Amplatzer™Amulet™ Observational Post-Market Study
Conditions: Atrial Fibrillation, Thromboembolism, Stroke
Sponsor: Abbott Medical Devices

 
Clinical Investigation Plan Cover Page 
 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
87173 CIP Posting Cover Page Ver B 
Template 
Page 1 of 1 
 
NCT Number: 02447081 
AMPLATZER Amulet Observational PMS 
AMPLATZER™ Amulet™ Observational Post-Market Study 
Study Document No: SJM-CIP-10053 
Version A 
Document Date: 21-APR-2015 
 
 
Sponsor  
 
 
St. Jude Medical, Inc. 
5050 Nathan Lane North 
Plymouth, MN 55442  
USA 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
                                                                                                                      Page 1 of 66 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
 
 
AMPLATZER™ Amulet™ Observational Post-Market Study 
Clinical Protocol 
 
Sponsor:  
 
 
St. Jude Medical, Inc. (SJM) 
5050 Nathan Lane North 
Plymouth, MN 55442  
USA 
Main +1 6517565400  
Fax +1 8772572381 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Principal Investigator 
SIGNATURE PAGE 
AMPLATZER™ Amulet™ Observational Post-Market Study 
Study Document No: SJM-CIP-10053 Version A 
 
I have read and agree to adhere to the clinical protocol (CP), including the Investigator’s Brochure 
(Appendix D), and all regulatory requirements applicable in conducting this clinical study. 
 
 
 
Principal Investigator 
 
 
Printed name: ____________________________________________ 
Signature: _______________________________________________ 
Date: ___________________________________________________ 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Coordinating Investigator/ National Investigator/ Medical Advisor 
SIGNATURE PAGE 
AMPLATZER™ Amulet™ Observational Post-Market Study 
Study Document No: SJM-CIP-10053 Version A 
 
I have read and agree to adhere to the clinical protocol (CP), including the Investigator’s Brochure 
(Appendix D), and all regulatory requirements applicable in conducting this clinical study.   
 
 
 
Coordinating Investigator/ National Investigator/ Medical Advisor 
 
 
Printed name: _____________________________________________ 
 
 
 
Signature: ________________________________________________ 
 
Date: ____________________________________________________ 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Table of Contents 
 
Synopsis ...................................................................................................................................... 7 
1.1 Study Contacts ....................................................................................................................... 10 
1.2 Certificate History .................................................................................................................. 11 
 
Background and Justification .................................................................................................... 12 
 
Risks and Benefits..................................................................................................................... 14 
3.1 Anticipated Clinical Benefits ................................................................................................. 14 
3.2 Anticipated Adverse Events and Adverse Device Effects ..................................................... 14 
3.3 Risks ....................................................................................................................................... 14 
3.4 Risk to Benefit Rationale ....................................................................................................... 14 
3.5 Residual Risks Associated with the Device ........................................................................... 14 
3.6 Steps to Control or Mitigate Risks ......................................................................................... 14 
 
Study Design ............................................................................................................................. 15 
4.1 Purpose ................................................................................................................................... 15 
4.2 Study Design and Scope ........................................................................................................ 15 
4.2.1 Subject population ........................................................................................................... 15 
4.2.2 Number of study subjects ................................................................................................ 15 
4.2.3 Enrollment period and study duration ............................................................................. 15 
4.3 Objectives .............................................................................................................................. 15 
4.3.1 Primary objectives ........................................................................................................... 15 
4.3.2 Secondary objectives ....................................................................................................... 16 
4.4 Inclusion and Exclusion Criteria ............................................................................................ 16 
4.4.1 Inclusion criteria .............................................................................................................. 16 
4.4.2 Exclusion criteria ............................................................................................................. 16 
4.5 Informed Consent Process ..................................................................................................... 17 
 
Device ....................................................................................................................................... 17 
5.1 Device Description................................................................................................................. 17 
5.2 Device Accountability ........................................................................................................... 18 
 
Study Procedures ...................................................................................................................... 19 
6.1 Screening/Enrollment/Baseline .............................................................................................. 21 
6.2 Implant/Procedure/Post-Procedure ........................................................................................ 22 
6.3 Scheduled Follow-ups ............................................................................................................ 23 
6.4 Interim/Unscheduled Visits ................................................................................................... 23 
6.5 Sponsor Representatives ........................................................................................................ 23 
6.6 Subject Study Completion ..................................................................................................... 24 
6.7 Compromising Factors ........................................................................................................... 24 
6.8 Subject Withdrawal ................................................................................................................ 24 
 
Compliance Statements ............................................................................................................. 24 
 
Serious Adverse Events, Serious Adverse Device Effects, Deaths and Device Deficiencies .. 25 
8.1 Serious Adverse Events ......................................................................................................... 25 
8.1.1 Serious adverse device effect .......................................................................................... 29 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
8.1.2 Assessing, recording and reporting serious adverse events, serious adverse device effects, 
and device deficiencies/complaints ............................................................................................. 29 
8.1.3 Subject death.................................................................................................................... 30 
8.2 Device Deficiency/Complaint Handling ................................................................................ 30 
 
Data Management ..................................................................................................................... 31 
9.1 Data Management Plan .......................................................................................................... 31 
9.2 Document and Data Control .................................................................................................. 31 
9.2.1 Document and data traceability ....................................................................................... 31 
9.2.2 Recording data ................................................................................................................. 31 
 Monitoring ................................................................................................................................ 32 
 Regulatory Inspections.............................................................................................................. 32 
 Statistical Methods .................................................................................................................... 32 
 Advisory Committees ............................................................................................................... 33 
13.1 Steering Committee ............................................................................................................... 33 
13.2 Clinical Events Committee .................................................................................................... 34 
13.3 Echocardiography Core Laboratory ....................................................................................... 34 
 Document Retention ................................................................................................................. 34 
 Amendments to the Clinical Protocol ....................................................................................... 34 
 Outsourcing of Sponsor Duties and Functions ......................................................................... 34 
 Investigation Suspension or Termination ................................................................................. 35 
17.1 Premature Termination .......................................................................................................... 35 
17.2 Study Conclusion ................................................................................................................... 35 
 Publication Policy ..................................................................................................................... 36 
 Bibliography ............................................................................................................................. 36 
Appendix A: Abbreviations ............................................................................................................... 40 
Appendix B: Protocol Revision History ............................................................................................ 41 
Appendix C: Declaration of Helsinki ................................................................................................ 42 
Appendix D: Investigator’s Brochure (IB) ........................................................................................ 43 
Appendix E: Echocardiography Core Laboratory Protocols ............................................................. 44 
Appendix F: List of Clinical Investigation Sites and Ethics Committees ......................................... 48 
Appendix G: Sample Informed Consent ............................................................................................ 49 
Appendix H: Case Report Forms ....................................................................................................... 61 
Appendix I: Device Deficiency/Complaint Handling ........................................................................ 62 
Appendix J: Modified Rankin Scale (mRS) ...................................................................................... 64 
Appendix K: Intracardiac Echocardiography (ICE) Sub-Study Requirements ................................. 65 
Appendix L: Cardiovascular Mortality Definition ............................................................................ 66 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
 
Figures 
Figure 1: The Amulet device and key components ................................................................................ 18 
Figure 2: Study flowchart for subject screening, consent, enrollment and follow-up ........................... 19 
 
Tables 
  Model numbers and key dimensions of the Amulet device and delivery system ...................... 18 
Table 2: Study visits and activities ........................................................................................................... 20 
Table 3: Study visits and electronic case report forms (Apppendix H) .................................................... 20 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
 SYNOPSIS 
Title of Clinical Study 
AMPLATZER™ Amulet™ Observational Post-Market Study 
Clinical Study Number 
SJM-CIP-10053  
Conformité Européenne 
(CE) Mark 
AMPLATZER™ Amulet™: 03 January 2013 
Change in AMPLATZER™ Amulet™ delivery cable: 23 September 2014 
 
 
Device 
The AMPLATZER™ Amulet™ Left Atrial Appendage Occluder 
(hereinafter referred to as the “Amulet device”) is a transcatheter, self-
expanding device constructed from a nitinol mesh and consists of a lobe and 
a disc connected by a central waist.  Polyester patches sewn into both the 
lobe and disc facilitate occlusion.  The lobe has stabilizing wires to improve 
device placement and retention.  The device has threaded screw attachments 
at each end for connection to the delivery and loading cables.  The device has 
radiopaque markers at each end and at the stabilizing wires that permit 
visibility during fluoroscopy. 
 
Amulet Device Models 
100099039 9-ACP2-007-016 Pkgd Sterile OUS 
100099040 9-ACP2-007-018 Pkgd Sterile OUS 
100099041 9-ACP2-007-020 Pkgd Sterile OUS 
100099042 9-ACP2-007-022 Pkgd Sterile OUS 
100099043 9-ACP2-010-025 Pkgd Sterile OUS 
100099045 9-ACP2-010-028 Pkgd Sterile OUS 
100099046 9-ACP2-010-031 Pkgd Sterile OUS 
100099047 9-ACP2-010-034 Pkgd Sterile OUS 
Clinical Registry 
Purpose 
To compile real world outcome data on the use of the Amulet device in non-
valvular atrial fibrillation (NVAF) subjects  
Trial Type 
Post-market observational study 
Clinical Design 
Prospective, multicenter, observational, non-randomized study 
Primary Objectives   
The Amulet observational post-market study has four primary objectives:  
1. Assessment of acute (0 - 7 days post procedure) serious adverse events  
2. Assessment of late ( > 7 days post-procedure) serious adverse events 
through 2 years 
3. Report the percentage of stroke (ischemic), systemic embolism and 
cardiovascular death through 2 years 
4. Report the percentage of bleeding events through 2 years 
Secondary Objectives 
The Amulet observational post-market study has three secondary objectives: 
1. Technical success - successful implantation of the Amulet device in the 
left atrial appendage (LAA)  
2. Procedural success – technical success and the absence of major adverse 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
events during hospitalization.  Major adverse events include death, 
stroke, embolism, pericardial or other major bleeding requiring 
intervention, device embolization, and major vascular complications 
3. Report percentage of subjects taking oral anticoagulation (OAC) and 
antiplatelet drugs through 2 years 
 
Investigators 
Electrophysiologist (EP) and/or Interventional Cardiologist (IC) 
Clinical Sites 
Up to 75 sites in Europe, Middle East and Africa (EMEA), Australia-New 
Zealand (ANZ), Latin America, Asia-Pacific (AP)  
Note: Amulet device regulatory/market approval in each country is required 
Sample Size 
1000 subjects 
Population  
Subjects with NVAF 
Inclusion Criteria 
1. Subject with history of paroxysmal, persistent or permanent NVAF 
2. Subject who is 18 years or older, or of legal age to give informed consent 
specific to state and national law 
3. Subject who is eligible for an Amulet LAA Occluder device according to 
current international guidelines and per physician discretion 
4. Subject who is willing and capable of providing informed consent, 
participating in all associated study activities  
Exclusion Criteria 
1. Subject with evidence of an intracardiac thrombus 
2. Subject with active infection or active endocarditis or other infections 
producing bacteremia 
3. Subject where the placement of the device would interfere with any 
intracardiac or intravascular structures 
4. Subject with any medical disorder that would interfere with completion 
or evaluation of clinical study results 
5. Women of childbearing potential who are, or plan to become, pregnant 
during the time of the study (method of assessment per physician 
discretion) 
6. Subject with LAA anatomy that does not accommodate a device per the 
sizing guidelines  
Post Procedure Care 
 Monitor the subject until discharge 
 Perform a transthoracic echocardiogram (TTE)/follow up before 
discharge to confirm the device is positioned correctly and no pericardial 
effusion is present  
 Follow the instructions for use (IFU) for the drug regimen (dual 
antiplatelet) post implant 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Clinical Follow-up 
Visits/Testing 
Subjects will be followed through two years post implant.   
Required Testing 
 Baseline evaluation: Informed consent, history and physical, pregnancy 
testing for women of childbearing age, 12-lead electrocardiogram (ECG), 
CHA2DS2-VASc score, HAS-BLED score, Modified Rankin Scale 
(mRS), medication assessment 
 Procedure: Transoesophageal echocardiogram (TOE) or intracardiac 
echocardiogram (ICE) only when combined with baseline/pre-procedural 
TOE, angiogram, adverse event assessment 
 Post procedure/Pre-Discharge:  TTE, medication assessment, adverse 
event assessment 
 1M to 3M: TOE, medication assessment, adverse event assessment 
 6M (+/- 2 weeks): Phone contact follow-up for medication and AE 
assessment  
 12M (+/- 6 weeks): Medication and adverse event assessment 
 24M (+/- 12 weeks): Phone contact follow-up for medication and adverse 
event assessment 
 Interim/unscheduled visits: per physician discretion 
Suspected Stroke/TIA 
Evaluation  
▪ All subjects suspected of a stroke should be seen by a stroke/TIA 
neurologist for evaluation and appropriate neurological testing done (i.e. 
magnetic resonance imaging (MRI), computed tomography (CT) 
▪ Modified Rankin Scale (Appendix J) 
▪ TOE should be conducted to verify the presence of device-related 
thrombus 
Clinical Procedures 
▪ Angiography with fluoroscopy 
▪ TOE with color flow Doppler 
▪ TTE post-procedure/pre-discharge 
▪ 12-lead ECG 
Clinical Duration 
The total study duration is expected to be 4 years.  This observational study 
will begin March 2015 with the first subject enrolled first half of 2015 and 
the last subject enrolled second half of 2016, the 2 year follow-up will be 
complete second half of 2018 
St. Jude Medical 
St. Jude Medical, Inc. 
Global Clinical Affairs Organization 
5050 Nathan Lane North 
Plymouth, MN  55442  
USA 
Main +1 6517565400 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
1.1 Study Contacts 
Clinical Department, LAA Program 
St. Jude Medical, Inc. 
Global Clinical Affairs Organization 
5050 Nathan Lane North 
Plymouth, MN  55442  
USA 
Main +1 6517565400 
Fax +1 8772572381 
 
Sarah Gallagher  
 
 
 
 
Anne Marie Harcarik 
Clinical Programs Manager  
 
 
Sr. Director Clinical Affairs 
LAA Occlusion  
 
 
 
 
LAA Occlusion 
St. Jude Medical  
 
 
 
 
St. Jude Medical 
5050 Nathan Lane North 
 
 
 
5050 Nathan Lane North 
Plymouth, MN 55442   
 
 
 
Plymouth, MN 55442 
USA 
 
 
 
 
 
 
USA 
Direct +1 6517566937  
 
 
 
Direct +1 6517566469 
Main +1 7635139227  
 
 
 
Main +1 7635139227 
Mobile +1 6514855744 
 
 
 
Mobile +1 6122195601 
Fax +1 8772572381 
 
 
 
 
Fax +1 8772572381 
sgallagher02@sjm.com 
 
 
 
AHarcarik@sjm.com 
 
Hindrik Robbe 
Vice President Field Clinical Affairs EMEA 
St. Jude Medical 
The Corporate Village | Da Vincilaan 11 Box F1 
1935 Zaventem Vlaams Brabant 
Belgium 
Main +32 27746849 
Mobile +32 499544060 
HRobbe@sjm.com 
 
Catherine Bourgeois 
Vice President Field Clinical Affairs AP & Japan 
St. Jude Medical 
17 Orion Road 
Lane Cove NSW 2066 
Australia 
Main +61 299361235 
Mobile +61 410330259 
CBourgeois@sjm.com 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
1.2 Certificate History 
 
Date 
Action 
03 January 2013 
Amulet CE Mark 
23 September 2014 
Change in Amulet delivery cable 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
 BACKGROUND AND JUSTIFICATION  
The loss of mechanical efficiency during atrial fibrillation (AF)* leads to insufficient contraction in the 
left atrium (LA)1.  Stagnation of blood flow in the LA leads to hypercoagulability and thus increased 
risk for thrombus formation in the LA or LAA.  Approximately 90% of all thrombi in subjects with 
NVAF forming in the LA originate in the LAA2.  The thrombus formation, in turn, exposes the subject 
to thromboembolic events.  Approximately 6% of embolic events result in peripheral embolism as 
opposed to ischemic stroke3. 
Echocardiographic risk factors for LAA thrombus formation include echocardiographic evidence of 
decreased LAA flow velocity and spontaneous echo contrast within the LA and LAA4, 5.  The normal 
flow pattern of the LAA is the ejection of blood from the appendage following atrial contraction at a 
velocity greater than 40cm/s6. Agmon et al. found that the relative risk reduction of ischemic stroke was 
2.6 times greater in subjects with LAA flow velocities < 20 cm/s than those with higher LAA 
velocities7. 
Ischemic strokes in subjects with AF caused major deficits as compared to ischemic strokes in subjects 
with carotid disease.  Subjects with AF had silent infarcts in the SPINAF study in which a CT scan was 
performed both initially and then again at the end of the average follow-up period of 1.7 years8. 
Non-valvular AF subjects were assessed to determine the risk of stroke based on the existence of 
independent risk factors.  In a study by Gage et al., the CHADS2 index was found to be the most 
accurate in predicting the risk of stroke in subjects with AF9.  The CHADS2 score assigns one point each 
for the presence of congestive heart failure, hypertension, age greater than 75, and diabetes mellitus and 
two points for history of stroke or transient ischemic attack (TIA).  The study found that AF subjects 
who were not treated with antithrombotics had an increased risk of stroke from 1.5% to 18.2% based on 
scores of one and six respectively.  
A study by Go et al., reviewed outcome data (11,526 subjects) in a large primary care setting and 
confirmed that thromboembolic risk increases progressively with CHADS2 score3.  The study also noted 
that oral anticoagulation with warfarin reduces the risk of stroke in most subjects with the exception of 
those at lowest risk (CHADS2 score of zero) and highest risk (CHADS2> 5) for stroke. 
In a meta-analysis conducted by Andersen et al., warfarin was found to be superior to aspirin and 
placebo in reducing the risk of both stroke and systemic embolism in subjects with NVAF10.  Hart et al. 
reported that adjusted dose warfarin reduces stroke by 64% (6 trials) and antiplatelet agents reduce 
stroke risk by 22%11.  The study also reported that risk of intracranial hemorrhage was doubled with 
adjusted dose warfarin compared with aspirin, although the absolute risk increase was by adjusted-dose 
warfarin vs. control.  
Subjects are often poorly compliant with anticoagulation, and anticoagulants are contraindicated in 
selected subsets of subjects.  The reasons given for being contraindicated included prior bleed, patient 
refusal/preference, high bleeding risk, frequent falls/frailty, need for dual antiplatelet therapy, unable to  
adhere/monitor warfarin, comorbid illness, prior intracranial hemorrhage, allergy, occupational risk and 
pregnancy. 
 
 
*See Appendix A for a listing of abbreviations used throughout this document 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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Recently, new drugs have been developed with less dietary and pharmacological interactions and less 
stringent requirements for frequent INR monitoring.  Major trials such as RE-LY and ROCKET AF 
demonstrated that dabigatran and rivaroxiban are non-inferior to warfarin in the prevention of stroke and 
systemic embolism12, 13. The ARISTOTLE Trial demonstrated apixaban was superior to warfarin in 
preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality in subjects 
with atrial fibrillation14. The ENGAGE AF-TIMI 48 Trial demonstrated both once-daily regimens of 
edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism 
and were associated with significantly lower rates of bleeding and death from cardiovascular causes15. 
Left atrial appendage occlusion (LAAO) is considered a viable alternative to OAC therapy for stroke 
prevention in patients with NVAF16-26. Evidence supporting LAAO mainly consists of PROTECT AF 
and PREVAIL, the major randomized studies published to date16-19. Five-year results of PROTECT AF 
showed superiority of the Watchman device in mortality and stroke reduction compared to optimal 
medical treatment with warfarin19. The Watchman device is constructed of nitinol (a nickel/titanium 
alloy) and is composed of 10 fixation anchors around the device perimeter that are designed to secure 
the device in the LAA (Boston Scientific, Minneapolis, MN, USA).          
There are several other endocardial LAAO devices currently in pre-clinical/clinical trial testing phases 
and one of these (WaveCrest) has CE Mark approval27:  
▪ Occlutech LAA Occluder (Occlutech, Helsingborg, Sweden)  
▪ Lifetech LAmbre (Lifetech, Shenzhen, PRC) 
▪ Sideris Transcatheter Patch (Custom Medical Devices, Texas, USA) 
▪ Ultrasept (Cardia, Eagan, MN, USA) 
▪ Pfm ((Pfm Medical, Inc., Carlsbad, CA, USA)  
▪ WaveCrest LAAO (Coherex Medical, Salt Lake City, UT, USA)  
AMPLATZER™ Cardiac Plug and the AMPLATZER™ Amulet™ device 
Both the AMPLATZER Cardiac Plug (ACP) and AMPLATZER Amulet devices have CE Mark 
approval.  The ACP device (St Jude Medical, St. Paul, MN, USA) is a self-expandable nitinol device, 
with fixation anchors.  The ACP device is a first generation device based on AMPLATZER occluder 
technology specifically designed for LAAO.  Refer to the Investigator’s Brochure (Appendix D) for 
data published on the ACP device. 
The ACP device demonstrated favorable feasibility and safety results in observational studies in 
Europe28-30.  Professor Park’s article details an investigator–initiated retrospective data collection to 
evaluate and demonstrate the initial European experience in patients treated with the ACP device 
between December 2008 and November 2009.  Favorable ACP registry study results were presented at 
EURO PCR in 2012 and 201429-30.  
The Amulet device is a second-generation ACP device.  To date there have been two single center self- 
reported studies of initial use of the Amulet device.  The first reported use by Lam et al. involved a 
retrospective review of 17 subjects from implant to 90 days follow-up at the Cardiovascular Center in 
Frankfurt31.  The second reported use by Freixa et al. involved 25 subjects enrolled at Barcelona 
University and patients were followed for 3 months32.  Both of these single center studies report high 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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implant success rates however, long-term safety and efficacy analysis were not conducted due to the 
short follow up period.  
Results from a multicenter study involving 22 sites, 1,047 consecutive patients and the ACP device 
showed high procedural success and a favorable outcome for the prevention of AF-related 
thromboembolism33.   
The aim of this observational post-market study is to compile real world outcome data on the use of the 
CE marked Amulet device in NVAF subjects. 
 RISKS AND BENEFITS  
3.1 Anticipated Clinical Benefits 
For subjects who can take OAC medication the potential benefit is that subjects may not need to be 
on long-term warfarin, or other OAC therapy and thus will not be exposed to associated 
complications.  This device may also provide potential benefits to subjects who cannot take OAC. 
Subjects who receive the device may also experience a decrease in the associated risk of 
thromboembolism. 
3.2 Anticipated Adverse Events and Adverse Device Effects 
Anticipated adverse events and adverse device effects may occur during and after the Amulet 
device implant procedure.  Serious adverse event definitions are provided in Section 8. 
3.3 Risks 
The risks associated with the Amulet device implant procedure are similar to those of other cardiac 
catheterization procedures.  Radiation risks associated with the procedure are comparable to a 
diagnostic catheterization procedure.  
The risks associated with the implanted Amulet device are similar to other implantable cardiac 
LAAO devices.  Refer to Section 8 for a complete list of potential anticipated serious adverse 
events, which are also included in the IFU included in the Investigator’s Brochure (Appendix D). 
3.4 Risk to Benefit Rationale 
Percutaneous LAAO offers an alternative to physicians who are caring for patients with AF who 
are at high risk for both bleeding and stroke.  
3.5 Residual Risks Associated with the Device 
The Amulet device is market approved in all the countries where the study will be conducted.  The 
risk profile of the Amulet device implant procedure is described in the labeling for the CE marked 
device, the risk analysis report, the IFU (included in the IB in Appendix D), and Section 8 of this 
protocol.  The overall events from a risk perspective are similar to the risks with minimally 
invasive implantable therapies.  Complication rates are within expected ranges and the risk/benefit 
profile is similar to alternate therapies.  
3.6 Steps to Control or Mitigate Risks 
The Sponsor will select investigators qualified by training and experience to participate in this 
study.  Participating sites will be selected based upon qualifications of the primary investigator. 
During the study, sites may be subject to quality assurance audits by the Sponsor (or designee), as 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
well as monitoring visits to assess data integrity and study compliance.  Additionally, the study 
will have an appointed independent Clinical Event Committee (CEC) that will review and 
adjudicate all reported serious adverse events.  Any additional risk is mitigated with vigilance 
reporting for a CE marked product. 
 STUDY DESIGN 
4.1 Purpose 
The Amulet device is a transcatheter, self-expanding nitinol device intended for use in preventing 
thrombus embolization from the LAA.  The purpose of the Amulet observational post-market 
study is to compile real world outcome data on the use of the CE marked Amulet device in NVAF 
subjects. 
4.2 Study Design and Scope 
The Amulet device will be clinically evaluated through this observational post-market study.  The 
study design is a prospective, multicenter, non-randomized observational post-market study, where 
all subjects eligible for enrollment will receive the Amulet device. 
4.2.1 Subject population 
The subject population will include participants that are > 18 years old and diagnosed with 
NVAF.  
4.2.2 Number of study subjects 
Approximately 1000 subjects will be enrolled in the study at up to 75 sites in EMEA, ANZ, 
Latin America, and AP. A list of clinical investigation sites and ECs will be kept under separate 
cover and is available upon request (Appendix F).  
4.2.3 Enrollment period and study duration 
Enrollment in the study will be complete within approximately 24 months of the first subject 
enrollment.  As the study requires follow-up visits through at least 2 years, the total study 
duration is expected to be 4 years.  
4.3 Objectives 
4.3.1 Primary objectives 
The Amulet observational post-market study has four primary objectives:  
1. Assessment of acute (0 - 7 days post procedure) serious adverse events  
2. Assessment of late ( > 7 days post-procedure) serious adverse events through 2 years 
3. Report the percentage of stroke (ischemic), systemic embolism, and cardiovascular death 
through 2 years 
- 
Cardiovascular death is defined as (see Appendix L) death due to proximate cardiac 
cause, death caused by non-coronary, non CNS vascular conditions, death from 
vascular CNS causes, hemorrhagic stroke, ischemic stroke, all procedure related deaths, 
sudden or unwitnessed death and death of an unknown cause34  

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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4.   Report the percentage of bleeding events through 2 years 
4.3.2 Secondary objectives 
The Amulet observational post-market study has three secondary objectives:  
1. Technical success – successful implantation of the Amulet device in the LAA 
2. Procedural Success – technical success and the absence of major adverse events during 
hospitalization.  Major adverse events include death, stroke, embolism, pericardial or other 
major bleeding requiring intervention, device embolization, and major vascular 
complications 
3. Report percentage of subjects taking OAC and antiplatelet drugs through 2 years 
4.4 Inclusion and Exclusion Criteria 
Subjects, who meet all of the inclusion criteria and none of the exclusion criteria, are eligible to 
participate in this study.  
All subjects who sign the informed consent will be assigned a study identification number and this 
will be recorded on an Inclusion/Exclusion electronic case report form (eCRF).  The subject ID 
number will be unique to each individual and will allow the participant to be linked if necessary, to 
name, alternative identification or contact information.  To ensure subject privacy and 
confidentiality of data, subject ID numbers will be used and maintained by study site personnel for 
the duration of the study. 
4.4.1 Inclusion criteria 
To participate in this clinical study, the subject must meet all of the following four inclusion 
criteria: 
1. Subject with a history of paroxysmal, persistent or permanent NVAF 
2. Subject who is 18 years or older, or of legal age to give informed consent specific  to state 
and national law 
3. Subject who is eligible for an Amulet LAAO device according to current international 
guidelines and per physician discretion 
4. Subject who is willing and capable of providing informed consent, participating in all 
testing associated with this clinical study 
4.4.2 Exclusion criteria 
Subjects are not eligible for clinical study participation if they meet any of the following six 
exclusion criteria: 
1. Subject with evidence of an intracardiac thrombus 
2. Subject with active infection or active endocarditis or other infections producing 
bacteremia 
3. Subject where the placement of the device would interfere with any intracardiac or 
intravascular structures 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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4. Subject with any medical disorder that would interfere with completion or evaluation of 
clinical study results 
5. Women of childbearing potential who are, or plan to become, pregnant during the time of 
the study (method of assessment per physician discretion) 
6. Subject with LAA anatomy that does not accommodate a device per the sizing guidelines 
4.5 Informed Consent Process 
The process for obtaining informed consent must comply with the ethical principles defined in the 
current version of the Declaration of Helsinki (Appendix C).  
Prior to enrollment in the clinical study, all subjects will be consented, as required by applicable 
regulations and the site’s ethics committee (EC).  Informed consent must be obtained from each 
subject prior to the device implant procedure. The consent form must be signed and dated by the 
subject and by the person obtaining the consent, where applicable.  
The principal investigator (PI) or his/her authorized designee will conduct the informed consent 
process. This process will include a verbal discussion with the subject on all aspects of the clinical 
study that are relevant to the subject’s decision to participate, and the subject should be allowed 
adequate time to review and ask questions.  
Documentation that informed consent was obtained will be recorded on the eCRF and in the 
subject’s medical record. The signature date on the consent form should be referenced. The 
original signed informed consent should be filed in the subject’s study chart and a copy of the 
signed consent form given to the subject per EC requirements.  
A template of the informed consent form is provided in Appendix G. Any changes to the template 
must be approved by SJM prior to ethics committee review and approval.  
A subject cannot be consented to the study prior to EC approval of the informed consent form. The 
subject shall be provided the informed consent form that is written in a language understandable to 
the subject and has been approved by the site’s EC.   
The subject is enrolled in the study when consent has been obtained and the dilator/delivery 
system is introduced. Failure to obtain informed consent from a subject prior to study enrollment 
must be reported to SJM as soon as possible and to the reviewing site’s EC consistent with the 
site’s EC reporting requirements.  
 DEVICE  
5.1 Device Description 
The Amulet device (Figure 1) is constructed from a nitinol mesh and consists of a lobe and a disc 
connected by a central waist.  The lobe ranges in diameter from 16 to 34 mm (Table 1) and has 
stabilizing wires for device placement and retention.  The disc is larger in diameter than the lobe, 
ranging from 20 to 41 mm; both the disc and the lobe contain polyester fabric to facilitate LAAO. 
There are threaded screw attachments at either end of the device for connection to the delivery and 
loading cable.  Radiopaque markers at either end of the device and at the location of the stabilizing 
wires allow for predictable placement of the device.  The stabilizing wires and polyester patch are 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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secured to the device using polyester thread.  A platinum/iridium thread is attached to the nitinol 
braid. 
Accessories packaged with the Amulet device include the loader, loading cable, loading cable vise, 
delivery cable, delivery cable vise, and hemostasis valve.  The Amulet device is recommended for 
delivery using the AMPLATZER TorqVue 45 x45 Delivery Sheath (12F and 14F). Refer to the 
Investigator’s Brochure (IB) (Appendix D) which includes the IFU for additional information. 
Figure 1:  The Amulet device and key components 
 
 
A. Screw attachments 
 
B. Waist of device 
C. Lobe 
D. Stabilizing wires 
E. Disc 
 
 
 Model numbers and key dimensions of the Amulet device and delivery system 
Part Number 
Amulet 
Device Size 
Left Atrial 
Disc Size (mm) 
Lobe Length 
(mm) 
# of 
stabilizing 
wires 
TorqVue 
Delivery System 
9-ACP2-007-016 
16mm 
22 
7.5 
6 
12F* 
9-ACP2-007-018 
18mm 
24 
7.5 
6 
12F* 
9-ACP2-007-020 
20mm 
26 
7.5 
8 
12F* 
9-ACP2-007-022 
22mm 
28 
7.5 
8 
12F* 
9-ACP2-010-025 
25mm 
32 
10 
8 
12F* 
9-ACP2-010-028 
28mm 
35 
10 
10 
14F 
9-ACP2-010-031 
31mm 
38 
10 
10 
14F 
9-ACP2-010-034 
34mm 
41 
10 
10 
14F 
*Per the IFU, if a 14 Fr delivery sheath is selected for use with a 16 mm-25mm device, tightly connect 
the 14 Fr sheath adaptor to the delivery sheath hub 
5.2 Device Accountability 
The Amulet device has CE Mark approval and is market released in the countries where this study 
will take place.  Therefore, there are no additional tracking requirements for this study.  
Information regarding opened, introduced, and implanted devices will be recorded on the 
Procedure eCRF.  

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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 STUDY PROCEDURES 
This study will be conducted in accordance with the clinical protocol and IFU included in the IB 
(Appendix D).  All persons participating in the conduct of the study will be qualified by education, 
training, or experience to perform study-related tasks.  
The study will not commence until SJM receives written approval from the EC and relevant regulatory 
authorities, and all required documents have been collected from the participating sites.  
Figure 2 below describes the study flowchart for subject screening, consent, enrollment and follow-up 
through the 2-year follow-up visit. Table 2 below outlines the testing and assessments required per 
study visit interval. Table 3 below outlines the eCRFs to be completed for enrolled subjects that receive 
the device, and as per the recommended study visit intervals. 
Potential Subject
Inclusion/Exclusion 
Assessment
Consented Screen Failure:
 
Non-Consented Screen Failure:
 
Consented Subject:
 
 - Does not meet I/E criteria
 - Subject not consented
 - Does not undergo baseline testing
     · No CRFs completed
 
 - Subject consented
 - Does not meet I/E criteria
 - Dilator not introduced
 - Subject withdrawn
    
 · Complete I/E,     
Withdrawal & 
AE CRFs
Enrolled Subject
 
Enrolled – Attempt to treat
 
 - Meets I/E
 - Device successfully 
    implanted
 - Dilator placed across septum
 - Meets I/E criteria but no device implanted
 - Subject withdrawn 7 days after procedure
     · Complete I/E, Procedure, Withdrawal  
         and AE CRFs
Follow up of enrolled subjects (required):
 - Procedure
· TOE or ICE
·
· Angiography with flouroscopy
· AE assessment
 - Pre discharge
· TTE
· AE assessment
· Medication assessment
 - 1 to 3 months post implant 
· TOE
· AE assessment
· Medication assessment
 - 6 months (+/-2 weeks; phone contact)
· AE assessment
· Medication assessment
 - 12 months (+/-8 weeks; office visit)
· AE assessment
· Medication assessment
 - 24 months (+/- 12 weeks; phone contact)
· AE assessment
· Medication assessment
 
Figure 2:  Study flowchart for subject screening, consent, enrollment and follow-up   
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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Table 2: Study visits and activities 
                              Visit 
 
Study  
Activity 
Enrollment 
& Baseline 
 
Procedure 
 
 
Discharge 
 
1-
3M 
6M 
Phone 
Visit 
(+/- 2 
weeks) 
 
12M 
(+/- 6 
weeks) 
 
24M 
Phone 
Visit 
(+/- 12 
weeks) 
Interim 
Follow-up 
Informed Consent 
Process 
X 
 
 
 
 
 
 
 
- History and  physical 
- Cardiovascular and  
   medical exam  
- CHA2DS2-VASc score  
- HAS-BLED score 
X 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
Medication Assessment 
X 
 
X 
X 
X 
X 
X 
X 
Modified Rankin Scale2 
X 
 
 
 
 
 
 
X4 
Angiography 
 
X 
 
 
 
 
 
 
TTE 
 
 
X 
 
 
 
 
 
TOE  
X,5 
X3,5 
 
X 
 
 
 
X4 
ICE 
 
X6 
 
 
 
 
 
 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
1Pregnancy test for women of childbearing potential 
2Perform additional Modified Rankin Scale assessment 90 days after a confirmed stroke or TIA 
3CT may be used as additional information and performed complimentary to the TOE, per institutional standard of care 
4Complete if stroke or TIA is confirmed  
5The Baseline TOE is optional if a TOE is performed on the day of procedure to rule out the presence of intracardiac  
  thrombus (including left atrial appendage thrombus) and to assess the size and shape of the LAA   
6ICE may be performed for placement of the device in a sub-set of centers pre-approved by SJM (see Appendix K) 
 
Table 3: Study visits and electronic case report forms (Appendix H) 
   
Visit 
eCRF 
Enrollment 
& Baseline 
Procedure 
 
Discharge 
 
1-3M 
 
6M 
Phone 
Visit 
 
12M 
 
24M 
Phone 
Visit 
 
Interim 
Follow-
up 
Baseline  
X 
 
 
 
 
 
 
 
Inclusion/ 
Exclusion 
X 
 
 
 
 
 
 
 
Procedure 
 
X 
 
 
 
 
 
 
Follow Up  
 
 
X 
X 
X 
X 
X 
X* 
Medication 
X 
X 
X 
X 
X 
X 
X 
X 
Protocol Deviation 
X** 
X 
X 
X 
X 
X 
X 
X 
*Complete if stroke or TIA is confirmed 
** Complete if informed consent/informed consent form was not appropriately obtained/completed, visit out of window, test 
not completed. 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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Additional eCRFs, reports and assessment noted below should be completed upon occurrence, and/or as 
applicable:  
 Withdrawal eCRF 
 Adverse Event eCRF  
 Protocol Deviation eCRF 
 Death eCRF 
 Follow-up eCRF for interim/unscheduled visits 
 Modified Rankin Scale (Appendix J) (complete 90 days after confirmed stroke /TIA) 
If a suspected stroke/TIA has occurred, the subject should be seen by a stroke/TIA neurologist for 
evaluation and appropriate neurological testing (i.e. CT or MRI, and CTA or MRA). If a stroke or TIA is 
confirmed, a TOE is required as soon as possible to confirm device placement, LAA flow parameters 
and presence/absence of device-related thrombus. See Section 8.1 for further details. 
6.1 Screening/Enrollment/Baseline 
The following baseline and enrollment activities are performed as part of the screening process:  
 Informed consent process 
 History and physical 
 Cardiovascular and medical exam 
 Pregnancy testing for women of childbearing age 
 12-lead ECG 
 TOE (optional if a TOE is performed on the day of procedure) 
 Modified Rankin Scale 
 Medication assessment 
 CHA2DS2-VASc score: 
 
CHA2DS2 -VASc 
Score 
Congestive heart failure/LV dysfunction 
1 
Hypertension 
1 
Age > 75 
2 
Diabetes mellitus 
1 
Stroke/TIA/TE 
2 
Vascular disease [prior myocardial 
infarction, peripheral artery disease or 
aortic plaque] 
1 
Age 65-74 
1 
Sex category [i.e. female gender] 
1 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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 HAS-BLED score: 
HAS-BLED 
Score 
Hypertension history (uncontrolled, > 160 
mmHg systolic) 
1 
Abnormal renal function/renal disease 
(dialysis transplant, creatinine > 2.6 mg/dL 
or > 200µmol/L) 
1 
Liver disease (cirrhosis, bilirubin > 2x 
normal AST/ALT/AP > 3x normal) 
1 
Stroke history 
1 
Bleeding, anemia, or predisposition to 
bleeding 
1 
Labile INR (Unstable/high INR’s, or poor 
time (< 60% time in therapeutic range) 
1 
Elderly - Age > 65 years 
1 
Drugs - Medication usage predisposing to 
bleeding (antiplatelet agents, NSAIDs) 
1 
Alcohol usage history (> 8 drinks/week) 
1 
 
The principal investigator or delegated study personnel is responsible for screening potential 
subjects to determine subject eligibility for the study.  Enrollment information (date of consent, 
inclusion/exclusion information, etc.) will be recorded in the subject’s hospital records and on the 
Baseline and Inclusion/Exclusion eCRF.  The Inclusion/Exclusion eCRF should be submitted 
within one week and will serve as notification of enrollment to the Sponsor upon receipt. 
If a subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject 
cannot participate in the study.  The Baseline/Screening and Inclusion/Exclusion eCRFs should be 
completed, in addition to the Withdrawal eCRF (consented screen failure), as applicable.  If the 
subject was enrolled (i.e. consented and the dilator/delivery system introduced), but meets the 
exclusion criteria during the procedure, the Baseline, Inclusion /Exclusion, Procedure, and 
Withdrawal eCRFs (complete 7 days after the attempted procedure) should be completed.  
Serious adverse events will be reported from the time the dilator/device delivery system has been 
introduced to the time the subject concludes the study.  An Adverse Event eCRF should be 
completed, as applicable.  
6.2 Implant/Procedure/Post-Procedure 
After the subject has met preliminary inclusion criteria, the implant procedure can be scheduled.  
The baseline TOE is optional if a TOE is performed on the day of procedure to rule out the 
presence of intracardiac thrombus (including left atrial appendage thrombus) and to assess size and 
shape of the LAA. 
See the IFU for procedural and post-procedural instructions.   
The post-procedure care should involve the following (refer also to Table 2): 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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▪ Perform a TTE prior to discharge to ensure the device is positioned correctly and no 
pericardial effusion is present 
▪ Aspirin (or an alternate antiplatelet) is recommended for subjects 6 months post implant 
▪ Clopidogrel (or an alternate antiplatelet) is recommended for implanted subjects and 
prescription should follow standard of care 
▪ Appropriate endocarditis prophylaxis is recommended 
▪ Instruct the subject on when to seek medical attention 
▪ Provide routine standard of care follow-up, including echocardiography, for evaluation of 
residual shunt (flow) and adverse events (including thrombus formation) 
▪ Go to www.amplatzer.net/device-registration-international.html to print the temporary 
subject identification card. Complete this card and provide it to the subject 
6.3 Scheduled Follow-ups 
Required follow-up visits will be at 1-3 months, 6-months telephone follow-up, 12-months, and 
24-month telephone follow-up.  Refer to Table 2 for required follow-up testing and assessments.  
6.4 Interim/Unscheduled Visits  
Interim/unscheduled visits will be considered those that occur in addition to the required visit 
interval schedule. If an unscheduled or interim visit occurs, a Follow-up eCRF should be 
completed to capture data collected at the visit as well as pertinent additional eCRFs (medication 
and adverse event assessments as applicable). In the event of a confirmed stroke or TIA, the 
Modified Rankin Scale eCRF should be completed 90 days after the event and echo imaging 
should be submitted to the core lab.  
6.5 Sponsor Representatives  
Trained Sponsor personnel may perform certain study activities to ensure compliance to the 
clinical protocol and may provide technical expertise.  Monitoring may be performed by SJM 
and/or authorized designees according to the International Organization for Standardization (ISO) 
14155 and MEDDEV guidelines for post market studies; and applicable SJM standard operating 
procedures and work instructions.  Qualified monitors will ensure investigators comply with this 
clinical protocol and ISO 14155 and MEDDEV post market requirements.  
To ensure study personnel accept, understand and complete their assigned responsibilities, 
monitors, field clinical personnel, and/or clinical country managers, may perform periodic site 
visits during the course of the study.  These actions will help to ensure the continued acceptability 
of the facilities, compliance to the clinical protocol and relevant regulations, and the maintenance 
of complete records. 
Monitoring will include review and resolution of missing or inconsistent results and source 
document verification (i.e. comparison of submitted study results to original reports) to assure the 
accuracy of the reported data. 
Sponsor representatives will periodically request source documents, resolution of discrepancies, 
submission of echocardiography imaging etc. for data cleaning and reporting purposes.  

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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6.6 Subject Study Completion 
After the 2-year follow-up visit is completed, subjects will be discontinued from the study and 
return to receiving medical care per their physician’s recommendations. 
6.7 Compromising Factors 
This is an observational post-market study evaluating real-world outcomes in subjects with LAAO. 
There are no anticipated or foreseeable factors that may compromise the outcome of the study or 
interpretation of results. 
6.8  Subject Withdrawal 
Subjects must be informed about their right to withdraw from the study at any time and for any 
reason without sanction, penalty, or loss of benefits to which the subject is otherwise entitled. 
Withdrawal from the study will not jeopardize their future medical care or relationship with the 
investigator.  Subjects will be asked to specify the reason for their termination, but have the right 
not to answer. 
The investigator may decide to withdraw a subject from the study at any time with reasonable 
rationale. The subject’s future care will not be influenced by a decision, voluntary or otherwise, to 
withdraw from the study. All reasonable efforts should be made to retain the subject in the study 
until completion of the study. 
Reasons for subject withdrawal include, but are not limited to: 
 Subject withdraws consent 
 Subject refuses to continue their participation  
 Subject does not meet the inclusion/exclusion criteria (withdraw attempt to treat subjects 7 
days after the date of the attempted procedure) 
 Subject is deceased (event or symptoms pertaining to outcome of death must be 
documented on an Adverse Event eCRF) 
 Subject’s participation is terminated by the PI or investigator, although the subject 
consented, since participation is no longer medically appropriate 
 Subject is ‘lost to follow up’ (subject does not adhere to the scheduled follow up visits but 
has not explicitly requested to be withdrawn from the study) 
 Site personnel should make reasonable efforts to locate and communicate with the subject 
in order to achieve subject compliance to the scheduled follow up visits 
If a subject withdraws from the study, the site will record the subject’s reasons for withdrawal on 
the Withdrawal eCRF. 
 COMPLIANCE STATEMENTS 
The study will be performed in accordance with the most current versions of the World Medical 
Association (WMA) Declaration of Helsinki (Appendix C), ISO 14155, MEDDEV post market 
requirements and any regional and/or national regulations and will be compliant to these International 
Standards and any regional and national regulations, as appropriate. 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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The investigator will not enroll subjects or obtain informed consent from any subject prior to obtaining 
EC approval, if applicable, and authorization from the Sponsor in writing for the study. The subject must 
sign the study informed consent form prior to any study-related procedures.  
If additional requirements are imposed by the EC, those requirements will be followed, if appropriate. If 
any action is taken by an EC, and regulatory requirements with respect to the study, that information 
will be forwarded to SJM. 
As the Sponsor, SJM has taken general liability insurance in accordance with the requirements of 
applicable local laws. Appropriate SJM country representatives will be utilized to interpret the 
requirements regarding the type of insurance that will be provided to subjects, and such information will 
be incorporated into the informed consent form, as applicable. If required, additional subject coverage or 
study specific insurance may also be provided by the Sponsor. 
 SERIOUS ADVERSE EVENTS, SERIOUS ADVERSE DEVICE EFFECTS, DEATHS AND 
DEVICE DEFICIENCIES 
Risks associated with the Amulet device are similar to other implantable cardiac occlusion devices. 
Some of the potential risks include but are not limited to those listed below. The definitions noted below 
are used for the purposes of this study. Radiation risks associated with the procedure are comparable to a 
diagnostic catheterization procedure. 
Only serious adverse events (SAEs) will be collected for this study. Serious adverse events are classified 
as serious adverse events or serious adverse device effects (SADEs). A planned hospitalization for a pre-
existing condition is not considered a serious adverse event. 
8.1 Serious Adverse Events  
A serious adverse event is an adverse event that led to: 
 Death 
 A serious deterioration in the health of the subject, that either resulted in: 
o A life-threatening illness or injury OR 
o A permanent impairment to a body structure or a body function OR 
o An in-patient or prolonged hospitalization OR 
o A medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body OR 
o A malignant tumor OR 
o Fetal distress, fetal death or a congenital abnormality or birth defect 
 
Potential serious adverse events include but are not limited to: 
▪ Air Embolus – symptomatic event resulting from the introduction of air into the 
circulatory system 
▪ Allergic reaction – idiosyncratic reaction to the device implanted or to nickel 
▪ Anesthesia reaction – undesired reaction to anesthetic agent 
▪ Arrhythmia – cardiac rhythm disturbance 
▪ Bleeding – *see definition of bleeding as defined by BARC at end of section   

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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▪ Cardiac arrest – failure of the heart to contract 
▪ Cardiac tamponade – constriction of the heart causing inefficient contraction resulting 
from accumulation of excess fluid in the pericardium 
▪ Death –  permanent cessation of all vital bodily functions  
▪ Device embolization – movement of the device from its intended location 
▪ Device migration – movement of the device within its intended location 
▪ Embolic event – acute vascular insufficiency or occlusion of the extremities or any non-
central nervous system organ associated with clinical, imaging, surgical/autopsy evidence 
of arterial occlusion in the absence of other likely mechanism (e.g., trauma, atherosclerosis, 
or instrumentation). When there is presence of prior peripheral artery disease, angiographic 
or surgical or autopsy evidence is required to show abrupt arterial occlusion 
▪ Fever – defined as a body temperature  > 37.5 or 38.3 °C (99.5 or 100.9 °F)[ 
▪ Foreign body embolization – movement of device material, delivery system material, or 
other material from its intended location 
▪ Hypotension – sustained systolic blood pressure  < 90 mmHg 
▪ Hypertension – systolic blood pressure of  > 160 mmHg 
▪ Infection – invasion and growth of a pathogenic organism within the body   
▪ Multi-Organ Failure – the failure of two or more systems, such as the cardiovascular and 
renal systems, and is a common consequence of sepsis (the presence of bacteria in the 
blood) and of shock (very low blood pressure) 
▪ Myocardial infarction (heart attack) – the death of heart muscle from the sudden 
blockage of a coronary artery by a blood clot   
▪ Perforation – physical penetration of a vessel or the myocardium 
▪ Pericardial effusion – abnormal fluid collection around the heart without hemodynamic 
compromise 
▪ Renal failure/dysfunction – inability of kidneys to perform normal functions 
▪ Respiratory failure – inability of the lungs to perform normal functions  
▪ Seizure – uncontrolled electrical activity in the brain, which may produce a physical 
convulsion, minor physical signs, thought disturbances, or a combination of symptoms 
▪ Significant Residual Flow – flow > 3 mm jet into the LAA 
▪ Stroke – an acute episode (lasting > 24 hours) of focal or global neurological dysfunction 
caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or 
infarction. Strokes are characterized as follows35:   
o Ischemic Stroke: an acute episode of focal cerebral, spinal, or retinal dysfunction 
caused by infarction of the central nervous system tissue.  Hemorrhage may be a 
consequence of ischemic stroke. In this situation, the stroke is an ischemic stroke with 
hemorrhagic transformation and not a hemorrhagic stroke.  
o Hemorrhagic Stroke: an acute episode of focal or global cerebral or spinal 
dysfunction caused by intraparenchymal, intraventricular, or subarachnoid 
hemorrhage 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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o Undetermined Stroke: an acute episode of focal or global neurological dysfunction 
caused by presumed brain, spinal cord, or retinal vascular injury as a result of  
hemorrhage or infarction but with insufficient information to allow categorization as 
ischemic or hemorrhagic stroke 
▪ Thrombus Formation – a blood clot 
▪ Transient Ischemic Attack (TIA)–  a transient episode (lasting ≤ 24 hours) of focal 
neurological dysfunction caused by brain, spinal cord, or retinal ischemia, without acute 
infarction on brain imaging 
▪ Valvular regurgitation/insufficiency – backflow of blood during contraction of the heart; 
caused by a defective heart valve 
▪ Vascular access site injury – damage at vascular access site (e.g., AV fistula, hematoma, 
and aneurysm) 
▪ Vessel Trauma/Injury – traumatic injuries that damage an artery or vein 
*Bleeding  
Classified as Type 0 – 5 according to the following BARC definitions36: 
Type 0: No bleeding 
Type 1: Bleeding that is not actionable and does not cause the patient to seek unscheduled 
performance of studies, hospitalization, or treatment by a healthcare professional; may include 
episodes leading to self-discontinuation of medical therapy by the patient without consulting a 
healthcare professional 
Type 2 (minor): Any overt, actionable sign of hemorrhage (e.g. more bleeding than would be 
expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit 
the criteria for Type 3, 4, or 5 but does meet at least one of the following criteria: (1) requiring 
nonsurgical, medical intervention by a healthcare professional, (2) leading to hospitalization or 
increased level of care, or (3) prompting evaluation  
Type 3 (major): 
Type 3a:  
▪ Any transfusion with overt bleeding  
▪ Overt bleeding plus a hemoglobin drop of  ≥ 3 to < 5 g/dL (provided hemoglobin drop is 
related to bleeding) 
Type 3b:  
 Overt bleeding plus hemoglobin drop  ≥ 5 g/dL (provided hemoglobin drop is related to 
bleed)  
 Cardiac tamponade  
 Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/ 
hemorrhoid) 
 Bleeding requiring intravenous vasoactive drugs 
 
 

 
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Type 3c: 
▪ Intracranial hemorrhage including subdural hemorrhages (does not include microbleeds or 
hemorrhagic transformation, does include intraspinal) 
▪ Subcategories confirmed by autopsy or imaging or lumbar puncture 
▪ Intraocular bleed compromising vision 
Type 4: Coronary artery bypass graft (CABG)–related bleeding: 
▪ Perioperative intracranial bleeding within 48 hours 
▪ Reoperation after closure of sternotomy for the purpose of controlling bleeding 
▪ Transfusion of  ≥ 5 units whole blood or packed red blood cells within a 48-hour period 
(only allogenic transfusions are considered transfusions for CABG-related bleeds)  
▪ Chest tube output ≥ 2 L within a 24-hour period 
Notes: If a CABG-related bleed is not adjudicated as at least a type 3 severity event, it will not be 
classified as a bleeding event. If a bleeding event occurs with a clear temporal relationship to 
CABG (i.e. within a 48-hour timeframe) but does not meet type 4 severity criteria, it will not be 
classified as a bleeding event.  
Type 5: Fatal bleeding 
Fatal bleeding is bleeding that directly causes death with no other explainable cause. 
BARC fatal bleeding is categorized as either definite or probable as follows: 
Type 5a: 
Probably fatal bleeding: bleeding that is clinically suspicious as the cause of death, but the 
bleeding is not directly observed and there is no autopsy or confirmatory imaging 
Type 5b: 
Definite fatal bleeding: bleeding that is directly observed (by either clinical specimen [blood, 
emesis, stool, etc.] or imaging) or confirmed on autopsy 
The site of fatal bleeding is specified as intracranial, gastrointestinal, retroperitoneal, pulmonary, 
pericardial, genitourinary, or other. 
Bleeding Academic Research Consortium (BARC) indicates fatal bleeding is meant to capture 
deaths that are directly due to bleeding with no other cause. The time interval from the bleeding 
event to the death should be considered with respect to likely causality, but there is no specific 
time limit proposed. Bleeding that is contributory but not directly causal to death is not classified 
as fatal bleeding but may be categorized as other forms of bleeding. Bleeding that leads to 
cessation of antithrombotic or other therapies may be contributory but again would not be 
classified as fatal bleeding.  
Confirmation of the stroke/TIA diagnosis  
In the event of a stroke/TIA the diagnosis must be confirmed by the following: 
▪ Neurologist or neurosurgical specialist  
▪ Neuroimaging (CT, or MR,and  CTA (computed tomography angiography) or MRA 
(magnetic resonance angiography)  

 
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Requirements post confirmed stroke/TIA 
In order to determine device placement, LAA flow parameters, and clinical outcomes of the  
stroke/TIA, the following must be completed: 
▪ TOE 
▪ Modified Rankin Scale assessment 90 days following confirmed stroke/TIA 
Thrombus 
If a thrombus is detected post- procedure, complete an Adverse Event eCRF.  The following data 
will be collected on the CRFs: 
 Medication regime at time thrombus 
 Medication(s) used to treat thrombus 
 Imaging performed to monitor thrombus and frequency of monitoring 
 Timeframe for resolution 
8.1.1 Serious adverse device effect  
A serious adverse device effect is a serious adverse event related to the device or procedure 
which resulted in any of the consequences characteristic of a serious adverse event, or that might 
have led to any of these consequences if suitable action had not been taken or intervention had 
not been made or if circumstances had been less opportune.   
8.1.2 Assessing, recording and reporting serious adverse events, serious adverse device 
effects, and device deficiencies/complaints 
Safety surveillance within this study and the safety reporting performed both by the investigator 
and Sponsor starts as soon as the dilator/device delivery system has been introduced. The safety 
surveillance and the safety reporting will continue until the last visit has been performed, the 
subject is deceased, the subject/investigator concludes their participation into the study or the 
subject/investigator withdraws the subject from the study. 
All serious adverse events (including deaths), serious adverse device effects, and device 
deficiency information (if applicable) will be collected throughout the clinical study and reported 
to the Sponsor. Investigators will record all serious adverse events, serious adverse device 
effects, and deaths on the appropriate eCRF. Device deficiencies will be reported per country 
reporting timeline requirements to the Sponsor outside of the database on an Event Report Form 
(Appendix I).  
For any serious adverse event (including deaths) and any serious adverse device effect, the 
investigator shall notify the Sponsor immediately of the investigator’s awareness of the event 
and provide the Sponsor with all necessary documentation needed. Device deficiencies will be 
reported to the Sponsor outside of the database on an Event Report Form (Appendix I), as soon 
as possible after first learning of the event. 
Records relating to the subject’s subsequent medical course must be maintained and submitted 
(as applicable) to the Sponsor until the event has subsided or, in case of permanent impairment, 
until the event stabilizes and the overall clinical outcome has been ascertained. Additional 

 
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information may be requested, when required, by the Sponsor in order to support the reporting of 
serious adverse events to the CEC, regulatory authorities and/or other authorities. 
Serious adverse events and serious adverse device effects should be monitored by the 
investigator until resolved.  The status of the subject’s condition should be documented at each 
follow-up visit.   
Events reportable to the Sponsor, EC, CAs and regulatory authorities (as applicable) include: 
 All serious adverse device effects 
 All serious adverse events (including deaths and whether or not the event is considered 
device or procedure related) 
 Device deficiencies (if applicable) that could have led to a serious adverse device effect f 
either suitable action had not been taken; if intervention had not been made or if 
circumstances had been less fortunate 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant 
authorities per country specific regulations.  
8.1.3 Subject death 
All subject deaths with all necessary documentation needed are to be reported to the Sponsor 
immediately upon the investigator’s awareness of the event. The Sponsor must report the death 
(classified as a serious adverse event) to the NCAs where the study has commenced  no later 
than 2 calendar days after awareness of the event.  An Adverse Event eCRF should be completed 
and include additional detail surrounding the death and cause of death. The principal investigator 
should also record observed device deficiencies and assessment, if applicable.  
8.2 Device Deficiency/Complaint Handling  
During the trial, the investigator will be responsible for reporting all device deficiencies per 
country reporting timeline requirements. A device deficiency is defined as an inadequacy of a 
medical device with respect to its identity, quality, durability, reliability, safety or performance and 
includes malfunctions, and inadequate labeling.  
If the device deficiency involves a serious adverse event, the investigator shall notify the Sponsor 
immediately of the investigator’s awareness of the event and provide the Sponsor with all 
necessary documentation needed.  
If the device deficiency does not involve a serious adverse event, the principal investigator should 
notify the SJM Product Surveillance Department by emailing the information about the device 
deficiency to the local country office or to: complaints_amplatzer@sjm.com or calling +1 
6517565400 as soon as possible after becoming aware of the device deficiency. This information 
will be collected outside of the database on an event report form located in Appendix I. The event 
report form should be completed by a local SJM representative or the investigator.  Please contact 
the local SJM representative to coordinate product returns as applicable. 
St. Jude Medical will manage all device deficiencies related to the identity, quality, durability, 
reliability, safety or performance of the marketed study device and reporting to the appropriate 
regulatory bodies.   

 
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 DATA MANAGEMENT 
Overall, the Sponsor will be responsible for data handling. The Sponsor and/or its affiliates will be 
responsible for compiling and submitting all required reports to governmental agencies. 
Data will be analyzed by the Sponsor and may be transferred to the Sponsor’s locations outside of 
Europe and/or any other worldwide regulatory authority in support of a market-approval application. 
St. Jude Medical respects and protects personally identifiable information that is collected or 
maintained. As part of its commitment, SJM is certified to the U.S. - European Union Framework and 
U.S. – Swiss Safe Harbor Framework Agreements regarding human resources and subject clinical trial 
personal information. The privacy of each subject and confidentiality of his/her information will be 
preserved in reports and when publishing any data. Confidentiality of data will be observed by all parties 
involved at all times throughout the clinical study. All data will be secured against unauthorized access. 
Electronic CRFs will be used in this study, as noted below and in the data management plan. Informed 
consent documents will be translated to each country’s language, as applicable. If additional 
documentation is required for any reason (e.g. procedural notes for an adverse event), it is to be 
appropriately redacted/de-identified prior to being sent to SJM. Source documents will be collected and 
translated, as needed, for CEC meetings, reporting, etc.  
The principal investigator or institution will provide direct access to source data during and after the 
clinical study for monitoring, audits, EC review and regulatory authority inspections.   
9.1 Data Management Plan 
A detailed data management plan (DMP) will be established to ensure consistency of the collected 
data. This document will include procedures used for data review, database cleaning, and issuing 
and resolving data queries. If appropriate, the DMP may be updated throughout the study duration. 
All revisions will be tracked and document controlled. 
Electronic CRF data will be captured in a validated electronic database management Oracle 
Clinical system hosted by SJM. Only authorized site personnel will be permitted to enter the data 
through the electronic data capture (EDC) system deployed by SJM. An electronic audit trail will 
be used to track any subsequent changes of the entered data. 
9.2 Document and Data Control 
9.2.1 Document and data traceability 
The investigator will ensure accuracy, completeness, legibility and timeliness of the data 
reported to the Sponsor on the eCRFs and in all required reports.  
9.2.2 Recording data  
Source documents will be created and maintained by the investigational site throughout the 
clinical study. Data reported on the eCRFs will be derived from, and be consistent with, these 
source documents, and any discrepancies will be explained in writing. 
The eCRFs will be signed and dated (validated eCRF) by the authorized site personnel, as 
specified in the Data Management Plan.  

 
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 MONITORING  
It is the responsibility of SJM as the Sponsor of the study to ensure the study is conducted, recorded, and 
reported according to the approved protocol, subsequent amendment(s), applicable regulations, and 
guidance documents. Monitoring will be conducted according to the SJM Clinical Monitoring standard 
operating procedure. 
Centralized monitoring will occur through routine internal data review.  This monitoring is designed to 
identify missing and inconsistent data, data outliers, and potential protocol deviations that may be 
indicative of site non-compliance.  On-site monitoring may occur at the discretion of the Sponsor if 
significant concerns arise. The investigator shall make subject and study records available to the clinical 
monitor for monitoring. 
 REGULATORY INSPECTIONS 
The investigator and/or delegate should contact SJM immediately upon notification of a governmental 
agency inspection at the site. A clinical monitor or designee will assist the investigator and/or delegate 
in preparing for the audit. 
An investigator, or any person acting on behalf of such a person with respect to the study, will permit 
authorized governmental agency employees, at reasonable times and in reasonable manner, to inspect 
and copy all records relating to the study. 
An investigator will permit authorized governmental agency employees to inspect and copy records that 
identify subjects, upon notice that governmental agency has reason to suspect that adequate informed 
consent was not obtained, or that reports required to be submitted by the investigator, to the Sponsor or 
EC have not been submitted or are incomplete, inaccurate, false or misleading. 
 STATISTICAL METHODS 
No formal hypothesis will be tested for this observational post-market study. However, point estimates 
and exact 95% confidence intervals will be provided for the following rates in the study: 
 Procedural serious adverse events (0 - 7 days) post procedure or before hospital discharge 
whichever latest) will be summarized for all subjects as well as stratified by imaging 
modality used for implanting the device (TOE and ICE)  
 Late serious adverse events through 2 years 
 Occurrence of ischemic stroke , systemic embolism and cardiovascular death through 2 
years 
 Occurrence of bleeding (including hemorrhagic stroke) events through 2 years 
Data collected on the following objectives will also be reported: 
▪ Technical success (secondary objective) 
▪ Procedural success (secondary objective) - This objective will be summarized for all 
subjects as well as stratified by imaging modality used for placement of the device (TOE 
and ICE) 
▪ OAC usage through 2 years (secondary objective) 

 
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▪ Serious Adverse Events – this may include, but is not limited to:  
o Significant bleeding events (e.g. cardiac tamponade, central nervous system (CNS) 
bleeding, and any bleeding related to the device or procedure that necessitates an 
operation) 
o Endocarditis 
o Device embolization (summarized by those that can be snared, and those that require 
surgical intervention) 
o Thrombus on device 
o All strokes 
o Transient ischemic attacks 
o Systemic embolism 
o Cardiovascular death 
▪ Closure at procedure and  1-3 months post implant 
o The echo core lab’s adjudication of residual flow will be used for this analysis.  The 
following guidelines will be used: 
▪ None – No color flow jet in or out of the LAA 
▪ Small leak:  < 3 mm diameter jet by color flow Doppler 
▪ Medium leak: 3-5 mm diameter by color flow Doppler 
▪ Large leak:  > 5 mm diameter jet by color flow Doppler 
Other variables may be summarized as deemed appropriate. The numerator for all rates will be the 
number of subjects who experience the corresponding event. The denominator for all rates will be 
subjects who experience the corresponding event plus all other subjects who achieve 2-years of follow-
up.  
Version 9.0 or higher of the SAS® statistical software package or other widely accepted statistical 
software will be used to provide all statistical analyses. Unless otherwise stated, attempts will not be 
made to adjust for multiple comparisons.  
 ADVISORY COMMITTEES 
13.1 Steering Committee 
The Steering Committee (SC) will be composed of medical practitioners who are experts in the 
field of AF and LAA occlusion.  The committee will serve as an advisory board during the course 
of the study as well as after its completion.  Specific responsibilities of the members will depend 
upon the consulting expertise needed by the Sponsor. At any time during the course of the study, 
the SC may offer opinions or make formal recommendations concerning aspects of the study that 
impact subjects. Additionally, the SC may act as an advisory panel for questions that arise during 
the course of the study. It will be the responsibility of the SC to write a publication policy and 
along with SJM, review manuscripts and conference presentations. 

 
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13.2 Clinical Events Committee  
The clinical events committee (CEC) is an independent physician group that will review and 
adjudicate serious adverse events that occur over the course of the study.  The CEC members will 
not be site investigators in the study. Responsibilities and membership of the CEC will be 
described in a CEC charter. Board membership may include cardiologists, electrophysiologists, 
neurologists and neuroradiologists.  
The primary responsibilities of the CEC over the course of the study are to review and refine 
serious adverse event definitions, and to review and adjudicate serious adverse events. 
13.3 Echocardiography Core Laboratory 
An independent echocardiography core laboratory (echo core lab) will analyze all TOEs, TTEs, 
and ICE images during the trial as required per the echo core lab protocol (Appendix E). The echo 
core lab will assess residual flow into the left atrial appendage around the device in the following 
manner: 
▪ None – No color flow jet in or out of the LAA 
▪ Small leak:  < 3 mm diameter jet by color flow Doppler 
▪ Medium leak: 3-5 mm diameter by color flow Doppler 
▪ Large leak:  > 5 mm diameter jet by color flow Doppler 
 DOCUMENT RETENTION 
After the termination of the study, the principal investigator will maintain all clinical study documents 
on file at the site for the minimum number of years required per local laws.  
 AMENDMENTS TO THE CLINICAL PROTOCOL 
Study related documents such as, the Investigator’s Brochure (IB) (Appendix D), protocol, eCRFs 
(Appendix H) informed consent form (Appendix G) and other subject information, or other clinical 
study documents will be amended as needed throughout the clinical study, and a justification statement 
will be included with each amended section of a document.  Proposed amendments to the protocol will 
be agreed upon between the Sponsor and the coordinating investigator (if applicable).  
The amendments to the protocol and the subject’s informed consent form will be notified to, or 
approved by, the EC and regulatory authorities, if required. The version number and date of amendments 
will be documented (Appendix B). 
The amendment will identify the changes made, the reason for the changes and if it is mandatory or 
optional to implement the amendment. Any amendment affecting the subject requires that the subject be 
informed of the changes, and a new consent be signed and dated at the subject’s next follow up. 
 OUTSOURCING OF SPONSOR DUTIES AND FUNCTIONS 
The Sponsor does not anticipate transferring any duties and functions related to the clinical study, 
including monitoring, to an external organization (such as a contract research organization or individual 
contractor).  If outsourcing does occur, the ultimate responsibility for the quality and integrity of the 
clinical study will reside with the Sponsor.  All requirements applying to the Sponsor will also apply to 

 
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the external organization inasmuch as this organization assumes the clinical study related duties and 
functions of the Sponsor. 
 INVESTIGATION SUSPENSION OR TERMINATION 
17.1 Premature Termination  
The Sponsor reserves the right to stop the study at any stage, with appropriate written notice to the 
investigator.  
Possible reasons for early termination of the study by the Sponsor, either at local, national or 
international level, may include, but are not limited to: 
▪ Sponsor’s decision 
▪ Request from regulatory authorities 
▪ Request of EC(s)  
▪ Concern for subject safety and welfare 
▪ Failure to secure subject informed consent prior to any protocol activity 
▪ Failure to report unanticipated adverse device effects within 72 hours to SJM and the EC 
▪ Repeated non-compliance with this clinical protocol or the clinical trial agreement 
▪ Inability to successfully implement this clinical protocol 
▪ Violation of the Declaration of Helsinki (refer to Appendix C) 
▪ Violation of applicable national or local laws and regulations 
▪ Falsification of data, or any other breach of ethics or scientific principles 
In such events, the study will be terminated according to applicable regulations.  The investigator 
may also discontinue participation in the clinical study with appropriate written notice to the 
Sponsor.  Should either of these events occur, the investigator should provide a written statement 
as to why the premature termination has taken place, and notify the EC and/or the CA (if 
applicable).  Follow-up for all enrolled subjects will be per center standard of care. 
A principal investigator, EC, or regulatory authority may suspend or prematurely terminate 
participation in a clinical study at the investigational sites for which they are responsible. 
17.2 Study Conclusion 
The study will be concluded when: 
▪ All follow up visits have been completed and subjects withdrawn AND 
▪ All sites are closed AND 
▪ The final report generated by SJM has been provided to sites or SJM has provided formal 
documentation of study closure 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
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 PUBLICATION POLICY 
The results of the clinical study are planned to be submitted for publication.  If a principal investigator 
will be involved in publishing the data, a publication agreement will be signed between the PI and 
Sponsor either as a separate publication agreement or within the clinical trial agreement.  
The investigator or site may not publish any information that the Sponsor believes to be confidential 
information.  The publication of the initial results of the Amulet observational post-market study shall be 
subject to review and release of the Sponsor’s publication committee, which shall confer with the site 
regarding such publication. 
For more information on publication guidelines, refer to the International Committee of Medical Journal 
Editors (ICMJE) on www.icmje.org.  This study will also be posted on ClinicalTrials.gov and results 
will be posted on ClinicalTrials.gov as required. 
 BIBLIOGRAPHY  
1. Ostermayer SH, Reisman M, Kramer PH, Matthews RV, Gray WA, Block PC, Omran H, 
Bartorelli AL. Percutaneous left atria appendage transcatheter occlusion (PLAATO System) to 
prevent stroke in high risk subjects with non-rheumatic atrial fibrillation: results from the 
international multi-center feasibility trials. J Am Col Cardiol. 2005; 46(1):9-14. 
2. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical subjects 
with atrial fibrillation.  Ann Thorac Surg. 1996; 61:755-9. 
3. Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, Jensvold NG, Selby JV, 
Singer DE. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do 
randomized trials translate into clinical practice? JAMA. 2003; 290(20):2685-92. 
4. Stollberger C, Schneider B, Finsterer J.  Elimination of the left atrial appendage to prevent stroke 
or embolism? Anatomic, physiologic, and pathophysiologic considerations.  Chest 2003; 
124(6):2356-62. 
5. Miller VT, Rothrock JF, Pearce LA, Feinberg WM, Hart RG, Anderson DC, Ischemic stroke in 
subjects with atrial fibrillation: effect of Aspirin according to stroke mechanism.  Stroke 
prevention in atrial fibrillation investigators. Neurology. 1993; 43(1):32-6. 
6. Alizadeh A, Maeki M, Bassiri H, Alasti M, Emkanjoo Z, Haghjoo M, Arya A, Bagherzadeh A, 
Faze Lifar A, Sadr-Ameli MA. Evaluation of atrial thrombus formation and atrial appendage 
function in subjects with pacemaker by transesophageal echocardiography.  Pacing Clin 
Electrophysiol. 2006; 29(11):1251-4. 
7. Agmon Y, Khandheria BK, Gentile F, Seward JS. Echocardiographic assessment of the left atrial 
appendage. J Am Coll Cardiol. 1999; 34; 1867-1877. 
8. Ezekowitz MD, James KKE, Nazarian SM, Davenport J, Broderick JP, Gupta Sr, Thadani V, 
Meyer ML, Bridgers SL.  Silent cerebral infarction in subjects with nonrheumatic atrial 
fibrillation.  The veterans affairs stroke prevention in nonrheumatic atrial fibrillation 
investigators.  Circulation. 1995; 92(8):2178-82. 

 
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This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, 
disclosed or used without the express written consent of St. Jude Medical 
 
9. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ.  Validation of 
clinical classification schemes for predicting stroke: results from the national registry of atrial 
fibrillation.  JAMA. 2001; 285(22):2864-70. 
10. Andersen LV, Vestergaard P, Deichgraeber P, Lindholt JS, Mortensen LS, Frost L. Warfarin for 
the prevention of systemic embolism in subjects with nonvalvular atrial fibrillation: a meta-
analysis. Heart. 2008; 94(12):1607-13. 
11. Hart RG, Pearce LA, Aguilar MI, Adjusted-dose warfarin versus aspirin for preventing stroke in 
subjects with atrial fibrillation.  Ann Intern Med. 2007; 147(8):590-2. 
12. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgre J, Yang S, Alings 
M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf S. 
Risk of bleeding with two doses of dabigatran compared with warfarin in older and younger 
patients with atrial fibrillation: an analysis of the randomized evaluation of long-term 
anticoagulant therapy (RE-LY) Trial. Circulation. 2011; 123(21): 2363-2372. 
13. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, 
Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KAA, Califf RM, 
and the ROCKET AF steering committee for the ROCKET AF investigators. Rivaroxaban 
versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-891. 
14. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, 
Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, 
Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan 
P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, 
Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients 
with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92.  
15. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, 
Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip 
LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. 
N Engl J Med. 2013 Nov 28;369(22):2093-104.  
16. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbiner M, Mullin CM, Sick P; 
PROTECT AF Investigators. Percutaneous closure of the left atrial appendage versus warfarin 
therapy for prevention of stroke in patients with atrial fibrillation: A randomized non-inferiority 
trial. Lancet 2009; 374:534-42. 
17. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage 
closure: results from the Watchman left atrial appendage system for embolic protection in 
patients with AF (PROTECT AF) clinical trial and the continued access registry. Circulation. 
2011; 123:417-24. 
18. Holmes DR, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, Huber K, Reddy VY. 
Prospective randomized evaluation of the Watchman left atrial appendage closure device in 
patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial.  J Am 
Coll Cardiol. 2014; 64:1-12. 

 
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Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
19. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, Kar S, Halperin J, 
Whisenant B, Swarup V, Holmes D. Long term results of PROTECT AF: The mortality effects 
of left atrial appendage closure versus warfarin for stroke prophylaxis in AF. Heart Rhythm 
Society 2013 Scientific Sessions; May 9, 2013; Denver, Co. 
20. Gangireddy Sr, Halperin JL, Fuster V, Reddy VY. Percutaneous left atrial appendage closure for 
stroke prevention in patients with atrial fibrillation; an assessment of net clinical benefit.  Eur 
Heart J. 2012; 33:2700-8. 
21. Park HW, Bethencourt A, Sievert H, Santoro G, Meier B, Walsh K, Lopez-Minquez JR, Meerkin 
D, Valdes M, Ormerod O, Leithauser B. Left atrial appendage closure with AMPLATZER 
cardiac plug in atrial fibrillation: Initial European experience. Catheter Cardiovasc Interv. 2011; 
77:700-6. 
22. Urena M, Rodes-Cabau J, Freixa X, Saw J, Webb JG, Freeman M, Horlick E, Osten M, Chan A, 
Marquis JF, Champagne J, Ibrahim R. Percutaneous left atrial appendage closure with the 
AMPLATZER cardiac plug device in patients with non-valvular atrial fibrillation and 
contraindications for anticoagulation therapy. J Am Coll Cardiol. 2013; 62:96-102. 
23. Meerkin D, Butnaru A, Dratva D, Bertrand OF, Tzivoni D. Early safety of the AMPLATZER 
cardiac plug for left atrial appendage occlusion. Int J Cardiol. 2013; 168:3920-5. 
24. Nietlspach F, Gloekler S, Krause R, Shakir S, Schmid M, Khattab AA, Wenaweser P, Windecker 
S, Meier B. Amplatzer left atrial appendage occlusion single center 10-year experience. Catheter 
Cardiovasc Interv. 2013; 82:283-9. 
25. Bartus K, Han FT, Bednarek J, Myc J, Kapelak B, Sadowski J, Lelakowski J, Bartus S, Yakubov 
SJ, Lee RJ. Percutaneous left aptrial appendage suture ligation using the LARIAT device in 
patients with atrial fibrillation: initial clinical experience. J Am Coll Cardiol. 2013; 62:108-18. 
26. Camm AJ, Lip GY, De Caterina R, Savelieve I, Atar D, Hohnloser SH, Hindricks G, Kirchof P: 
ESC Committee for Practice Guidelines (CPG). The 2012 focused update of the ESC guidelines 
for the management of atrial fibrillation.  Developed with the special contribution of the 
European Heart Rhythm Association. Eur Heart J. 2012; 33-2719-47. 
27. Saw J, Lempereur M. Percutaneous left atrial appendage closure procedural techniques and 
outcomes. JACC: Cardiovascular Interventions Vol. 7 No 11 2014. 
28. Park JW, Bethencourt A, Sievert H, Santoro G, Meier B, Walsh K, Lopez-Minquez JR, Meerkin 
D, Valdés M, Ormerod O, Leithäuser B. Left atrial appendage closure with AMPLATZER 
cardiac plug in atrial fibrillation: Initial European experience. Catheterization and Cardiovascular 
Interventions, 2011; 77: 700–706. 
29. Walsh K, Sievert H, Lickfett L, Omran H, Hennen B, Schraeder R, Garcia E, Park JW, 
Schillinger W, Lopez-Minguez JR, Valdes M, Ormerod O, Neuzil P, Hildick-Smith D, Lezaun 
R: Left atrial appendage closure with the AMPLATZER cardiac plug: Results of the European 
post-market observational study. Presented at EURO PCR May 2012. 
30. Sievert H, Park JW, Schillinger W, Lickfett L, Lopez-Minquez JR, Omran H, Walsh K, Ormerod 
O, Neuzil P, Schraeder R, Hildick-Smith, D: Long-term follow-up from a left atrial appendage 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
occlusion European multicentre post market observational study. Presented at EURO PCR May 
2014. 
31. Lam SC, Bertog S, Gafoor S, Vaskelyte L, Boehm P, Ho RW, Franke J, Hofmann I, Sievert H. 
Left atrial appendage closure using the amulet device: An initial experience with the second 
generation Amplatzer cardiac plug. Catheter Cardiovasc Interv. 2014. 
32. Freixa X, Abualsaud A, Chan J, Nosair M, Tzikas A, Garceau P, Basmadjian A, Ibrahim R. Left 
atrial appendage occlusion: initial experience with the AMPLATZER™ Amulet™. Int J Cardiol. 
2014 Jul 1;174(3):492-6. 
33. Tzikas A, Shakir S, Gafoor S, Omran H, Berti S, Santoro G, Kefer J, Landmesser U, Nielsen-
Kudsk JE, Cruz-Gonzalez I, Sievert H, Tichelbäcker T, Kanagaratnam P, Nietlispach F, Aminian 
A, Kasch F, Freixa X, Danna P, Rezzagh M, Vermeersch P, Stock F, Stolcova M, Costa M, 
Ibrahim R, Schillinger W, Meier B, Park JW. Left atrial appendage occlusion for stroke 
prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. 
EuroIntervention. 2015 Jan 22;10(10). 
34. Tzikas A, Holmes DR, Gafoor S, Ruiz CE, Blomström-Lundqvist C, Diener HC, Cappato R, Kar 
S, Lee RJ, Byrne R, Ibrahim R, Lakireddy D, Soliman O, Näbauer M, Schneider S, Brachman J, 
Saver JL, Tiemann K, Sievert H, Camm J, Lewalter T. Percutaneous left atrial appendage 
occlusion: the Munich consensus document on definitions, endpoints and data collection 
requirements for clinical studies.  Draft LAAO Consensus Document. To be submitted to 
EuroHeart Journal. March 2015. 
35. Hicks KA, Hung HM, Mahaffey KW, Mehran R, Nissen SE, Stockbridge NL, Targum SL, 
Temple R on behalf of the Standardized Data Collection for Cardiovascular Trials Initiative  
(2014). Standardized Definitions for Cardiovascular and Stroke Endpoint Events in Clinical 
Trials. Draft Definitions for CDISC. August 24, 2014. 
36. Mehran R, Rao SV, Bhatt DL. Standardized bleeding definitions for cardiovascular clinical 
trials: A consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 
123(23):2736–47.  

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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Appendix A: Abbreviations 
Abbreviation 
Term 
ACP 
AE 
AF 
AP 
ANZ 
CA 
CE 
CEC 
CP 
CRF 
CNS 
CT 
DMP 
EC 
ECG 
eCRF 
EDC 
EMEA 
EP 
IB 
IC 
ICMJE 
IFU 
INR 
ISO 
LAA 
LAAO 
MRI 
mRS 
NCA 
NVAF 
OAC 
PI 
SADE 
SAE 
SC  
SJM 
TIA 
TOE 
WMA 
Amplatzer Cardiac Plug 
Adverse Event 
Atrial Fibrillation 
Asia-Pacific 
Australia-New Zealand 
Competent Authority 
Conformité Européenne 
Clinical Events Committee 
Clinical Protocol 
Case Report Form 
Central Nervous System 
Computed Tomography 
Data Management Plan 
Ethics Committee 
Electrocardiogram 
Electronic Case Report Form 
Electronic Data Capture 
Europe, Middle East, Africa 
Electrophysiologist 
Investigator’s Brochure 
Interventional Cardiologist 
International Committee of Medical Journal Editors 
Instructions For Use 
International Normalized Ratio 
International Organization for Standardization 
Left Atrial Appendage 
Left Atrial Appendage Occlusion 
Magnetic Resonance Imaging 
Modified Rankin Scale 
National Competent Authority 
Non-Valvular Atrial Fibrillation 
Oral Anticoagulant 
Principal Investigator 
Serious Adverse Device Effect 
Serious Adverse Event 
Steering Committee 
St. Jude Medical, Inc. 
Transient Ischemic Attack 
Transoesophageal Echocardiography 
World Medical Association 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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Appendix B: Protocol Revision History 
Revision History 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Initial 
Release -
N/A 
A 
See Windchill 
(internal document 
control system) 
Initial Document Release 
Initial 
Release 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix C: Declaration of Helsinki 
The 2013 version of the Declaration of Helsinki is available at: 
http://www.wma.net/en/20activities/10ethics/10helsinki/.  Please check the website during the course of 
the study for updated revisions. 
 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix D: Investigator’s Brochure (IB) 
The IB for the Amulet device provides safety and performance data from pre-clinical and clinical 
studies.  The IB will be updated throughout the course of the clinical study as significant new 
information becomes available (e.g. a significant change in risk, etc.).  
The principal investigators, coordinating investigators, national investigators, and medical advisors will 
acknowledge the receipt of the IB and all subsequent amendments, and will keep all information 
confidential.   
The Investigator’s Brochure will be kept under separate cover and is available upon request. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix E: Echocardiography Core Laboratory Protocols 
Transoesophageal Echocardiagraphy (TEE) Protocol 
ALL views to be provided in the following sequence: 
I. TEE Scanning Protocol  
The following TEE protocol is recommended to ensure uniformity across clinical study sites. 
TEE studies are performed at baseline, during the procedure, at the 1-3 month and applicable 
follow-up/interim visits.  The TEE study should image the left atrium (LA) and left atrial 
appendage (LAA) in multiple planes (i.e., 0°- ~110°).  The purpose of the TEE is to obtain 
information regarding: a) LA/LAA thrombus; b) LAA ostium measurements; c) length distal to 
the LAA ostium; d) flow into the LAA and e) to assess for procedural complications, such as 
device migration, pericardial effusion, etc. 
II. Adjustment of the Ultrasound Instrument: 
a. Adjust transmission power (gain) to minimize/eliminate “blooming” of specular 
reflectors. 
b. Adjust the time gain compensation in such way that the image exhibits uniform 
brightness. 
c. Adjust the color Doppler gain below the point where random color noise appears. 
d. Set pulse repetition frequency with Nyquist velocity for CFD at ~35-45 cm/sec. 
e. Use a velocity variance map with a “medium” color filter; set color tissue priority at a 
level that avoids overlay of color signals onto tissue structures. 
f.   Perform TEE at 5-7.5 MHz, with all other settings as mentioned above. 
g. Perform both longitudinal and transverse plane sweeps to ensure full coverage of 
LA/LAA. 
h. Record 3-5 consecutive beats for all cine-loop images; record at least 3-5 consecutive 
beats for all Doppler velocity tracings – record these as still frames (provide 2-3 still 
frames) at 100mm/s sweep speed.  
i. Ensure that the ECG is recorded for all cine-loops and still-frame images. 
 
III. TEE Imaging Study to be Obtained in the Following Views: 
a. The 5-chamber view (Omniplane 0°) with the aortic valve in the center of the screen 
and the LA in the right upper corner. 
• Standard 2D imaging. 
• Zoom mode of LA and LAA; place color flow Doppler (CFD) around device to 
document communication between LA and LAA (post procedure only). 
• Zoom mode of LA and LAA; align Pulse Wave (PW) Doppler sample volume to 
record LAA-LA blood flow.  The PW sample should be placed 0.5 to 1 cm from 
the ostium into the LAA. 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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• 2D imaging of LV at mid-papillary muscle level (short axis), from gastric view. 
b. The high LA/LAA view (Omniplane ~60°)  
Optional views (these may be difficult to obtain in some subjects): 
• Zoom mode of LA and LAA; place CFD around device to document 
communication between LA and LAA (post procedure only).  
• LA/LAA views; align PW Doppler sample volume to record LAA-LA blood 
flow.  The PW sample should be placed 0.5 to 1 cm from the ostium into the 
LAA. 
c. The longitudinal imaging plane (Omniplane ~80-110°) with LA/LAA in field of 
view. 
• Zoom mode of LA and LAA; place CFD around device to document 
communication between LA and LAA (post procedure only). 
• Zoom image of LA-LAA; align PW Doppler sample volume to record LAA blood 
flow.  The PW sample should be placed 0.5 to 1 cm from the ostium into the 
LAA. 
IV. Technical Notes for Completion of Echocardiographic Studies 
a. Study subjects are to be identified only by study site and study subject number.  This 
information will be entered in the ultrasound system patient data section in adherence to 
applicable privacy laws.  No subject names should be displayed in the submitted studies. 
b. Two-dimensional imaging to be performed in harmonic mode; the ECG tracing should be 
displayed on all images (still frames and cine-loops), clearly showing P wave/QRS 
morphology during the echocardiographic study.  Avoid recording extra systolic (PVC) 
beats. 
c. For all spectral Doppler velocities, please use a display speed of 100 mm/sec, and 
optimize the velocity profile by moving the baseline up or down and showing the 
maximal velocity obtained at the top of the scale. 
d. Clinical sites should retain a digital copy of the echocardiographic study in DICOM and 
the study should be analyzed locally.  The Echocardiography Core Laboratory WILL 
NOT return submitted studies.  An echocardiographic analysis WILL NOT be provided 
by the Echocardiography Core Laboratory to the clinical sites.  The Echocardiography 
Core Laboratory Report will only be used for the purposes of the Amulet study and NOT 
for diagnosis and/or clinical management of subjects enrolled in the Amulet study. 
V. Variables that can be Recorded by the Study Sites for optimum imaging 
a. Thrombus in the LA and/or LAA 
b. LAA ostium measurements 
c. Length distal to the LAA ostium 
d. Spontaneous Echo Contrast (SEC) in the LA 
e. Thrombus in the RA and/or RAA 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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f. Spontaneous Echo Contrast (SEC) in the RA 
g. LAA-LA communication/flow (see E below) 
h. Left Ventricular Ejection Fraction (LVEF) 
i. Presence, location, and size of any aortic plaques 
j. Mitral or aortic valve stenosis or regurgitation 
k. In addition the following data points may also be documented: presence of  
1. Atrial septal defect  
2. Patent foramen ovale 
3. Prosthetic valve 
4. Intracardiac thrombus 
5. Atrial septal device 
VI. Measurements to be analyzed by the Echocardiography Core Lab 
a. Thrombus in the LA and/or LAA 
b. LAA ostium measurements 
c. Length distal to the LAA ostium 
d. Thrombus in the RA and/or RAA 
e. Spontaneous Echo Contrast (SEC) in the LA 
f. Presence, location and size of any aortic plaque 
g. LAA-LA communication/flow (see VII below) 
VII. Assessment of Flow in Left Atrial Appendage to be analyzed by the Echocardiography 
Core Lab 
a. None:  No color flow jet in or out of the LAA  
b. Small leak:   < 3 mm diameter jet by color flow Doppler or multiple leaks that are 
cumulatively < 3 mm diameter jet by color flow Doppler 
c. Medium leak:  3-5 mm diameter by color flow Doppler or multiple leaks that are 
cumulatively 3-5 mm diameter jet by color flow Doppler 
d. Large leak:   > 5 mm diameter jet by color flow Doppler or multiple leaks that are 
cumulatively > 5 mm diameter jet by color flow Doppler 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Transthoracic Echocardiogram (TTE) Protocol 
With the subject in the left lateral position, standard transthoracic imaging should be obtained in 
the parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical 
3-chamber views.  For the evaluation of left ventricular systolic function a sweep of the entire 
chamber from base to apex should be imaged from the parasternal short axis view.  Evaluation of 
all 4 valves should include color flow doppler, and continuous and pulse wave doppler 
interrogation.  With the subject lying supine, the atrial septum should be evaluated in the 
subcostal long axis view by both 2D imaging alone and with color flow doppler. 
Any post procedure complication such as pericardial effusion must be documented. 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix F: List of Clinical Investigation Sites and Ethics Committees 
A list of clinical investigative sites and ECs will be kept under separate cover and is available upon 
request.  
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix G: Sample Informed Consent 
 
INFORMED CONSENT 
AMPLATZER™ Amulet™ Observational Post-Market Study 
 
STUDY TITLE AND NUMBER:  AMPLATZER Amulet Observational Post-Market Study 
 
SPONSOR: 
 
St. Jude Medical, Inc. (SJM) 
 
PRINCIPAL INVESTIGATOR: 
 
 
______________________________________________ 
SITE NAME: 
______________________________________________ 
Participant declaration of consent for participation in the Amulet Observational Post-Market Study. 
 
Name of participant: 
 
 
 
 
 
Date:  
 
____________________ 
 
Introduction  
This form explains why this research study is being done and what your role will be if you decide to 
participate in this research study.  This form also talks about the possible risks that may happen if you 
take part in this research study.  The study is sponsored by SJM.  This company manufactures medical 
devices to treat various medical conditions. 
 
Please read this form, and ask your study doctor any questions you may have about the study so your 
questions are answered before you decide if you want to take part in the study.  Please take your time 
and talk about this information with your family, friends, or family doctor.   
 
This consent form may contain some words that you do not understand.  It is important that you 
understand what is in this form.  It will explain the different activities you will be asked to do or 
participate in if you take part in the study and what the risks might be; whether or not you do take part is 
entirely your choice.  Please ask the study doctor or the study staff to explain any words or information 
that you do not understand. 
 
If you decide you want to take part in the study, you will be asked to sign the consent section before any 
study-related activities are performed. By signing this form you are telling us that you: 
• 
Understand what you have read 
• 
Consent to take part in the study  
• 
Consent to have the tests and treatments that are described  
• 
Consent to the use of your personal and health information as described. 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Taking part in this study is entirely voluntary.  If you don’t wish to take part, you don’t have to.  You 
will receive the best possible care whether or not you take part in the study.  Refusing participation will 
not involve any penalty or loss of benefit.  If you decide to take part in this study, you must sign your 
name at the end of this form.  No study activity can be performed until you sign this form. 
 
What is the purpose of this study? 
The purpose of the Amulet observational post-market study is to compile real world performance of the 
commercially available Amulet device in people 18 years or older with paroxysmal, persistent or 
permanent nonvalvular atrial fibrillation.  Data collected for the study will be used to assess closure of 
the left atrial appendage and complications after the procedure, and the percentages of stroke and 
cardiovascular death.  The purpose of the study is also to evaluate the success rate of the Amulet device 
implant, and the use of oral anticoagulants and antiplatelet medications participants take. 
 
Why am I being invited to take part in this study? 
You are being asked to take part in this study because your doctor has determined you have paroxysmal, 
persistent or permanent nonvalvular atrial fibrillation. Normally, electrical signals from the upper 
chambers of the heart (atria) travel to the lower chambers of the heart (ventricles) and cause them to beat 
in a regular way.  During atrial fibrillation, the electrical signals in your heart are abnormal and cause 
the upper chambers of the heart to beat too fast and irregularly. 
 
This irregular beating of the heart leads to a slowing of the blood flow in the upper chambers of the 
heart.  In the left upper chamber there is a small pouch called the left atrial appendage (LAA).  Slowing 
of blood, especially in the LAA, may cause blood clots to form. Blood clots can move from the LAA 
and travel to the brain, causing a stroke or transient ischemic attack (TIA), also called a ministroke.  
These blood clots can also travel to other parts of the body and block blood vessels.  
 
The commercially available Amulet device could be beneficial to you because it may decrease the 
chance of a new blood clot forming and moving from your heart’s left atrial appendage to other parts of 
your body. Figure 1 shows the Amulet device in its final position in the LAA. 
 
 
Figure 1.  Placement of the Amulet device in the left atrial appendage 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Your doctor has given you this form to tell you about the Amulet observational post-market study and to 
ask for your consent to participate.  Once you understand the study and agree to take part, your signature 
on the last page of this form documents your willingness to participate. 
 
What is the device being tested?  
The Amulet device is a self-expanding device which is made from a nitinol (nickel-titanium alloy) mesh 
and has a lobe and a disc connected by a central waist.  The lobe has small wires that help keep the 
device in place.  The device has screw attachments at each end so it can be delivered to the heart.  The 
device has special metal bands at each end that allow it to be seen on fluoroscopy, which is a kind of X-
ray.  The Amulet device has regulatory approval and is commercially available in all countries where 
this study is taking place. 
 
 
A. Screw attachments 
B. Waist of device 
C. Lobe 
D. Stabilizing wires 
E. Disc 
 
Figure 2.  The Amulet device and its key components 
 
What will be requested from you if you take part in this research study? 
In order to evaluate the Amulet device, no testing outside of what is routine care for someone with atrial 
fibrillation will be done.  Any tests done for the study are part of your normal care and would be done 
even if you were not in the study.  There are no experimental procedures in this study.  Your doctor will 
report serious adverse events to the Sponsor and the appropriate regulatory authorities.  Table 1 
describes study specific activities and procedures. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Table 1.  
Study-Specific Activities/Procedures 
 
                Visit 
 
 
Study  
Activity 
Enrollment 
& Baseline 
Procedure 
 
 
Discharge 
 
1-3 
Months  
6M 
Phone 
Visit 
(+/- 2 
weeks) 
 
12M 
(+/- 6 
weeks) 
 
24M 
Phone 
Visit 
(+/- 12 
weeks) 
Interim 
Visit 
Informed Consent 
Process 
X 
 
 
 
 
 
 
 
- History and  Physical  
- Cardiovascular and  
   medical exam  
- CHA2DS2-VASc score  
- HAS-BLED score 
X 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
Medication Assessment 
X 
 
X 
X 
X 
X 
X 
X 
Modified Rankin Scale2 
X 
 
 
 
 
 
 
 
X4 
Angiography 
 
X 
 
 
 
 
 
 
TTE 
 
 
X 
 
 
 
 
 
TOE  
X, 5 
X3, 5 
 
X 
 
 
 
X4 
ICE 
 
X6 
 
 
 
 
 
 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
1Pregnancy test for women of childbearing potential 
2Perform additional Modified Rank Scale assessment 90 days after a confirmed stroke  
3CT can be used as additional information and  performed complimentary to the TOE, per institutional standard of care 
4Complete if stroke or TIA is confirmed 
5The Baseline TOE is optional if a TOE is performed on the day of procedure to rule out the presence of intracardiac  
 thrombus (including left atrial appendage thrombus) and to assess the size and shape of the LAA 
6ICE may be performed for placement of the device in a sub-set of sites pre-approved by SJM 
 
Screening/Baseline Evaluation  
This research study includes a screening/baseline evaluation to determine if you are a candidate for the 
study.  Your doctor or other study personnel will ask you medically related questions.  
You will have the following tests done after you agree to be part of this study and sign this document. 
These tests are common tests for someone with atrial fibrillation, and might be performed even if you do 
not join this study:  
• Informed consent process 
• History and physical 
• Cardiovascular and medical history 
• CHA2DS2-VASc – a set of questions used to assess the level of risk for stroke 
• HAS-BLED scale – a set of questions used to assess the level of risk for bleeding 
events 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
• 12-lead electrocardiogram (ECG) - used to measure the electrical activity of the heart 
by placing electrodes on the chest, arms, and legs 
• Transoesophageal echocardiography (TOE) – used to show how well your heart 
chambers and valves are working and to detect possible blood clots in the heart, and 
in the sac around your heart  
o Note the Baseline TOE is optional if a TOE is performed the day of procedure 
• Modified Rankin Scale – a commonly used scale for measuring the degree of 
disability or dependence in the daily activities of people who have suffered a stroke or 
other causes of neurological disability 
• Pregnancy test (if you are female of child-bearing age) 
• Medication assessment – you will be asked to confirm which antiplatelet and blood-
thinning medications you are taking 
Once all study required tests have been completed, your doctor will decide if you qualify to take part in 
the Amulet observational post-market study.  If you do not qualify for the study, your participation will 
end and you will be withdrawn from the study.    
Procedure  
If you meet all of the inclusion and none of the exclusion criteria, you will be scheduled for the Amulet 
device implant procedure which takes about 1-2 hours.  If you are taking antiplatelet or blood-thinning 
medications, your doctor will tell when you should stop them before your implant procedure. 
A trained Sponsor representative may be present at the implant to answer any questions related to the 
Amulet device, the procedure and the study.  
Conscious sedation (medicine that will make you relaxed and sleepy yet awake) or general anesthesia 
(medicine that will make you sleep) will be used.  Your doctor will first perform a TOE of your heart to 
determine the size of your LAA, and to ensure there are no blood clots in your heart.  Transoesophageal 
echocardiography (TOE) is a test that uses sound waves to create high-quality moving pictures of the 
heart and its blood vessels.  Your doctor will not continue with the procedure if the TOE shows your 
LAA is not suitable for the implant or if there is a thrombus (blood clot) in your heart.  Your doctor may 
decide you do not need the Amulet device or that another type of surgery or commercially available 
device would be better for you. If you meet any of the exclusion criteria during the procedure, you will 
be withdrawn from the study. 
If your doctor determines you meet all of the inclusion criteria and none of the exclusion criteria, a small 
incision will be made in your groin area to insert a delivery catheter through a vein in your leg.  A 
catheter is a sterile, flexible, hollow tube that is put into a blood vessel to let fluids in or out of your 
body, or to deliver medical devices to your heart.  The doctor will make a small puncture through your 
septum (the muscular tissue that separates the two sides of the upper heart), in order to gain entry into 
the upper left heart chamber to place the Amulet device.  
If pre-approved by the Sponsor, your doctor may use an intracardiac echocardiography (ICE) procedure 
to help place the device in your heart.  Intracardiac echocardiography (ICE) is an imaging technique that 
allows physicians to get a clear picture of the inner workings of the heart.  A small ultrasound probe is 
placed into a vein in the groin, then threaded into the area of the heart being worked on.  ICE may be 
used as a diagnostic tool, or for guiding the physician during minimally invasive procedures inside the 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
heart.  The ICE procedure is completely painless and involves only the use of a local anesthetic at the 
site of insertion. 
You are considered enrolled in the study when the device delivery system is introduced into your body. 
An appropriately sized Amulet device will be passed through the catheter and placed in your LAA.  To 
ensure the Amulet device is placed correctly in your LAA, your doctor will use routine measurements 
such as angiography and TOE.  Angiography is a medical imaging technique used to visualize the inside 
of blood vessels and organs of the body, with special interest in the arteries, veins, and the heart 
chambers.  This is done by injecting a radio-opaque contrast agent into the blood vessel and imaging 
using X-ray based techniques such as fluoroscopy.  After your doctor is satisfied with the position of the 
device, the catheter is removed.  The Amulet device will remain permanently in your heart.  Over time, 
the tissue in your body will cover and grow around the device to further hold it in place.  After the 
procedure, you may have some minor pain in the groin area where the catheter was inserted.  
If you meet all of the inclusion and none of the exclusion criteria, and the delivery system was 
introduced into your body but you did not receive the device (attempt to treat), your participation will 
end and you will be withdrawn from the study. 
Pre-Discharge Visit 
You may be kept overnight for observation after the procedure.  A pre-discharge transthoracic 
echocardiography (TTE) will be done to assess for any post procedure complications and to verify the 
position of the device in your heart.  A TTE is another type of echocardiogram that uses high-pitched 
sound waves sent through a transducer (a hand-held plastic instrument which looks like a microphone) 
that is placed on different areas of your chest.  The transducer picks up echoes of the sound waves as 
they bounce off the different parts of your heart and turns them into moving pictures of your heart that 
can be seen on a video screen.  Your health and medication status will be assessed.  If you are 
discharged on antiplatelet medication, it is recommended you take aspirin for six months and Plavix for 
one month.  If you are discharged on warfarin, INR testing should be performed periodically to ensure 
your INR is in the range of 2-3.  Your doctor will determine when you should discontinue antiplatelet 
medications or warfarin.  If you discontinue any of these medications before your 6 month visit, you 
should tell your doctor.  
Follow-up Visits 
It is important to keep all follow-up appointments scheduled for you.  The study requires in clinic 
follow-up visits about 6 weeks and 12 months after your procedure.  These visits take approximately 
half a day.  During these visits you will be asked about your health and the medications you are taking.  
You will also undergo a TOE at your 6 week visit to make sure your Amulet device has not moved and 
has closed your LAA.   
The study requires telephone visits about 6 months and a minimum of 2 years and potentially 3, 4 and 5 
years after your procedure.  These telephone visits will take about 30 minutes.  Your doctor or nurse will 
call you and ask about your health and the medications you are taking.  If you had a stroke, you should 
tell your study doctor and return to the clinic about 90 days after the event.  
You will be notified of your discontinuation date, which could occur a minimum of 2 or a maximum of 
5 years after your procedure date depending on the duration of the study. 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Interim/Unscheduled Visits 
If you are seen by your doctor in addition to the recommended visits listed in Table 1, you will be asked 
about your health and the medications you are taking.  
If you had a stroke or TIA, a Modified Rankin Scale assessment will be performed about 90 days after 
the event to assess the degree of your disability and dependence in daily activities.  You are required to 
have a TOE if you have a stroke or TIA.  You may be seen by a neurologist and additional testing may 
be performed.  The results from the TOE will be used to make sure the Amulet device is still in the 
correct location and that your LAA is closed. 
How long will the study last and how many will take part? 
If you agree to take part in this research study, your involvement will last a minimum of 2 years and will 
not exceed 5 years.  About 1000 people will take part in this research study at about 75 sites worldwide.  
What are the possible risks and discomforts? 
There are risks, discomforts, and inconveniences associated with any study to you (or to an embryo, 
unborn child or nursing infant if you become pregnant).  These deserve careful thought.  The risks 
associated with participation in this study include risks with the study design, complications during and 
after the procedure, and risks with the collection of your data.  The risks are listed below but will vary 
from person to person.  There may be other risks that are unknown at this time.  You should talk with 
your study doctor if you have any questions. 
Risks with Study Design 
The Sponsor will select investigators qualified by training and experience to participate in this study.  
Participating sites will be selected based upon qualifications of the primary investigator.  During the 
study, sites may be subject to quality assurance audits by the Sponsor (or designee), as well as 
monitoring visits to assess data integrity and study compliance.  Additionally, the study will have an 
appointed independent Clinical Events Committee (CEC) who will review and adjudicate all reported 
adverse events, as well as have general study oversight of subject safety and data integrity. 
Risks with Baseline and Follow-Up Testing  
The potential risks associated with review of your medical record include but are not limited to: 
• Who will have access to the data 
• Specifying how and at what point in the research personal information will be 
separated from other data 
• Whether the data will be retained at the conclusion of the study and for how long 
These risks will be mitigated by ensuring: 
• There is an adequate plan to protect identifiers from improper use and disclosure 
• There is an adequate plan to destroy identifiers at the earliest opportunity 
• Protected health information (PHI) will not be re-used or disclosed for another 
purpose 
You may experience some anxiety when asked abut your health, medications, and neurological status. 
You may be inconvenienced by traveling to the study site for your study visits, or for having to miss 
work to take part in the study. 
Risks and Complications with the Implant Procedure 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Your doctor will explain the risks and discomforts of the implant procedure and the risks of the 
commercially available Amulet device. 
There may be other risks or discomforts to you (or to an embryo, unborn child or nursing infant if you 
become pregnant) that are not known at this time.  
New findings 
Your doctor will discuss with you important new information that is learned during the course of this 
study that may affect your condition or willingness to continue to take part in this research study.  You 
will also be informed of the reasons for changes to the clinical protocol.  If you decide to withdraw or if 
your doctor decides it is in your best interest to withdraw due to the new findings, your doctor will 
explain the reasons and arrange the necessary steps for your care to continue outside of the study. 
What are the risks for women of childbearing age? 
To confirm to the extent medically possible that you are not pregnant, you agree to have a pregnancy 
test done before beginning this research study.    
If you are a woman who is able to become pregnant, it is expected that you will use an effective method 
of birth control to prevent exposing a fetus to a potentially dangerous agent with unknown risk.  If you 
are pregnant or currently breast feeding, you may not participate in this study.  You understand that if 
you are pregnant, if you become pregnant, or if you are breast-feeding during this study, you or your 
child may be exposed to an unknown risk.  Subjects who become pregnant while taking part in the study 
should tell their study doctor right away. 
Residual Risks 
The overall events from a risk perspective are similar with respect to minimally invasive implantable 
therapy.  Complication rates are within expected ranges and the risk/benefit profile is similar to 
alternative therapies. 
What are the possible benefits to you or others? 
If you decide to take part in this study and have the Amulet device implanted, you may not need to be on 
long-term warfarin oral anticoagulation therapy.  You may also benefit from a decrease in the risk of 
getting a blood clot due to atrial fibrillation, but there is no guarantee this will happen.    
The information gathered in this study may benefit others by adding to the understanding of treatment 
options for patients with nonvavular atrial fibrillation.  
If you do not want to take part in this research study, what other options are available to you? 
If you choose not to participate in this study at this time, your doctor will discuss other options available 
to you.  Treatment options may include the use of commercially available devices including the Amulet 
device outside of the study, surgery and/or drugs to prevent the occurrence of blood clots, which can 
cause stroke, or not having any treatment at all.  You may also choose not to participate. 
If you choose to take part in this study, what are the costs? 
Your medical insurance will be billed for all standard costs for the Amulet device, the procedure and the 
follow-up visits, which are standard of care.  
Will you receive payment for taking part in this research study? 
No payment will be made to you for taking part in this research study. 
What if the device needs to be removed? 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
In the event your Amulet device or any part has to be removed, it may be returned to SJM for analysis.  
Should you withdraw from this study and choose to have your Amulet device or any part of it removed, 
the cost will be your responsibility. 
In the event of your death, your implanted Amulet device may be removed and returned to SJM for 
analysis.  The study doctor will get your family’s approval prior to removing the device.   
Insurance 
To compensate for financial loss due to study-related damage to health, the manufacturer has concluded 
legally prescribed clinical trial insurance coverage for all subjects.  During the period of the clinical trial 
other medical treatment should only take place in consultation with the investigator, with the exception 
of emergency situations.  Upon suspicion of study-related damage to health, you must immediately 
notify the treating investigator so that he can inform the insurance office on your behalf.  You can 
expect to receive a copy of the report.  The insurance is concluded with Allianz Global Corporate & 
Specialty. 
What if you are injured because of this study? 
If you suffer any injuries, illnesses, or complications as a direct result of participation in this study, 
conducted in accordance with the study protocol, you should contact your study doctor as soon as possible 
and you will be assisted with arranging appropriate medical treatment.  For those expenses that are not 
covered by your insurance, SJM will pay the costs of reasonable and necessary treatment of injuries, 
undesirable side effects, or adverse reactions caused by study procedures that are not standard of care for 
you, or caused by a defect or malfunction of the study device and/or problems with the study procedure 
during the study.  The reimbursement may be provided directly to you, or to <<insert site name>> for cost 
incurred in treating the study-related injury, illness or complication.  No other arrangement has been made 
for financial payments or other forms of compensation (such as lost wages, lost time or discomfort) with 
respect to such injuries.  If emergency medical treatment is needed, your study doctor will provide medical 
care to the extent permitted under the applicable national, regional, or local law.  You do not waive any legal 
rights by signing this consent form.   
During the study, if you experience any injuries, illnesses, or complications from taking part in this 
research study, please contact Dr. ______________ at ___________. 
What are your rights if you decide to take part or stop participation in this research study? 
Your signature on this consent form means that you have received information about this research study 
and that you agree to be a part of the research study.  
You may stop taking part in the research study at any time without penalty or loss of benefits to which 
you are otherwise entitled.  If you wish to stop taking part in this research study for any reason, you 
should contact Dr. _____________ at___________.   
If you withdraw your consent during the study, the study doctor and relevant study staff will not collect 
additional personal information from you, although personal information already collected will be 
retained to ensure that the results of the research study project can be measured properly and to comply 
with the law.  You should be aware that data collected by the Sponsor up to the time you withdraw will 
be part of the study results. 
Your study doctor or designee will discuss with you what follow-up is required if you decide to 
withdraw, or are withdrawn from the research study before the study is finished.  Your doctor or the 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Sponsor of the study (SJM) may also stop your participation in the research study at any time, without 
your consent, for any reason.  The Sponsor can suspend or prematurely terminate the study for safety, 
business purposes, or other reasons. 
How will your information be kept confidential? 
If you decide to take part in this study, your medical records and personal information will be kept 
confidential to the extent allowed by national, regional and local law.  However, information from the study 
may be exported to countries where different data protection laws apply.  The data protection laws in other 
countries may be less strict than those of your country.  
If you decide to participate in the research study, the study Sponsor and others who work with the study, 
such as the study staff and Ethics Committee (EC) will see health information about you.  The EC is a 
group of people who perform independent review of research studies as required by laws governing this 
type of research study.  Other regulatory agencies, the EC and the Sponsor’s representatives may inspect 
and copy your medical records. 
The information collected about you may be used in several ways. Information about you and your health 
that might identify you may be given to others to carry out the research study.  Your study doctor may use 
some of the information in making decisions about your care.  
The Sponsor may use the information in any of the following ways:  
• To analyze and make conclusions about the results of the study 
• In documents sent to the government agencies throughout the world  
• For reporting undesirable events to government health agencies 
• To provide overall study results to other study doctors, including in publications 
• To conduct new medical research studies, to reanalyze the study results in the future or to 
combine your information with information from other studies 
• To develop new medical products and procedures, and other product-development 
related activities 
Your name will not be provided for publications in medical journals.  While using the information in these 
ways, the Sponsor may give study data to its affiliated companies in the U.S. or other countries.  The 
Sponsor may also share the information with its business partners or companies it hires to provide study-
related services.  Information received during the research study will not be used for any mailing lists or 
sold to anyone for marketing purposes. 
The study will not collect the initials of your name. The study will only collect the month and year of your 
birth.  Your permission for the use, retention, and sharing of your identifiable health information will 
continue indefinitely.  
A description of this clinical study will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  This Web site will not include information that can identify you.  At most, the Web site will include a 
summary of the results.  You can search the Web site at any time.   
Information about the clinical investigation will be available on another public database, if not available on 
http://www.ClinicalTrials.gov or if it is required by local regulations. 
Who can you contact for study information? 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
If you have any questions about the study or taking part in this research study, or if you have suffered a 
study-related injury, please contact Dr. ______________ at ___________. 
 
In addition, if you have any concerns, complaints or questions about your rights as a research study 
participant or an injury that you believe is a study-related, please contact the EC: 
 
Name of person at EC: 
 
Title of person at EC: 
 
EC phone number: 
 
EC email, if known: 
 
 
Consent and authorization for participation in this research study 
Taking part in this research study is entirely voluntary.  You are making a decision on whether or not to 
take part in the research study.  Your signature indicates that you have read the information in this form 
and have decided to take part in the research study.  You will be given a signed copy of this form to 
keep.   
√   I have read and understood the information of this Amulet obervational post-market study and the 
research staff has answered all of my questions regarding the study. 
√   I have had enough time to think about my participation in this Amulet obervational post-market study 
and I am aware that participation in this study is voluntary.  
√   I realize that I may decide to refuse participation or stop participation at any time without affecting 
the quality of my heath care or the relationship with my physician.  
√   I am free to withdraw at any time, without giving any reason and without my medical care or legal 
rights being affected.  There will not be any penalty if I decide to withdraw from the study. 
√   I understand and agree that personal information about me will be collected from my medical records 
and processed by SJM or any other entity involved in the study.  My medical information, information 
collected during the study and study results may be looked at, used, and disclosed by responsible 
individuals from SJM, a U.S. company, and its affiliates (located in the U.S. and other countries), and 
other people who work for SJM to provide services related to the device and this study, regulatory 
authorities, the Ethics Committee and, when it is relevant to my taking part in this research.  I give 
permission for these individuals to have access to my medical information, information collected during 
the study, and study results. 
√   I authorize and instruct my physician(s) and the institution to release personal  
information about me necessary to conduct this Amulet observational post-market 
study. 
√  I understand I am free to access my personal information and to have errors corrected. 
√  My data gathered in this study may be stored (after anonymized) in a database and may be used and 
disclosed by SJM. 
√  Data collected from the time I sign this document until the time I withdraw from the study will be 
used after I withdraw. 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
√  I will not financially benefit from this study. 
√  I understand how to contact the research team.  
√  My attendance at study visits is important to the study and I should follow the study doctor‘s 
instructions. 
√  I am willing to participate in this study. 
Please check one option below: 
 I agree that my personal physician is informed about my participation in this study. 
 
 I disagree that my personal physician is informed about my participation in this study. 
 
Name of Participant    
(please print): 
Signature 
Date 
 
Name of Person Obtaining 
Consent (please print) 
Signature 
Date 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix H: Case Report Forms 
Case Report Forms will be kept under separate cover and sent to ethics committees and sites, as 
applicable.  

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix I: Device Deficiency/Complaint Handling 
The international division Event Report Form should be completed by a SJM representative or the site 
per country reporting timeline requirements and supplemental information (in English) attached.  Device 
deficiencies/complaints should be emailed to SJM at: Complaints_Amplatzer@sjm.com.  Please contact 
your local SJM representative to coordinate product returns. 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix J: Modified Rankin Scale (mRS) 
Subject Identifier: ______________________________ 
Rater Name: __________________________________ 
Date: ________________________________________  
 
Score 
 
Description__________________________________________________________ 
0 
No symptoms at all 
 
1  
 
No significant disability despite symptoms; able to carry out all usual duties and  
activities 
 
2 
Slight disability; unable to carry out all previous activities, but able to look after own 
affairs without assistance 
 
3  
 Moderate disability; requiring some help, but able to walk without assistance 
 
4 
Moderately severe disability; unable to walk without assistance and unable to attend to 
own bodily needs without assistance 
 
5 
Severe disability; bedridden, incontinent and requiring constant nursing care and 
attention 
 
6 
Dead 
 
TOTAL (0-6):    _____ 
 
Comments: 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix K: Intracardiac Echocardiography (ICE) Sub-Study Requirements 
Requirements for intracardiac echocardiography (ICE) imaging include: 
▪ Notification to SJM Clinical when ICE will be used for study implants: 
Contact 
Email 
Address 
Telephone/Mobile/Fax 
Anne Marie Harcarik 
Sr. Director Clinical Affairs 
 
AHarcarik@sjm.com 
LAA Occlusion 
St. Jude Medical 
5050 Nathan Lane North 
Plymouth, MN 55442 
  USA 
Direct +1 6517566469 
Main +1 7635139227 
Mobile +1 6122195601 
Fax +1 8772572381 
 
Sarah Gallagher 
Clinical Programs Manager 
sgallagher02@sjm.com 
LAA Occlusion 
St. Jude Medical 
5050 Nathan Lane North 
Plymouth, MN 55442 
USA 
Direct +1 6517566937 
Main +1 7635139227 
Mobile +1 6514855744 
Fax +1 8772572381 
 
 
▪ Minimum of 5-10 ACP or Amulet cases using ICE performed by the study 
implanter/investigator 
▪ Baseline TOE LAA measurements to assess the presence of thrombus and LAA anatomy  
▪ Combined fluoroscopic and ICE guidance during the Amulet implant procedure to confirm 
device positioning and deployment 
▪ Verification by ICE or fluoroscopy to confirm device stability  
 
 

 
Study Document No: SJM-CIP-10053 Version A              
Study Name: AMPLATZER™ Amulet™ Observational 
Post-Market Study 
 
 
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disclosed or used without the express written consent of St. Jude Medical 
 
Appendix L: Cardiovascular Mortality Definition 
 
Cardiovascular Mortality 
▪ Death due to proximate cardiac cause e.g. myocardial infarction, 
cardiac tamponade, worsening heart failure, or endocarditis 
▪ Death caused by non-coronary, non-CNS vascular conditions 
such as: pulmonary embolism, ruptured aortic aneurysm, 
dissecting aneurysm or other vascular disease 
▪ Death from vascular CNS causes from: 
o hemorrhagic stroke 
o ischemic stroke 
▪ All procedure-related deaths including those related to a 
complication of the procedure or treatment for a complication of 
the procedure 
▪ Sudden or unwitnessed death defined as non-traumatic, 
unexpected fatal event occurring within one hour of the onset of 
symptoms in an apparently healthy subject. If death is not 
witness, the definition applies when the victim was in good 
health 24 hours before the event 
▪ Death of unknown cause