Protego DF4 Post Approval Registry
Conditions: Implantable Defibrillator User
Sponsor: Biotronik, Inc.

 
 
 
 
Clinical Protocol 
for the 
Protego DF4 
Post Approval Registry 
 
 
 
 
 
 
 
 
 
NCT02243696 
 
April 14, 2014 
 
 
 
 
BIOTRONIK, Inc. 
6024 Jean Road, Lake Oswego, Oregon 97035 
 
This document contains confidential information for use only by investigators 
participating in the clinical registry. Therefore, this document should be maintained in a 
secure location and should not be copied or made available for review by any 
unauthorized personnel. 

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TABLE OF CONTENTS 
1. INTRODUCTION .................................................................................................................................... 6 
1.1 Name of Device .............................................................................................................................. 6 
1.2 Registry Overview .......................................................................................................................... 6 
1.3 Background .................................................................................................................................... 6 
1.3.1 GALAXY Lead Registry: Clinical Experience with Linox ICD Lead .................................... 7 
1.3.2 Protego Animal Study ......................................................................................................... 9 
1.4 Device Description........................................................................................................................ 10 
1.4.1 Protego Lead Description ................................................................................................. 10 
1.4.2 Design Differences between Protego and Linoxsmart ......................................................... 11 
1.4.3 DF4 Device Header Description ....................................................................................... 12 
1.4.4 BIOTRONIK Home Monitoring® ....................................................................................... 13 
2. REGISTRY DESIGN ............................................................................................................................ 16 
2.1 Registry Endpoints ....................................................................................................................... 18 
2.1.1 Primary Endpoint 1: Protego DF4 Lead Safety – 5-Year Adverse Event-Free Rate ........ 18 
2.1.2 Primary Endpoint 2: Protego DF4 Lead Safety – Individual 5-Year Adverse              
Event-Free Rates ......................................................................................................................... 18 
2.1.3 Secondary Endpoints ........................................................................................................ 19 
2.1.4 Additional Data of Interest ................................................................................................. 19 
2.2 Registry Size ................................................................................................................................ 19 
2.3 Sample Size Analysis ................................................................................................................... 20 
2.3.1 Attrition .............................................................................................................................. 21 
2.4 Data Analyses .............................................................................................................................. 21 
2.4.1 Endpoint Analysis .............................................................................................................. 21 
2.4.2 Trend Analyses ................................................................................................................. 22 
2.4.3 Missing Data ..................................................................................................................... 22 
2.4.4 Poolability Analysis ........................................................................................................... 23 
3. PROTOCOL REQUIREMENTS ........................................................................................................... 24 
3.1 Subject Population........................................................................................................................ 24 
3.1.1 Indications ......................................................................................................................... 24 
3.1.2 Contraindications .............................................................................................................. 24 
3.1.3 Inclusion Criteria ............................................................................................................... 24 
3.1.4 Exclusion Criteria .............................................................................................................. 25 
3.2 Registry Procedures ..................................................................................................................... 25 
3.2.1 Registry Pre-Screening ..................................................................................................... 26 
3.2.2 Enrollment Visit ................................................................................................................. 26 
3.2.3 Protego Implant ................................................................................................................. 27 
3.2.4 Routine Follow-ups ........................................................................................................... 28 
3.2.5 Unscheduled Interim Follow-ups ....................................................................................... 29 
3.3 Registry Exits ................................................................................................................................ 30 
3.3.1 Withdrawal of Consent ...................................................................................................... 30 
3.3.2 Subject Death .................................................................................................................... 30 
3.3.3 Protego Lead or Pulse Generator Extraction .................................................................... 31 
3.3.4 Lost to Follow-up ............................................................................................................... 31 
3.3.5 Registry Participation Complete ........................................................................................ 31 
4. REGISTRY ORGANIZATION .............................................................................................................. 32 
4.1 Sponsor ........................................................................................................................................ 32 
4.2 Clinical Events Committee ........................................................................................................... 32 
5. DATA COLLECTION ........................................................................................................................... 33 
5.1 Electronic Data Capture (EDC) .................................................................................................... 33 

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5.2 Case Report Forms (CRFs) ......................................................................................................... 33 
5.3 Data Clarification/Data Quality Control......................................................................................... 34 
5.4 Subject Retention ......................................................................................................................... 34 
5.5 Subject Data Confidentiality ......................................................................................................... 34 
6. RISKS AND RISK MINIMALIZATION ................................................................................................. 35 
7. REGISTRY MONITORING ................................................................................................................... 37 
7.1 Summary ...................................................................................................................................... 37 
7.2 Registry Monitors .......................................................................................................................... 37 
7.3 Monitoring Visits ........................................................................................................................... 38 
7.4 Centralized Monitoring ................................................................................................................. 38 
8. REGISTRY COMPLETION .................................................................................................................. 39 
9. PROTOCOL COMPLIANCE ................................................................................................................ 40 
9.1 Protocol Violations ........................................................................................................................ 40 
9.2 Protocol Deviations....................................................................................................................... 40 
10. ADVERSE EVENTS ............................................................................................................................. 41 
10.1 Reportable Adverse Events .......................................................................................................... 41 
10.1.1 Implant Procedure-Related Adverse Events ..................................................................... 41 
10.1.2 Pulse Generator-Related Adverse Events ........................................................................ 42 
10.1.3 Lead-Related Adverse Events .......................................................................................... 42 
10.1.4 Non-Procedure Non-System Related Adverse Events ..................................................... 43 
10.2 Endpoint Analysis ......................................................................................................................... 43 
10.3 Adverse Events for the Analysis of the Primary and Secondary Endpoints................................. 44 
10.3.1 Adverse Events for the Analysis of Primary Endpoints 1 and 2 ....................................... 44 
10.3.2 Adverse Events for the Analysis of Secondary Endpoint 3 .............................................. 45 
10.4 Adverse Event Reporting ............................................................................................................. 45 
11. IRB APPROVAL................................................................................................................................... 46 
11.1 Other Institutions and Physicians ................................................................................................. 46 
12. INFORMED CONSENT ........................................................................................................................ 47 
13. RECORDS AND REPORTS ................................................................................................................ 48 
13.1 Investigator Records..................................................................................................................... 48 
13.2 Investigator Reports ..................................................................................................................... 48 
13.3 Sponsor Records .......................................................................................................................... 49 
13.4 Sponsor Reports ........................................................................................................................... 50 
APPENDIX A: DEFINITION OF TERMS .................................................................................................... 51 
APPENDIX B: TIMELINE ........................................................................................................................... 54 
 
 
 
 
 
 
 
 
 

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TABLE OF FIGURES 
 
Figure 1: Freedom from Primary Endpoint Adverse Events (%) ................................................................... 9 
Figure 2: Protego Lead ............................................................................................................................... 11 
Figure 3: DF4 Connector and Lead ............................................................................................................ 11 
Figure 4: Linoxsmart SD Schematic ............................................................................................................... 12 
Figure 5: Protego SD Schematic ................................................................................................................ 12 
Figure 6: Orientation of DF-1/IS-1 Ilesto Headers ...................................................................................... 12 
Figure 7: Orientation of DF4/IS-1 Ilesto Headers ....................................................................................... 12 
Figure 8: Home Monitoring® Transmission Path ........................................................................................ 13 
Figure 9: Home Monitoring® Quick View Summary Report ....................................................................... 15 
Figure 10. Study Design Flowchart ............................................................................................................. 17 
 
TABLE OF TABLES 
 
Table 1: Linox Smart Lead Related Adverse Events .................................................................................... 8 
Table 2: Primary Endpoint Case Summary ................................................................................................... 9 
Table 3: Primary Safety Endpoints Sample Sizes ...................................................................................... 21 
Table 4: Registry Visit Assessment Schedule ............................................................................................ 26 
Table 5: Investigator Reporting Responsibilities ......................................................................................... 49 
Table 6: Sponsor Reporting Responsibilities .............................................................................................. 50 
 

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Protego DF4 Post Approval Registry 
 
PROTOCOL SIGNATURE PAGE 
 
The signature below constitutes the receipt and review of the Protego DF4 Post 
Approval Registry protocol and any attachments, and provides the necessary 
assurances that this study will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable U.S. federal regulations, ICH and GCP 
guidelines. 
 
 
PRINCIPAL INVESTIGATOR: 
 
 
Signed: 
 
 
 
 
Name (please print) 
 
 
 
 
 
Signature 
 
Date 
 

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SUMMARY 
Title: 
 Protego DF4 Post-Approval Registry 
Design: 
Prospective, single-arm, non-randomized, multi-center registry  
Purpose: 
To confirm long-term safety and reliability of BIOTRONIK’s Protego 
DF4 lead, as used in conjunction with a BIOTRONIK DF4 compatible 
implantable cardioverter defibrillator (ICD) or cardiac resynchronization 
therapy defibrillator (CRT-D) pulse generator. The evaluation of safety 
will be based on the analysis of Protego lead related adverse events. 
The Protego DF4 registry will provide data to permit characterization of 
any Protego lead failures contributing to loss of bradycardia or shock 
therapy. Additionally, acute and chronic Protego lead parameters will be 
evaluated. 
Subject Population: 
Subjects who are indicated for an ICD or a CRT-D. Subjects must be 
successfully implanted with a BIOTRONIK Ilesto DF4 ICD or CRT-D or 
future market released BIOTRONIK DF4 ICD or CRT-D. Enrollment can 
be up to 30 days prior to or 30 days after implant with the DF4 system. 
Enrollment: 
This registry will include 1,694 subjects implanted with the Protego DF4 
system. The collection of data will continue for 5 years post-implant for 
each enrolled subject. 
Clinical Sites: 
Up to 75 U.S. and International sites. 
Primary Endpoints: 
1. Evaluation of the overall incidence of adverse events (AEs) related to 
the Protego lead or device header 
2. Evaluation of the incidence of each individual type of AE that 
contributes to Primary Endpoint 1 
Secondary Endpoint: 
1. Pacing threshold, sensing and impedance measurements for the 
Protego lead through 5 years post-implant 
2. Shock impedance for the Protego lead through 5 years post-implant 
3. AE rates for AEs excluded from primary safety endpoints 1 and 2, 
through 5 years post-implant 
Clinical Events 
Committee Chair: 
TBD 
Sponsor: 
BIOTRONIK, Inc. 
Clinical Studies Department 
6024 SW Jean Road 
Lake Oswego, Oregon 97035 
 

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1. 
INTRODUCTION 
1.1 
NAME OF DEVICE 
This protocol details the FDA post-approval registry for BIOTRONIK’s Protego DF4 
implantable cardioverter defibrillator (ICD) lead, further referred to as the Protego lead 
throughout this document. Currently this includes the following models: Protego SD 
(active fixation, dual coil), Protego TD (passive fixation, dual coil), Protego S (active 
fixation, single coil), and Protego T (passive fixation, single coil). Under this protocol, the 
Protego lead is utilized in conjunction with any market-released BIOTRONIK Ilesto or 
future US market released ICD or cardiac resynchronization therapy defibrillator (CRT-
D) device with a DF4 header.  
1.2 
REGISTRY OVERVIEW  
The purpose of this post-approval registry is to confirm the safety and reliability of the 
Protego lead as used in conjunction with any compatible BIOTRONIK Ilesto or future 
US market released DF4 ICD or CRT-D device. Data will be collected from up to 1694 
subjects from implant through 5 years of follow-up.  
Subjects eligible for the registry include those that will be implanted with a Protego lead 
within the 30 days following enrollment procedures or have been implanted with a 
Protego lead within 30 days of enrollment. Prior to enrollment procedures, subjects will 
be screened to ensure eligibility and will sign an informed consent. Consent and 
enrollment must occur at a maximum of 30 days prior to or post implant of the Protego 
lead. 
Safety will be evaluated based on the analysis of all Protego lead and device header-
related adverse events. Acute and chronic lead parameters for sensing, pacing 
thresholds, and pacing and shock impedance will be evaluated for the Protego lead. 
Additionally, acute and chronic lead parameters for sensing, pacing thresholds, and 
pacing impedance will be evaluated for all BIOTRONIK leads, including right atrial and 
left ventricular leads. 
All devices included in the registry are legally marketed and prescribed by physicians 
according to approved indications for use. 
1.3 
BACKGROUND 
The Protego DF4 Post-Approval Registry is designed to document the clinical 
experience of the Protego leads as required by the FDA through P980023/S057, dated 
July 3, 2014.  
The term DF4 refers to an industry standard header/lead connection scheme between 
an ICD/CRT-D device and the ICD lead. The DF4 header/lead system features a single 
connection between the ICD/CRT-D device and the ICD lead. As a result, the number of 
connectors for an ICD lead is reduced with a DF4 header/lead system compared to a 

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DF-1/IS-1 system, which simplifies the implantation procedure, reduces the likelihood of 
lead-to-port mismatch, and decreases the number of setscrews necessary to secure the 
lead into the header. Section 1.4.2 provides further details on differences between the 
DF4 and DF-1/IS-1 connection schemes. Additionally, by eliminating the lead yoke, the 
system pocket bulk can be reduced. 
The Protego lead is a 7.8 French transvenous ICD lead designed for permanent right 
ventricular pacing, sensing, and delivery of defibrillation/cardioversion shocks to the 
heart. Protego is the successor of the Linoxsmart ICD lead (Linoxsmart SD/TD 
P980023/S038, approved September 17, 2010, Linoxsmart S/T P980023/S043, approved 
February 28, 2011), the only major difference being the replacement of the traditional 
DF-1/IS-1 connectors of the Linoxsmart lead with the DF4 connector. The Linox lead 
family has been extensively studied in the ongoing GALAXY registry. 
1.3.1 
GALAXY Lead Registry: Clinical Experience with Linox ICD Lead 
BIOTRONIK is currently conducting GALAXY, an after-market registry to confirm the 
long-term safety and reliability of the FDA approved Linox family of ICD leads. The 
GALAXY Registry is registered on clinicaltrials.gov, NCT00836589. This multi-center, 
prospective, non-randomized registry has been ongoing since enrollment began in 
January 2009 and has been closed to enrollment since November 2011. There were 
1999 subjects enrolled in the registry, 196 of which were implanted with Linoxsmart leads. 
The sensing and pacing behavior was evaluated as well as the rate of lead related 
complications over the available follow-up period. The mean pacing threshold across all 
Linox and Linoxsmart lead models was 0.63 ± 0.33 V. The mean sensing amplitude was 
12.83 ± 5.43 mV. The mean lead impedance was 556.7 ± 124.8 ohms. There were 5 
(2.55%) subjects who experienced a primary adverse event (AE) reported as related to 
the Linoxsmart lead (Table 1) and 29 (1.45%) subjects who experienced a primary AE 
related to the Linox Lead Family.  

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Table 1: Linox Smart Lead Related Adverse Events 
Adverse Event 
Linoxsmart Leads 
(n=196) 
All Linox Lead Models 
 (N=1,999) 
Subjects 
with AE, n 
% Subjects 
with AEs 
AEs, n 
Subjects 
with AE, n 
% Subjects 
with AEs 
AEs, n 
Primary Endpoint AEs 
Other ICD lead related: 
Lead oversensing or noise 
3 
1.53% 
3 
13 
0.65% 
13 
Lead dislodgement > 180 
days 
1 
0.51% 
1 
5 
0.25% 
5 
Lead impedance out of 
range, High impedance, 
Potential conductor 
fracture  
1 
0.51% 
1 
5 
0.25% 
5 
Lead impedance out of 
range, Low impedance, 
Potential insulation break 
0 
0.00% 
0 
5 
0.25% 
5 
Lead undersensing or loss 
of sensing 
0 
0.00% 
0 
2 
0.10% 
2 
Other ICD lead related: 
Tension pneumothorax 
0 
0.00% 
0 
1 
0.05% 
1 
Total Primary Endpoint 
AEs 
5 
2.55% 
5 
29 
1.45% 
31 
Secondary Endpoint AEs Related to the ICD Lead 
Lead dislodgement < 180 
days 
2 
1.02% 
2 
22 
1.10% 
22 
High pacing threshold, 
intermittent capture, no 
lead capture 
0 
0.00% 
0 
7 
0.35% 
7 
Cardiac perforation with or 
without tamponade 
0 
0.00% 
0 
4 
0.20% 
5 
Total Secondary Endpoint 
AEs  
2 
1.02% 
2 
33 
1.65% 
34 
Total Primary or 
Secondary AEs 
7 
3.57% 
7 
60 
3.00% 
65 
Figure 1 shows the calculated Kaplan-Meier actuarial graph demonstrating the freedom 
from all primary endpoint adverse events adjudicated by the Clinical Events Committee. 
Table 2 displays the associated case summary. A common, final follow-up date of 
November 4, 2013, is assumed for all active subjects.  
The standard error (SE) for the estimated survival (freedom from AEs) was calculated 
using the method of Peto et al. The last adverse event occurred on day 1,465, and the 
current estimated freedom from adverse events is 97.5% (SE 1.0%) for implant times 
1,465 days or longer. These estimates may change as additional follow-up data are 
collected.  
 

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Figure 1: Freedom from Primary Endpoint Adverse Events (%) 
       
 
Table 2: Primary Endpoint Case Summary 
Total Subjects, n 
Subjects with 
Adverse Event, n 
Censored 
n 
% 
1999 
29 
1970 
98.5% 
1.3.2 
Protego Animal Study 
The safety and efficacy of the BIOTRONIK Linoxsmart DF4 SD lead along with the Iforia 
or Ilesto 7 DF4 ICD (equivalent devices) were evaluated by comparison to the FDA-
approved BIOTRONIK Linoxsmart SD lead. The Protego family of ICD leads was 
developed and tested with the engineering project name “Linoxsmart DF4”. Therefore, all 
references to this device name are synonymous with the Protego family of ICD leads.  
The animal study began May 30, 2013, was randomized, and compared the two ICD 
systems implanted in a total of 24 healthy canine subjects (N=12/group) over a period of 
12 weeks. Ventricular pacing capture threshold (PCT), painless shock impedance (PSI), 
serious adverse device event -free rate (SADE-free), R-wave amplitude, and ventricular 
pacing impedance (VPI) of the ICD systems implanted for 12 weeks were the focus of 
primary and secondary endpoints.  
All primary endpoints were achieved, as the DF4 system demonstrated non-inferiority of 
PCT and equivalence of PSI in all three shock pathways relative to the DF-1 system, 
along with a 100% SADE-free rate. In addition, all secondary endpoints were achieved, 

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as the DF4 system demonstrated non-inferiority of R-wave amplitude and equivalence 
of VPI relative to the DF-1 system. The results of this study demonstrate that the 
BIOTRONIK Iforia/Ilesto DF4 ICD equipped with the Linoxsmart DF4 SD lead is 
comparable in terms of efficacy and safety to its predecessor, the BIOTRONIK 
Iforia/Ilesto DF-1/IS-1 ICD equipped with the Linoxsmart SD lead. 
1.4 
DEVICE DESCRIPTION 
1.4.1 
Protego Lead Description 
The Protego ICD lead is a 7.8 F transvenous, steroid-eluting, endocardial lead for use 
with any ICD/CRT-D with a DF4 connector port (Figure 2). Protego leads are variants of 
currently marketed Linoxsmart ICD leads with IS-1 and DF-1 connectors. The functionality 
of each lead is identical to the respective predecessor Linoxsmart ICD lead.  
The Protego S and Protego T leads have two sensing and pacing electrodes (distal tip 
and ventricular ring electrode) and one defibrillation electrode (ventricular shock coil). 
The Protego SD and Protego TD leads have two sensing and pacing electrodes (distal 
tip and ventricular ring electrode) and two defibrillation electrodes (ventricular and 
superior vena cava shock coils).  
These leads, in conjunction with an ICD or CRT-D device, perform the following 
functions: 
- 
sense electrical signals from cardiac tissue and conduct those signals to the device; 
- 
conduct bradycardia and anti-tachycardia pacing pulses emitted from the device to 
cardiac tissue; 
- 
conduct defibrillation shocks of both high and low energies from the device to 
cardiac tissue. 
The Protego leads are intended for permanent placement in the right ventricle. The tip 
and ring electrodes form the most distal portion of the lead and provide dedicated 
bipolar sensing and pacing. 
All Protego leads have one shock electrode that is positioned in the right ventricle. The 
Protego SD and Protego TD dual-coil ICD leads have an additional shock electrode for 
placement in the superior vena cava (SVC). All Protego leads feature Silglide® surface 
treatment, designed to reduce the force required to maneuver the lead during the 
implant procedure.  
The 
Protego 
S 
and 
Protego 
SD 
leads 
feature 
an 
electrically 
active 
extendable/retractable fixation helix for use in lead placement. The helix is extended 
and retracted by rotating the contact pin with a fixation tool. Both the fixation helix and 
ring electrode are comprised of a platinum/iridium alloy base with fractal iridium. The 
Protego T and Protego TD leads feature a passive fixation tip coated with fractal iridium.  

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The distal tip of all Protego ICD leads consists of a steroid eluting collar which contains 
the active ingredient dexamethasone acetate (DXA). Upon exposure to body fluids, the 
steroid elutes from the collar. Release of the steroid is intended to decrease the 
inflammatory response at the contact site between the lead tip and the endocardium, 
thereby decreasing the elevated pacing thresholds of the endocardial lead that often 
occur after lead implantation. 
The DF4 connector of Protego ICD leads was designed in compliance with ISO 27186; 
the specifications such as geometry, tensile loads, etc., of the DF4 connector meet the 
requirements of this standard. The DF4 connector allows use with ICDs/CRT-Ds that 
have connector ports conforming to ISO 27186.  
Figure 2: Protego Lead 
 
1.4.2 
Design Differences between Protego and Linoxsmart  
Differences between the currently approved Linoxsmart leads and the Protego leads are 
limited to the replacement of DF-1 and IS-1 connectors with a DF4 connector and a 
modified transition area between connector and lead body (Figure 3). The electrical 
components of Protego leads located from lead body to the lead tip remain unchanged 
compared to Linoxsmart leads. 
Figure 3: DF4 Connector and Lead 
 

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1.4.3 
DF4 Device Header Description 
The DF4 connector features a single connection between the ICD/CRT-D and the ICD 
lead. As a result, the number of connectors for ICD leads is reduced from two or three 
connectors for a single shock coil or a dual shock coil DF-1/IS-1 ICD lead (see Figure 4 
and Figure 6), respectively, to a single connection with a DF4 ICD lead (see Figure 5 
and Figure 7).  
Figure 4: Linoxsmart SD Schematic 
 
Figure 5: Protego SD Schematic 
 
Figure 6: Orientation of DF-1/IS-1 Ilesto Headers 
 
Figure 7: Orientation of DF4/IS-1 Ilesto Headers 
 
VR – Single Chamber Device, DR – Dual Chamber Device, HF – Triple Chamber Device 

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Due to these modifications, DF4 systems require a more complex design of the 
generator connector cavity. Three of the four setscrews that are necessary for a dual 
coil DF-1/IS-1 shock lead have been replaced by spring contacts. Additionally, strict 
requirements are put on the seals that have to prevent leaking current as well as 
prevent liquid from entering the header cavity. Conformity with this standard ensures 
that the DF4 generator connector can be connected to any DF4-labelled lead. For 
purposes of the Protego DF4 post-approval registry, the BIOTRONIK Protego ICD lead 
is required. 
1.4.4 
BIOTRONIK Home Monitoring® 
Current expert consensus advocates 3- to 6-month device evaluations either in-person 
or by remote monitoring for ICD/CRT-D devices1.  
BIOTRONIK Home Monitoring® is a communication system which allows the automatic 
transmission of diagnostic patient data from the device to the physician at any time. The 
technology implements the use of wireless communications to provide the physician 
with daily patient monitoring and trend analysis information between office follow-up 
visits. A block diagram of the transmission path is shown in Figure 8, and the 
transmission steps are described as follows: 
- 
Communication starts with the implant, which activates a very low power RF 
transmitter circuitry integrated within the pulse generator.  
- 
The patient’s device accepts patient data from the implant and transfers this digital 
information using a cellular short messaging system (SMS) or telephone landline 
connection to a BIOTRONIK Service Center for evaluation. 
- 
The BIOTRONIK Service Center receives incoming data and generates a 
customized summary which is available to the physician online via secure Internet 
access, or can be forwarded to the physician via fax. 
Figure 8: Home Monitoring® Transmission Path 
 
 
                                            
1 Wilkoff BL, et al. HRS/EHRA expert consensus on the monitoring of cardiovascular implantable 
electronic devices (CIEDs): description of techniques, indications, personnel, frequency and ethical 
considerations. Heart Rhythm 2008;5:907-25 

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BIOTRONIK conducted the TRUST study to evaluate the safety and effectiveness of 
Home Monitoring®. BIOTRONIK received FDA approval (P050023/S020, approved May 
12, 2009) of the following labeling claims regarding Home Monitoring®: 
- 
BIOTRONIK Home Monitoring® information may be used as a replacement for 
device interrogation during in-office follow-up visits. 
- 
A strategy of care using BIOTRONIK Home Monitoring® with office visits when 
needed has been shown to extend the time between routine, scheduled in-office 
follow-ups of BIOTRONIK implantable devices in many patients. Home Monitoring® 
data is helpful in determining the need for additional in-office follow-up. 
- 
BIOTRONIK Home Monitoring® patients—who are followed remotely with office 
visits when needed—have been shown to have similar numbers of strokes, invasive 
procedures and deaths as patients followed with conventional in-office follow-ups. 
- 
BIOTRONIK Home Monitoring® provides early detection of arrhythmias. 
- 
BIOTRONIK Home Monitoring® provides early detection of silent, asymptomatic 
arrhythmias. 
- 
Automatic early detection of arrhythmias and device system anomalies by 
BIOTRONIK Home Monitoring® allows for earlier intervention than conventional 
in-office follow-ups. 
- 
BIOTRONIK Home Monitoring® allows for improved access to patient device data 
compared to conventional in-office follow-ups since device interrogation is 
automatically scheduled at regular intervals. 
In the Ilesto ICD and CRT-D devices, Home Monitoring® provides event and system 
information similar to what is currently available during office follow-up visits. The 
highlighted information in the Home Monitoring® Quick View Summary Report, Figure 
9, displays the study related follow-up data automatically transmitted on a daily basis 
including: battery status, pacing impedance, pacing threshold, sensing amplitude 
(mean/min) for both the atrial and ventricular leads. In addition, Home Monitoring® 
provides automatic daily information on arrhythmias, lead trends, current device 
programming, event episodes, therapy provided, and long term data trends.  
 
 

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Figure 9: Home Monitoring® Quick View Summary Report 
 

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2. 
REGISTRY DESIGN 
This multi-center, prospective, non-randomized registry is designed to gather safety 
data on BIOTRONIK’s Protego leads. All subjects enrolled in the registry will be 
implanted with a US market released BIOTRONIK DF4 ICD or CRT-D pulse generator 
and a Protego lead.  
Potential subjects will be identified by the investigator from their general patient 
population and must have an approved indication for receiving an ICD or CRT-D device. 
Additionally, potential subjects must satisfy the registry inclusion and exclusion criteria 
(Sections 3.1.3 and 3.1.4). If a patient has been determined to be eligible, informed 
consent is obtained prior to initiating any registry related procedures. After written 
informed consent has been obtained, enrollment visit data will be collected. Written 
informed consent and enrollment visit data collection may be obtained ± 30 days from 
the date of implant. If consent is obtained and eligibility is determined prior to implant, 
patients are considered ‘provisionally enrolled’ until they are successfully implanted, at 
which time they are considered fully enrolled. Device data and any adverse events will 
be collected from the date the first implant attempt onwards. If a patient is enrolled post-
implant, device data and any adverse events since the date of the first implant attempt 
will be collected retrospectively at the enrollment visit.  
After enrollment, subjects will be seen for an evaluation at three and six months post 
implant, and every six months thereafter for five years. Subjects with Home Monitoring® 
capabilities will be seen for an in-office follow-up at least once every 12 months and 
have the option to substitute a Home Monitoring® follow-up for every other in-office 
follow-up to result in the six month follow-up schedule. Registry visits completed using 
Home Monitoring® data will be accompanied by a phone call to the subject for a short 
verbal assessment. Subjects without a Home Monitoring® system will be seen for an in-
office follow-up at three and six months post implant, and at least once every six months 
thereafter.  
Figure 10 provides an overview of the clinical registry design. Details of subject eligibility 
requirements are noted in Section 3.1 and details of other registry specific procedures 
and data collection are noted in Section 3.2 and Section 5. 

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Figure 10. Study Design Flowchart 
 

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2.1 
REGISTRY ENDPOINTS 
This registry includes the assessments of two primary safety endpoints related to the 
Protego DF4 lead, and several secondary endpoints that evaluate the safety and 
effectiveness of the BIOTRONIK ICD/CRT-D system with a Protego DF4 lead. 
2.1.1 
Primary Endpoint 1: Protego DF4 Lead Safety – 5-Year Adverse Event-
Free Rate 
The purpose of primary endpoint 1 is to evaluate the overall incidence of adverse 
events related to the Protego DF4 lead or header (as defined in Section 10) from 
implant through 5 years. Assuming that the expected Protego DF4 lead or header-
related adverse event rate at 5 year post-implant (proportion of subjects with at least 
one AE in the timeframe from implant through 5 year post-implant) is 7.5% or less, then 
the primary safety endpoint will be evaluated in the following testable hypothesis in 
superiority format.  
Ho: The adverse event-free rate (AEFR) for subjects receiving the Protego DF4 lead at 5 
years post-implant is less than or equal to 92.5% 
 
AEFR ≤ 92.5% 
Ha: The adverse event-free rate (AEFR) for subjects receiving the Protego DF4 lead at 5 
year post-implant is greater than 92.5% 
 
AEFR > 92.5% 
A rejection of the null hypothesis would demonstrate that the adverse event-free rate is 
greater than 92.5%. 
2.1.2 
Primary Endpoint 2: Protego DF4 Lead Safety – Individual 5-Year 
Adverse Event-Free Rates 
Each of the individual types of adverse events contributing to primary endpoint 1 will be 
evaluated separately in the following superiority hypothesis. 
Ho: The individual adverse event rate (AEIndividual) for a given type of AE for the 
Protego DF4 lead at 5 years post-implant is greater than or equal to 1% 
 
AEIndividual ≥ 1% 
Ha: The individual adverse event rate (AEIndividual) for a given type of AE for the 
Protego DF4 lead at 5 years post-implant is less than 1% 
 
AEIndividual < 1% 
If the two-sided, 95% upper confidence bound is no more than 1% for individual adverse 
events, then the null hypothesis will be rejected for that AE type.  

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2.1.3 
Secondary Endpoints 
There are no formal tests of hypotheses associated with secondary endpoints 1-3. 
1. Pacing threshold, sensing and impedance measurements for the Protego DF4 
lead through 5 years post-implant. 
 
2. Shock impedance for the Protego lead through 5 years post-implant. 
3. Adverse event rates for protocol defined, CEC adjudicated AEs excluded from 
primary safety endpoints 1 and 2, through 5 years post-implant. 
2.1.4 
Additional Data of Interest 
Additional information will be collected to characterize the registry population, implanted 
system, and progress of the registry. The collected information will include baseline 
demographics, medical history, implanted system, system revisions, Protego 
extractions, returned product analysis, and compliance. Specifically, data of interest will 
include: 
- 
Baseline demographics, including age, gender, weight, height, New York Heart 
Association (NYHA) class, ejection fraction, and race and ethnicity (optional) 
- 
Medical history, including indication for device  
- 
Implanted device data, including pulse generator and leads models, serial numbers, 
and implant dates from initial implant and/or revisions 
- 
Implant procedure data (collected retrospectively if implant occurred prior to 
enrollment) 
- 
Pacing threshold, sensing and impedance measurements for implanted BIOTRONIK 
RA and LV leads 
- 
Site reported adverse events excluded from primary and secondary endpoint 
analysis 
- 
Protego DF4 extraction experience 
- 
Results from returned product analysis 
- 
Compliance to protocol requirements and registry visit schedule 
2.2 
REGISTRY SIZE 
To document the clinical experience of the Protego DF4 lead as required by the FDA, 
the Protego DF4 post-approval registry is designed to follow 1694 subjects for 5 years 
post-implant at up to 75 U.S. and International sites.  

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The investigation is designed to limit the number of patients involved while still exposing 
the device to a sufficiently large patient population in order to ensure a representative 
and statistically meaningful sample. 
2.3 
SAMPLE SIZE ANALYSIS 
The estimated sample sizes required to evaluate primary endpoints 1 and 2 are based 
on a superiority comparison of the overall Protego DF4 lead AE free-rate to 92.5% at 
5 years, and a non-powered, superiority comparison for those individual lead-related 
AEs to 1% at 5 years. The sample size for primary safety endpoint 1 was calculated 
based on the following assumptions:  
Assumptions for primary safety endpoint 1 
- 
Study Design: nonrandomized registry 
- 
Test basis: exact binomial test 
- 
Type I error (alpha): 0.025 (one-sided for superiority) 
- 
Statistical power: 80% 
- 
Estimated AE-Free Rate at 5 years: 95.0% for Protego Leads 
- 
Performance goal for AE-Free Rate at 5 years: 92.5% 
For primary safety endpoint 1, a total of 750 evaluable Protego leads would be required 
to demonstrate superiority to an AE free-rate of 92.5% (see Table 3). Assuming a 10% 
loss to follow-up rate per year over 5 years of follow-up (average of 8.2% of original 
population per year), a total of 1271 (=750/0.95) subjects with an ICD lead would be 
required to be enrolled to evaluate primary safety endpoint 1.  
Assumptions for primary safety endpoint 2 
- 
Estimated individual AE rate at 5 years: 0.4% 
- 
Allowable two-sided, upper 95% confidence bound: 1% 
For primary safety endpoint 2, a total of 1000 evaluable subjects with Protego DF4 
leads would be required to demonstrate a two-sided, upper 95% confidence bound of 
1%, assuming an expected individual AE rate of 0.4% (see Table 3). Assuming a 10% 
loss to follow-up rate per year over 5 years of follow-up (average of 8.2% of original 
population per year), a total of 1694 (=1000/0.95) subjects would be required for 
evaluation of primary safety endpoint 2.  

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2.3.1 
Attrition 
For the sample size calculation, a maximum loss to follow-up of 10% per year (41% 
over 5 years) was assumed. The loss to follow-up rate encompasses all causes for 
subjects to be exited from the registry, including death, device explants, subject directed 
withdrawals, physician-directed withdrawals, and loss of contact with the subject.  
Table 3: Primary Safety Endpoints Sample Sizes 
 
Primary Safety Endpoint 1 
Primary Safety Endpoint 2  
Sample Size of Evaluable 
Subjects 
750 subjects 
1000 subjects 
Total Adjusted for Attrition 
1271 subjects 
1694 subjects 
2.4 
DATA ANALYSES 
The analysis population for all primary endpoints in the registry will be the intention-to-
treat (ITT) population. This population analysis will include all subjects who provide 
informed consent, met the enrollment criteria, and in whom a Protego lead was 
successfully implanted. Subjects enrolled prior to the Protego lead implant but not 
successfully implanted due to a Protego lead related complication (such as cardiac 
perforation caused by the Protego lead) will also be included in the ITT population.  
Descriptive statistics will be used to present and summarize the data collected in the 
clinical registry. Frequency distributions and cross tabulations will be presented for 
discrete variables. Means, standard errors, and ranges will be presented for continuous 
variables. 
Confidence intervals for the AE free-rate will also be estimated based on Kaplan-Meier 
estimates for freedom from adverse events together with the associated standard errors. 
2.4.1 
Endpoint Analysis 
Primary safety endpoint 1 will be evaluated by performing an exact binomial test 
comparing the observed proportion (overall AE free-rate at 5 years) to 92.5%. 
Equivalently, the two-sided 95% lower confidence bound for the absolute difference 
between the overall AE free-rate and 92.5% must exceed zero. 
The evaluation of primary safety endpoint 2 will be based on the exact, two-sided 95% 
confidence interval for the observed, individual AE rates at 5 years. The upper bound of 
these 95% confidence intervals must be less than 1%. 
Secondary endpoints 1 and 2, which summarize pacing thresholds, sensing, impedance 
measurements and shock impedance measurements for the Protego lead, will be 
reported via standard measures, including means, standard deviations, medians, 
minimums, and maximums.  

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Secondary endpoint 3, which includes AEs that were excluded from primary safety 
endpoint 1, through 5 years post-implant will also be summarized as AE rates together 
with their associated, exact 95% confidence intervals.  
2.4.2 
Trend Analyses 
The primary safety endpoints are evaluated at 5 years post-implant against pre-
specified performance levels (92.5% for overall freedom from Protego lead-rated AEs, 
1% for individual AE rates). To monitor the ongoing incidence of any potential AEs 
against the accumulating follow-up exposure post-implant, Kaplan-Meier survival curves 
will be prepared at the reporting intervals for these safety outcomes. Root causes for 
any failures, regardless of the incidence rates, will be investigated.  
If the observed cumulative survival rates fall below the 5-year target values (92.5% of 
overall freedom from AEs, 99% for individual AEs) at any time during the registry, or are 
projected to fall below the target values, then BIOTRONIK will summarize the observed 
data and the results of its failure investigations, and report the findings to the FDA at or 
before the next scheduled status report. If at any time a single unanticipated adverse 
event or device failure, or combination of events, is believed to have implications 
regarding the safety of current or future subjects, then this will be reported to the FDA 
within the statutory timeframes. 
2.4.3 
Missing Data 
All possible steps will be taken to minimize missing data in the registry. This includes 
but is not limited to monitoring of registry forms for completeness and supporting efforts 
to track and maintain contact with registry subjects during the follow-up period.  
The reasons for any missing data in the registry will be documented. BIOTRONIK will 
examine both missing-data patterns, which describe which values are observed and 
which are missing, and the missing-data mechanisms, which concerns the relationship 
between missingness and the values of variables in the registry data set2. 
For evaluation of the long-term primary registry endpoints (safety endpoints 1 and 2), 
only subjects who achieve 5 years of follow-up or have experienced an adverse event 
prior to 5 years will be included in the final evaluation of the associated hypotheses. The 
secondary endpoint of other AEs at 5 years, excluded from the primary safety analyses, 
will be analyzed in similar manner. There will be no imputation for these missing 
adverse event outcomes. 
For purposes of Kaplan-Meier survival analyses, described in Section 2.4.2, all AE data 
on enrolled subjects will be included with follow-up times censored at the time of 
withdrawal or last completed follow-up visit representing the time of the last known AE 
status. 
                                            
2 R.J.A. Little and D.B. Rubin, 2002, Statistical Analysis with Missing Data, 2nd edition, Wiley and Sons 

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Secondary endpoints, which include successful sensing and pacing, pacing thresholds, 
sensing and impedance measurements will be analyzed in two ways. First, all available 
results will be summarized by scheduled visit through the 5 years of registry follow-up. 
Secondly, a last value carried forward (LVCF) will be used to estimate the values at the 
final 5-year follow-up evaluation for subjects who withdraw prior to 5 years. 
2.4.4 
Poolability Analysis 
The distribution in AE free-rates across centers will be examined. The significance of 
differences in rates between centers will be initially tested using a Kruskal-Wallis test 
statistic, with an associated p-value of 0.15 or less considered evidence of center 
differences.  
A Cochran-Mantel-Haenszel test with continuity adjustment will be used to assess the 
poolability of data collected across the different centers. If evidence is found of center 
differences, then the reasons for the differences will be explored using Cox and logistic 
regression methods to determine if any baseline subject risk factors are explanatory. 

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3. 
PROTOCOL REQUIREMENTS 
3.1 
SUBJECT POPULATION 
The investigator is responsible for screening all potential subjects and selecting those 
who are appropriate for registry inclusion. Those selected for participation should be 
from the investigator's general patient population according to the indications below. 
Additionally, potential subjects will be evaluated against the inclusion and exclusion 
criteria described in Sections 3.1.3 and 3.1.4. 
3.1.1 
Indications 
The Protego lead is a 7.8 French (8 F introducer) transvenous, steroid-eluting, bipolar, 
DF4 compatible ICD lead intended for permanent implantation in the right ventricle to 
provide pacing/sensing in the right ventricle and defibrillation/cardioversion shocks to 
the heart. For this registry, the Protego lead is utilized in conjunction with any market-
released BIOTRONIK Ilesto or future US market released ICD/CRT-D device with a 
DF4 header. 
3.1.2 
Contraindications 
Transvenous endocardial leads are contraindicated in the presence of severe tricuspid 
valvular disease and in patients with a mechanical tricuspid valve. The Protego DF4 
lead is additionally contraindicated for patients who cannot tolerate a single systemic 
dose of dexamethasone acetate (DXA) of up to 1.3 mg for active fixation leads or 1.0 
mg for passive fixation leads. 
3.1.3 
Inclusion Criteria 
To support the objectives of this investigation, patients are required to meet the 
following inclusion criteria prior to enrollment:  
- 
Implanted within the last 30 days or candidate for implantation of a BIOTRONIK ICD 
or CRT-D DF4 compatible system along with the Protego DF4 lead 
- 
Meets ICD or CRT-D system implant recommendations as defined in guidelines 
published by relevant professional societies 
- 
Able to understand the nature of the registry and provide informed consent 
- 
Available for follow-up visits on a regular basis at the investigational site for the 
expected 5 years of follow-up 
- 
Age greater than or equal to 18 years 

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3.1.4 
Exclusion Criteria 
To support the objectives of this investigation, the exclusion criteria at the time of patient 
enrollment include the following requirements: 
- 
Enrolled in any investigational cardiac device trial 
- 
Planned cardiac surgical procedures or interventional measures within the next 6 
months 
- 
Expected to receive heart transplantation or ventricular assist device within 1 year 
- 
Life expectancy of less than 1 year 
- 
Presence of another life-threatening, underlying illness separate from their cardiac 
disorder 
- 
Patients reporting pregnancy at the time of enrollment 
3.2 
REGISTRY PROCEDURES 
Patients will be enrolled ± 30 days from implant of a BIOTRONIK DF4 compatible ICD 
or CRT-D device and Protego lead. BIOTRONIK Home Monitoring® should be activated 
in subjects who have a Home Monitoring® system. Home Monitoring® data can be 
utilized to assist in triage and diagnosis of lead-related adverse events between 
scheduled follow-ups. Subjects with a Home Monitoring® system will be seen for a 
routine in-office follow-up at least every 12 months and have the option to be followed 
by Home Monitoring® between routine in-office follow-ups at the intervening 6 month 
intervals. Subjects without a Home Monitoring® system will be seen for a routine in-
office follow-up at least every 6 months. 
Registry Procedure Visits: 
- 
Enrollment 
- 
Implant (collected retrospectively if before enrollment) 
- 
Routine follow-up evaluations at 3 months post-implant and every 6 months post-
implant for 5 years 
- 
Interim evaluations for Protego lead-related events or system revisions 
Table 4 summarizes the visit assessment schedule. 
 
 
 
 
 

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Table 4: Registry Visit Assessment Schedule 
 
Enrollment 
Implant1 
Routine Follow-up 
3 Months and 6-60 
Months 
 (every 6 months ± 
1 month)2 
Interim 
Evaluation 
(if applicable) 
Informed Consent (enrollment) 
X 
 
 
 
Demographics and Medical History 
X 
 
 
 
Collect Implant Information 
X3 
X3 
 
X 
Device Evaluation 
 
X 
X 
X 
Adverse Event Assessment 
 
X 
X 
X 
Complete eCRF 
X 
X 
X 
X 
1Implant must be completed within 30 days of or no more than 30 days prior to enrollment/informed consent. 
2Subjects using Home Monitoring® will be seen for a routine in-office follow-up at least every 12 months and may be followed by 
Home Monitoring® between routine in-office follow-ups at the intervening 6 month intervals. Subjects not using Home Monitoring® 
will be seen for a routine in-office follow-up at least every 6 months. If a registry visit is conducted via Home Monitoring® the site is 
required to call the subject on the date of the Home Monitoring® data collection and document the Investigators assessment of 
possible adverse events since the last registry visit. 
3If implant was completed prior to enrollment, implant data is collected retrospectively at the enrollment visit. If the subject was 
enrolled prior to implant, implant data will be collected and entered at the time of the implant procedure. 
3.2.1 
Registry Pre-Screening 
Prior to enrollment, the patient’s medical history must be reviewed in order to ensure 
they are an appropriate candidate for the registry. In addition, all patients must satisfy 
the registry inclusion and exclusion criteria prior to enrollment, including being a 
candidate for or having been implanted with a BIOTRONIK Protego lead and DF4 
compatible ICD or CRT-D within the last 30 days. 
3.2.2 
Enrollment Visit 
If the patient has been determined to be eligible for the registry, informed consent must 
be obtained from the patient prior to initiating any registry related procedures. The 
consent process, including discussion of the registry, will be documented in the patient’s 
medical record. A patient is considered enrolled in the registry upon signing the 
Informed Consent Form and undergoing an attempt to implant the Protego DF4 lead. If 
a patient is consented and undergoes enrollment procedures prior to implant, they are 
considered ‘provisionally enrolled’ until they are successfully implanted, at which time 
they are considered fully enrolled. The visit at which informed consent is obtained is the 
enrollment visit and occurs ± 30 days from the date of implant. If implant occurs prior to 
enrollment, the date of implant and system information must be available for the patient 
to be enrolled. Patient demographics are to be obtained at the enrollment visit; however, 

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height and weight may be historical if this information is not available, with proper 
source documentation. 
The following data collection and reporting procedures are performed at the enrollment 
visit: 
- 
Obtain Informed Consent 
- 
Collect subject demographics (gender, height, weight, etc.) 
- 
Medical history of subject, including device implant indications 
- 
Complete all required eCRFs 
3.2.3 
Protego Implant 
Implant will be completed ± 30 days from the enrollment visit. Implant details and device 
data will be collected retrospectively if implant occurred prior to enrollment. 
The following data collection and reporting procedures are performed at implant: 
- 
Collect implant information 
o Date of implant 
o Implant approach/method, and venous access 
o Implant success 
o If DFT testing was completed during implant, shock energy and impedance used 
during test 
- 
Collect 
information 
on 
implanted 
system 
(pulse 
generator 
and 
leads 
manufacturer/model, serial numbers, etc.). 
- 
Record electrical parameters of the implanted leads. Perform all pacing threshold 
measurements at 0.4 ms or 0.5 ms pulse width. 
- 
Record any lead-related, pulse generator-related and procedure-related adverse 
events during implant and complete an Adverse Event eCRF. Protego lead related 
adverse events should be reported even if the implant attempt is unsuccessful. 
- 
Program parameters to best suit the needs of the subject. 
- 
Complete all required eCRFs. 
Patients that are provisionally enrolled, but never successfully implanted with the 
Protego lead, will be considered screen failures. If they undergo an implant attempt, but 
are not successfully implanted due to a Protego lead related adverse event (such as 

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cardiac perforation caused by the Protego lead) they will also be included in the 
intention-to-treat (ITT) population.  
3.2.4 
Routine Follow-ups 
Three and six months (± 30 days) after successful implant and every six months (± 30 
days) thereafter, subjects will undergo an assessment of their implanted system. 
Subjects with Home Monitoring® capabilities will be seen for a routine in-office follow-up 
at least once every 12 months and have the option to substitute a Home Monitoring® 
evaluation for every other in-office follow-up to result in the six month follow-up 
schedule. Additionally, each Home Monitoring® follow-up will be accompanied by an 
assessment via telephone call within 7 days, documenting clinical signs and symptoms. 
Subjects not using Home Monitoring® will be seen for a routine in-office follow-up at 
least once every six months.  
Each site Principal Investigator (PI) will be trained to identify and schedule follow-ups to 
meet the required visit expectation. Additionally, the EDC will provide assistance in 
identifying properly scheduled follow-ups according to this protocol. 
The following study procedures are performed at routine in-office follow-ups: 
- 
Interrogate and print initial programmed parameters and view stored diagnostic data. 
- 
Record and print electrical parameters of the implanted leads. Perform all pacing 
threshold measurements at 0.4 ms or 0.5 ms pulse width. 
- 
Evaluate device diagnostics, electrical parameters and programmed parameters to 
ensure the device is correctly pacing, sensing, and providing appropriate therapy. 
- 
Record and print cumulative episode counters. 
- 
Determine if there have been any adverse events (as defined in Section 10). If any 
are recorded, complete an Adverse Event eCRF. 
- 
Interrogate and print the final programmed parameters. 
- 
Complete all appropriate eCRFs. 
The following study procedures are performed for a Home Monitoring® evaluation: 
- 
Collect programmed parameters and view stored diagnostic data. 
- 
Record electrical parameters of the implanted leads. 
- 
Evaluate device diagnostics, electrical parameters and programmed parameters to 
ensure the device is correctly pacing, sensing, and providing appropriate therapy. 
- 
Record cumulative episode counters. 

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- 
Perform phone interview within 7 days of Home Monitoring® report. 
- 
Determine if there have been any adverse events (as defined in Section 10). If any 
are recorded, complete an Adverse Event eCRF. 
- 
Complete all appropriate eCRFs.  
3.2.4.1 
Device Programming 
If Home Monitoring® evaluations will be used for routine follow-up visits, atrial and 
ventricular capture control should be programmed to “ON” or “ATM,” and Home 
Monitoring® activated. If atrial and ventricular capture control is not programmed 
“ON”/”ATM” or goes off automatically due to AF, high intrinsic rate, or other reason, the 
investigator will provide reasons in the EDC system. 
3.2.5 
Unscheduled Interim Follow-ups 
Unscheduled interim follow-ups may occur anytime during the registry. Data collection is 
only required when a subject is seen for Protego lead-related reasons or due to a 
protocol defined adverse event. Other hospital or clinic visits that are unrelated to the 
device are not required to be entered into the EDC system. 
3.2.5.1 
Protego Related Interim Follow-ups 
For unscheduled interim in-office follow-ups related to the Protego lead (but not 
including a system revision), the data collection and reporting requirements are the 
same as those required for routine follow-ups (Section 3.2.4). 
3.2.5.2 
System Revisions 
For interim evaluations that involve a system revision (even if the Protego lead is not 
directly affected), the following are required: 
- 
Collect implant information 
o Date of revision 
o Implant approach/method, and venous access 
o Implant location of pulse generator and implanted leads 
- 
Record extraction experience (if applicable). 
- 
Collect information on newly implanted system (pulse generator and leads 
manufacturer/model, serial numbers, etc.). 
- 
Record electrical parameters of the implanted leads. Perform all pacing threshold 
measurements at 0.4 ms or 0.5 ms pulse width. 

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- 
Record any lead-related, pulse generator-related and procedure-related adverse 
events during implant and complete the Adverse Event eCRF. 
- 
Set programming parameters to best suit the needs of the subject. 
- 
Complete System Revision and Out of Service (OOS) eCRF, as applicable.  
If the Protego lead is replaced with another Protego lead, the subject will continue 
participation in the registry based on the original implant date and visit schedule. If the 
Protego lead is explanted and the subject does not receive a new Protego lead, the 
subject will be withdrawn from the registry. See Section 3.3.3 for details on withdrawals 
due to lead or pulse generator extraction. 
3.3 
REGISTRY EXITS 
Once a subject is enrolled and successfully implanted, every effort should be made to 
continue to follow the subject in the registry. However, it is inevitable that some subjects 
will decline to participate further, change geographic location, or become non-compliant 
with the visit schedule. 
3.3.1 
Withdrawal of Consent  
If consent is withdrawn, obtain the date of withdrawal and reason for withdrawal of 
consent, then complete a Registry Exit eCRF. 
3.3.2 
Subject Death 
In the event of subject death during registry participation, personnel at the 
investigational site are asked to notify BIOTRONIK as soon as possible by completing 
an Out of Service and Registry Exit eCRF. If subject death was associated with an 
adverse event, an Adverse Event eCRF will also be required.  
The following information should be reported for any subject death: 
- 
Death certificate or death report, signed by the investigator, that includes: 
o Date and time of death 
o Place death occurred 
o Identification of the rhythm at the time of death, if known (include any available 
documentation) 
o Immediate cause of death 
o Any other circumstances surrounding the death 
o Whether death was device or procedure related 

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- 
Timing for Institutional Review Board (IRB) or Ethics Committee (EC) notification (if 
required by the IRB/EC) 
- 
Protego lead return status 
Whenever possible, devices that are explanted must be returned to BIOTRONIK for 
analysis. 
3.3.3 
Protego Lead or Pulse Generator Extraction 
Any subject who has the Protego lead explanted or capped, and is not implanted with 
another Protego lead, will be withdrawn from the registry. Additionally, any subject who 
has their BIOTRONIK pulse generator explanted and replaced with a non-BIOTRONIK 
device will also be withdrawn from the registry (even if the Protego lead remains). Only 
complete a registry exit eCRF after documentation of the system revision procedure 
(see Section 3.2.5.2) is available. For example, if the Protego lead and pulse generator 
are explanted due to infection, the subject should not be exited until a non-registry 
lead/system is implanted or documentation is available stating that the subject will not 
be re-implanted with a registry qualifying lead/system. Report the exit on the Registry 
Exit eCRF and any adverse events resulting from the explant procedure. 
Whenever possible, devices that are explanted must be returned to BIOTRONIK for 
analysis. 
3.3.4 
Lost to Follow-up 
Subjects lost to follow-up are those for whom contact is lost despite the investigator’s 
best efforts to locate the subject. Registry sites should attempt to contact these subjects 
in order to maintain registry visit compliance and all contact attempts should be 
documented. At a minimum, the site should make and document two attempts to 
contact the subject by phone and one attempt by certified mail. 
In the event the subject cannot be contacted using the above methods, the subject 
should be exited from the registry by completing a Registry Exit eCRF.  
3.3.5 
Registry Participation Complete 
All subjects are expected to be followed for a minimum of 59 months accounting for the 
visit expectation of 60 months (5 years) ± 1 month. After a subject completes their final 
routine visit in this time interval, their study participation is complete and the subject 
should be exited from the registry by completing a Registry Exit eCRF.  
 

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4. 
REGISTRY ORGANIZATION 
4.1 
SPONSOR 
BIOTRONIK is the sponsor of the Protego DF4 post-approval registry. A sponsor is 
defined as an entity that initiates but does not conduct an investigation. BIOTRONIK’S 
responsibility as the clinical registry sponsor is to ensure protocol and regulatory 
compliance through proper monitoring of the investigation. BIOTRONIK is required to 
ensure that the registry device is used under the immediate direction of an investigator.  
4.2 
CLINICAL EVENTS COMMITTEE  
A Clinical Events Committee (CEC) consisting of at least 3 independent 
electrophysiologists will be established to review and adjudicate adverse events that 
occur during the registry. The CEC will be blinded to the clinical registry site and subject 
identity, and to minimize bias, members will not participate as investigators. The CEC 
will create a registry specific charter defining the adverse event adjudication process, 
specifically detailing review guidelines along with appropriate response timelines. 
All protocol defined adverse events included in the primary and secondary endpoint 
analysis (see Section 10.3.1 and Section 10.3.2) will be adjudicated by the Clinical 
Events Committee. The Clinical Events Committee (CEC) will have the responsibility to 
adjudicate the classification and category of each reported adverse event. In addition, 
the CEC will also indicate whether the adverse event is related, possibly related, not 
related, or has an unknown relation to the Protego lead.  
 

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5. 
DATA COLLECTION 
5.1 
ELECTRONIC DATA CAPTURE (EDC) 
MedNet Solutions Incorporated is a privately held company that specializes in web-
based clinical data management technology. MedNet will host the EDC system and 
provide a secure environment that is accessible to authorized individuals through the 
internet. BIOTRONIK will implement a registry specific configuration using this software 
to meet the data collection requirements of the protocol. The EDC system is 21 CFR 
Part 11 compliant and is the platform for electronic case report form (eCRF) data entry, 
clinical data discrepancy resolution, and access to reports for BIOTRONIK, specified 
investigational sites, and any other parties authorized by BIOTRONIK. 
5.2 
CASE REPORT FORMS (CRFS) 
Original data will be collected at each investigational site and recorded into the EDC 
system, audited and monitored by BIOTRONIK, via completion of electronic CRFs 
(eCRFs). The investigator will be required to use an electronic signature to approve the 
content of the data reported in the eCRFs. 
Information from electronically delivered source data (e.g. programmers) will be 
captured and stored in a validated environment until the end of the registry. 
Subject follow-up is required for all subjects enrolled in this clinical registry. The 
required follow-up visit dates are based on Protego lead implant date, and are to be 
used for the calculation of the dates of the routine follow-up schedule. The following 
eCRFs will be available in the EDC system: 
- 
Informed Consent 
- 
Enrollment  
- 
Implant Procedure 
- 
Implant Test Values 
- 
Routine Follow-ups (± 30 days) 
- 
Unscheduled Interim Follow-up 
- 
Adverse Event 
- 
System Revision 
- 
Out of Service 
- 
Registry Exit 
- 
Protocol Noncompliance 
- 
Data Clarification 

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5.3 
DATA CLARIFICATION/DATA QUALITY CONTROL 
BIOTRONIK will review registry data. At any time, reports can be generated on data 
completion and missing data for each investigational site. An EDC system will be used 
to track received and expected follow-up data and eCRFs for each participant. This 
system provides the capability to monitor the status, volume, and disposition of data as 
well as to identify data completed, due, overdue, and backlogged. In addition, all 
registry data will undergo extensive automatic edit and plausibility checks which provide 
information to the investigational sites to help improve and maintain data quality control 
procedures designed to detect inaccuracies and inconsistencies.  
To ensure protocol compliance at all participating investigational sites, BIOTRONIK 
monitors will conduct monitoring visits (see Section 7).  
To ensure compliance with federal regulations, internal policies and procedures, and the 
registry protocol, the EDC vendor will also be monitored and/or audited by BIOTRONIK 
or a BIOTRONIK representative during the course of the registry. 
5.4 
SUBJECT RETENTION 
Although the registry sample size has been calculated with a 10% subject attrition rate 
per year (41% total in 5 years), subject retention in a 5 year registry may pose 
additional, unforeseen challenges. BIOTRONIK will provide additional tools to the sites 
in an effort to minimize the number of subjects that are lost to follow-up. The EDC 
system includes an overview of each subject’s follow-up schedule, including the 
windows for each follow-up. The EDC system also provides a subject follow-up 
scheduling tool in the form of a Visit Scheduler Report. This report allows research 
personnel to become alerted to and track all registry subjects that should be scheduled 
for upcoming follow-ups. Monitoring visits include a review of subjects that may be lost 
to follow-up (see Section 7).  
5.5 
SUBJECT DATA CONFIDENTIALITY 
All information sent to BIOTRONIK pertaining to each subject will be kept confidential at 
BIOTRONIK and is subject to FDA audit. Source documents used to support endpoint 
adjudication by the CEC in the Protego DF4 registry will have all confidential subject 
identifiers redacted prior to transmission. Reports submitted to the physician or 
publications of registry results will not make any reference to subject names. 
In order to verify the registry data and ensure registry integrity, monitors from 
BIOTRONIK, the FDA, and the reviewing Institutional Review Board (IRB) may review 
and/or copy the registry records. 
 
 

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6. RISKS AND RISK MINIMALIZATION 
All devices included in this registry are legally marketed and being prescribed by 
physicians according to FDA approved indications for use. 
As with any implantable device, there are always potential risks that accompany the 
device. The following list provides the potential risks that may occur with the Protego 
DF4 lead in combination with an ICD or CRT-D device. 
- 
Acceleration of arrhythmias 
- 
Air embolism 
- 
Allergic reactions to contrast media 
- 
Arrhythmias 
- 
Bleeding  
- 
Body rejection phenomena 
- 
Cardiac tamponade 
- 
Chronic nerve damage 
- 
Damage to heart valves 
- 
Damage to lead during implant procedure 
- 
Device migration 
- 
Elevated pacing thresholds 
- 
Embolism 
- 
Erosion or pocket erosion 
- 
Extrusion 
- 
Fluid accumulation 
- 
Hematomas, cysts, or fibrotic tissue 
- 
Incomplete lead connection with the pulse generator 
- 
Infection 
- 
Inappropriate detection of ventricular arrhythmias 
- 
Inappropriate therapy, including inappropriate shocks 
- 
Keloid formation 
- 
Lead abrasion and discontinuity 
- 
Lead migration / dislodgment 
- 
Lead fracture / insulation damage 
- 
Lead perforation 
- 
Lead-related thrombosis 

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- 
Local tissue reaction / fibrotic tissue formation 
- 
Muscle or nerve stimulation 
- 
Myocardial damage 
- 
Myopotential sensing 
- 
Pacemaker mediated tachycardia 
- 
Pneumothorax 
- 
Potential death due to inability to defibrillate or pace 
- 
Psychological effects (dependency, depression, fear of premature battery depletion, 
fear of shocking while awake, fear that shocking ability may be lost, anxiety about 
device resulting from frequent shocks, imagined (phantom) shock) 
- 
Random component failure 
- 
Shunting current or insulating myocardium during defibrillation with internal or 
external paddles 
- 
Thromboembolism 
- 
Undersensing of intrinsic signals 
- 
Valvular damage 
- 
Venous occlusion 
- 
Venous or cardiac perforation 
- 
Ventricular ectopy 
These risks can be minimized through use of strict aseptic technique, compliance with 
the registry protocol and technical implant procedures, adherence to the guidelines for 
selection of subjects, close monitoring of the subject’s physiologic status during the 
implant and follow-up procedures, and by promptly supplying BIOTRONIK with all 
pertinent information required by this protocol.  
BIOTRONIK foresees no additional risks associated with this registry beyond those 
stated in the labeling for the respective pulse generators and leads. 
 

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7. 
REGISTRY MONITORING 
7.1 
SUMMARY 
BIOTRONIK’s responsibility as the clinical registry sponsor is to ensure protocol and 
regulatory compliance through proper monitoring of the investigation. BIOTRONIK 
requires IRB/EC review and a subject Informed Consent Form for all after-market 
research. Monitoring may be conducted on-site at the investigational site or remotely by 
BIOTRONIK monitors.  
Through on-site or centralized monitoring, BIOTRONIK will assess the site’s 
performance in the following areas:  
- 
Verification that informed consent was obtained and documented properly 
- 
Adherence to protocol eligibility criteria and requirements 
- 
Conduct and documentation of procedures and assessments related to: 
o Study endpoints 
o Protocol required safety assessments 
o Evaluating, documenting, and reporting unanticipated adverse device effects, 
subject deaths, and withdrawals, especially when a withdrawal may be related to 
an adverse event. 
- 
Investigator oversight and delegation of authority to study personnel 
- 
Verification of study-specific required documentation 
- 
Conduct and documentation of procedures essential to trial integrity 
- 
Adherence to the applicable FDA regulations regarding the obligations of the 
investigator and maintenance of records. 
As the investigator, the physician is responsible for conducting the registry in 
accordance with the signed agreement, the investigational plan (protocol), applicable 
laws, FDA regulations, and any conditions of approval imposed by the reviewing 
IRB/EC. The principal investigator must also accept responsibility for all aspects of the 
registry including the actions of any sub-investigators participating in the registry at the 
investigational site. 
7.2 
REGISTRY MONITORS 
Monitors are trained, qualified, and designated by BIOTRONIK management to oversee 
the progress of an investigation at the clinical site. Additional monitors may be 
appointed as necessary. 

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The address to submit registry information to BIOTRONIK is: 
BIOTRONIK, Inc. 
Attn: Protego DF4 Registry 
Clinical Studies Department 
6024 Jean Road 
Lake Oswego, Oregon 97035 
Registry information may be submitted by fax to: 800 723-9220 
For registry assistance, call: 800 547-0394 
For technical assistance 24 hours a day, call: 800 547-0394 
7.3 
MONITORING VISITS 
A monitor will conduct monitoring visits at investigational sites in accordance with the 
Monitoring Plan. Sites are required to support these visits and the study monitoring 
effort. On-site monitoring visits will also provide an assessment of the continued 
acceptability of the facilities to continue participation in the registry.  
7.4 
CENTRALIZED MONITORING  
Centralized monitoring will be conducted throughout the course of the study in 
accordance with the Monitoring Plan. Some examples of data that may be monitored 
remotely include device data and adverse events reported in the EDC system. Sites are 
required to support centralized monitoring by providing source documents to 
BIOTRONIK in order to source data verify data reported in the EDC system and 
resolving queries in a timely manner.  
 

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8. 
REGISTRY COMPLETION 
BIOTRONIK will notify the post-approval registry site upon completion or termination of 
the registry or investigator’s participation in the registry. At BIOTRONIK’s request, an 
investigator will return any study specific equipment and pertinent information in their 
possession. BIOTRONIK will provide a final report to each investigational site as 
required by FDA regulations. After FDA has granted approval to terminate this post-
approval registry, BIOTRONIK personnel may conduct a registry closure visit according 
to the monitoring plan. During this visit, BIOTRONIK will verify registry records and 
ensure that the investigator understands any applicable regulatory requirements 
including those related to record retention. The investigator must retain records related 
to the registry for a period of 2 years after the registry is completed. 
In the event that the registry is suspended or terminated, the investigator must inform all 
enrolled subjects who at that time have not yet completed the registry. Standard patient 
care will be ensured by the registry site.  
 

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9. 
PROTOCOL COMPLIANCE 
The investigator is responsible for conducting the registry in accordance with the signed 
agreement, the investigational plan (protocol), applicable laws, FDA regulations, and 
any conditions of approval imposed by the reviewing IRB/EC. The investigator shall 
notify BIOTRONIK and the reviewing IRB/EC in writing no later than 5 working days 
after any significant deviation from the investigational plan to protect the life or physical 
well-being of a subject in an emergency. Except in such emergency, prior approval by 
BIOTRONIK is required for significant deviations from the investigational plan.  
BIOTRONIK categorizes protocol noncompliance instances as either violations or 
deviations. Both protocol violations and deviations will be reported to FDA during interim 
reports. 
9.1 
PROTOCOL VIOLATIONS 
Protocol violations are defined as instances where the protocol requirements and/or 
regulatory guidelines were not followed, and are generally more serious in nature. 
Protocol violations are considered to potentially affect the scientific soundness of the 
plan and/or the rights, safety, or welfare of subjects. Protocol violations include, but are 
not limited to: 
- 
Failure to obtain consent 
- 
Subject inclusion/exclusion violations and protocol requirement violations that affect 
the primary endpoints of the registry design 
These violations will be reported to FDA in accordance with applicable regulatory 
timelines and the site must notify the reviewing IRB/EC per the IRB/EC’s reporting 
requirements. The site should provide a copy of the IRB/EC protocol noncompliance 
notification (as applicable) to BIOTRONIK. Protocol violations must also be reported to 
BIOTRONIK via Protocol Noncompliance eCRFs. 
9.2 
PROTOCOL DEVIATIONS  
Protocol deviations are deviations from the requirements of the protocol in such a 
manner whereby data is unusable or not available. Protocol deviations are less serious 
in nature and do not require IRB/EC notification as long as they do not have an effect on 
the rights, safety, or welfare of the registry subject. Protocol deviations include, but are 
not limited to: 
- 
Procedure not performed within the allowed follow-up window 
- 
Required data not obtained 
The site must report protocol deviations to BIOTRONIK via Protocol Noncompliance 
eCRFs. Both protocol deviations and violations will be reported to FDA in progress 
reports. 

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10. ADVERSE EVENTS 
An adverse event (AE) is defined as any unfavorable and unintended event that occurs 
during the course of the study. The investigator will be required to assess and classify 
each reported adverse event as related to either the implant procedure, implanted pulse 
generator, Protego lead, right atrial lead, left ventricular lead, or as non-procedure non-
system related. For subjects enrolled prior to implant, only adverse events from the first 
implant attempt onward will be collected. 
The investigational site should report each adverse event via an Adverse Event eCRF 
and provide a copy of the IRB/EC adverse event notification to BIOTRONIK.  
10.1 
REPORTABLE ADVERSE EVENTS 
The following AEs (sorted by classification) will be reported. The classifications listed 
below are general classifications for site reporting purposes. Detailed information for 
many classifications is located in Appendix A. The CEC charter may include alternate 
classifications for some adverse events. 
10.1.1 
Implant Procedure-Related Adverse Events 
An AE will be classified as procedure-related if any one of the following occurred as a 
result of the implant procedure: 
- 
Arrhythmias associated with the implantation of the lead 
- 
Cardiac perforation with or without tamponade  
- 
Coronary sinus dissection 
- 
Damage to lead during procedure (e.g. accidental cut to lead body during pocket 
revision, device replacement, etc.) 
- 
Hematoma 
- 
Primary infection  
- 
Lead dislodgement during a procedure (e.g. during pocket revision, device 
replacement, etc.) 
- 
Lead reversed in header 
- 
Loose set-screw 
- 
Non-healing pocket dehiscence requiring intervention 
- 
Pneumothorax  
- 
Pocket pain 
- 
Pulmonary embolism  
- 
Venous occlusion 

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10.1.2 
Pulse Generator-Related Adverse Events 
An AE will be classified as pulse generator-related if any one of the following occurred: 
- 
DF4 header connector malfunction 
- 
DF4 header fluid intrusion 
- 
Device migration 
- 
Premature battery depletion 
- 
Pulse generator failure 
- 
Skin erosion 
10.1.3 
Lead-Related Adverse Events 
An AE will be classified as lead-related if any one of the following occurred: 
- 
Cardiac perforation  
- 
Diaphragmatic/extracardiac stimulation 
- 
High pacing threshold3 
- 
Intermittent capture / no lead capture 
- 
Lead conductor fracture 
- 
Lead dislodgement  
- 
Lead impedance out of range, high impedance4 
- 
Lead impedance out of range, low impedance4 
- 
Lead failure 
- 
Lead oversensing not due to external noise 
- 
Lead oversensing due to external noise 
- 
Lead-related thrombosis 
- 
Lead-related infection 
- 
Lead undersensing or loss of sensing 
- 
Other unexpected complications that are identified through imaging and considered 
related to the ICD lead or DF4 connector 
 
                                            
3 High pacing threshold is defined as: 
A. At implant, threshold that is greater than 3.0V at 0.4ms or 0.5ms, OR 
B. At follow-up, threshold that has increased two fold from the chronic (3 month follow-up) threshold 
value and is greater than 3.5V at 0.4ms or 0.5ms. 
4 Lead impedance out of range is defined as a pacing impedance measurement of ≤ 200 Ohms or ≥ 2000 
Ohms or a shock impedance measurement of ≤20 Ohms or ≥150 Ohms. 

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For each of these lead-related AEs, indicate: 
- 
Confirmed lead integrity failure 
- 
Suspected lead integrity failure 
- 
No lead integrity failure 
10.1.4 
Non-Procedure Non-System Related Adverse Events 
An AE will be classified as non-procedure non-system related if any of the following 
occur and require a system revision or explant: 
- 
Twiddler’s syndrome 
- 
Secondary infection 
- 
Ablation sequelae 
10.2 
ENDPOINT ANALYSIS 
All protocol defined adverse events included in the primary and secondary endpoint 
analysis will be adjudicated by the Clinical Events Committee (CEC) (see Section 2.1). 
The CEC will have the responsibility to adjudicate the classification and category of 
each reported adverse event as implant procedure, implanted pulse generator, lead, or 
non-procedure non-system related. For each adverse event, the CEC will indicate 
whether the adverse event relatedness to the Protego lead is: not related, related, 
possibly related, or unknown.  
In evaluation of the two primary endpoints for the post-approval registry, the estimates 
of AE rates will be based on the number of subjects with at least one “related” AE as a 
proportion of total subjects. Subjects with a final adjudicated related AE classification of 
“possibly related”, “not related” or “unknown” will not have that individual event 
contribute to or be included in the evaluation of primary safety endpoints. The same 
rules will be used for purposes of Kaplan-Meier survival analyses, described in Section 
2.4.2.  
Secondary endpoint 3, which includes AEs that were excluded from primary safety 
endpoint 1 through 5 years post-implant, will also be summarized as AE rates along 
with their associated, exact 95% confidence intervals. 

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10.3 
ADVERSE EVENTS FOR THE ANALYSIS OF THE PRIMARY AND 
SECONDARY ENDPOINTS 
10.3.1 
Adverse Events for the Analysis of Primary Endpoints 1 and 2 
If any of the following invasive actions occur in order to resolve an above listed Protego 
lead-related AE, the AE will be included in the primary safety endpoint analysis: 
- 
Lead surgically repositioned 
- 
Lead surgically explanted 
- 
Lead surgically replaced 
- 
Lead surgically abandoned 
- 
Other lead-related surgery performed  
Additionally, if any of the following non-invasive actions occur in order to resolve an 
above listed Protego lead-related AE, the Protego lead-related AE will be included in the 
primary endpoint analysis: 
- 
Lead pacing polarity or pacing mode reprogrammed due to suspected lead 
failure.  
- 
Lead abandoned and pacing disabled due to clinical failure or suspected lead 
failure 
- 
Lead use continued based on medical judgment despite a known clinical failure 
or suspected lead failure 
AEs that are corrected by reprogramming the pulse generator (other than the above) 
and resolved without invasive action will not be considered an adverse event counted 
towards the primary endpoints. For example, electrical reprogramming of the pacing 
polarity to eliminate extra-cardiac stimulation will not be considered an adverse event. 
Similarly, increasing pacing output as a result of an elevated threshold without further 
intervention does not count toward the primary endpoint analysis. 
Subject deaths as a result of a Protego lead-related AE will be included in the primary 
endpoint analysis. 
Primary endpoints 1 and 2 will exclude 1) lead dislodgements that occur within 30 days 
after lead implant or a lead revision procedure and 2) high pacing threshold, intermittent 
capture, no lead capture within 30 days after lead implant or a lead revision procedure. 
However, these will count towards the adverse event secondary endpoint. 
In addition, the following two pulse generator-related adverse events will be included in 
the analysis of primary endpoints 1 and 2: DF4 header connector malfunction and DF4 
header fluid intrusion. 

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10.3.2 
Adverse Events for the Analysis of Secondary Endpoint 3 
If any of the following invasive actions occur in order to resolve an above listed RA or 
LV lead-related AE, the AE will be included in the secondary endpoint analysis: 
- 
Lead surgically repositioned 
- 
Lead surgically explanted 
- 
Lead surgically replaced 
- 
Lead surgically abandoned 
- 
Other lead-related surgery performed  
Additionally, if any of the following non-invasive actions occur in order to resolve an 
above listed RA or LV lead-related AE, the AE will be included in the secondary 
endpoint analysis: 
- 
Lead pacing polarity or pacing mode reprogrammed due to suspected lead 
failure.  
- 
Lead abandoned and pacing disabled due to clinical failure or suspected lead 
failure 
- 
Lead use continued based on medical judgment despite a known clinical failure 
or suspected lead failure 
All Implant Procedure-related adverse events are included in secondary endpoint 
analysis, as well as Pulse Generator-related and Non-Procedure Non-System-related 
adverse events that require invasive intervention to resolve. 
Adverse events excluded from the primary endpoint, as listed in Section 10.3.1, are also 
included in this secondary endpoint analysis. 
10.4 
ADVERSE EVENT REPORTING 
The adverse events that an IRB/EC considers reportable are dependent on the 
particular IRB/EC. To avoid underreporting, BIOTRONIK recommends that, at a 
minimum, the investigator reports the procedure-related, lead-related, and pulse 
generator-related adverse events that occur during the Protego Post-Approval Registry 
to BIOTRONIK and the IRB/EC. 
The registry site will report the adverse event on the Adverse Event eCRF. Additionally, 
registry sites may report adverse events through MedWatch, FDA’s adverse event 
reporting tool for market-released devices. As defined in BIOTRONIK’s internal 
procedures, these adverse events may be reported by BIOTRONIK through 
manufacturer’s MedWatch reports. 

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11. IRB APPROVAL 
Institutional Review Board (IRB) approval is required from each institution prior to 
participation in this post-approval registry. Subject enrollment may not begin until the 
IRB and BIOTRONIK have granted approval for the investigational site. IRB approval is 
also required throughout the duration of this clinical investigation. If IRB approval is 
withdrawn, BIOTRONIK must be notified within 5 working days.  
11.1 
OTHER INSTITUTIONS AND PHYSICIANS 
This post-approval registry is not transferable to other institutions attended by the 
investigator unless prior approval is obtained from both BIOTRONIK and the 
appropriate IRB/EC. Additional investigational sites may be included in this registry. 
However, there are certain situations where an investigator might not be immediately 
available to provide the necessary medical care for a subject with a registry device (e.g. 
when a subject goes to the emergency room for medical treatment). In any such 
situations, the IRB/EC and the investigator must continue to provide oversight for that 
subject’s medical care and rights as a research subject. BIOTRONIK will ensure that the 
necessary support personnel are available to any physician providing immediate care 
for a subject in order to answer questions about the device and provide guidance in 
collecting the necessary documentation required for the clinical registry.  
 

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12. INFORMED CONSENT  
Prior to the subject’s participation in the investigation, informed consent is required from 
all subjects. Informed consent should be obtained in accordance with the FDA 
regulations (21CFR, Part 50). The investigator is required to inform BIOTRONIK and the 
reviewing IRB/EC within 5 days if any subject was not appropriately consented to 
participate in the registry. BIOTRONIK is then required to report any failure to obtain 
subject consent to the FDA within 5 working days of learning of such an event. In order 
to assist with the consent process, BIOTRONIK will provide a template subject consent 
form to investigational sites participating in the registry. 

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13. RECORDS AND REPORTS 
13.1 
INVESTIGATOR RECORDS 
Investigators are required to maintain on file the following accurate, complete and 
current records relating to this investigation: 
- 
All correspondence relating to the registry with another investigator, an IRB/EC, 
BIOTRONIK, a monitor, or the FDA, or any other regulatory authority. (e.g., a letter 
sent from the investigator to the IRB/EC). 
- 
A copy of the registry protocol 
- 
Signed investigator or research agreement 
- 
Signed Financial Disclosure Form 
- 
A copy of the IRB/EC letter approving the research registry 
- 
A copy of the IRB/EC approved subject Informed Consent Form 
- 
All clinical forms and documentation, including: 
o a copy of the signed subject consent form 
o all supporting documentation for data entered into the EDC system 
o records of any adverse device effect, including supporting documentation 
o records pertaining to subject deaths during the investigation 
o documentation and rationale for any deviations from the clinical protocol 
o any other records required by BIOTRONIK 
13.2 
INVESTIGATOR REPORTS 
Investigators are required to prepare and submit to BIOTRONIK the following complete, 
accurate, and timely reports on this registry when necessary: 
- 
Notification of a subject death during the investigation 
- 
Notification of the withdrawal of IRB/EC approval 
- 
Annual progress reports prepared for the IRB/EC 
- 
Notification of any deviations from the investigational plan 
- 
Notification that an informed consent was not obtained from the subject 

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- 
Final summary report prepared for the IRB/EC 
- 
Any other information upon the request of an IRB/EC, FDA, or BIOTRONIK 
Table 5 outlines the responsibilities, including time constraints, for submitting the above 
reports.  
Table 5: Investigator Reporting Responsibilities 
Type of Report 
Report to 
BIOTRONIK 
Report to 
IRB/EC 
Time Constraints  
of Notification 
Subject Death During 
Investigation 
Required 
Required 
BIOTRONIK as soon as possible and as 
required by reviewing IRB/EC 
Adverse Event 
Required 
IRB/EC 
dependent 
Within 10 calendar days after notification of 
the event 
Unanticipated Adverse 
Device Effect 
Required 
Required 
Within 10 working days after notification of 
the effect 
Subject Withdrawal 
Required 
 
Within 5 working days 
Withdrawal of IRB/EC 
Approval 
Required 
 
Within 5 working days 
Progress Report 
Required 
Required 
Submitted not less often than yearly 
Significant Deviations from 
Investigational Plan 
Required 
Required 
Within 5 working days after emergency to 
protect life or physical well-being of subject, 
otherwise prior approval by BIOTRONIK is 
required 
Informed Consent Not 
Obtained 
Required 
Required 
As soon as possible after discovery 
13.3 
SPONSOR RECORDS 
BIOTRONIK will maintain the following records: 
- 
All correspondence that pertains to the registry with the investigator(s), IRB/EC, and 
FDA 
- 
Investigator agreements, financial disclosures, and current curriculum vitae 
- 
Name and address of each investigator and each IRB/EC that is involved with the 
investigation 
- 
Adverse events and complaints 
- 
Adverse device effects (whether anticipated or unanticipated) 
- 
Electronic case report form data 
- 
Completed subject informed consent forms 
- 
Clinical investigation plan and report of prior investigations 

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- 
Screening visit reports 
- 
Monitoring reports 
- 
Clinical progress reports 
- 
Statement of the extent to which the good manufacturing practice regulation is part 
21CFR820 will be followed in manufacturing the device 
13.4 
SPONSOR REPORTS 
Table 6: Sponsor Reporting Responsibilities 
Type of Report 
Prepared by 
BIOTRONIK for 
Time Constraints 
of Notification 
Withdrawal of IRB/EC 
Approval 
FDA, all reviewing IRBs/ECs 
and participating investigators 
Within 5 working days of receipt of 
notice of withdrawal of approval 
Withdrawal of FDA Approval 
Reviewing IRBs and 
participating investigators 
Notification will be made within 5 
working days. 
Progress Report 
FDA, all reviewing IRBs/ECs 
A progress report will be submitted at 
least annually 
Recall and Disposition 
FDA, all reviewing IRBs/ECs 
Notification will be made within 30 
working days and will include the 
reasons for any request that an 
investigator return, repair or otherwise 
dispose of any devices. 
Final Report 
FDA, all reviewing IRBs/ECs 
and participating investigators 
Notify FDA within 30 working days of the 
completion or termination of the 
investigation. A final report will be 
submitted within 6 months after 
completion or termination of the registry. 
 

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APPENDIX A: DEFINITION OF TERMS 
AE (Adverse Event) – An unwanted affect detected in participants either implant 
procedure-related, pulse generator-related, lead-related, or other. The term is used 
whether or not the effect can be attributed to the leads in the study. For the purposes of 
this study, the CEC will indicate whether the adverse event relatedness to the Protego 
lead is: not related, related, possibly related, or unknown. 
ACC/AHA – American College of Cardiology/American Heart Association 
Cardiac Perforation – Penetration of the lead tip through the myocardium (including 
microperforation), either clinically suspected or confirmed by chest x-ray, fluoroscopy, 
echocardiogram, intracardiac electrogram and/or visually. 
CEC – Clinical Events Committee 
Clinical Failure – Inability of the lead to correctly sense or pace in the heart, not 
attributable to a mechanical malfunction of the lead or pulse generator that remains 
unresolved despite reprogramming and/or repositioning.  
CFR – Code of Federal Regulations  
Conductor Fracture – See Lead Fracture  
Confirmed Failure – A lead having clinically relevant characteristics that are outside 
the performance limits established by BIOTRONIK while implanted and in service, as 
confirmed by analysis, except for changes in characteristics that are due to induced 
malfunctions. Lead damage caused during or after explant is not considered a failure. 
Chronic Threshold – Chronic threshold is defined as the pacing threshold determined 
at the subject’s 3 month follow-up visit. 
eCRF – Electronic Case Report Form 
EDC – Electronic Data Capture system 
Exit Block – The failure of an intact pacing system to capture the heart because the 
stimulation threshold exceeds the output of the pacemaker. 
Explantation – Surgical removal of a lead during the acute implant stage, whereby the 
lead has not been chronically implanted and can be easily removed by simple traction. 
Extracardiac Stimulation – Clinical observation of inadvertent nerve/muscle 
stimulation other than cardiac muscle, such as the diaphragm or pectoral muscles. 
Extraction of a Lead – Surgical removal of a chronically implanted lead.  

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Failure to Capture or Loss of Capture – Intermittent or complete failure to achieve 
cardiac stimulation at programmed output delivered outside of the cardiac refractory 
period. 
High Pacing Threshold – One of the following definitions must be met: 
1. At implant, thresholds for the Protego lead that are greater than 3.0 V at 0.4 ms or 
0.5 ms, or 
2. At follow-up, pacing thresholds for the Protego lead that have increased two fold 
from the chronic threshold value, and are greater than 3.5V at 0.4 ms or 0.5 ms. 
Insulation Breach/Break – Visual, electrical, or radiographic evidence of a disruption 
or break in the insulation of a lead. 
Intermittent Capture – Ineffective and inconsistent cardiac stimulation at irregular 
intervals in response to cardiac pacing delivered outside of the cardiac refractory period 
with a pacing output that exceeds the safety margin (which is twice the measured 
pacing threshold).  
IRB – Institutional Review Board 
Lead 
Dislodgment 
or 
Lead 
Migration 
– 
Radiographic, 
electrical 
or 
electrocardiographic evidence of electrode displacement from the original implant site or 
electrode displacement that adversely affects pacing, and/or lead performance. 
Lead Fracture – Visual, electrical and/or radiographic evidence of mechanical break 
within the lead conductor (connectors, coils and/or electrodes). 
Lead Impedance Out of Range – Pacing impedance is considered abnormal if a 
measurement is ≤ 200 ohms or ≥ 2000 ohms. Shock impedance is considered abnormal 
if a measurement is ≤ 20 ohms or ≥ 150 ohms. 
Loss of Sensing – Complete failure to sense any intrinsic events that occur outside the 
programmed refractory periods at programmed sensitivity settings. 
LV lead – Left ventricular lead 
Non-healing Pocket Dehiscence – Separation of wound edges around the pocket of 
the implanted pulse generator that have not healed. 
Oversensing – Misinterpretation of cardiac or non-cardiac events as cardiac 
depolarization, such as T-waves, skeletal muscle potentials, and extracardiac 
electromagnetic interference (EMI). 
Pneumothorax – Air or fluid in the pleural space surrounding the lung leading to 
collapse or partial collapse of the lung. 

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Premature Battery Depletion – Reaching Elective Replacement Indicator (ERI) before 
the predicted date. 
Mechanical Failure – Malfunction of the lead through a break in the conductor, 
insulation or connector pin leading to loss of pacing/sensing. 
RA lead – Right atrial lead 
Skin Erosion – Deterioration of tissue over an implanted device or the movement of a 
lead toward or through the skin. 
Suspected Generator Failure – Pulse generator issue that is potentially an electrical 
malfunction. 
Suspected Lead Failure – Lead issue that is potentially a mechanical or electrical 
malfunction. 
Tamponade – Compression of the heart caused by blood accumulation in the space 
between the myocardium and the pericardium. 
Thrombosis – The development of a blood clot in a vein or artery. 
Twiddler’s Syndrome – A condition where the pulse generator leads are dislodged by 
the subject unwittingly rotating the subcutaneous pulse generator. 
Undersensing – Intermittent failure to sense any intrinsic events that occur outside the 
programmed refractory period.  
 

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APPENDIX B: TIMELINE 
The timeline of the Protego DF4 Post-Approval Registry is dependent on the PMA 
Supplement date, the ability to recruit sufficient number of interested centers and the 
ability to enroll subjects at an estimated rate of 0.5 subjects/site/month. 
Milestone 
Window 
Estimated Date 
Protego DF4 FDA approval 
Approval 
June 2014 
First IRB approval of clinical site 
Approval + 4 months 
October 2014 
First site open to enrollment 
Approval + 5 months 
November 2014 
First subject enrolled 
Approval + 6 months 
December 2014 
5 clinical sites opened to 
enrollment 
Approval + 7 months 
January 2015 
Enrollment of 10 subjects 
Approval + 8 months 
February 2015 
25 clinical sites opened to 
enrollment 
Approval + 10 months 
April 2015 
Enrollment of 50 subjects 
Approval + 12 months 
June 2015 
Enrollment of 100 subjects 
Approval + 15 months 
September 2015 
50 clinical sites opened to 
enrollment 
Approval + 17 months 
November 2015 
75 clinical sites opened to 
enrollment 
Approval + 24 months 
June 2016 
Enrollment of 500 subjects 
Approval + 28 months 
October 2016 
Enrollment of 1000 subjects 
Approval + 41 months 
November 2017 
Enrollment of 1694 subjects 
(Enrollment Complete) 
Approval + 59 months 
May 2019 
End of registry based on 5 years 
follow-up from last-subject-enrolled 
Approval + 120 months  
(10 years) 
June 2024 
Final report submitted to FDA 
Approval + 126 months  
December 2024