Improve Sudden Cardiac Arrest Study
Phase: NA
Conditions: Sudden Cardiac Arrest, Ventricular Arrythmia
Sponsor: Medtronic Cardiac Rhythm and Heart Failure

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Medtronic Confidential 
 
 
 
Improve SCA Study 
Clinical Investigation Plan 
Version 1.0  
23 Dec 2013 
Regional Sponsors  
United States (Worldwide Sponsor) 
Medtronic, Inc. 
Cardiac Rhythm Disease Management 
Clinical Research 
8200 Coral Sea Street NE 
Mounds View, MN U.S.A. 55112 
1-800-328-2518 
India 
India Medtronic Private Ltd. 
1241, Solitaire Corporate Park, 
Building No 12, 4th Floor, 
Andheri-Ghatkopar Link Road, Andheri (E) 
Mumbai MH 400093 
India 
Europe, Middle East, Africa  
Medtronic, Bakken Research Center B.V. 
Cardiac Rhythm Disease Management 
Clinical Research 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
China 
Medtronic (Shanghai) Management Co., Ltd. 
Block 11, No. 3000 Long Dong Avenue 
Pudong 
Shanghai 201203 
China 
Latin America 
Medtronic USA, Inc. 
Doral Corporate Center II 
3750 NW 87th Avenue, Suite 700 
Miami, FL 33178 
USA 
Latin America Headquarters 
Medtronic Taiwan 
Medtronic (Taiwan) Ltd. 
2F, No.2, Sec.1, Dunhua S. Rd. Songshan Dist. 
Taipei City 105, Taiwan (R.O.C.) 
ASEAN (Association of Southeast Asian Nations) 
Medtronic International Ltd. 
49 Changi South Avenue 2  
Singapore, 486056 
  
 
 

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TABLE OF CONTENTS 
 
Listing of Appendices ...................................................................................................... 4 
Listing of Tables ............................................................................................................... 5 
Listing of Figures .............................................................................................................. 5 
Sponsor Contact Information .............................................................................................. 6 
Contract Research Organizations (CROs) .......................................................................... 7 
Steering Committee ............................................................................................................ 8 
1 
Introduction ..................................................................................................... 10 
1.1 
Study Purpose ............................................................................................. 10 
1.2 
Study Description and Scope ....................................................................... 12 
2 
Background and Justification .......................................................................... 13 
2.1 
Syncope or pre-syncope .............................................................................. 13 
2.2 
Low ejection fraction (low EF) ...................................................................... 14 
2.3 
Non-sustained ventricular tachycardia (NSVT) ............................................. 15 
2.4 
Frequent premature ventricular contractions (PVCs) .................................... 16 
2.5 
1.5 Prevention Definition .............................................................................. 17 
2.6 
ICD and CRT-D therapy ............................................................................... 19 
3 
System Description and Intended Use ............................................................ 21 
3.1 
Market-Released Medtronic ICD or CRT-D Device ...................................... 21 
3.1 
Market-Released Lead(s) ............................................................................. 22 
3.2 
Medtronic CareLink Monitor and Medtronic CareLink Network ..................... 22 
3.3 
Market-Released Medtronic Programmer .................................................... 22 
3.4 
Changes to the Study System ...................................................................... 22 
4 
Regulatory Compliance .................................................................................. 23 
5 
Methodology ................................................................................................... 25 
5.1 
Study Objectives .......................................................................................... 25 
5.1.1 
Primary objective 
25 
5.1.2 
Secondary objective 
25 
 
 
 
5.2 
Subject Selection Criteria ............................................................................. 25 
5.2.1 
Inclusion criteria 
25 
5.2.2 
Exclusion criteria 
26 
5.3 
Minimization of Bias ..................................................................................... 26 
6 
Study Procedures ............................................................................................ 27 
6.1 
Investigator Selection Criteria ...................................................................... 27 
6.2 
Site Activation .............................................................................................. 27 
6.3 
Equipment Requirements ............................................................................. 28 
6.4 
Data Collection ............................................................................................ 28 

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6.5 
Patient Informed Consent Process ............................................................... 29 
6.6 
Enrollment and Baseline .............................................................................. 31 
6.6.1 
Indication Classification 
32 
6.7 
The 1.5 Prevention Criteria Testing .............................................................. 32 
6.7.1 
Pre-syncope/Syncope 
32 
6.7.2 
Low left ventricular ejection fraction (low LVEF) 
33 
6.7.3 
Frequent premature ventricular contractions (PVCs) 
33 
6.7.4 
Non-sustained ventricular tachycardia (NSVT) 
33 
6.8 
Quality of Life (QoL) EQ-5D Assessment ..................................................... 34 
6.9 
Implant ......................................................................................................... 34 
6.9.1 
Implant Refusal 
34 
6.9.2 
Implant Acceptance 
34 
6.9.3 
Device programming at implant 
35 
6.10 
Subject Follow-up-up Visits .......................................................................... 36 
6.10.1 Subjects with no device 
37 
6.10.2 Subjects with device 
38 
6.10.3 Device programming 
38 
6.10.4 Deviations (all subjects) 
38 
6.11 
Device Change ............................................................................................ 38 
6.12 
Study Exit .................................................................................................... 39 
6.12.1 Lost to follow-up 
39 
6.13 
Subject Death .............................................................................................. 40 
6.14 
Medications .................................................................................................. 40 
7 
Investigational Device/Software Storage, Handling and Traceability ............ 41 
8 
Study Deviations ............................................................................................. 42 
9 
Adverse Events and Device Deficiencies ....................................................... 44 
9.1 
Subject Death .............................................................................................. 44 
9.1.1 
Death data collection 
44 
9.1.2 
Death classification and reporting 
44 
9.2 
Vigilance Reporting ...................................................................................... 45 
10 
Risk Analysis .................................................................................................. 47 
10.1 
Potential Benefits ......................................................................................... 47 
10.2 
Potential Risks ............................................................................................. 47 
11 
Planned study closure, early termination of study or study suspension ......... 48 
11.1 
Planned Study Closure ................................................................................ 48 
11.2 
Early Termination or Suspension ................................................................. 48 
11.2.1 Study-wide termination or suspension 
48 
11.2.2 Investigator/site termination or suspension 
48 
11.3 
Procedures for Termination or Suspension .................................................. 49 
11.3.1 Medtronic-initiated and regulatory authority-initiated 
49 
11.3.2 Investigator-initiated 
49 
11.3.3 Ethics committee-initiated 
49 
12 
Statistical methods and data analysis .............................................................. 50 
12.1 
General considerations ................................................................................ 50 

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12.2 
Primary Objective #1: Appropriate Therapy.................................................. 51 
12.2.1 Hypothesis 
51 
12.2.2 Performance Requirements 
51 
12.2.3 Rationale for Performance Criteria 
51 
12.2.4 Analysis Methods 
52 
12.2.5 Determination of Patients/Data for Analysis 
52 
12.2.6 Sample Size 
52 
12.2.7 Sample Size Re-estimation 
53 
12.3 
Secondary Objective: Mortality ..................................................................... 54 
12.3.1 Hypothesis 
54 
12.3.2 Analysis Methods 
54 
12.3.3 Power 
54 
12.3.4 Determination of Patients/Data for Analysis 
55 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
13 
Data and quality management ......................................................................... 57 
14 
Warranty/Insurance information ..................................................................... 58 
14.1 
Warranty ...................................................................................................... 58 
14.2 
Insurance (Central and Eastern Europe, Middle East and Africa)) ............... 58 
14.3 
Insurance (India) .......................................................................................... 58 
14.4 
Insurance (Association of Southeast Asian Nations (ASEAN) ...................... 58 
14.5 
Insurance (Greater China) ........................................................................... 58 
14.6 
Insurance (Korea) ........................................................................................ 59 
14.7 
Insurance (Latin America) ............................................................................ 59 
15 
Monitoring ...................................................................................................... 60 
15.1 
Monitoring Visits .......................................................................................... 60 
16 
Required Records and Reports ........................................................................ 61 
16.1 
Investigator Records .................................................................................... 61 
16.2 
Investigator Reports ..................................................................................... 62 
16.3 
Sponsor Records ......................................................................................... 62 
16.4 
Sponsor Reports .......................................................................................... 63 
 
LISTING OF APPENDICES 
 
Appendix A:  Study Overview ........................................................................................ 65 
Appendix B: Preliminary Publication Plan ...................................................................... 68 
Appendix C: Data Monitoring Committee (DMC) ........................................................... 70 

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Appendix D: Draft Data Collection Elements ................................................................. 71 
Appendix E: Patient Informed Consent Templates ........................................................ 72 
Appendix F: Participating Investigators and Institutions ................................................. 73 
Appendix G: Labeling .................................................................................................... 74 
Appendix H: Committees ............................................................................................... 75 
Appendix I: Abbreviations and Acronyms ...................................................................... 76 
Appendix J: Clinical Investigation Plan Signature Page (if applicable) ........................... 79 
 
LISTING OF TABLES 
 
Table 1: Global Study Sponsor Contact Information ........................................................ 6 
Table 2: CRO Information ............................................................................................... 7 
Table 3: Steering Committee Contact Information ........................................................... 8 
Table 4: 1.5 Prevention Definition .................................................................................. 18 
Table 5: Improve SCA Programming Requirements ...................................................... 20 
Table 6: System Component Information ...................................................................... 21 
Table 7: Data collection and study procedure requirements at subject visits ................. 29 
Table 8: Programming requirements at implant ............................................................. 36 
Table 9: Follow-up windows .......................................................................................... 37 
Table 10: Power for 1.5 Prevention Mortality Endpoint .................................................. 55 
Table 11: Investigator reports applicable for all geographies per Medtronic requirements
 ...................................................................................................................................... 62 
Table 12: Sponsor reports for all geographies ............................................................... 63 
Table 13:  List of Abbreviations and Acronyms .............................................................. 76 
 
LISTING OF FIGURES 
Figure 1: Study Design .................................................................................................. 11 
Figure 2: Time to First Appropriate VT/VF Therapy in the OMNI Clinical Study ............. 51 
 
 
 

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SPONSOR CONTACT INFORMATION 
Medtronic contact information is provided below. This information is subject to change 
during the course of the study. Updates to study contact information will be sent to the 
sites as needed. 
Table 1: Global Study Sponsor Contact Information 
Study Sponsors and Contacts  
Worldwide study leader 
 
Sarah Willey, Sr. Clinical Research Specialist 
Direct Phone: (+1-763)-526-2813 
sarah.a.willey@medtronic.com 
Worldwide monitoring leader 
 
Marion Thomas, Therapeutic Area Specialist, CRDM 
Direct Phone: (+49-2159) 8149-0 
Marion.thomas@medtronic.com 
Korea 
 
So-Jeong You,  Sr Clinical Research Specialist  
Direct Phone: (+82-2) 3404-7742 
Direct Fax: (+82)2-539-0962 
sojeong.you@medtronic.com 
Latin America 
 
Cristy De La Cruz, Clinical Research Specialist 
Direct Phone: (+1-763) 505-8645 
Direct Fax: (+1-763) 367-1741 
cristy.a.de.la.cruz@medtronic.com 
Association of Southeast Nations (ASEAN) 
 
Tung Kieu, Training/Education Manager 
Direct Phone: (+65) 5064-4429 
Tung.t.kieu@medtronic.com 
India 
 
Haresh Sachanandani, Manager, Clinical Studies 
Direct Phone: (+91-22) 33074700 
Haresh.g.sachanandani@medtronic.com 
Greater China  
(covering China and Taiwan) 
 
Macrina Wong, Sr Clinical Research Manager 
Direct Phone: 852 2919 1386 
Direct Fax: 852 2907 3998 
macrina.wong@medtronic.com 
Central & Eastern Europe (CEE), and 
Middle East and Africa (MEA) 
 
 
Katrien Vandersteegen, Clinical Research Specialist 
Direct Phone: (+31-43) 35-66728 
katrien.vandersteegen@medtronic.com 
 
 
 

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CONTRACT RESEARCH ORGANIZATIONS (CROs) 
Contract research organization (CRO) information is provided in the table below. 
Additional CROs may be added at a later time; contact information may be provided 
under separate cover upon request. 
Table 2: CRO Information 
Contact Information  
Duties Performed 
Cognizant Technology Solutions 
Sanjoy Sengupta, Program Manager 
500 Frank W. Burr Blvd. 
Teaneck, NJ 07666 
Direct Phone: (201) 801-0233 
Direct Fax: (201) 801-0243 
• 
Development of study electronic case report forms, edit 
checks, and study management reports. 
• 
Review of electronic case report forms, management of 
discrepancies, and coding of medications and deviations. 
 
 

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STEERING COMMITTEE 
Nine steering committee members were chosen for this study and are listed below.  
Additional members may be added at a later date. The steering committee members are 
appointed by the sponsor to assist in development and execution of this investigation.  
Table 3: Steering Committee Contact Information 
Committee Member  
Contact Information 
Shu Zhang, MD, PhD 
Coordinating Investigator 
Address: 
  Fuwai Cardiovascular Hospital 
 167 North Lishi Road 
  Beijing, China 100037 
Telephone: 8610.88398833 
Fax: 8610-88398443 
 
Professional Position:  
  Professor of Medicine,  
  Chief of Department of Cardiology, 
  Director of Arrhythmia Center & Clinical EP Lab 
Balbir Singh, MD, DM, FACC, MNAMS 
Address: 
  Medanta, The Medicity Hospital 
  Sector 38  
  Gurgaon, Haryana  
  India122041 
Telephone: 91.124.4141414 
 
Professional Position:  
  Senior Consultant Interventional Cardiology,  
  Chairman- Electrophysiology & Pacing 
Diego Rodriguez Guerrero, MD, FHRS 
Address: 
Instituto de Cardiología - Fundación Cardioinfantil 
Centro Internacional de Arritmias 
Calle 163 A #13B- 60 
  Bogota, Colombia 
Telephone: +57 3188012199 
Fax: +57.1.6290880 
 
Professional Position:  
  Electrophysiologist, Cardiologist 
Azlan Hussin, MBBS, MRCP, FNHAM, 
FAPSIC, FACC 
Address: 
  Institut Jantung Negara 
  145 Jalan Tun Razak 
  Kuala Lumpur, Malaysia 50400 
Telephone: +603. 2617.8442 
Fax: +603.2600.6634 / 2692.8425 
 
Professional Position: 
  Consultant Cardiologist & Electrophysiologist 
Chi Keong Ching, MBBS, MRCP, FAMS Address: 
  National Heart Centre of Singapore  
  Mistri Wing 
  17 Third Hospital Ave. 
  Singapore, Singapore 168752 
Telephone: +65.643.67541 
Fax: + 65.622.38274 
 
Professional Position:  
  Director, Cardiac Pacing and Electrophysiology 

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Committee Member  
Contact Information 
Dejia Huang, MD, MS 
Address 
  West China Hospital 
  No. 37 Guo Xue St.,  
  Chengdu China 610041 
Telephone: (86) 028.85422353 
Fax: (86) 028 85582944 
 
Professional Position: 
  Professor and Chief of Cardiology   
Young-Hoon Kim, MD 
Address: 
  Korea University Medical Center   
  A126-1 5th St. Anam-dong Sungbuk-ku 
  Seoul, Korea 136-705 
Telephone: +82.2.920.5923  
Fax: +82.2.927.1478 
 
Professional Position: 
  Chief of Cardiology Division 
  Director of Electrophysiology Laboratory 
Yen-Bin Liu, MD, PhD 
Address: 
  National Taiwan University Hospital   
  No. 7, Chung Shan S. Rd  Zhong Zheng District 
  Taipei City, Taiwan 10002 
Telephone: +886 223123456 ext 65149 
Fax: +886 2 29357012 
 
Professional Position: 
  Cardiologist 
  Associate Professor, Department of Internal Medicine 
Alexandr Robertovich Chasnoits, PhD 
Address: 
  Republican Scientific Practical Centre Cardiology   
  R. Luxembourg Str. 110 
  Minsk, Belarus 220036 
Telephone: +375 172135035 
Fax: +375 172861466 
 
Professional Position: 
  Assistant Professor- Electrophysiology 
  Interventional Cardiologist 
 
  
 
 

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1 INTRODUCTION 
1.1 Study Purpose  
The purpose of this study is to demonstrate that primary prevention patients with 
one or more additional risk factors (1.5 prevention criteria: syncope/pre-syncope, 
non-sustained ventricular tachycardia (NSVT), frequent pre-ventricular contractions 
(PVCs), and low left ventricular ejection fraction (LVEF)) are at a similar risk of life-
threatening ventricular arrhythmias (LTVA) when compared to secondary 
prevention patients, and would receive similar benefit from an implantable 
cardioverter defibrillator (ICD), or cardiac resynchronization therapy- defibrillator 
(CRT-D) implant. To assess the risk of LTVA, the primary endpoint will measure 
the rate of appropriate therapies delivered by an ICD (or CRT-D) following 
detection of ventricular tachycardia or ventricular fibrillation. Additional objectives 
evaluating mortality, cost effectiveness, reason for implant refusal, and Chagas 
disease will be analyzed. 
All subjects enrolled in the study meet current AHA/ACC/HRS1 or ESC2 Class I 
guidelines for an ICD (or CRT-D) implant. For the purposes of this study, the 
impact of high voltage therapy on LTVAs is of primary interest, so throughout the 
document ICD includes devices with or without concomitant CRT therapy (CRT-D). 
Subjects who enroll in the study and proceed with a device implant must be 
implanted with a Medtronic single, dual, or triple chamber defibrillator that has 
received appropriate license or regulatory approval for the specific geography in 
which it is being implanted, and is released commercially by Medtronic. Any 
market-released, commercially available lead(s) can be used in this study.  
                                                 
1 Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, 
Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney 
MO. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive 
summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice 
Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of 
Cardiac Pacemakers and Antiarrhythmia Devices). Circulation. 2008;117:2820–2840.  
2 Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, 
Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C. ACC/AHA/ESC 2006 guidelines for 
management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the 
American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology 
Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With 
Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006;48:e247–e346 
 

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Patient who is indicated 
for ICD or CRT-D arrives. 
Interested in study?
Sign Informed 
Consent (Enrolled). 
Complete Baseline 
Assessment.
Yes
Done, no further 
actions
No
Secondary Prevention 
Subject 
Agree to Implant?
Primary Prevention 
Subject
Meet 1.5 Criteria? 
1.5 Prevention Subject
Agree to Implant?
1.0 Prevention Subject
Agree to Implant?
Implant. Follow every 6 
mo. until death, exit, or 
closure
“C”
Collect Rationale for no 
implant. Follow every 6 mo. 
until death, exit, or closure
“D”
Implant. Follow every 6 
mo. until death, exit, or 
closure
“E”
Collect Rationale for no 
implant. Follow every 6 mo. 
until death, exit, or closure
“F”
Yes
No
Yes
No 
Yes
No
Collect Rationale for no 
implant. Exit Subject
“B”
No
Implant. Follow every 6 mo. 
until death, exit, or closure
“A”
Yes


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1.2 Study Description and Scope  
Medtronic, Inc. is sponsoring the Improve SCA study, a prospective, non-
randomized, non-blinded, global, interventional, multi-site post-market study. The 
study is expected to be conducted at approximately 100 sites worldwide, and to 
achieve approximately 2300 implants, the study is expected to enroll 
approximately 4800 subjects. However, a sample size re-estimation will occur 
partway through the study, so the actual sample size may be as high as 8000 
subjects enrolled (see page 52). Based on input from the Improve SCA steering 
committee, it is estimated that sites will enroll an average of 3 subjects per site per 
month. 
Participating geographies are expected to include, but are not limited to: 
Association of Southeast Asian Nations (ASEAN), Central and Eastern Europe 
(CEE), Greater China (including China and Taiwan), India, Latin America, Middle 
East and Africa (MEA), and South Korea. 
There is no minimum requirement for enrollments per site for this study. To ensure 
a widespread distribution of data and minimize site bias in study results, the 
maximum number of subjects enrolled at a single site will be approximately 5% of 
the expected total study subjects. 
It is anticipated enrollment will take approximately 2 years, beginning in April 2014; 
however, enrollment could take longer if there is a sample size increase as 
indicated above. The study will be closed approximately two years after the final 
subject enrollment. At approximately 22 months past the final enrollment, centers 
will be notified that study closure is about to occur and that they should attempt to 
make one final study contact with each subject to maximize overall study follow-
up. 
Both primary and secondary prevention subjects will be included in the study. 
Primary prevention subjects will be further divided into two groups, depending on 
whether or not they meet the 1.5 prevention criteria described above in Section 
1.1. In each of these groups, there are two non-randomized arms: subjects who 
receive an implant, and subjects who do not receive an implant. Therefore, there 
are a total of six arms in the study (labeled A-F), described above in Figure 1. The 
primary analysis focuses on comparing arms A (secondary prevention subjects 
who receive an implant) and C (1.5 prevention subjects who receive an implant) for 
time to appropriately treated ventricular tachycardia/ventricular fibrillation (VT/VF). 
In order to compare arms and adjudicate VT/VF, Medtronic devices must be used.  
Subjects who receive an implant of a non-Medtronic ICD/CRT-D should be exited 
from the study following implant, as this will impact the ability to determine the 
appropriateness of ICD/CRT-D therapies. 
 
 

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2 BACKGROUND AND JUSTIFICATION  
The use of ICDs in patients who have survived an episode of sudden cardiac 
arrest (SCA) or sustained ventricular tachycardia (VT) is well established. 
However, the use of ICDs in patients without a history of SCA or sustained VT 
episode but at high risk of such an episode is less established in some 
geographies. The prevention of sudden cardiac death is an important goal, and the 
ICD plays a vital role by terminating sudden or unexpected arrhythmias leading to 
sudden cardiac arrest. 
Secondary prevention refers to the use of ICDs for the prevention of sudden 
cardiac death in patients who have survived a prior sudden cardiac arrest or 
sustained VT, whereas primary prevention refers to the use of ICDs in individuals 
who are at risk for, but have not yet had a documented episode of sustained VT, 
VF, or resuscitated cardiac arrest.  
The intent of the Improve SCA study is to examine four risk factors in primary 
prevention patients which may be associated with a higher risk of SCA, thus 
forming a ‘1.5 prevention’ patient group. These 1.5 criteria are: syncope or pre-
syncope, very low ejection fraction (LVEF <25%), non-sustained ventricular 
tachycardia (NSVT), and frequent premature ventricular contractions (PVCs). The 
results of this study may be beneficial in helping clinicians identify and refer the 
highest-risk primary prevention patients for ICDs, help local societies expand 
guidelines to include primary prevention of SCA utilizing ICDs, and provide 
additional local evidence to allow patients to make an informed decision whether to 
receive an ICD. 
The 1.5 prevention criteria were developed in 2008 in collaboration with physicians 
in China to assist in the identification of primary prevention patients at highest risk 
of SCA. While each of these factors have been independently associated with an 
increased risk of LTVA and/or SCA, no prospective data have been collected to 
determine if one or more of these factors in a primary prevention ICD population is 
associated with an increased likelihood of receiving an appropriate ICD therapy. 
Furthermore, the geographies represented in the Improve SCA study have been 
underrepresented in previous primary prevention trials and, thus, there are limited 
local data demonstrating the benefit of ICDs in these geographies’ primary 
prevention patients. 
2.1 Syncope or pre-syncope 
Pre-syncope is dizziness, lightheadedness, or feeling faint, while syncope refers to 
a sudden loss of consciousness with loss of postural tone with spontaneous 
recovery. ICD therapy is indicated for secondary prevention of SCA (Class IA) in 
patients with syncope of undetermined origin with clinically relevant, 
hemodynamically significant sustained VT or VF induced at electrophysiology 
study3. In addition, an ICD is Class IIa indicated for primary prevention of SCA in 
patients with unexplained syncope, significant LV dysfunction, and non-ischemic 
                                                 
3 Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, 
Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO 
2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based 
therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American 
Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 
2013;61:e6–75. Available online at: www.hrsonline.org 

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dilated cardiomyopathy. Thus, a history of syncope in patients with heart failure 
may suggest an increased risk of a future LTVA. 
In SCD-HeFT, 162 (6%) patients had syncope before randomization, 356 (14%) 
had syncope after randomization, and 46 (2%) had syncope before and after 
randomization4. Syncope was associated with appropriate therapies in the ICD 
arm and across study arms and it was associated with increased mortality risk.  
Sánchez et al. evaluated 102 consecutive patients from Sept. 1996 to Dec. 2000 
who presented with unexplained syncope, depressed left ventricular function, 
regardless of etiology, and a negative electrophysiologic study (EPS).5 The study 
suggested that empiric ICD therapy improved long-term outcomes in patients with 
unexplained syncope, ischemic or non-ischemic cardiomyopathy, and negative 
EPS. 
Of 7814 participants in the Framingham Heart Study followed for an average of 17 
years (1971-1998), 822 reported syncope.6 Cardiac syncope doubled the risk of 
death from any cause and increased the risk of fatal and nonfatal cardiovascular 
events. Regardless of cardiovascular disease history, participants with a diagnosis 
of cardiac syncope were more likely to have a worse outcome than those without 
syncope.   
A collaborative study between a cardiology and neurology department examined 
five years follow-up of 183 patients hospitalized for syncope. They reported the 
etiological diagnosis of syncope was of cardiovascular cause in 73% of patients7 (5 
% of non-cardiovascular cause, 22% of unknown cause). Syncope of cardiac 
causes had the highest mortality rate, of 63%. Racco et al. suggested that cardiac 
syncope had the worst prognosis, and therefore needed recurrent clinical 
examinations and prompt treatment.  
The relation of syncope to sudden death was evaluated in 491 consecutive 
patients without a history of cardiac arrest.8 The actuarial incidence of sudden 
death by 1 year was significantly greater in patients with (45%) than in those 
without (12%, p < 0.00001) syncope.   
Collectively, these data suggest that a history of syncope may be an important risk 
factor in patients with cardiovascular disease at risk for SCA. 
2.2 Low ejection fraction (low EF)  
A patient’s left ventricular ejection fraction, or LVEF, is the percentage of blood in 
the lower chamber of the heart that is pumped out from the heart with each 
heartbeat. A normal EF is 50% or more. An EF of ≤35% is currently considered a 
                                                 
4 Olshansky B, Poole JE, Johnson G, et al. Syncope Predicts the Outcome of Cardiomyopathy Patients. Analysis 
of the SCD-HeFT Study. JACC 2008; 51:1277-1282. 
5 Sánchez JM, Katsiyiannis WT, Gage BF, et al. Implantable cardioverter-defibrillator therapy improves long-term 
survival in patients with unexplained syncope, cardiomyopathy, and a negative electrophysiologic study. Heart 
Rhythm 2005; 2:267-373. 
6 Soteriades ES, Evans JC, Larson MG, et al. Incidence and Prognosis of Syncope. N Engl J Med 2002; 347:878-
885. 
7 Racco F, Sconocchini C, Alesi C, et al. Long-Term Follow-Up after Syncope. A Group of 183 Patients Observed 
for 5 Years. Minerva Cardioangiol 2000; 48:69-78. 
8 Middlekauff HR, Stevenson WG, Stevenson LW, et al. Syncope in Advanced Heart Failure: High Risk of 
Sudden Death Regardless of Origin of Syncope. JACC 1993; 21:110-116. 

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primary risk factor for SCA9, and in this study, an EF less than 25% is considered 
very low EF, an indication for a 1.5 prevention patient.  
LVEF has been shown to significantly predict mortality. Data compiled from four 
randomized trials, pooled to create a cohort of 2828 patients, showed that each 
10% reduction in LVEF between 15 and <40% independently conferred a 39% 
increase in risk for arrhythmic cardiac mortality over a 2-year period.10 The lowest 
number of patients needed to prevent one death with an ICD was when an EF 
≤25%. 
2.3 Non-sustained ventricular tachycardia (NSVT) 
Ventricular tachycardia (VT) is a rapid heartbeat originating in the ventricles. VT is 
potentially life-threatening because it may lead to ischemia, ventricular fibrillation 
(VF), asystole, and sudden cardiac death. In this study, VT is defined as three or 
more consecutive ventricular beats at a rate of more than 100 beats per minute. 
Non-sustained ventricular tachycardia (NSVT) is VT which spontaneously 
terminates within 30 seconds. Otherwise the VT is defined as sustained VT. 
A meta-analysis of 11 studies (published from 1989 - 2007; N=4387) found NSVT 
to be a statistically significant predictor for arrhythmic events in patients with LV 
dysfunction.11 
An analysis by Moore et al. of the SCD-HeFT trial looked at overall mortality by 
NSVT episode frequency. They found that in 673 patients who had NSVT, 271 had 
1 NSVT and 402 had ≥1 NSVT episodes on baseline Holter Monitor. The authors 
concluded that the presence of ≥2 NSVT episodes conferred an increased overall 
mortality when compared to less frequent NSVT episodes.12  
A Canadian trial that looked at predictors of appropriate ICD therapy in patients 
receiving primary prevention ICDs showed that ICD therapy occurred in 19% of 
421 primary prevention patients with both ischemic and non-ischemic 
cardiomyopathy and was predicted most strongly by NSVT and a lack of beta 
blocker use.13  
Results from 1135 primary prevention patients from the OMNI study showed a 
significant correlation between presence of device-detected NSVT and true VT/VF 
episodes.14 The vast majority of (91.3%) patients with true VT/VF episodes also 
                                                 
9 Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, 
Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO 
2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based 
therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American 
Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 
2013;61:e6–75. Available online at: www.hrsonline.org 
10 Yap YG, Duong T, Bland JM, et al. Optimising the dichotomy limit for left ventricular ejection fraction in 
selecting patients for defibrillator therapy after myocardial infarction. Heart. 2007 Jul;93(7):832-6. Epub 2007 Jan 
19. 
11 Sousa M, Morillo C, Rabelo F, et al. Non-sustained Ventricular Tachycardia as a Predictor of Sudden Cardiac 
Death in Patients with Left Ventricular Dysfunction: A Meta-Analysis. Eur J Heart Fail 2008; 10:1007-1014. 
12 Chen J, Johnson G, Hellkamp A, et al. Rapid Rate Non-sustained Ventricular Tachycardia found on ICD 
Interrogation: Relationship of NSVT to Outcomes in the SCD-HeFT Trial. DOI: 10.1016/j.jacc.2013.02.046. 
13 Verma A, Sarak B, Kaplan A, et al. Predictors of Appropriate Implantable Cardioverter Defibrillator (ICD) 
Therapy in Primary Prevention Patients with Ischemic and Nonischemic Cardiomyopathy. PACE 2010; 33:320-
329. 
14 Ziegler P, Zhang S, Arora V, et al. Is the Presence of Non-Sustained Ventricular Tachycardias Associated with 
True Ventricular Tachycardias and Ventricular Fibrillation in Primary Prevention Patients? Presented at HRS 
2013. 

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have device-detected episodes of NSVT, and extended periods of NSVT 
monitoring may be useful for identifying patients who would derive a greater 
benefit from ICD implantation for primary prevention.  
2.4 Frequent premature ventricular contractions (PVCs) 
Premature ventricular contractions (PVCs), also known as premature ventricular 
complexes or ventricular premature contractions (VPCs), are abnormal heartbeats 
that begin in the ventricles. Because the beat occurs early, PVCs interrupt the 
normal synchrony of the heartbeat and can cause the heart to pump blood less 
effectively. A link between PVCs and ventricular tachycardias is well documented. 
Sixty episodes of VF among 29 patients were identified in MADIT II trial (n = 724 
primary prevention ICD patients randomized from 1232). A single PVC initiated 46 
(77%) VF episodes whereas an SLS sequence (short-long-short; ectopic activity 
with a disruption of the baseline rhythm by a premature depolarization, followed by 
a pause, then by a short-coupled premature depolarization) accounted for 14 
(23%) episodes. The study showed that VF is more commonly initiated by a PVC 
than by an SLS sequence among the MADIT II population.15  
In a study by Hadhjoo et al. of 50 patients with an ICD, 182 episodes of 
monomorphic VT were examined. PVC-induced episodes were the most frequent 
pattern (58%).16 Saeed et al. showed that patients with poor EF (<35%) had more 
PVCs immediately preceding VT and high frequency of extra-systolic initiation 
(66%) in 268 episodes of monomorphic VT identified in 52 patients.17 Taylor et al. 
examined 260 episodes of polymorphic and monomorphic VT, and categorized the 
initiating beat of the VT; 85% were initiated by late-coupled ventricular ectopic 
beats, 13% by early-coupled ectopic beats, and only 2% by SLS sequences.18  
In 69 patients implanted with ICD (21 for primary prevention), 364 episodes of VT 
in 40 post-infarct and 29 idiopathic dilated cardiomyopathy (IDC) patients were 
analyzed. Onset with variable patterns of PVC was observed in 45% and 65% and 
short-long-short in 29% and 14% of post MI and IDC patients, respectively.19  
Roelke et al. evaluated 73 spontaneous monomorphic VT episodes stored in ICDs 
among 22 post-infarction patients.20 VT onset was more common with a single 
PVC (45%) than with either 2 (22%) or more (33%) PVCs. 
Finally, results from the GISSI-2 study showed that in 8676 patients followed for 6 
months post-MI, ventricular arrhythmias were present in approximately 64% of the 
                                                 
15 Anthony, R., et al., Mechanisms of VF Initiation in MADIT II Patients with ICDs, PACE, 2008, 31: 4-10. 
16  Haghjoo M, Arya A, Sadr-Ameli AS. Pattern of Initiation of Monomorphic Ventricular Tachycardia in Recorded 
Intracardiac Electrograms. India Pacing Electrophysiol J 2005; 5(4):263-271. 
17 Saeed M, Link MS, Mahapatra S, et al. Analysis of Intracardiac Electrograms Showing Monomorphic 
Ventricular Tachycardia in Patients with Implantable Cardioverter-Defibrillators. Am J Cardiol 2000; 85:580-587. 
18 Taylor E, Berger R, Hummel J, et al. Analysis of the Pattern of Initiation of Sustained Ventricular Arrhythmias 
in Patients with Implantable Defibrillators. J Cardiovasc Electrophysiol 2000; 11:719-726. 
19  Grimm W, Walter M, Menz V, et al. Circadian Variation and Onset Mechanisms of Ventricular 
Tachyarrhythmias in Patients with Coronary Disease versus Idiopathic Dilated Cardiomyopathy. PACE 2000; 
23:1939-1943. 
20 Roelke M, Garan H, McGovern B, et al. Analysis of the Initiation of Spontaneous Monomorphic Ventricular 
Tachycardia by Stored Intracardiac Electrograms. JACC 1994; 23:117-122. 

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patients, and almost 20% showed frequent (more than 10 PVCs per hour). In 
addition, NSVT was present in 6.8% of the patients.21  
These data suggest that PVCs are a common initiator of ventricular 
tachyarrhythmias and a high burden of PVCs is associated with an increased risk 
of LTVA. 
2.5 1.5 Prevention Definition 
Based on the data above, a primary prevention patient is considered to be in the 
1.5 prevention subgroup if they meet one or more of the conditions in Table 4. 
 
 
                                                 
21  Maggioni AP, Zuanetti G, Franzosi MG, et al. Prevalence and Prognostic Significance of Ventricular 
Arrhythmias after Acute Myocardial Infarction in the Fibrinolytic Era: GISSI-2 Results. Circulation 1993; 87:312-
322. 

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Table 4: 1.5 Prevention Definition 
Condition 
Details 
Syncope or pre-
syncope 
Within the past 12 months: 
• 
Pre-syncope/ dizziness/ lightheadedness, due to suspected VT 
• 
Syncope, due to suspected VT 
• 
Unexplained Syncope or pre-syncope, after ruling out these causes: 
• 
Syncope, due to carotid sinus hypersensitivity  
• 
Vasovagal Syncope  
• 
Syncope, due to bradycardia  
• 
Syncope, due to SVT 
Low LVEF 
LVEF < 25% measured within 6 months of enrollment or implant. 
 
If history of MI, LVEF must be collected at least: 
• 
40 days post-MI if there was no revascularization 
• 
90 days post-MI if there was revascularization (e.g., percutaneous 
coronary intervention (PCI), coronary artery bypass graft (CABG) 
NSVT 
A history of NSVT since HF diagnosis in Medical Records 
 
OR 
 
A history of NSVT documented from an IPG (implantable pulse generator) 
on an EGM strip in the medical records, where the physician rules out SVT 
or ventricular artifact 
 
OR 
 
NSVT measured on an ambulatory monitor (e.g., Holter, patch) 
 
 
WHERE 
 
Non-sustained VT is defined as 3 or more consecutive beats at >100 beats 
per minute lasting less than 30 seconds. 
Frequent PVCs 
History of Frequent PVCs within 12 months  
 
OR 
 
Frequent PVCs on an ambulatory monitor (e.g., Holter) test lasting at least 
20 hours  
 
OR 
 
A history of frequent PVCs documented from an IPG on an EGM strip in the 
medical records, where the physician rules out SVT or ventricular artifact. 
 
WHERE  
 
“Frequent PVCs” is defined as an average of 10 or more PVCs per hour 
while monitored 
 
If history of MI, PVCs must be collected at least: 
• 
40 days post-MI if there was no revascularization 
• 
90 days post-MI if there was revascularization (e.g., percutaneous 
coronary intervention (PCI), coronary artery bypass graft (CABG) 
 

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2.6 ICD and CRT-D therapy 
ICD therapy terminates ventricular tachyarrhythmias and improves survival of 
patients at risk for sudden cardiac death.22,23 Medtronic ICDs/CRT-Ds provide anti-
tachycardia pacing (ATP) and shocks to terminate tachycardias originating in the 
ventricles – ventricular tachycardia (VT) and ventricular fibrillation (VF).  Medtronic 
has engaged in over 20 years of research to establish ICD programming 
guidelines and develop new detection algorithms to reduce or eliminate 
inappropriate and unnecessary shocks that result in significant patient morbidity.  
The PainFree SST trial demonstrated that only about 2% of ICD/CRT-D patients 
will experience an inappropriate shock after one year of follow-up using the most 
recent Medtronic ICD/CRT-Ds and current programming recommendations 24,25. 
While the Improve SCA trial does not require use of the most recent Medtronic 
ICD/CRT-Ds, doing so will assure the lowest possible inappropriate shock rate 
when using the required ICD programming described below. These requirements 
have been developed and proven effective in the Medtronic research studies.  
The table below provides the highlights of the Improve SCA programming 
requirements and the study that demonstrated the value of the parameter. Older 
devices will not have all programming capabilities. Due to the large number of 
potential ICD/CRT-D devices to be implanted, tools with specifications for 
individual devices will be provided to investigators under separate cover as 
needed. 
 
 
                                                 
22 AVID Investigators. comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients 
resuscitated from near-fatal ventricular arrhythmias. NEJM 1997;337:1576-1583 
23 Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart 
failure. NEJM 2005; 352:225-237. 
24 Schloss EJ, Auricchio A, Kurita T, et al. PainFree SST Trial Primary Results Low Shock Rates in Patients with 
Dual and Triple Chamber ICDs Using Novel Detection Algorithms. Heart Rhythm Society, Denver CO, May 10, 
2013. 
25 Meijer A, Auricchio A, Kurita T, et al. PainFree SST Trial Primary Results Inappropriate shock rates in patients 
with single chamber ICDs using a novel suite of detection algorithms. EUROPACE, 25 Jun 2013. 

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Table 5: Improve SCA Programming Requirements  
Key Programming 
Parameters 
Evidence based 
Requirement 
Study Source 
VFDI 
300 ms 
PainFree SST26,27 
VF NID 
30/40 
PREPARE28, RELEVANT29, ADVANCE 
III30 
VTDI 
360 ms 
PainFREE II31, MVP 32, PainFree SST 
VT NID 
24 
PainFree SST 
Wavelet 
ON, 70% 
WAVE33, PainFree SST 
PR Logic 
ON 
GEM DR34, EMPIRIC35 
SVT Limit 
260 ms 
PainFree SST 
LIA 
ON 
PainFree SST 
T Wave Rejection 
ON 
PainFree SST 
Lead Noise Rejection 
ON 
PainFree SST 
ATP for VT 
ON, 8@88% 
PainFREE II, EMPIRIC,  
ATP During Charge 
ON, 8@88% 
EnTrust Clinical Trial 
 
                                                 
26 Schloss EJ, Auricchio A, Kurita T, et al. PainFree SST Trial Primary Results Low Shock Rates in Patients with 
Dual and Triple Chamber ICDs Using Novel Detection Algorithms. Heart Rhythm Society, Denver CO, May 10, 
2013. 
27 Meijer A, Auricchio A, Kurita T, et al. PainFree SST Trial Primary Results Inappropriate shock rates in patients 
with single chamber ICDs using a novel suite of detection algorithms. EUROPACE, 25 Jun 2013 
28 Wilkoff BL, Williamson BD, Stern RS, et al. Strategic programming of detection and therapy parameters in 
implantable cardioverter-defibrillators reduces shocks in primary prevention patients: Results from the PREPARE 
(Primary Prevention Parameters Evaluation) Study. J Am Coll Cardiol. 2008 Aug 12;52(7):541-50. 
29 Gasparini M, Menozzi C, Proclemer A., et al. A simplified biventricular devirillator with fixed long detection 
intervals reduces implantable cardioverter defibrillator (ICD) interventions and heat failure hospitalizations in 
patients with non-ischaemic cardiomyopathy implanted for primary prevention: the RELEVANT [Role of long 
dEtection windown programming in patients with LEft VentriculAr dysfunction, Non-ischemic eTiology in primary 
prevention treated with a biventricular ICD] study. European Heart Journal (2009) 30, 2758–2767 
30 Gasparini M, Proclemer A, Klersy C, et al. Effect of long-detection interval vs standard-detection interval for 
implantable cardioverter-defibrillators on Antitachycardia pacing and shock delivery: The ADVANCE III 
randomized clinical trial. JAMA. 2013 May 8;309(18):1903-11. 
31 Wathen MS, DeGroot PJ, Sweeney MO, et al. Prospective Randomized Multicenter Trial of Empirical 
Antitachycardia Pacing Versus Shocks for Spontaneous Rapid Ventricular Tachycardia in Patients With 
Implantable Cardioverter-Defibrillators Pacing Fast Ventricular Tachycardia Reduces Shock Therapies 
(PainFREE Rx II) Trial Results. Circulation. 2004;110:2591-2596. 
32 Sweeney MO, Ellenbogen KA, Betzold R, et al. Multicenter, prospective, randomized trial of a new atrial-based 
Managed Ventricular Pacing Mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol 2005;16:1–7. 
33 Klein G, Gillberg JM, Tang A, Inbar S, et al. Improving SVT discrimination in single Chamber ICDs - A new 
electrogram morphology based algorithm. J Cardiovasc Electrophysiol 2006; in press. 
34 Wilkoff BL, Kuhlkamp V, Volosin K, et al. Critical analysis of dual-chamber implantable cardioverter-defibrillator 
arrhythmia detection: Results and technical considerations. Circulation 2001;103:381-386. 
35 Wilkoff BL, Ousdigian KT, Sterns LD et al. A comparison of empiric to physician-tailored programming of 
implantable cardioverter-defibrillators: Results from the prospective randomized multicenter EMPIRIC Trial. J Am 
Coll Cardiol. 2006 Jul 18;48(2):330-9. Epub 2006 Jun 22. 
 

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3 SYSTEM DESCRIPTION AND INTENDED USE 
Subjects with an ACC/AHA/HRS or ESC Class I guideline-recommended need for 
an ICD (or CRT-D) implant for either primary or secondary prevention of SCA may 
be enrolled in the study. Subjects who enroll in the study and proceed with a 
device implant must be implanted with a Medtronic single, dual, or triple chamber 
defibrillator that has received appropriate license or regulatory approval and is 
commercially available by Medtronic in the geography in which the implant will 
take place. Any market-released, commercially available lead(s) can be used in 
this study.  
The study will be conducted using the components described in the table below. 
Instructions for use of the devices used in this study are provided in their 
respective manuals. Additional study components which may be utilized in this 
study for subjects who receive an implant include Medtronic CareLink® Monitor 
and CareLink® Network, and Medtronic programmers. These components are 
described in the following sections. 
Table 6: System Component Information  
Model Number 
Component 
Investigational or  
Market-released 
Device Components 
-- 
Any Medtronic single, dual, triple chamber  
ICD or CRT-D device 
Market-released  
-- 
Any right ventricular (RV) lead  
Market-released  
-- 
Any right atrial (RA) lead  
(if part of dual chamber ICD/CRT-D system) 
Market-released  
-- 
Any left ventricular (LV) lead  
(if part of CRT-D system) 
Market-released  
Accessory Components 
2090 
Medtronic Programmer  
Market-released  
2490C 
Medtronic CareLink Monitor  
(where applicable) 
Market-released  
2067 or 2067L 
Medtronic RF telemetry head 
(where applicable) 
Market-released 
 
3.1 Market-Released Medtronic ICD or CRT-D Device 
Subjects who enroll in the study and proceed with a device implant must be 
implanted with a Medtronic single, dual, or triple chamber defibrillator that has 
received appropriate license or regulatory approval and is commercially available 
by Medtronic in the geography in which the implant will take place. Examples from 
the Medtronic family of devices include but are not limited to the Medtronic InSync 
III Protect, Marquis, Secura, Consulta, Maximo II, Concerto, Virtuoso, Protecta, 
Viva, Evera, Egida, Evera, EnTrust, Brava, GEM III. Other devices may become 
available during the course of the clinical study and may be used if the 
aforementioned criteria are met. The device must not have been previously 
implanted in another patient. 

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3.1 Market-Released Lead(s) 
Any market-released, commercially available lead(s) may be used in this study. 
Any RV lead may be used, and an RA or LV lead may be implanted if deemed 
necessary per the physician’s medical assessment. Examples include the 
Medtronic Attain Ability or the Medtronic CapSureFix leads. Any lead under recall, 
even if not in the country of implant, should not be implanted in study patients. 
3.2 Medtronic CareLink Monitor and Medtronic CareLink Network 
The Medtronic CareLink Monitor and the Medtronic CareLink Network are 
indicated for use in the transfer of patient data from some Medtronic implantable 
cardiac devices based on physician instructions and as described in the product 
manual. These products are not a substitute for appropriate medical attention in 
the event of an emergency and should only be used as directed by a physician.   
The Medtronic CareLink Network enables subjects to remotely transfer data from 
their device to the clinic. Subjects may be requested to use the Medtronic 
CareLink Monitor to send their device data to the clinic. Study site personnel can 
access the data by logging onto the CareLink website via the internet. 
The use of the Medtronic CareLink Home Monitor is not required for this study and 
it may not be available in all participating geographies. However, if the subject 
uses CareLink to transmit their device data, the data may be used in the analysis 
of the study objectives, where allowed by local law. 
3.3 Market-Released Medtronic Programmer 
Medtronic’s market-released Model 2090 programmer (or future models, which 
become market released in the geographies where this study takes place) must be 
available at each site to support study visits. Programmers will be used to gather 
lead electrical data, interrogate devices, program devices, and save device data.   
3.4 Changes to the Study System 
Medtronic may incorporate additional Medtronic ICD/CRT-D devices with 
appropriate therapies as well as Medtronic and non-Medtronic leads into this study 
as they receive appropriate license or regulatory approval. Likewise, future 
CareLink monitors, network updates, and programmers may also be incorporated 
into this study; study documentation will be updated if and where necessary. 
 
 

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4 REGULATORY COMPLIANCE 
The Improve SCA study is a prospective, non-randomized, non-blinded, global, 
interventional, multi-site, post-market study, as specific programming and follow-up visits 
are required (i.e., this is not a registry study). This study is required to be in compliance 
with the Clinical Investigation Plan (CIP), Clinical Trial Agreement (CTA) and local 
laws/regulations within respective geography the study is being conducted. 
The Improve SCA study was designed to reflect good clinical practice (GCP) principles 
including 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. 
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. The study will also be conducted in accordance with the ethical principles 
that have their origin in the Declaration of Helsinki. The principles of the Declaration of 
Helsinki are implemented in this study by means of the Patient Informed Consent (PIC) 
process, MEC/IRB/HREC (all henceforth referred to as an “Ethics Committee”) approval, 
study training, clinical trial registration, pre-clinical testing, risk benefit assessment, and 
publication policy. 
• 
In Central and Eastern Europe and Middle East and Africa, local regulations will 
be followed.  
• 
In India, applicable India regulations will be followed. 
• 
In Latin America, applicable local regulations will be followed. 
• 
In China, applicable local regulations will be followed. 
• 
In Taiwan, applicable local regulations will be followed. 
• 
In Korea, Standards for Management of Clinical Trials for Medical Devices 
(KGCP) <Amended on March 23, 2013> (Attachment 2-2 of Enforcement 
Regulations of the Medical Device Act) and other applicable Korean regulations 
will be followed.  
• 
In Singapore, Health Products (Medical Devices) Regulations 2010 and other 
local applicable regulations will be followed. 
• 
In Malaysia, National Medical Research Register (NMRR) requirements are 
applicable although the medical device is not regulated in Malaysia, e.g., 
Guidelines for Application of Clinical Trial Import License and Clinical Trial 
Exemption in Malaysia. In addition, applicable local regulations will be followed. 
The study will be publicly registered prior to first enrollment in accordance with the 
Declaration of Helsinki on http://clinicaltrials.gov (PL 110-85, Section 810(a)). 
Approval of the CIP is required from the following groups prior to any study procedures 
at a study site:  
• 
Medtronic  
• 
Principal investigators (where required by local law, e.g., Malaysia, China, India) 
• 
Geography-specific regulatory authorities (if regulatory approval is required)  
• 
Each site’s Ethics Committee  

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Similarly, approval of subsequent revisions to the CIP is required at each study site from 
the above-mentioned groups prior to implementation of the revised CIP at that site. 
Each site’s Ethics Committee will also be required to approve any subject recruitment 
materials, if used.  
 
 

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5 METHODOLOGY 
5.1 Study Objectives 
This prospective, non-randomized, interventional, non-blinded, multi-site global 
post-market study will evaluate the outcomes of ICD patients who meet 1.5 
prevention criteria, as described in Section 6.7.  
5.1.1 Primary objective 
• 
Demonstrate that appropriate VT/VF therapy rates (shock and ATP) for 
subjects meeting 1.5 prevention criteria implanted with a Medtronic 
device (ICD/CRT-D) are equivalent (within 30%) to rates in subjects 
meeting secondary prevention criteria. 
5.1.2 Secondary objective 
• 
Compare the mortality rates for patients meeting 1.5 prevention criteria 
between those implanted with a device (ICD/CRT-D) and those not 
implanted. 
 
 
 
 
  
 
 
 
 
 
 
5.2 Subject Selection Criteria 
Patients of both genders who have a guideline recommendation for a single, dual, 
or triple chamber defibrillator will be approached regarding enrollment in the study. 
Subjects receiving a device implant will be required to have a Medtronic device 
implanted because data stored in the device will be retrieved and analyzed by 
Medtronic as part of the study.  
Subjects currently implanted with an implantable pulse generator (IPG) are eligible 
for participation in the study, assuming the previous device is explanted at the time 
of implant. 
5.2.1 Inclusion criteria 
• 
Subject has a Class I indication for implantation of an ICD according to 
the ACC/AHA/HRS or ESC Guidelines 
• 
Subject (or subject’s legally authorized representative) is willing and able 
to sign and date the Patient Informed Consent Form.  

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5.2.2 Exclusion criteria 
• 
Subject is ≤ 18 years of age 
• 
Subject with any exclusion criteria as required by local law (e.g., age, 
pregnancy, breast feeding) 
• 
Subject is enrolled in a concurrent study that has not been approved for 
concurrent enrollment by the Medtronic Clinical Trial Leader 
• 
Subject has any contraindication for ICD/CRT-D 
Ethics Committee approval of the Improve SCA Clinical Investigation Plan and 
Patient Informed Consent Form must be obtained for each site, prior to that site 
enrolling patients in the study. Refer to Section 6.2 for a more complete list of 
requirements which must be met prior to enrolling patients in the study. Enrollment 
of the subject must occur prior to performing any study-required testing (e.g., 
ambulatory monitoring for testing of 1.5 Criteria).  
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 will be collected at baseline for potentially analyzing 
differences that may affect the endpoints. 
• 
All study clinicians and Medtronic personnel will be trained on the 
corresponding aspects of the study using standardized training materials. 
• 
All study clinicians and Medtronic personnel will be trained on, and required 
to follow the CIP. 
• 
An Episode Review Committee will be formed to review and classify 
arrhythmia episodes based on study definitions. 
• 
To ensure a wide distribution of data between sites, the maximum 
enrollments per site will be no more than 5% of the expected enrollment.  
 
 

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6 STUDY PROCEDURES 
All clinical investigators managing the subject’s heart failure must be qualified 
physicians, experienced in the diagnosis and treatment of subjects with heart failure. All 
EP/implanting physicians must be experienced and/or trained in the handling of ICD 
and/or CRT-D devices. Site personnel training and task delegation by the Principal 
Investigator will be completed prior to participation in this study. 
Medtronic will provide study training relevant and pertinent to the involvement of 
personnel conducting study activities and investigator responsibilities.  
Medtronic personnel may perform the following activities during the study, under 
supervision of the Principal Investigator: 
• 
Technical support at all visits under the supervision of a study investigator, but 
no data entry, shall be performed by Medtronic personnel or their 
representatives at sites 
• 
Monitoring and auditing activities 
6.1 Investigator Selection Criteria  
The following requirements were considered in the selection of sites: 
• 
Primary Investigator has experience with the implantation of ICDs and/or 
CRT-Ds  
• 
Site has the ability (high speed internet) and willingness to submit data 
through an internet based electronic data capture (EDC) system (Oracle 
Clinical) 
• 
Site has adequate volume of patients meeting all of the inclusion/none of 
the exclusion criteria such that the site can target a minimum of 3 study 
enrollments per month, with at least 1/3 of enrollments expected to be 
primary prevention patients 
• 
Site has Medtronic market-released programmer available for all study 
visits 
• 
Site has sufficient staff (at least one primary investigator and study 
coordinator/other staff) and Medtronic support to execute and maintain 
compliance to the protocol, including data collection and record retention 
requirements 
• 
Acknowledgement of, and agreement to, comply with applicable regulatory 
and local requirements governing clinical study conduct 
6.2 Site Activation  
During the activation process (prior to a site’s involvement in study activities), 
Medtronic personnel or delegates will train site personnel on the clinical 
investigation plan, relevant standards and regulations, patient informed consent 
(PIC) process, written clinical trial agreements, and data collection and reporting 
tools. If new members join the study site team, they must receive training on the 
applicable clinical study requirements relevant to their role before contributing to 
the clinical study. 
Prior to performing study-related activities, all local regulatory requirements must 
be fulfilled, including, but not limited, to the following:  

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• 
Ethics Committee approval (and voting list, as required by local law) of the 
most current version of the CIP and Patient Informed Consent form  
• 
Regulatory authority approval or notification (as required per local law)  
• 
Fully executed Clinical Trial Agreement (CTA) , including a description of 
financial aspects 
• 
Current (within the last two years) of Principal Investigator 
o CV must be signed and dated (Central & Eastern Europe, Middle 
East and Africa, Latin America; best practice in all other 
geographies) 
o CV of other investigators prior to their activation, and CV of other 
key members of the investigation site team where required by local 
law 
• 
Documentation of delegated tasks  
• 
Completion and documentation of study training.  
Additional requirements imposed by the Ethics Committee and regulatory authority 
shall be followed, if applicable.  
In addition, all participating site staff must be trained on the current version of the 
CIP pertinent to their role in the study and must be delegated by the Principal 
Investigator to perform study-related activities.   
Medtronic will provide each study site with written documentation of study 
site/investigator readiness in the form of a Site Activation Letter; this letter must be 
received by the site prior to subject enrollment. If additional investigators are 
added, they will be notified of readiness once all requirements are met.  
6.3 Equipment Requirements 
The following equipment must be available at each site to support study activities 
(to be verified before site activation): 
• 
Access to equipment to measure ejection fraction, including but not limited 
to an echocardiography machine, Cardiac Magnetic Resonance Imaging 
(MRI), or Multi Gated Acquisition Scan (MUGA). 
• 
Ambulatory method of measuring PVC burden and NSVT for at least 24 
hours at baseline (e.g., Holter, CardioNetTM Mobile Cardiac Outpatient 
Telemetry (MCOT)TM).  
Calibration and maintenance of equipment listed above will be done by the site 
(documented proof of said activities should be available upon request by 
Medtronic). 
6.4 Data Collection 
Clinical data is collected at designated time points throughout the study. Data will 
be collected using an electronic data management system for clinical studies. 
Anonymized data will be collected, and data will be stored in a secure, password-
protected database which will be backed up each day. Data will be reviewed using 
programmed and manual data checks. Data queries will be made available to 
study sites for resolution. Study management reports may be generated by 

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Medtronic to monitor data quality and study progress. At the end of the study, the 
data will be frozen and retained indefinitely by Medtronic. Data collection 
requirements are summarized in Table 7 below. 
Table 7: Data collection and study procedure requirements at subject visits 
Study Procedure 
Baseline 
Implant/ 
Implant 
Refusal 
Contact Visits 
(scheduled and 
unscheduled) 
Device 
Change 
Study 
Exit/ 
Death 
Patient informed consent 
x 
 
 
 
 
Eligibility Verification 
(Inclusion/ exclusion 
assessment) 
x 
 
 
 
 
Baseline assessment  
(e.g., Demographics, NYHA 
assessment, indication for 
implant) 
x 
 
  
 
 
Medical History 
x 
 
 
 
 
Cardiovascular Medications 
x 
 
x 
(Amiodarone 
only) 
 
 
1.5 Criteria Assessment 
x 
 
 
(6 month visit)  
x*** 
 
QoL Assessment (EQ-5D) 
x** 
 
x**  
(6 month visit) 
 
 
Implant/Implant Refusal 
 
x 
 
 
 
Device Interrogation File (.pdd) 
or  
CareLink Transmission 
 
x*  
x* 
x 
(before & 
after) 
x*‡ 
Vital status 
 
 
x 
 
x 
Study Deviations 
As they occur  
Subject Exit 
Subject Death 
*if subject receives device implant 
**1.5 subjects only 
*** if new implant of an ICD/CRT-D 
‡if possible 
 
6.5 Patient Informed Consent Process 
Patient informed consent (PIC) is defined as legally effective, documented 
confirmation of a subject’s (or their legally authorized representative or guardian) 
voluntary agreement to participate in a particular clinical study after sufficient 
information has been given to the subject on all aspects of the clinical study that 
are relevant to the subject’s decision to participate. This process includes 
obtaining a PIC and other privacy language as required by law that has been 
approved by the study site’s Ethics Committee and personally signed and dated by 
the subject (or their legally authorized representative or guardian). A subject may 
only give his/her consent after information has been given to the subject on all 
aspects of the clinical investigation that are relevant to the subject’s decision to 

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participate. Consent may be given by the legally authorized representative only if a 
subject is unable to make the decision to participate in a clinical investigation by 
him/herself. In such cases, the subject shall also be informed about the clinical 
investigation within his/her ability to understand. 
Prior to enrolling subjects, each site’s Ethics Committee will be required to approve 
the PIC Form, and other privacy language as required by law. The document(s) 
must be controlled (i.e., versioned and dated) to ensure it is clear which version(s) 
were approved by the Ethics Committee. Any adaptation of the sample Consent 
Form must be reviewed and approved by Medtronic and the Ethics Committee 
reviewing the application prior to enrolling subjects.  
Prior to initiation of any study-specific procedures, Informed Consent (as 
documented in the PIC form) must be obtained from the subject (or their legally 
authorized representative or guardian). Likewise, privacy or health information 
protection regulation may require subjects to sign additional forms to authorize 
sites to submit subject information to the study sponsor. The Informed Consent 
process must be conducted by the Principal Investigator or an authorized 
designee, and the Consent Form and other privacy language as required by law 
must be given to the subject (or their legally authorized representative or guardian) 
in a language he/she is able to read and understand. The process of Informed 
Consent must be conducted without using coercion or undue improper influence 
on or inducement of the subject to participate by the investigator or other site 
personnel. 
The process of obtaining Informed Consent shall: 
• 
Ensure that the Principal Investigator or his/her authorized designee 
conducts the Informed Consent process 
• 
Not waive or appear to waive subject’s legal rights 
• 
Use language that is non-technical and understandable to the subject 
• 
Provide ample time for the subject to read and understand the informed 
consent form and to ask questions, receive answers and consider 
participation 
• 
Include a personally dated signature of the subject(or legally authorized 
representative) acknowledging that their participation in the study is 
voluntary 
• 
Include a personally dated signature by the Principal Investigator or his/her 
authorized designee responsible for conducting the Informed Consent 
process, where required by local law (e.g., Central & Eastern Europe, 
Middle East & Africa)  
If the PIC 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 (e.g., 
Holter monitor data collection solely for 1.5 Prevention evaluation). It is best 
practice for the Informed Consent process to be documented in the subject’s case 
history, regardless of circumstance. 
In the event the subject cannot read and/or write, witnessed (impartial third party) 
Informed Consent will be allowed, provided detailed documentation of the process 
is recorded in the subject’s case history and the witness signs and dates the PIC 
form. Informed Consent shall be obtained through a supervised oral process, with 

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an independent witness present. The PIC as well as any other relevant information 
must be read aloud and explained to the prospective subject or his/her legally 
authorized representative. The subject should “make his mark” (sign or otherwise 
physically mark the document so as to indicate consent) on the PIC form as well, 
attesting that the information was accurately explained and that informed consent 
was freely given. The PIC Form should document 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 of the signed PIC form must be filed in the hospital/clinical chart 
and/or with the subject’s study documents. A copy of the signed and dated PIC 
form, as well as and other privacy language as required by law, shall be provided 
to the subject.   
The PIC form and other privacy language as required by law must be available for 
monitoring and auditing. Any Medtronic Field (or delegate) personnel who support 
the implant must be able to review the subject’s signed and dated PIC form and 
verify its completeness prior to proceeding with the implant. In the event the 
Medtronic Field (or delegate) personnel identify a PIC form as being incomplete, 
the implant must not be allowed to occur until the consent of the subject can be 
adequately and appropriately obtained. 
Any changes to a previously approved PIC form throughout the course of the study 
must be approved by Medtronic and the Ethics Committee reviewing the 
application before being used to consent a prospective study subject. The 
document(s) must be controlled (i.e., versioned and dated) to ensure it is clear 
which version(s) were approved by the Ethics Committee. All important new 
information should be provided to new and existing subjects throughout the study. 
Confidentiality of data must be observed by all parties involved at all times 
throughout the clinical investigation. Privacy of each subject and confidentiality of 
his/her information must be preserved in reports and when publishing any data. All 
data shall be secured against unauthorized access. 
6.6 Enrollment and Baseline 
At the point in time when a patient or legally authorized representative and 
investigator or authorized designee have signed and dated the Patient Informed 
Consent Form, the patient is considered a subject enrolled in the study. The date 
the subject signed the PIC form must be documented in the subject’s medical 
records.  
Enrollment/baseline data will be collected for all enrolled subjects. The following 
information is required to be collected at the baseline visit: 
• 
Patient Informed Consent Date (Enrollment Date) 
• 
Demographics 
• 
NYHA classification  
• 
Indication for Implant 
• 
Medications 
• 
 Eligibility Verification (Inclusion/Exclusion Criteria) 
• 
Medical History 

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• 
1.5 Criteria Assessment (Syncope, LVEF, NSVT, and PVC burden) 
• 
Quality of Life Questionnaire (EQ-5D36) (for 1.5 subjects only) 
6.6.1 Indication Classification 
At baseline, document the subject’s classification of primary or secondary 
prevention at the time of enrollment into the Improve SCA study using the following 
definitions: 
Primary prevention subjects: subjects who are at risk for lethal arrhythmias but 
who have not yet experienced a spontaneous documented sustained symptomatic 
ventricular arrhythmic event; primary prevention subjects with non-spontaneous 
sustained ventricular arrhythmias only induced during an electrophysiology study 
will still be classified as primary prevention. 
Secondary prevention subjects: subjects who have survived an arrhythmic sudden 
cardiac death event due to VF, or sustained VT, or who have syncope of 
undetermined origin with clinically relevant hemodynamically significant sustained 
VT or VF induced at an EP study.  
With the exception of secondary prevention subjects, in the event a subject 
refuses an implant at baseline, but later changes their mind, a device change CRF 
should be completed and that subject will be included in the primary objective as 
an implanted subject. Secondary prevention subjects should remain exited from 
the study. 
6.7 The 1.5 Prevention Criteria Testing  
At the baseline visit, all subjects who have been identified as primary prevention 
indication subjects will be assessed to see if they further meet 1.5 Prevention 
Criteria; secondary prevention subjects do not need to undergo 1.5 Criteria testing. 
If one or more criteria are met, this subject will be classified as a 1.5 Subject. All 
criteria should be assessed, even if it is known that the subject already meets one 
of the four criteria. Patients should complete 1.5 testing prior to being asked if they 
want to have a device implanted. 
 The four criteria which will be assessed include: 
• 
Pre-syncope/syncope 
• 
Low left ventricular ejection fraction (low LVEF) 
• 
Frequent premature ventricular contractions (PVCs) 
• 
 Non-sustained ventricular tachycardia (NSVT) 
These criteria are described in Table 4 as well as below.  
6.7.1 Pre-syncope/Syncope 
History of recent pre-syncope/syncope will be collected from medical records, 
where recent is considered 12 months prior to subject enrollment (signing informed 
consent). In instances where no patient medical records are available, it is 
                                                 
36 © 1990 EuroQol Group EQ-5DTM is a trade mark of the EuroQol Group. 

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permissible for the investigator to rely on patient memory. This should be 
documented in the medical records.  
In this study, a history of syncope classifies a subject as a 1.5 subject when the 
syncope is due to suspected VT. Unexplained syncope or pre-syncope will also 
classify a subject as a 1.5 subject, after ruling out vasovagal syncope, syncope 
related to bradycardia, and syncope related to supraventricular tachycardia (SVT). 
6.7.2 Low left ventricular ejection fraction (low LVEF) 
In this study, a low LVEF is defined as a left ventricular ejection fraction (LVEF) of 
<25%. The measurement must be recent, that is, measured within 6 months prior 
to subject enrollment (signing informed consent) or implant. However, if no recent 
measurement is available, the measurement should be taken at baseline during 
the 1.5 Criteria assessment. There are no pre-specified requirements for how the 
LVEF must be measured. Examples include: radionuclide cardiography/MUGA, 
echocardiography, or MRI. 
If the subject has a history of myocardial infarction (MI), LVEF must be collected at 
least: 
• 
40 days post-MI if there was no revascularization 
• 
90 days post-MI if there was revascularization, e.g., percutaneous coronary 
intervention (PCI), coronary artery bypass graft (CAGB) 
6.7.3 Frequent premature ventricular contractions (PVCs)  
In this study, frequent PVCs are defined as a subject having a PVC burden of 10 
or more per hour (average) while monitored. The measurement must be recent, 
that is, measured within 12 months prior to subject enrollment (signing informed 
consent) or implant. If no recent measurement is available, or previous monitoring 
showed no PVCs, the investigator should test for PVC burden at baseline visit, 
using at least a 24 hour ambulatory test method (e.g., 24-hour Holter Monitor). 
Testing for longer than 24 hours is encouraged where available, but should be for 
at least 20 hours. 
If the subject has a history of myocardial infarction (MI), PVC burden must be 
collected at least: 
• 
40 days post-MI if there was no revascularization 
• 
90 days post-MI if there was revascularization, e.g., percutaneous coronary 
intervention (PCI), coronary artery bypass graft (CAGB) 
6.7.4 Non-sustained ventricular tachycardia (NSVT) 
In this study, NSVT is defined as 3 or more consecutive beats at >100 beats per 
minute lasting less than 30 seconds. If no recent measurement is available, or 
previous monitoring showed no NSVTs, the investigator should test for NSVT at 
the baseline visit using at least a 24 hour ambulatory test method (e.g., 24-hour 
Holter Monitor). Testing for longer than 24 hours is encouraged where available 
(e.g., Corventis Patch).  
If the subject has an implantable pulse generator (IPG) at enrollment, NSVT may 
be identified via IPG reading but must be confirmed either via 24-hour ambulatory 
test method, or via documentation on EGM strip in order to rule out SVT or 

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ventricular artifact. If NSVT cannot be confirmed, it should conservatively be 
assumed that subject does not meet the 1.5 Prevention Criteria for NSVT. 
6.8 Quality of Life (QoL) EQ-5D Assessment 
The EQ-5D questionnaire will be completed at the baseline visit and at the 6 
month follow-up visit for all 1.5 prevention subjects; it is not required for secondary 
prevention subjects or for subjects that do not meet any of the 1.5 criteria. For this 
reason, at baseline the EQ-5D questionnaire should be completed after the 1.5 
criteria are evaluated. If the EQ-5D questionnaire is skipped, a Study Deviation is 
required. 
This quality of life assessment has five dimensions: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. Questionnaires will be provided 
in a language understood by the patient along with instructions for proper 
administration.  
6.9 Implant 
All subjects enrolled are required to meet primary or secondary guidelines for 
implant. It is not ethical to randomize subjects to not receive an implant when they 
are indicated to receive one. Thus, subjects will not be randomized; instead, they 
will be asked if they choose to receive an ICD/CRT-D. If the subject agrees to 
implant they must receive a Medtronic device, as the primary endpoint evaluates 
appropriate therapy rates which must be retrieved and reviewed from the 
ICD/CRT-D. If a non-Medtronic device is implanted, the subject should be exited 
from the study.  
A successful implant is defined as the subject having received an ICD/CRT-D and 
at least an RV lead. If a non-Medtronic device is implanted, the subject can still 
have a ‘successful’ implant; however, the subject should be exited from the study. 
Non-Medtronic leads are allowed as long as they are not under regulatory recall.  
6.9.1 Implant Refusal 
Subjects that choose not to receive a device implant will be asked the reason for 
refusal, which will be documented on the ‘Implant/Implant Refusal’ Case Report 
Form. Following refusal, primary indication subjects will be followed every 6 
months until study closure or exit. These subjects will contribute to the study’s 
secondary endpoint of mortality (see Section 12.3). Secondary indication subjects 
will exit the study upon refusal of implant. 
With the exception of secondary prevention subjects, if a subject initially refuses 
implant, but later decides to receive an implant, a ‘Device Change’ CRF shall be 
completed (see Section 6.11). 
6.9.2 Implant Acceptance 
The following information is required to be collected for subjects that receive an 
ICD/CRT-D implant: 
• 
Date of implant 
• 
System implant information 
• 
Device interrogation 

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6.9.3 Device programming at implant 
Prior to the subject leaving the hospital, verify that the subject is programmed 
according to Table 8. Some settings are not available in all devices. If a certain 
parameter is not available to be programmed on a device, it is not a study 
deviation. 
Pre-programmed settings will be provided to sites by Medtronic via USB (Get-Save 
tool), which facilitates uploading correct programming requirements. The tool does 
not work in some older device models (e.g., Maximo, Marquis, and earlier 
Medtronic ICD models); however, the utilization of this tool is strongly 
recommended when possible. The pre-programmed USB upload does not contain 
investigational programming or software; the purpose is to increase compliance of 
study-required programming at implant.  
Consistent programming is desirable in order to compare groups during statistical 
analysis. Programming changes during the study that are required in order to treat 
a subject’s medical condition are permitted. Compliance to the device 
programming will be verified by Medtronic via device interrogations throughout the 
study, and a Study Deviation Case Report Form should be reported in instances 
where the programming requirements are not followed. 
 
 

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Table 8: Programming requirements at implant 
Parameter 
Required Programming 
VFDI 
300 ms 
VFNID  
30/40 
VT Enable 
ON 
VTDI 
360 ms 
VTNID 
24 
SVT limit 
260 ms 
High Rate Timeout 
  
    All Zones 
OFF 
    VF Zone Only 
DR/CRT-D: OFF; VR: ON - .75min Timeout 
AF/AFl Rejection 
ON 
Sinus Tach 
ON 
Wavelet* 
ON, 70% 
EGM 2 
Can-RV Coil or RV Coil - SVC Coil 
Wavelet Template 
Perform manual template collection at all 
visits 
T wave discrimination 
ON 
RV Lead Noise 
ON+.75min timeout 
RV Lead Integrity 
ON 
Stability 
OFF 
Onset 
OFF 
Monitor Zone 
ON (Monitor) 
   VT Monitor Interval 
450 ms 
   VT Monitor NID 
32 
Confirmation+ 
ON 
VF Therapy #1 
ATP During Charging and Max Output 
Shock 
   ATP Delivery R-R 
240 ms 
   Therapy Type 
Burst 
   Smart Mode 
ON 
   Chargesaver  
ON, Successful ATP:1 
VT Rx 1 
ATP Burst 8@88% (3 seq) 
Monitored EGMs 
EGM 1 and EGM 2 
EGM 1 
Atip-Aring or RV Sense Vector 
Pre-Arrhythmia EGM 
ON continuous for first 12 months of follow-
up 
*Wavelet is only available VR devices and Protect/Evera DR/CRT and Viva CRT devices.  
PR Logic is not available in VR devices. 
6.10 Subject Follow-up-up Visits 
Subjects should have a scheduled follow-up visit every 6 months post-implant 
(Arms A, C, and E) or implant refusal (Arms D, and F) until study closure, subject 
exit or death, with the exception of secondary prevention subjects who do not 
receive an implant (Group B); these subjects will be exited following implant 
refusal (Figure 1).  

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After completion of the Implant/Implant Refusal eCRF, Medtronic will provide the 
target dates and windows for each visit to the implanting site. Perform scheduled 
follow-up visits every 6 months according to Table 9. Follow-up visit windows are 
based on days post-implant. If a subject is seen beyond their 60-month visit, 
windows will continue on the same pattern with a width of 120 days. Should a 
subject visit fall outside the pre-specified window, a study deviation must be 
reported and the original follow-up schedule maintained for subsequent visits.  
Data analyses will include follow-up visits, regardless of whether the visits occur 
within the time window. Therefore, a late visit is preferred over a missed visit but 
must be accompanied by a deviation.  
Table 9: Follow-up windows 
Study Follow-up 
Visit 
Window 
(Calculated days post-implant) 
Window Start 
(days post-implant) 
Target 
(days post-implant) 
Window End 
(days post-implant) 
6 month 
123 
183 
243 
12 month 
305 
365 
425 
18 month 
488 
548 
608 
24 month 
671 
731 
791 
30 month 
853 
913 
973 
36 month 
1036 
1096 
1156 
42 month 
1218 
1278 
1338 
48 month 
1401 
1461 
1521 
54 month 
1584 
1644 
1704 
60 month 
1766 
1826 
1886 
 
Complete a Subject Contact CRF for each follow-up visit. If more than one visit 
(contact) occurs during a window, complete an additional unscheduled Subject 
Contact visit CRF. 
During follow-up visits, information will be collected on the subject’s vital status 
and use of Amiodarone, and subjects with an implanted device will have the 
device interrogated, either in office or via CareLink. Subjects who have access to 
CareLink will be asked to transmit data every 3 months when possible, and will not 
be required to do an in-person visit. 
At 6-months post-implant, EQ-5D will be assessed again for all 1.5 subjects, 
regardless of implant status. Instructions for administering this test over the phone 
will be provided. 
At approximately 22 months past the final enrollment, centers will be notified that 
study closure is about to occur and that they should attempt to make one final 
study contact with each subject to maximize overall study follow-up. 
6.10.1 Subjects with no device 
Subject contact visits are not required to be performed in person (e.g., phone call is 
acceptable). 
At the 12 month and 24 month visits, primary prevention subjects (1.0 or 1.5) who 
were not implanted with a device will be offered additional ambulatory monitoring 

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(e.g., Holter). The rationale for this additional test is that NSVT and PVC burden 
may not show up on every test given their frequency of occurrence and relatively 
short monitoring time. If NSVT or frequent PVCs are noted at a later ambulatory 
test, the subject may want to reconsider having an implant. Although this 
ambulatory monitoring should be offered to subjects, if a subject refuses, a Study 
Deviation is not required. 
If a subject (either after a Holter or for any other reason) does decide to undergo 
an implant, they will be included in the primary objective analysis beginning from 
the time of implant (see section 12.2 for details). In these cases, a Device Change 
eCRF must be completed. 
Because these subjects implanted later in the study can be used in the primary 
analysis, available 1.5 criteria should be collected at the time of implant. If LVEF 
has been retested since the 1.5 Criteria Assessment or Syncope has been noted, 
this can be recorded, but no additional tests for these will be offered. These 
variables will be recorded on the 1.5 Criteria section of the Device Change eCRF.  
6.10.2 Subjects with device  
Subject contact visits are not required to be performed in person if the device data 
can be transmitted remotely, for example, through CareLink. The use of CareLink 
in this study is strongly encouraged. If device data cannot be transmitted remotely, 
the subject should come into the office for the device interrogation. 
Device interrogation (save-to-disk)  
For all visits occurring at the study site, an initial full “Interrogate ALL” device 
interrogation file (.pdd) must be obtained and saved in a digital format (e.g., USB 
memory stick). It is recommended that data are not cleared during any 
interrogation or save-to-disk. Retain one copy (USB memory stick) for the subject 
file and submit the other copy to Medtronic via Clinical Transfer. 
Device data will be reviewed in a timely manner by an Episode Review Committee. 
This committee will consist of independent physicians and potentially Medtronic 
engineers to evaluate appropriateness of therapy (ICD/CRT-D shock or anti-
tachycardia pacing (ATP). Episodes will be reviewed, and therapy appropriateness 
will be identified based on adjudicated rhythm and the device episode log 
information. This information will be used for the primary objective analysis. 
6.10.3 Device programming 
Verify that the device is programmed according to Table 8. 
6.10.4 Deviations (all subjects) 
A study deviation is defined as an event within a study that did not occur according 
to the CIP or the Clinical Trial Agreement. Study deviations must be reported to 
Medtronic according to Section 6.10.4. 
6.11 Device Change 
A Device Change eCRF will be completed if one of the following occurs: 
• 
Device is explanted, and replaced (e.g., device reaches end of life, device 
upgrade)  
• 
Device is explanted, and not replaced 

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• 
New ICD/CRT-D device implant (i.e., subject initially refuses an implant 
[baseline], but later decides to have a device implanted) 
o In this case, complete the 1.5 Criteria section of the Device Change 
eCRF. 
• 
Device is permanently disabled and not replaced. 
If a new device is implanted during a device change, a device interrogation should 
be performed prior to explant (in the instance of a device replacement) and again 
after new device implant. System information (e.g., device manufacturer) will be 
collected for the new device. Subject follow-up visit windows will not change 
following a Device Change, even if the device is explanted and not replaced. 
6.12 Study Exit 
A Study Exit eCRF is required when living subjects exit the study. Following exit, 
subjects will continue to receive standard medical care by their treating physician. 
All data available through the time of the subject’s exit will be used for analysis.  
Subjects must be urged to remain in the study as long as possible but may be 
exited from the study for any of the following situations: 
• 
Subject does not meet inclusion/exclusion criteria 
• 
Subject is implanted with a non-Medtronic device 
• 
Subject lost to follow-up 
• 
Subject chooses to withdraw  
• 
Investigator deems withdrawal necessary (e.g., medically justified, failure of 
subject to maintain adequate study compliance)  
The following information is required to be collected at study exit: 
• 
Date of exit 
• 
Date of last contact (this will be different from date of exit if the subject is 
lost to follow-up) 
• 
Reason for exit 
• 
Final device interrogation (interrogate all) (if available) 
At the end of the study, subjects will not be required to complete an Exit CRF. 
Instead, a study contact visit form should be completed when subject is notified 
of closure. 
At exit, it is recommended that pre-arrhythmia EGM is programmed to ‘off’ to 
save battery life.  
6.12.1 Lost to follow-up 
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, the site must follow the regulations set forth by the governing Ethics 
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6.13 Subject Death 
In the event of subject death, a Death eCRF should be completed. An Exit eCRF 
will not be completed if a Death eCRF is completed. The following information will 
be required to be collected: 
• 
Date of death 
• 
Primary cause of death, if known 
• 
Description of subject’s death, if available 
• 
Death classification, as determined by the Primary Investigator (See 
Section 9.1.2) 
• 
Final device interrogation (e.g., Save-to-disk), if possible 
For ICD/CRT-D systems, the VT and VF detection capabilities should be disabled 
at death to avoid inadvertent shocks. If any system component is returned to 
Medtronic, internal return product reporting systems may be used to gather 
additional information about the returned device/component. 
6.14 Medications 
Cardiovascular medication categories specific for systolic heart failure will be 
collected at the baseline visit for characterization of the population, including:  
• 
Anti-arrhythmics 
• 
Anticoagulants 
• 
ACE Inhibitors 
• 
Angiotensin II Receptor Blockers/Inhibitors 
• 
Diuretics 
• 
Vasodilators 
 
It is expected that patients will be on chronic, guideline-directed medical therapy at 
baseline (e.g., Beta Blockers, ACE inhibitors minimally); this is consistent with both 
the ACC/AHA/HRS and ESC Guidelines. Following device implant, Amiodarone 
should be discontinued for subjects taking it prophylactically (e.g., for preventative 
reasons). Amiodarone use for symptom control is permitted. Subjects will be asked 
at follow-up visits if they are taking Amiodarone. No other medication changes will 
be tracked throughout the study.  
 
 

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7 INVESTIGATIONAL DEVICE/SOFTWARE STORAGE, 
HANDLING AND TRACEABILITY 
All products used in this study are market released in the geographies they are used, 
and therefore will not be tracked in the study. Device and lead information of implanted 
product will be collected at implant (e.g., model number).  
If there are additional local requirements related to implanted information beyond what is 
collected by Medtronic on the electronic Case Report Form, this is the Investigator’s 
responsibility and should be recorded in the subject’s medical records, but will not be 
collected by Medtronic (e.g., national registration card number, identification code linked 
to names and contact information, log of all subjects enrolled in the clinical study, lot or 
batch number). 
 
 

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8 STUDY DEVIATIONS 
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. Examples of study 
deviations include, but are not limited to, the following: 
• 
Subject enrolled during lapse of Ethics Committee approval 
• 
Patient informed consent not obtained prior to participation in the study 
• 
Incorrect version of the PIC provided to the subject 
• 
Visit outside of the protocol defined window 
• 
Visit not completed 
• 
Protocol-required testing or programming not done 
• 
Source data permanently missing 
• 
Unauthorized physician or study personnel performing study procedures 
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 visits, 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 end point analysis). However, prior approval from Medtronic 
is required for such situations.  
All study deviations must be reported on the Case Report Form 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. 
In the event the deviation involves 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, the deviation must be 
reported to the Ethics Committee as well as Medtronic within five (5) working days. 
Reporting of all other study deviations should comply with Ethics Committee policies 
and/or local laws and must be reported to Medtronic as soon as possible upon the site 
becoming aware of the deviation. Reporting of deviations must comply with Ethics 
Committee policies, local laws, and/or regulatory agency requirements.  Refer to Section 
16.2 for reporting requirements and timeframes for reporting to Medtronic and/or 
regulatory bodies.  
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, or 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 

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enrollment until the problem is resolved or ultimately terminating the investigator's 
participation in the study.  
 
 

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9 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
The products used in the clinical trial are market approved/released and used within the 
current indications for use as indicated in the product labeling. The collection of adverse 
event data is not required to meet the objectives of this clinical trial; it is the responsibility 
of the Investigator to abide by any adverse event reporting requirements stipulated by 
the site’s Institutional Review Board (IRB) or Medical Ethics Committee (MEC). User 
(Investigator) reporting of events to regulatory authorities related to market 
approved/released products may be required. Refer to local regulations for reporting 
requirements.  
Device deficiencies are not required to be collected because it is a post-market study. 
However, if there should be any alleged device-related death, serious injury, device 
malfunction, or complaint reported, the event should be reported as described in Section 
9.2.   
9.1 Subject Death 
9.1.1 Death data collection 
All subject deaths must be reported by the investigator to Medtronic on a 
Subject Death form as soon as possible after the investigator first learns of the 
death.   
9.1.2 Death classification and reporting 
Sufficient information will be collected by the Investigator in order to properly 
classify the subject’s death, though not all of these data will be collected by the 
Sponsor. 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. 
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: A death in which there is no clinical evidence 
to support: 
• 
A direct relatedness to the system component or 
• 
A probable cause relatedness to the system component or 
• 
No relatedness to the system component 
 

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The Investigator’s assessment of primary cause of death and cardiac classification 
will be used in the study and will not be adjudicated by an Adverse Event 
Adjudication Committee, as no investigational devices are being used and cause 
of death is not related to any of the study objectives. 
Regulatory reporting of Subject Deaths will be completed according to local 
regulatory requirements.  
9.2 Vigilance Reporting 
All devices used in this study are market-released. Therefore, Post Market 
Surveillance and product complaint reporting is applicable to all market-released 
devices used in the study, including leads.  
The reporting of product complaints is not part of the clinical study. The following 
reporting requirements are included as reminders. In addition, since non-Medtronic 
leads are permitted in the study, investigators are responsible for reporting product 
complaints of non-Medtronic product to the appropriate manufacturer. It is the 
responsibility of the investigator to abide by the reporting requirements in place for 
that particular geography. Refer to local regulations for reporting requirements. 
The reporting process will be outlined in the safety plan. 
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. 
It is the responsibility of the investigator to report all product complaint(s) 
associated with a medical device distributed by Medtronic, regardless 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. It 
is the responsibility of the investigator to abide by the reporting requirements in 
place for that particular geography.  
Medtronic will notify the regulatory authorities (e.g. Competent Authority) according 
to the applicable local regulations applicable for the following incidents immediately 
upon learning of them: 
• 
Any malfunction or deterioration in the characteristics and/or performance 
of a device, as well as any inadequacy in the labeling or instructions for 
use which led or might have led to the death or serious deterioration in 
the state of health of a patient, user, or other person. 
• 
Any technical or medical reason resulting in withdrawal of a device from 
the market by the manufacturer. 
• 
A serious deterioration in the state of health includes: 
o Life-threatening illness or injury 
o Permanent impairment of a body function or permanent damage 
to a body structure 
o A condition necessitating medical or surgical intervention to 
prevent permanent impairment of a body function or permanent 
damage to a body structure. 

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These device deficiencies are not intended to be collected in the clinical study, as 
reporting should be done through regular channels for post-market products. 
However, if Medtronic is informed of any of these items within the study, it will be 
reported.  
 
 

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10 RISK ANALYSIS  
Medtronic follows rigorous Quality Assurance and Control procedures throughout the life 
of a product, from the business analysis phase through development, market release, 
and post-market surveillance.  
All devices used in the Improve SCA study are commercially released and used in 
accordance with their approved labeling. There are potential risks and side effects 
associated with a device implant. The risk associated with the study is consistent with 
market-released ICD/CRT-D systems. There are no experimental procedures involved in 
this study. As such, a Data Monitoring Committee (DMC) will not be utilized. 
10.1 Potential Benefits 
Participation in the Improve SCA study may offer no benefit. Subjects enrolled in 
the study may have additional contact with their physicians or other medical care 
staff beyond their normal standard of care visits, which may provide benefit from a 
patient care perspective. The information gained from this study could result in the 
improved management of primary prevention indicated patients through improved 
referral linkages, reimbursement coverage updates, and user adoption. 
Additionally, information collected from this study may assist in the design of new 
product(s)/therapy(ies), and/or instructions for use.  
10.2 Potential Risks 
The study programming requires Pre-arrhythmia EGM to be programmed on for at 
least the first 12 months following implant, which allows the device to store more 
data. While this is not considered investigational programming, this programming 
reduces device longevity. The benefit of using this programming is that it is useful 
in arrhythmia episode adjudication, which is required for the analysis of the primary 
study objective.  
 
 

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11 PLANNED STUDY CLOSURE, EARLY TERMINATION 
OF STUDY OR STUDY SUSPENSION 
11.1 Planned Study Closure 
Study Closure is a process initiated by distribution of a study closure letter. Study 
closure is defined as closure of a clinical study that occurs when requirements 
have been satisfied per the CIP and/or by a decision by Medtronic or regulatory 
authority), whichever occurs first. The study closure process is complete upon 
distribution of the Final Report or after final payments, whichever occurs last. 
Ongoing Ethics Committee oversight is required until the overall study closure 
process is complete. Following closure, subjects should be seen by their 
physicians per their normal standard of care. Refer to Section 6.12 on Page 39 for 
additional information regarding study exit procedures. 
11.2 Early Termination or Suspension 
Early Termination of the Study 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. 
Study Suspension is a temporary postponement of study activities related to 
enrollment. This is possible for the whole study or a single site. 
11.2.1 Study-wide termination or suspension 
Possible reasons for considering study suspension or termination of the study 
include but are not limited to: 
• 
Decision by Medtronic or regulatory body (where the study is operating 
under regulatory body authority)  
• 
Enrollment is slower than anticipated 
11.2.2 Investigator/site termination or suspension 
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 
• 
Persistent non-compliance to the clinical investigation (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)  

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11.3 Procedures for Termination or Suspension 
11.3.1 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 
• 
In the case of study termination or suspension for reasons other than a 
temporary Ethics Committee approval lapse, the investigator will promptly 
inform the Ethics Committee and the institution (where required per 
regulatory requirements) 
• 
In the case of study termination, the investigator must inform the subjects, 
or legally-authorized designees or guardians 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 
11.3.2 Investigator-initiated 
• 
The investigator will 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 Ethics Committee and regulatory 
authority (where required per regulatory requirements) 
• 
The investigator will promptly inform the subjects, or legally-authorized 
designees or guardians 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 
11.3.3 Ethics committee-initiated 
• 
The investigator will inform Medtronic and provide a detailed written 
explanation of the termination or suspension within 5 business days 
• 
Subject enrollment must stop until the suspension is lifted 
• 
Subjects already enrolled should continue to be followed in accordance 
with Ethics Committee 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, or legally-authorized 
designees or guardians and/or the personal physician of the subjects, with 
the rationale for the study termination or suspension 
• 
The investigator will inform local regulatory authority, where required per 
regulatory requirements 
 

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12 STATISTICAL METHODS AND DATA ANALYSIS 
12.1 General considerations 
Data analysis will be performed by Medtronic statisticians. 
The data will not be analyzed until study completion, which will be approximately 
two years after the final study enrollment. 
Where applicable, missing data is addressed within each objective. 
Generally, subjects will be included in their baseline groups in analyses. For 
example, a subject who is in a primary prevention arm will remain in that arm even 
if he later falls into the secondary prevention group due to a VT/VF episode. The 
exception will be subjects who get implanted later in the study. These subjects will 
be included in the primary endpoint in the group to which they belonged 
(secondary, 1.5, or 1.0) at the time of implant.   
There are 6 study cohorts (see Figure 1 on page 11 for more detail): 
• 
Group A: Secondary prevention subjects implanted with an ICD or CRT-D 
• 
Group B: Secondary prevention subjects not implanted with an ICD or 
CRT-D 
• 
Group C: Primary prevention subjects who meet 1.5 criteria and are 
implanted with an ICD or CRT-D 
• 
Group D: Primary prevention subjects who meet 1.5 criteria and are not 
implanted with an ICD or CRT-D 
• 
Group E: Primary prevention subjects who do not meet 1.5 criteria (1.0 
subjects) and are implanted with an ICD or CRT-D  
• 
Group F: Primary prevention subjects who do not meet 1.5 criteria (1.0 
subjects) and are not implanted with an ICD or CRT-D  
The Statistical Analysis Plan (SAP) is a separate document that will include a 
comprehensive description of the statistical methods to be included in the final 
study report and main manuscript. Any change to the data analysis methods 
described in the CIP will require an amendment only if it changes a principal 
feature of the protocol. Any other change to the data analysis methods described 
in the protocol, and the justification for making the change, will be described in the 
clinical study report.  
 
 

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12.2 Primary Objective #1: Appropriate Therapy 
Demonstrate that appropriate VT/VF therapy rates (shock and ATP) for subjects meeting 
1.5 prevention criteria implanted with a Medtronic device (ICD/CRT-D) are equivalent 
(within 30%) to rates in subjects meeting secondary prevention criteria. 
12.2.1 Hypothesis 
The goal of this hypothesis test is to demonstrate that the overall rate of appropriate 
VT/VF therapy (shock and ATP) over the observed post-implant time in the study is non-
inferior in implanted 1.5 prevention patients compared to implanted secondary 
prevention patients with a non-inferiority margin of 30%. 
 
H0: Hazard ratio of Implanted 1.5 patients to implanted secondary patients ≤ 0.70  
HA: Hazard ratio of Implanted 1.5 patients to implanted secondary patients > 0.70  
12.2.2 Performance Requirements 
The null hypothesis will be rejected if the one-sided 95% lower confidence bound of the 
hazard ratio of implanted 1.5 subjects to implanted secondary prevention subjects is 
greater than 0.70.  
12.2.3 Rationale for Performance Criteria 
Data from the OMNI clinical study was analyzed retrospectively. Figure 2 shows the 
results, where the hazard ratio between secondary and all primary subjects was 0.76, 
and the hazard ratio between secondary subjects and the 1.5 subgroup of primary 
prevention was 0.91. This demonstrates that the 1.5 subgroup may be much more 
similar to the secondary prevention group than the overall primary prevention group.   
Figure 2: Time to First Appropriate VT/VF Therapy in the OMNI Clinical Study 
 
 
 
The non-inferiority margin of 30% (corresponding to a hazard ratio of 0.70) was chosen 
because it is higher than the observed hazard ratio of 1.0 to 1.5 in the OMNI study, 
which was 0.68. This would demonstrate both that the rate of appropriate VT/VF 
therapies is similar between 1.5 prevention and secondary prevention patients and that 
% with Appropriately Treated VT/VF
   0%
  10%
  20%
  30%
  40%
  50%
Months Since Implant
0
12
24
36
48
60
  22.5%
  31.1%
  34.9%
  38.8%
  16.3%
  23.5%
  27.4%
  31.6%   33.6%
Secondary
Primary
6
348
232
181
140
122
31
1894
1392
1075
801
Number Reamining
Secondary
Primary
594
P-value=<.01
HR=0.76 (0.62-0.93)
% with Appropriately Treated VT/VF
   0%
  10%
  20%
  30%
  40%
  50%
Months Since Implant
0
12
24
36
48
60
  22.5%
  31.1%
  34.9%
  38.8%
  19.4%
  27.6%
  31.3%
  35.5%
Secondary
Group 1.5
6
348
232
181
140
122
7
990
698
515
379
Number Reamining
Secondary
Group 1.5
268
P-value=0.38
HR=0.91 (0.73-1.13)

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the 1.5 prevention patients’ curve is likely closer to the secondary prevention curve than 
to the overall primary prevention curve. 
In this objective, the direct comparison is only between secondary and 1.5 subjects 
because it is believed that there will not be enough implanted 1.0 subjects as it is 
expected that relatively few of these subjects will elect to receive a device.  
12.2.4 Analysis Methods 
The hypothesis will be tested using a Cox proportional hazards model with survival time 
and first appropriate VT/VF episode as the dependent variable and group (secondary or 
1.5) as the independent variable. A 95% one-sided lower confidence bound for the 
hazard ratio and a p-value will also be calculated.  The data will be presented in a format 
similar to the right panel of Figure 2. 
Adequate power is needed to perform the hypothesis test. Without adequate power, a 
non-significant test has little meaning. Therefore, the hypothesis test will not be 
performed and a p-value will not be calculated if there are fewer than 400 subjects in the 
implanted 1.5 prevention group. In that case, event rates and confidence intervals will be 
presented. 
Time 0 will be the implant date and subjects will be censored on the date of their latest 
device interrogation. Only spontaneous, appropriately treated VT/VF episodes as 
adjudicated by the episode review committee will count toward the endpoint. 
VT/VF episodes that cannot be adjudicated (due to not saving full episode data or any 
other reason) will be ignored. Often, these episodes are followed by episodes that can 
be adjudicated, and since the endpoint is time to first episode, effects on the results from 
these events will be minimal. In addition, these should be balanced between the 
comparison groups.   
12.2.5 Determination of Patients/Data for Analysis  
All 1.5 prevention and secondary prevention subjects with an ICD/CRT-D implant will be 
included in the primary analysis hypothesis test. This includes subjects implanted with a 
device after the initial enrollment period. These later implants will be included if they are 
secondary or 1.5 at the time of implant.  
12.2.6 Sample Size  
A simulation program was written to determine the sample size for the study.  
Assumptions are based on the OMNI data and estimates from steering committee 
physicians: 
• 
60% of enrollments will be secondary prevention and 40% primary prevention 
• 
50% of primary subjects will be in the 1.5 group 
• 
57% of secondary subjects will get an ICD (includes CRT-D) 
• 
45% of 1.5 subjects will get an ICD 
• 
22% of 1.0 subjects will get an ICD 
• 
Annual attrition (includes exits and deaths) will be 10% 
• 
The study will end two years after the last enrollment 

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• 
4000 patients will take 2 years to enroll with enrollment beginning slowly, then 
accelerating to a steady 246 per month. 
• 
Expected rates of appropriately treated VT/VF in secondary subjects follow 
Figure 2, with a higher rate in the first year (22.5%), then a constant rate (11.1%) 
thereafter. 
• 
The hazard ratio of 1.5 to secondary is 0.91  
Under the above assumptions and using the hypothesis test stated above, 4800 subjects 
will have 80% power to reject the null hypothesis. With 4800 enrolled patients, it is 
expected that approximately 1650 secondary prevention subjects will be implanted, 430 
1.5 prevention subjects will be implanted, and 200 1.0 subjects will be implanted. 
12.2.7 Sample Size Re-estimation  
Because most of the assumptions above are based only on investigator opinion, the 
sample size will be re-estimated during the study using the same simulation methods, 
but changing the following assumptions using the study data: 
• 
% of enrollments will be secondary prevention  
• 
% of primary patients in the 1.5 group 
• 
% of secondary patients who will get an ICD (includes CRT-D) 
• 
% of 1.5 patients who will get an ICD 
• 
% of 1.0 patients who will get an ICD 
• 
Annual attrition (includes exits and deaths) 
• 
Enrollment rate 
With this re-estimation of sample size, the length of follow-up after the last enrollment 
may be changed as well. 
Because no comparisons will be done at the point of re-estimation, alpha is not affected 
and the final analysis can compare the p-value to a 0.05 alpha level. 
The sample size re-estimation will occur at the later of: 
• 
One year after the 400th subject has been enrolled 
• 
The time of the 2000th enrollment.  
It is the study sponsor’s discretion to increase (to a maximum of 8000 subjects) or 
decrease the sample size, or decrease or increase the length of follow-up after last 
enrollment.  
If fewer subjects are required, the study sponsor may either lower the sample size, or 
increase the power of the study (possibly keeping the original sample size).  If more 
subjects are required, the study sponsor may elect to not increase the sample size, but 
may increase the length of follow-up to ensure adequate power for the study.   
Study sites will be notified of any change in sample size and length of follow-up (if 
applicable) at that time. The investigational plan will not be changed.  

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12.3 Secondary Objective: Mortality 
Compare the mortality rates for patients meeting 1.5 prevention criteria between those 
implanted with a device (ICD/CRT-D) and those not implanted. 
12.3.1 Hypothesis 
Although this is an exploratory objective and is not powered, a hypothesis test will be 
done and compared to an alpha level of 0.05. To preserve overall type I error, this test is 
only valid if the primary endpoint is statistically significant. 
Compare the mortality rates for patients meeting 1.5 prevention criteria between those 
implanted with a device (ICD/CRT-D) and those not implanted. 
H0: Hazard ratio of non-implanted to implanted 1.5 patients = 1 
HA: Hazard ratio of non-implanted to implanted 1.5 patients ≠ 1 
12.3.2 Analysis Methods 
This analysis will be a comparison of mortality in 1.5 implanted and non-implanted 
subjects. Time 0 will be the date of enrollment, and all living subjects will be censored on 
the last date they were confirmed to be alive. 
The analysis, to control for potential imbalance between groups due to not randomizing 
the subjects to implant or no implant, will include covariates in a Cox proportional 
hazards model along with implant/no implant as the independent variable. The 
covariates will include age, sex, country of enrollment, ischemic, LVEF, QRS duration, 
NYHA, history of syncope, history of NSVT, and history of PVCs. Further baseline 
covariates or time-dependent covariates may be added in the statistical analysis plan 
prior to any analysis. ICD/CRT-D will not be a covariate since it will not be known 
whether non-implanted subjects would have received a CRT-D or not. However, the 
covariates include all the variables that are commonly used to determine CRT-D use.  
12.3.3 Power 
This objective is not powered and the likelihood of a statistically significant test is not 
known. So, it should not be a surprise if the endpoint is not statistically significant. 
The following table shows what the power of the endpoint would be under various 
scenarios if doing a log-rank test. It is not known what effect adding covariates in a Cox 
proportional hazards model will have on the power.   
In a retrospective analysis of SCD-HeFT, 1.5 prevention subjects without an ICD had a 
25.7% mortality rate at 3 years compared to 18.5% for 1.5 subjects with an ICD. Under 
the sample size assumptions, it is expected that approximately 430 1.5 subjects will be 
implanted and 540 will not. 
 
 

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Table 10: Power for 1.5 Prevention Mortality Endpoint 
1.5 
implanted 
sample 
size 
1.5 not 
implanted 
sample 
size 
Assumed 3-year Mortality 
26% no ICD 
18% ICD 
26% no ICD 
20% ICD 
26% no ICD 
22% ICD 
22% no ICD 
14% ICD 
30% no ICD 
22% ICD 
450 
550 
88% 
63% 
32% 
93% 
82% 
350 
650 
85% 
60% 
30% 
91% 
79% 
360 
440 
80% 
53% 
27% 
87% 
73% 
350 
350 
74% 
48% 
24% 
83% 
67% 
12.3.4 Determination of Patients/Data for Analysis  
All subjects in the 1.5 prevention cohort at the time of enrollment will be included.  
 
 

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13 DATA AND QUALITY MANAGEMENT 
Data will be collected and signed and dated by the principal investigator or his/her 
authorized designee(s) using an electronic data management system for clinical studies.  
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 indefinitely by Medtronic. 
Procedures in the CIP require source documentation. Source documentation will be 
maintained at the site. Source documents, which may include worksheets, patient 
medical records, programmer printouts, and interrogation files, must be created and 
maintained by the investigational site team.   
The data reported on the eCRFs shall be derived from source documents and be 
consistent with these source documents, and any discrepancies shall be explained in 
writing. In some cases, items on the CRFs may be considered source as long as there is 
evidence of the visit in the subject’s record. Even when the eCRF may be considered as 
source, an alternate method of source documentation is always strongly encouraged.  
The eCRF may be considered source for deviations.  
Device data from CareLink transmissions will be uploaded to secure servers. Device 
interrogation files collected via electronic media at office visits will be sent to Medtronic. 
Upon receipt via transmissions or electronic media, device data will be maintained with 
databases and retrieved for analysis and reporting. 
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 Board review, and regulatory inspection(s) by providing direct 
access to source data/documents, study related documents, materials, and equipment. 
 
 

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14 WARRANTY/INSURANCE INFORMATION 
14.1 Warranty 
Warranty information is provided in the product packaging for the commercially 
released devices and leads; additional copies are available upon request.  
14.2 Insurance (Central and Eastern Europe, Middle East and Africa)) 
Medtronic Bakken Research Center B.V. 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 Trial insurance 
statement/certificate will be provided to the Ethics Committee. 
14.3 Insurance (India) 
India Medtronic Pvt. 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 Board. 
14.4 Insurance (Association of Southeast Asian Nations (ASEAN) 
Medtronic International 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 Board. 
14.5 Insurance (Greater China) 
Medtronic (Shanghai) Management Co., Ltd. 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. As Ethics Committee of local clinical center may have 
special requirements on the insurance policy or other formal arrangement, it is 
necessary to provide a Clinical Study insurance statement/certificate to the Ethics 
Committee for review and obtain favorable opinion. 
 
Medtronic (Taiwan) 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 Board. 

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14.6 Insurance (Korea) 
Medtronic Korea Co., 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 Board. 
14.7 Insurance (Latin America) 
Medtronic Logistics LLC is a wholly owned subsidiary of Medtronic USA, 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/Institutional Review Board. 
 
 

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15 MONITORING 
It is the responsibility of Medtronic to ensure proper monitoring of this clinical study 
per regulations. Trained Medtronic personnel or delegates appointed by Medtronic 
may perform study monitoring at the study site in order to ensure that the study is 
conducted in accordance with the CIP, the Clinical Trial Agreement, and applicable 
regulatory and local requirements. Medtronic, or delegates, must therefore be 
allowed access to the subjects’ case histories (clinic and hospital records, and 
other source data/documentation) upon request as per the Patient Informed 
Consent, and Clinical Trial Agreement. The consent form or other privacy 
language where required by law must be available for monitoring and auditing. The 
principal investigator should also be available during monitoring visits.   
15.1 Monitoring Visits 
Frequency of monitoring visits may be based upon subject enrollment, duration of 
the study, study compliance, number of deviations, findings from previous 
monitoring visits and any suspected inconsistency in data that requires 
investigation. Regulatory documents (e.g., Ethics Committee approval letters, 
Clinical Trial Agreements) may be reviewed at each study site. Monitoring for the 
study, including site qualification visits, site initiation visits, interim monitoring visits, 
and closeout visits, will be done in accordance to the study-specific monitoring 
plan. 
Monitoring visits may be conducted periodically 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 subject CRFs. 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.  
Further details of monitoring will be given in the study monitoring plan. 
 
 

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16 REQUIRED RECORDS AND REPORTS 
16.1 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 (i.e., the study 
binder provided to the investigator) or Subject Study Binder. CRFs may 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 for a period 
of two years (or longer as local law or hospital administration requires) after the 
investigation is terminated.  
• 
All correspondence between the Ethics Committee, Sponsor, monitor, 
regulatory authority and/or the investigator that pertains to the 
investigation, including required reports.  
• 
Subject’s case history records, including:  
o Signed and dated informed consent form:  
▪ 
In China, Central and Eastern Europe, Middle East, Africa, 
India, Korea, Malaysia, Singapore, Taiwan, signed and 
dated by subject or legally authorized representative and 
investigator. If patient unable to read and/or write, 
supervised oral process with an independent witness who 
need to be present throughout the process; witness need to 
sign in addition to subject and investigator.  
▪ 
In Latin America: signed and dated by Person conducting 
consent process and subject, one or two witnesses are 
required according to specific country law and the study PIC 
template should be modified accordingly. 
o Medical history 
o Implant and follow-up data (if applicable) 
o Documentation of the dates and rationale for any deviation from the 
protocol 
• 
Electronically signed and dated CRFs and blank set of CRFs, if required by 
local law.  
• 
All approved versions of the CIP and PIC  
• 
Signed and dated Clinical Trial Agreement.  
• 
Current (within the last 2 years) CV of Principal Investigator  
o CV must be signed and dated (Central and Eastern Europe, Middle 
East, Africa, Latin America; best practice in all other geographies)  
o CV of other investigators prior to their activation, and CV of other 
key members of the investigation site team where required by local 
law 
• 
Documentation of delegated tasks.  

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• 
Ethics Committee approval documentation including written information 
that the investigator or other study staff, when member of the Ethics 
Committee, did not participate in the approval process.  
o Approval documentation must include the list of documents 
approved identified by version and/or date and the Ethics Board 
composition where required per local law.   
• 
Regulatory authority notification, correspondence and approval, as required 
per local law. 
• 
Study training records for site staff.  
• 
Insurance certificates, where required per local law (ASEAN, Central and 
Eastern Europe, Middle East, Africa, India, Greater China, Korea and Latin 
America).  
• 
Any other records that local regulatory agencies require to be maintained.  
• 
Final Study Report including the statistical analysis.  
16.2 Investigator Reports 
The investigator is responsible for the preparation (review and signature) and 
submission to the sponsor of all case report forms, deaths, and any deviations 
from the clinical investigation plan. 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.  
The investigator shall prepare and submit in a complete, accurate and timely 
manner the reports listed in this section, as well as any other reports required by 
local law. 
Table 11: Investigator reports applicable for all geographies per Medtronic 
requirements 
Report  
Submit to 
Description/Constraints 
Withdrawal of Ethics 
Board approval 
Sponsor  
The investigator must report a withdrawal of approval by 
the reviewing Ethics Board of the investigator’s part of the 
investigation within 5 working days. 
Study Deviations  
Sponsor and 
Ethics Board 
Any deviation from the clinical investigational plan shall be 
recorded together with the explanation of the deviation. 
 
Notice of deviations from the CIP to protect the life or 
physical well-being 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.  
Final Report 
Ethics Board and  
Relevant 
Authorities 
This report must be submitted within 3 months of study 
completion or termination. 
Progress Report 
Sponsor and 
Ethics Board 
Provide if required by local law or Ethics Board. 
 
16.3 Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records: 

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• 
All correspondence which pertains to the investigation 
• 
Signed Clinical Trial Agreements, current (within the last 2 years) CV of 
Principal Investigator (signed and dated if required) and key members of 
the investigation site team (as required by local law), and delegated task 
list 
• 
All signed and dated electronic case report forms submitted by investigator, 
including eCRF corrections 
• 
Informed consent templates, and other information provided to the subjects 
and advertisements, 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 (and corresponding investigator) in which the 
clinical study will be conducted 
• 
Regulatory authorities correspondence, notification or approval as required 
by national legislation 
• 
Insurance certificates, if applicable (e.g., Central and Eastern Europe, 
Middle East, Africa, India, Greater China and Korea, Latin America) 
• 
Names/contact addresses of monitors 
• 
Statistical analyses and underlying supporting data 
• 
Final report of the clinical study 
• 
The Clinical Investigation Plan and study related reports, and revisions 
• 
Study training records for site personnel and Medtronic personnel involved 
in the study 
• 
Any other records that local regulatory agencies require to be maintained.  
16.4 Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely 
reports listed in the table below. 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.  
Table 12: Sponsor reports for all geographies 
Report  
Submit to 
Description/Constraints 
Withdrawal of 
IRB/MEC approval 
Investigators, 
Head of 
Institution, 
Ethics 
Committee, and  
relevant 
authorities 
Investigators, Ethics Committees will be notified only if 
required by local laws or by the Ethics Committee. 

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Report  
Submit to 
Description/Constraints 
Withdrawal of 
Competent Authority 
(CA) approval  
Investigators, 
Head of 
Institution, 
Ethics 
Committee, and 
regulatory 
authorities, upon 
request 
Investigators, Ethics Committee will be notified only if 
required by local laws or by the Ethics Committee. 
Progress Reports,  
if applicable 
Ethics Committee 
and 
regulatory 
authorities, upon 
request 
These will be submitted to the Ethics Committee only if 
required by the Ethics Committee. 
Final report 
Investigators,  
Ethics 
Committee, and 
Regulatory 
authorities, upon 
request 
This will be submitted to the Ethics Committee only if 
required by the Ethics Committee. 
Study deviation  
Investigators 
Site specific study deviations will be submitted to 
investigators periodically.   
 
Electronic versions of the Medtronic reports will be kept on a password-protected 
document management system. After closure of the study, all records and reports 
will be archived indefinitely. 
 
 

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Appendix A:  Study Overview  
 
 
Study Purpose 
The purpose of this study is to demonstrate that primary prevention patients with 
additional risk factors (1.5 prevention criteria) are at a similar risk of life threatening 
ventricular arrhythmias when compared to secondary prevention patients, and would 
benefit from an ICD/CRT-D implant.  
 
Study Scope and Design 
Medtronic, Inc. is sponsoring the Improve SCA study, a prospective, non-randomized, 
non-blinded, global, interventional, multi-site post-market study.  
The study is expected to be conducted at approximately 100 sites worldwide, and to 
achieve approximately 2300 implants, the study is expected to enroll approximately 4800 
subjects. However, a sample size re-estimation will occur partway through the study, so 
the actual sample size may be as high as 8000 (see page 52). Based on input from the 
Improve SCA steering committee, it is estimated that sites will identify an average of 3 
subjects per site per month. 
Participating geographies are expected to include, but not limited to: Association of 
Southeast Asian Nations (ASEAN), Central and Eastern Europe (CEE), Greater China 
(including China and Taiwan), India, Latin America, Middle East and Africa (MEA), and 
South Korea. 
There is no minimum requirement for enrollments per site for this study. To ensure a 
widespread distribution of data and minimize site bias in study results, the maximum 
number of subjects enrolled at a single site will be limited to enroll approximately 5% of 
total study subjects. 
 
Study Objectives 
Primary Objective 
Demonstrate that appropriate therapy rates for subjects meeting 1.5 prevention 
criteria implanted with a Medtronic device (ICD/CRT-D) are equivalent (within 
30%) to rates in subjects meeting secondary prevention criteria. 
 
Secondary Objective 
Compare the mortality rates for patients meeting 1.5 prevention criteria between 
those implanted with a device (ICD/CRT-D) and those not implanted. 
 
 
 
 
  
 
 

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• 
 
. 
 
Subject Selection 
Patients of both genders who have a guideline recommendation for a single, dual, or 
triple chamber defibrillator will be approached regarding enrollment in the study. 
Subjects receiving a device implant will be required to have a Medtronic device 
implanted, because data stored in the device will be retrieved and analyzed by 
Medtronic as part of the study. Subjects currently implanted with an implantable pulse 
generator (IPG) are eligible for participation in the study, assuming the previous device 
is explanted at the time of implant. 
Inclusion Criteria 
• 
Subject has a Class I indication for implantation of an ICD according to the 
ACC/AHA/HRS or ESC Guidelines 
• 
Subject (or subject’s legally authorized representative) is willing and able to 
sign and date the Patient Informed Consent Form.  
Exclusion Criteria 
• 
Subject is ≤ 18 years of age 
• 
Subject with any exclusion criteria as required by local law (e.g., age, 
pregnancy, breast feeding) 
• 
Subject is enrolled in a concurrent study that has not been approved for 
concurrent enrollment by the Medtronic Clinical Trial Leader 
• 
Subject has any contraindication for ICD/CRT-D 
 
Study Procedures 
Subjects meeting ACC/AHA/HRS or ESC Class I guidelines for an ICD (or CRT-D) 
implant are eligible for enrollment and will be considered enrolled upon informed consent 
completion. At baseline, subjects will be assessed to determine if they fall into the 
primary prevention, 1.5 prevention, or secondary prevention group. A 1.5 prevention 
assessment will include an assessment of syncope/pre-syncope, low left ventricular 
ejection fraction, non-sustained ventricular tachycardia, and frequent premature 
ventricular contractions. In addition, a quality of life questionnaire (EQ-5E) will be 
collected at baseline and at the 6 month follow-up visit for 1.5 prevention subjects.  
Subjects will not be randomized, but will be asked if they desire an ICD/CRT-D implant. 
All subjects will be followed every six months until exit or closure, with the exception of 
secondary prevention subjects who do not receive an implant who will be exited 
following implant. Device data will be collected via interrogations at all follow-up visits 
(either via CareLink or in-office visit); information on device changes will be collected if 
applicable. At the 12 and 24 month visits, primary prevention (1.0 and 1.5 subjects) will 
be provided with the option of another ambulatory test to reassess the 1.5 criteria. 

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Study Duration 
The study will be closed approximately two years after the final subject enrollment.  At 
approximately 22 months past the final enrollment, centers will be notified that study 
closure is about to occur and that they should attempt to make one final study contact 
with each subject to maximize overall study follow-up.  
 

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Appendix B: Preliminary Publication Plan 
Publications from the Improve SCA Study will be handled according to Cardiac Rhythm 
Disease Management Standard Operating Procedures and as indicated in the Clinical 
Trial Agreement. 
Publication Committee 
The Steering Committee will serve as members of the Publication Committee, in addition 
to Medtronic representative(s). This committee will manage study publications with the 
goal of publishing findings from the data. The Publication Committee will develop the 
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) execute the Publication Plan,  
4) oversee the publication of primary, secondary and 
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, Secondary and 
 Publications 
The Publication Committee reviews, prioritizes, and manages all publications including 
primary, secondary and 
 publications. Primary and secondary publications are 
those that address analyses of any or all primary objectives or secondary objectives, 
respectively, as specified in the Clinical Investigation Plan.  
 
 
 
 
 
 
   
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. 

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Authors, including Medtronic personnel, must at a minimum meet all of the conditions 
below: 
• 
Substantial contribution to conception and design, or acquisition of data, or 
analysis and interpretation of data 
• 
Drafting the article or revising it critically for important intellectual content 
• 
Final approval of the version to be published 
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. 
All investigators not listed as co-authors will be acknowledged as the “Medtronic Improve 
SCA Study Investigators” and will be individually listed according to the guidelines of the 
applicable scientific journal when possible and affiliation. Any other contributors will be 
acknowledged by name with their specific contribution indicated. 
 
Transparency 
Transparency of study results will be maintained by the following means: 
• 
a final report, describing the results of all objectives and analysis, will be 
distributed to all investigators, Ethics Committees and Competent Authorities of 
participating countries when required by local law 
• 
registering and posting the study results on ClinicalTrials.gov based on the 
posting rules stipulated  
• 
submitting for publication the primary study results  
• 
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 sites study data accessible to the corresponding 
investigator after the completion of the study, if requested 
 
 

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Appendix C: Data Monitoring Committee (DMC) 
 
A Data Monitoring Committee (DMC) is not needed for this study. This decision was 
made based on the following criteria:  
• 
there are no interim analysis to test the primary objective, 
• 
all devices used in the Improve SCA study are commercially released and used 
in accordance with their approved labeling, and, 
• 
there are no experimental procedures involved in this study and therefore 
Medtronic does not anticipate incremental risks introduced to the subject as a 
result of participation in this study 
 
 
 

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Appendix D: Draft Data Collection Elements 
 
Draft Case Report Forms for the Improve SCA study will be provided under separate 
cover. Final CRFs 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 E: Patient Informed Consent Templates 
Geography-specific PIC templates will be provided under separate cover. 
 
 

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Appendix F: Participating Investigators and Institutions 
At the time of the Improve SCA Clinical Investigation Plan Version 1.0 completion, site 
confirmation was not finalized. A complete list of participating investigators and 
institutions where study activities will be conducted will be distributed under a separate 
cover when available upon request.  
 
 

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Appendix G: Labeling 
All components used within the Improve SCA study will be market released. Labeling for 
all market approved system components can be found with each package insert.  
 
 

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Appendix H: Committees 
The Improve SCA Study will have the following committees: 
Steering Committee 
The steering committee members are appointed by the sponsor to assist in development 
and execution of this investigation. Nine steering committee members were chosen for 
this study. Additional members may be added at a later date. A listing of the members is 
provided in Table 3. 
 
Publication Committee 
The Steering Committee will serve as members of the Publication Committee, in addition 
to Medtronic representative(s). This committee will manage study publications with the 
goal of publishing findings from the data. The Publication Committee will develop the 
final Publication Plan as a separate document.  
 
Episode Review Committee  
An Episode Review Committee (ERC) will be responsible for evaluating device-treated 
ventricular episodes according to 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. Inappropriate 
therapy will be identified based on adjudication rhythm truth and device episode log 
information.  
This committee will consist of independent physicians and may include Medtronic 
personnel. At the time of the Improve SCA Clinical Investigation Plan Version 1 
completion, committee members had not been identified. The ERC Member list will be 
under a separate cover when available upon request. 
 
Education Committee 
An education committee will be appointed to help with the development of educational 
and enrollment tools to support referring physicians. Education committee members will 
consist of approximately five interventional cardiologists or physicians with similar 
background or experience from various geographies. The educational committee is not 
finalized at the time of this CIP approval, and a listing of members will be provided when 
finalized upon request.  
 
 

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Appendix I: Abbreviations and Acronyms  
 
Table 13:  List of Abbreviations and Acronyms 
ACC 
American College of Cardiology 
ACE 
Angiotensin-Converting Enzyme 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AEAC 
Adverse Events Adjudication Committee 
AF 
Atrial Fibrillation 
AHA 
American Heart Association 
ARB 
Angiotensin Receptor Blocker 
ASEAN 
Association of Southeast Asian Nations 
ATP 
Anti-tachycardia Pacing 
BPM 
Beats per Minute 
CABG 
Coronary Artery Bypass Graft 
CAD 
Coronary Artery Disease 
CD 
Compact Disc 
CEE 
Central and Eastern Europe 
CFR 
Code of Federal Regulations 
CIP 
Clinical Investigation Plan 
CRF/ e-CRF 
Case Report Form / electronic-CRF 
CRT 
Cardiac Resynchronization Therapy 
CRT-D 
Cardiac Resynchronization Therapy- Defibrillator 
CTA 
Clinical Trial Agreement 
CV 
Curriculum Vitae 
DMC  
Data Monitoring Committee 
ECG 
Electrocardiogram 
EP 
Electrophysiology/ Electrophysiologist 
ERC 
Episode Review Committee 
ESC 
European Society of Cardiology 
FDA 
Food and Drug Administration 

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HF 
Heart Failure 
HRS 
Heart Rhythm Society 
ICD 
Implantable Cardioverter Defibrillator 
IRB 
Investigational Review Board 
KG 
Kilogram 
LBBB 
Left Bundle Branch Block 
LLT 
Lowest Level Term 
LV 
Left Ventricular 
LVEF 
Left Ventricular Ejection Fraction 
MEA 
Middle East and Africa 
MEC 
Medical Ethics Committee 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
NNT 
Number Needed to Treat 
NSVT 
Non-sustained Ventricular Tachycardia 
NYHA 
New York Heart Association 
OPC 
Objective Performance Criterion 
P/A 
Posterior/Anterior 
PI 
Principal Investigator 
PIC 
Patient Informed Consent 
PMA 
Pre-Market Approval 
POR 
Power On Reset 
PPR 
Product Performance Report 
PSA 
Pacing System Analyzer 
PVC 
Premature Ventricular Contraction 
QALY 
Quality Adjusted Life Years 
QoL 
Quality of Life 
RA 
Right Atrium 
RV 
Right Ventricle 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 

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SCA 
Sudden Cardiac Arrest 
SCD 
Sudden Cardiac Death 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SVT 
Supraventricular Tachycardia 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 
VT 
Ventricular Tachycardia 
VF 
Ventricular Fibrillation 
 
 

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Appendix J: Clinical Investigation Plan Signature Page 
(if applicable)  
 
Improve SCA Study 
 
The Improve SCA study is a prospective, non-randomized, non-blinded, global, 
interventional, multi-site post-market study. The purpose of this study is to demonstrate 
that primary prevention patients with one or more additional risk factors (1.5 prevention 
criteria) are at a similar risk of life-threatening ventricular arrhythmias when compared to 
secondary prevention patients, and would receive similar benefit from an ICD (or CRT-
D) implant. 
 
Clinical Investigation Plan Version 1.0 - December 23, 2013 
 
I/we acknowledge that I/we have read, understood and agreed to abide by all conditions, 
instructions and restrictions contained in the above mentioned Clinical Investigation Plan. 
I/we agree to carry out all of its items in accordance with applicable regulations and in 
full compliance with the guidelines. 
 
 
 
 
Hospital  
 
 
 
 
 
 
 
Title, First and last Name   
Signature  
Date