOMA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HAEMOPNEUMOTHORAX 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HAEMORRHAGE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
HYPOTENSION 
8 (8, 0.77%) 
0.39% - 1.54% 
8 (8, 0.77%) 
0.39% - 1.54% 
HYPOXIA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
IMPAIRED HEALING 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.20%) 
0.05% - 0.78% 
IMPLANT SITE CELLULITIS 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.71% 
IMPLANT SITE EROSION 
0 (0, 0%) 
-- 
2 (2, 0.20%) 
0.05% - 0.80% 

 
 
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Table 28: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
IMPLANT SITE HAEMATOMA 
21 (21, 2.03%) 
1.33% - 3.10% 
23 (23, 2.23%) 
1.49% - 3.34% 
IMPLANT SITE HAEMORRHAGE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
IMPLANT SITE INFECTION 
8 (8, 0.78%) 
0.39% - 1.54% 
14 (14, 1.38%) 
0.82% - 2.31% 
IMPLANT SITE INFLAMMATION 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
IMPLANT SITE PAIN 
10 (10, 0.97%) 
0.52% - 1.79% 
19 (18, 1.78%) 
1.13% - 2.81% 
IMPLANT SITE RASH 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
INAPPROPRIATE DEVICE STIMULATION OF TISSUE 
3 (3, 0.29%) 
0.09% - 0.90% 
4 (4, 0.39%) 
0.15% - 1.03% 
INAPPROPRIATE DEVICE THERAPY 
1 (1, 0.10%) 
0.01% - 0.69% 
6 (6, 0.61%) 
0.27% - 1.35% 
INCISION SITE HAEMORRHAGE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
IODINE ALLERGY 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
JUGULAR VEIN THROMBOSIS 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
KELOID SCAR 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
LEAD DISLODGEMENT 
14 (14, 1.35%) 
0.80% - 2.27% 
20 (20, 1.96%) 
1.27% - 3.02% 
MEDICAL DEVICE CHANGE 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.74% 
MEDICAL DEVICE COMPLICATION 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
MEDICAL DEVICE DISCOMFORT 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
MUSCLE SPASMS 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.22%) 
0.05% - 0.89% 
MUSCLE STRAIN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
MYOCARDIAL INFARCTION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
OEDEMA PERIPHERAL 
3 (3, 0.29%) 
0.09% - 0.90% 
4 (4, 0.39%) 
0.15% - 1.04% 
ORTHOSTATIC HYPOTENSION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
OVERSENSING 
1 (1, 0.10%) 
0.01% - 0.68% 
4 (4, 0.41%) 
0.15% - 1.08% 
OXYGEN SATURATION DECREASED 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PAIN IN EXTREMITY 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
PERICARDIAL EFFUSION 
8 (8, 0.77%) 
0.39% - 1.54% 
9 (9, 0.87%) 
0.45% - 1.67% 
PERICARDITIS 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.71% 
PHANTOM SHOCK 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 

 
 
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Table 28: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
PLEURAL EFFUSION 
7 (7, 0.68%) 
0.32% - 1.41% 
8 (8, 0.78%) 
0.39% - 1.55% 
PLEURITIC PAIN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PNEUMONIA 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
PNEUMONIA ASPIRATION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PNEUMOTHORAX 
4 (4, 0.39%) 
0.15% - 1.03% 
4 (4, 0.39%) 
0.15% - 1.03% 
PNEUMOTHORAX TRAUMATIC 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PROCEDURAL HYPOTENSION 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
PROCEDURAL NAUSEA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PULMONARY EMBOLISM 
0 (0, 0%) 
-- 
1 (1, 0.10%) 
0.01% - 0.72% 
PULMONARY OEDEMA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PUNCTURE OF PERIOSTEUM 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
PYREXIA 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
RENAL FAILURE 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
RENAL FAILURE ACUTE 
3 (3, 0.29%) 
0.09% - 0.90% 
3 (3, 0.29%) 
0.09% - 0.90% 
SHOULDER PAIN 
4 (4, 0.39%) 
0.15% - 1.03% 
4 (4, 0.39%) 
0.15% - 1.03% 
SLEEP APNOEA SYNDROME 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
SUBCLAVIAN VEIN THROMBOSIS 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
SUPRAVENTRICULAR TACHYCARDIA 
0 (0, 0%) 
-- 
2 (2, 0.21%) 
0.05% - 0.85% 
SUTURE RELATED COMPLICATION 
0 (0, 0%) 
-- 
2 (2, 0.20%) 
0.05% - 0.79% 
SYNCOPE VASOVAGAL 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
THERMAL BURN 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
UNDERSENSING 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
UPPER RESPIRATORY TRACT INFECTION 
1 (1, 0.10%) 
0.01% - 0.69% 
1 (1, 0.10%) 
0.01% - 0.69% 
URINARY RETENTION POSTOPERATIVE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
VENOUS OCCLUSION 
1 (1, 0.10%) 
0.01% - 0.68% 
2 (2, 0.20%) 
0.05% - 0.79% 
VENTRICULAR ASYSTOLE 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 
VENTRICULAR FIBRILLATION 
1 (1, 0.10%) 
0.01% - 0.68% 
1 (1, 0.10%) 
0.01% - 0.68% 

 
 
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Table 28: System and/or Procedure Related AEs Associated with Transvenous ICD Systems (n=1035) 
 
Within 30-days of Implant 
Within 12-months of Implant 
MedDRA Preferred Term 
No. Events 
(No. Subjects, %) 
95% CI 
No. Events 
(No. Subjects, %) 
95% CI 
VENTRICULAR TACHYCARDIA 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
WHEEZING 
2 (2, 0.19%) 
0.05% - 0.77% 
2 (2, 0.19%) 
0.05% - 0.77% 
 
Procedure Related Adverse Events from Previous Clinical Studies Using a 
Similar Research System 
Limited clinical experience relevant to the EV ICD System is available from the previously conducted 
Medtronic ASD, SPACE, ASD2, and the EV ICD Pilot studies that utilized similar research systems and 
protocol steps as those in the EV ICD Pivotal Study.  
In the ASD study, in total ten adverse events were observed. Three adverse events were attributed to 
the ASD Procedure. The first ASD Procedure-related adverse event occurred in the patient where the 
ASD lead was observed implanted in the pleural cavity immediately adjacent to the mediastinum. This 
patient, who underwent a planned indicated surgical procedure requiring midline sternotomy after the 
ASD procedure, had documented decrease in oxygen saturation levels and small bilateral effusions 
reported by the site, diagnosed as chest infection (Note: physician classified this event as not related to 
the ASD Procedure). The small bilateral effusions resolved within five days after onset, and there were 
no further chronic sequelae to the patient.  
The second ASD Procedure-related adverse event was associated with a patient scheduled for CABG 
surgery that had bruising along the left internal mammary artery bed following the ASD tunneling 
procedure, which resulted in a saphenous vein graft being used instead of left internal mammary graft 
in the final (planned) surgical procedure. There were no further sequelae to this patient, and it was 
commented that this may not have been an adverse event, if the graft location had not been changed 
due to the bruising.  
The third ASD Procedure-related adverse event was a patient who had erythema on the back one day 
post-procedure, related to the defibrillation pad of the external defibrillation system (used as a safety 
back-up). The erythema resolved within one day after onset, and there were no further chronic 
sequelae to the patient.  

 
 
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None of the reported adverse events was classified as “related to the ASD Research System” by the 
AEAC.  
In the SPACE study, 14 adverse events were observed, all without chronic sequelae to the patient.  
Two of the adverse events were attributed to the SPACE Procedure. A pericardial effusion was noted in 
one patient (the first patient enrolled in the SPACE study overall) following the patient’s planned 
sternotomy procedure, with the effusion resolved the same day and without extension of the subject’s 
hospital stay beyond standard timeframe; there were no further planned actions deemed necessary 
and no further adverse effects reported for this patient. The second SPACE Procedure-related adverse 
event occurred in a patient whose planned procedure included sternotomy and bypass graft. This 
patient reported incision site pain three days post-procedure that reduced by 16 days and required no 
further follow-up or action. 
In the ASD2 study, there were 20 adverse events (15 serious, 5 non-serious) experienced in 16 subjects.  
Of the 79 subjects who underwent the ASD2 implant procedure, there were seven adverse events in 
seven subjects adjudicated as causally (five) or possibly (two) related to the ASD2 procedure.   
Three of the five adverse events adjudicated as causally related to the ASD2 procedure were classified 
as non-serious and included bleeding at the incision site, erythema and an episode of transient atrial 
fibrillation precipitated during VF induction. The other two adverse events adjudicated as causally 
related to the ASD2 procedure were classified as serious and included one reaction to anesthesia and 
one pericardial effusion with tamponade.  The subject with pericardial effusion was a 62-year-old with 
ischemic cardiomyopathy who developed cardiac tamponade and prolonged hypotension intra-
operatively. Hemodynamic stability was restored through surgical intervention, but the prolonged 
hypotension resulted in hypoxic cerebral injury. With no meaningful neurologic activity after 72 hours, 
supportive care was withdrawn at the family’s request and the subject expired. 
There were two adverse events adjudicated as possibly related to either the ASD2 procedure or the 
subject’s final planned procedure/system: one pericarditis and one cardiac arrest. The subject with 
pericarditis received a dual-chamber ICD implant after the ASD2 procedure, but presented with a 
pericardial effusion on echocardiography three days later. After pericardiocentesis the subject’s 
complaints resolved with no further sequelae. The subject with cardiac arrest was an 81-year-old with 
diabetes and ischemic cardiomyopathy who was admitted for decompensated heart failure, urosepsis 
and persistent AF.  After medical management of these conditions, the subject was enrolled and 
underwent the ASD2 study procedure and planned dual-chamber ICD implantation without incident.  
The subject was then transferred in stable condition to a secondary site where asystole was detected 
36 hours post-procedure.  Despite cardiopulmonary resuscitation for 30 minutes, the subject expired. 

 
 
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In the EV ICD Pilot study, as of 11 March 2019, among 21 subjects undergoing an implant attempt of 
the system, there were 28 adverse events in 11 subjects.  Six reported adverse events in four subjects 
were adjudicated to be causally related to the implant procedure and/or the EV ICD System.  Five of 
the events (impaired healing, pleuritic pain (2), postoperative wound infection, implant site swelling) 
were causally related to the procedure, while one of the two pleuritic pain observations was also 
related to the EV ICD lead and the other subject with pleuritic pain eventually experienced a lead 
displacement (related to the EV ICD device and lead) leading to an inappropriate shock and system 
removal.  Five of the six events were determined to be non-serious; the lead displacement event was 
classified as a major complication as it involved a system revision. 
Adverse events in literature 
There are limited published data available regarding the adverse events associated with the 
implantation of a subcutaneous ICD. A summary of adverse events and their published incidence of 2 
studies are listed below:  
1. Weiss R, Knight BP, Gold MR, Leon AR, Herre JM, Hood M, Rashtian M, Kremers M, Crozier I, 
Lee KL, Smith W, Burke MC. Safety and Efficacy of a Totally Subcutaneous Implantable 
Cardioverter Defibrillator. Circulation. 2013 Aug 27;128(9):944-53.  
 
This study was a prospective, nonrandomized, multicenter trial of 314 subjects implanted with a 
subcutaneous ICD followed for 180 days. The following adverse events were reported in the 
manuscript.  
Table 29: Safety and Efficacy of a Totally Subcutaneous Implantable Cardioverter Defibrillator, Reported 
Adverse Events  
Adverse Event 
Patients 
Infections 
 
Total Number 
18 
System Explant 
4 
No System Explant 
14 
Inappropriate Shocks 
 
Total Number 
41 
Resulting from normal device function 
16 
Inappropriate Sensing 
25 
Cardiac Oversensing 
22 
Non-Cardiac Oversensing 
3 
Death 
 
Total Number 
8 
Non-cardiac, non-sudden and unrelated to implant 
5 

 
 
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Adverse Event 
Patients 
Unwitnessed death, device interrogation showed 
successful treatment of a singular ventricular 
arrhythmia 
1 
Unwitnessed death, no interrogation available, 
diagnosed with atypical pneumonia and hypoxia 
before death 
1 
Unknown cause of death 
1 
 
2. Maass AH, de Groot JR, van Oostrom AJ, Theuns DA, Jordaens LJ, Wilde AA, Knops RE. The 
entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a 
large Dutch cohort. J Am Coll Cardiol. 2012 Nov 6;60(19):1933-9.  
 
This was a retrospective study using the files of 118 consecutive patients implanted with a 
subcutaneous ICD system. Patient experience through 18 months post-implant was included in the 
dataset. Adverse events observed included the following:  
Table 30: The entirely subcutaneous implantable cardioverter-defibrillator: initial clinical experience in a large 
Dutch cohort, Reported Adverse Events 
Adverse Event 
Patients 
Episodes 
Inappropriate Shocks 
 
 
Total Number 
15 
33 
T-wave oversensing 
9 
11 
Myopotentials 
3 
4 
Double Counting 
1 
15 
Atrial Flutter 
1 
2 
TENS Therapy 
1 
1 
Complications 
 
 
Total Number 
16 
 
Lead Dislodgement 
3 
 
Device Dislodgement 
1 
 
Infection 
7 
 
Premature Battery Depletion 
2 
 
Skin Erosion 
2 
 
Explant because of need for ATP 
1 
 
 

 
 
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Additional Adverse Events 
The above incidences of each adverse event were reported from the collection of similar Medtronic 
studies. Events that have been experienced in other Medtronic studies that have the potential to be 
experienced by subjects, or may have been reported with different terminology also include: 
Anemia, Aneurysm or pseudo-aneurysm, Angina pectoris, Aphasia, Arterio-venous fistula, Asystole, 
Atrial septal defect, Back pain, Blood or air embolism, Bruising, Cardiac dissection, Cardiogenic shock, 
Cellulitis, Constrictive pericarditis, Coronary artery constriction, Coronary artery disease, Coronary 
artery occlusion, Coronary vein occlusion, Device capture issue, Device connection issue, Device lead 
issue, Device pacing issue, Device protrusion, Device signal detection issue, Diaphoresis, Dressler's 
syndrome, Dysplasia, Ecchymosis, Edema, Electrical conduction disorders, Electrical shock, 
Electromagnetic interference, Endocarditis, Erythema, Exit block, Extravasation, Failure to terminate a 
ventricular tachycardia/ ventricular fibrillation, Fatigue, Fever, Headache, Heart block, Heart rate 
increase, Hematuria, Hyperkalemia, Hypertension, Impedance decreased, Impedance increased, 
Implant site abscess, Implant site complication, Implant site discomfort, Implant site drainage, Implant 
site seroma, Implant site swelling, Inappropriate device detection, Inappropriate device programming, 
Inflammation, Insomnia, Lead insertion tool delivery problem, Local swelling, Loss of consciousness, 
Mental status change, Musculoskeletal discomfort, Myocardial damage, Myocardial irritability, Neck 
pain, Necrosis, Neurological symptoms, Numbness at incision site, Numbness in hand, Panic attack, 
Paresthesia, Pericardial rub, Phlebitis, Poor hemodynamic recovery, Presyncope, Reduced cardiac 
output, Reduced perfusion, Respiratory failure, Restlessness, Retrosternal pain, Scar or scarring, Sepsis, 
Septic shock, Skin injuries, Skin reaction, Sleep apnea, Stroke, Subcutaneous emphysema, Sudden 
cardiac death, Thoracic pain, Thrombocytopenia, Thromboembolism, Thrombosis, Nerve damage, 
Transient ischemic attack, Urticaria, Valve damage, Vascular trauma, Vasovagal reaction, Venous 
insufficiency, Venous stenosis, Ventricular extrasystole, Vessel perforation or laceration, Vessel spasm, 
Vomiting, Weakness. 
 
 

 
 
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Appendix F: Participating Investigators and Institutions 
A complete list of participating investigators and institutions will be provided under separate cover. 
 
 

 
 
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Appendix G: Ethics Committee and Competent Authority List 
A complete list of participating Regulatory Bodies, Competent Authorities, and Ethics Committees and 
their Chairperson(s) that will be utilized as part of the study will be distributed under separate cover, 
upon request.  

 
 
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Appendix H: Previous Clinical Investigations 
A complete bibliography and summary of relevant literature, summary and results of preclinical testing, 
and summary of results of previous clinical investigations is provided in the Investigator’s Brochure. 
 
 

 
 
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Appendix I: Chronic Defibrillation Testing Protocol 
Each subject will be induced to produce up to two episodes of SSVA and allowed two shock attempts to 
convert each SSVA from the EV ICD, for up to a total of 4 potential shocks from the EV ICD (see Figure 
11). Starting therapy polarity is at the discretion of the physician (in the programmed setting). 
 
Figure 11: Diagram outlining the process of chronic SSVA induction and defibrillation testing  
 
Episode 1 
Program Rx1 and Rx2 therapies as follows: 
  
Rx1 
Rx2 
NID 
30/40 
NA 
Redetect NID 
NA 
9/12 
VF Therapy Status 
ON 
ON 
Energy 
30J 
40J 
Pathway 
As 
programmed 
As 
programmed 
If Episode 1, Rx1 or Rx2 is successful in terminating the episode, the EV ICD System will have passed 
chronic defibrillation testing criteria. No additional inductions are required, and it is recommended to 
leave the system implanted with no changes. 

 
 
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Episode 2 
  
Rx1 
Rx2 
NID 
9/12 
NA 
Redetect NID 
NA 
9/12 
VF Therapy Status 
ON 
ON 
Energy 
40J 
40J 
Pathway 
Opposite of 
programmed 
Opposite of 
programmed 
If Episode 2, Rx1 or Rx2 is successful in terminating the episode, the EV ICD System will have passed 
chronic defibrillation testing criteria. No additional inductions are required, and it is recommended to 
leave the system implanted with no changes. 
If both Rx1 and Rx2 fail in Episode 2, the EV ICD System will have failed chronic defibrillation testing 
criteria and the next steps are at the physician’s discretion. Medtronic recommends EV ICD device or 
lead revision (at a minimum), or system removal.  
Prior to inducing and throughout the chronic defibrillation protocol, it is recommended to consider the 
following to improve defibrillation outcome or troubleshooting in the event of failure of first 
episode(s):  
• 
Check for/resolve high impedance values 
• 
Check for/resolve air in tunnel (e.g., fluoroscopy) 
• 
Check for/resolve gastric bubbles (gas) 
• 
Press on device pocket during testing 
• 
Perform defibrillation during held end tidal expiration (end expiration apnea) 
 
 

 
 
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Appendix J: Applicability to CMS Beneficiaries 
There is a high prevalence of ventricular tachycardia treatable by ICD therapy in the Medicare 
population. Medicare claims data from 2017 (the most recent currently available) shows 52,967 ICD 
insertion procedures (with transvenous leads) and an additional 1,657 procedures for subcutaneous 
ICD insertions.xxx As described in the background section of this CIP, subcutaneous ICD systems are 
currently the only available non-transvenous ICD systems. We anticipate that the EV ICD system will 
provide alternative option for provider consideration in cases where non-transvenous ICD systems are 
necessary to provide access to potentially life-saving ICD therapy in patients where vascular access is 
challenging or compromised.   
The EV ICD trial is designed to ensure applicability of the results to the Medicare population. Of the up 
to 60 sites worldwide, approximately 20 will be in the US. In addition, while the EV ICD study will be 
open to patients aged 18 and older, the trial will aim to enroll approximately 30% of patients in the US 
65 years of age or older.  
 
                                                            
xxx Medicare Physician/Supplier Procedure Summary data. Available at: https://www.cms.gov/Research-Statistics-Data-and-
Systems/Statistics-Trends-and-Reports/Physician-Supplier-Procedure-Summary/index.html 

 
 
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Appendix K: Investigator Statement (where applicable) 
Study product Name 
Extravascular ICD System 
Sponsor 
Medtronic, Inc. 
8200 Coral Sea Street NE 
Mounds View, MN  
USA 55112 
 
Local Sponsor 
Australia 
Medtronic Australasia Pty Ltd 
2 Alma Road 
Macquarie Park 
NSW, 2113 
Australia 
+61 2 9857 9000 
 
Canada 
Medtronic of Canada, Ltd. 
99 Hereford Street Brampton 
Ontario, L6Y 0R3 Canada 
+1-905-460-3800 
 
Europe, Middle East, Africa 
Medtronic, Bakken Research Center B.V. 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
+31-43-35-66-566 
 
Hong Kong 
Medtronic Hong Kong Medical Ltd. 
1104-11, 11/F, Tower 1, 
The Gateway, Harbour City, Kowloon 
Hong Kong SAR, China 
+852-2919-1300 
 
 
Japan 
Medtronic Japan Co., Ltd. 
1-2-70 Konan, Minato-ku, 

 
 
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Tokyo Japan 108-0075 
Shinagawa Season Terrace 22F 
 
Phone: (+81) 3-6774-4611 
Fax: (+81) 3-6774-4605 
 
New Zealand 
Medtronic New Zealand Limited  
Level 3, Building 5  
666 Great South Road  
Penrose  
Auckland 1051 
New Zealand  
+64 9 634-1049 
Clinical Investigation Plan Identifier 
MDT16028 
Version Number/Date  
1.0, 02-JUL-2019 
Addendum for 6-Month Defibrillation 
Testing Version Number/Date 
To be completed if applicable 
Addendum for Regional Reporting 
Requirements Version Number/Date 
To be completed if applicable 
I have read the CIP, including all appendices and applicable addenda, and I agree that it contains all 
necessary details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time designated. 
I agree to carry out all of its items in accordance with applicable regulations and in full compliance 
with the guidelines. I agree to ensure that the confidential information contained in this document 
will not be used for any purpose other than the evaluation and conduct of the clinical investigation 
without the prior written consent of Medtronic. 
I will provide all study personnel under my supervision copies of the CIP and access to all information 
provided by Medtronic. I will discuss this material with them to ensure that they are fully informed 
about the products and the study. 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Institution: 
 
Date: 
 
 

 
 
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17. Version History 
 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
Initial version. 
Diedre Ribbens, Sr. Clinical 
Research Specialist