AMPLATZER™ LAA Occluder Post Approval 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 C 
Template 
 
 
NCT Number: NCT02964208 
AMPLATZER LAAO-PAS 
AMPLATZER™ LAA Occluder Post Approval Study (PAS) 
Study Document No: SJM-CIP-10122 
Version C 
Date: 19-NOV-2018 
 
 
Sponsor  
 
 
Abbott 
        
 
 
 
5050 Nathan Lane North 
      
  
 
 
Plymouth, MN 55442 
        
 
 
 
USA 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 1 of 59 
 
 
AMPLATZER LAAO- PAS 
AMPLATZER™ LAA Occluder Post Approval Study 
(PAS) 
Clinical Protocol 
 
Study Document No: SJM-CIP-10122 
Version C 
Date: 19NOV2018 
Clinical Investigation Plan (CIP) 
 
 
Sponsor: 
 
 
Abbott 
5050 Nathan Lane North 
Plymouth, MN 55442 
USA 
 
  
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 2 of 59 
 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
AMPLATZER™ LAA Occluder Post Approval Study (PAS) 
 
Study Document No: SJM-CIP-10122 Version C 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
 
Principal Investigator 
 
Printed name: 
Signature: 
Date: 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 3 of 59 
 
 
Coordinating Investigator/ National Investigator 
 
SIGNATURE PAGE 
 
AMPLATZER™ LAA Occluder Post Approval Study (PAS) 
Study Document No: SJM-CIP-10122 Version C 
 
 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation.  
 
 
Coordinating Investigator/ National Investigator   
 
Printed name: 
Signature: 
Date: 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 4 of 59 
 
Table of Contents 
1 
Synopsis .......................................................................................................................................... 7 
1.1 
Study Contacts ........................................................................................................................ 9 
 
Introduction .................................................................................................................................... 10 
 
Background and Justification ......................................................................................................... 10 
 
Study Design .................................................................................................................................. 11 
4.1 
Purpose ................................................................................................................................. 11 
4.2 
Study Design and Scope ....................................................................................................... 11 
4.2.1 
Subject population ............................................................................................................. 12 
4.2.2 
Number of study subjects .................................................................................................. 12 
4.2.3 
Enrollment period and study duration ............................................................................... 12 
4.3 
Endpoints .............................................................................................................................. 12 
4.3.1 
Primary endpoints ............................................................................................................. 12 
4.3.2 
Secondary endpoint .......................................................................................................... 12 
4.3.3 
Descriptive Endpoints/Outcomes Measures ..................................................................... 12 
4.4 
Enrollment Criteria ................................................................................................................ 13 
4.5 
Informed Consent Process .................................................................................................... 13 
 
Device ............................................................................................................................................ 13 
5.1 
Device Descriptions .............................................................................................................. 13 
5.2 
Device Accountability ............................................................................................................ 16 
 
Study Procedures .......................................................................................................................... 16 
6.1 
Screening/Enrollment/Baseline ............................................................................................. 19 
6.2 
Implant/Procedure/Post-Procedure ....................................................................................... 20 
6.3 
Attempt to treat ...................................................................................................................... 21 
6.4 
Scheduled Follow-ups ........................................................................................................... 21 
6.5 
Unscheduled Visits ................................................................................................................ 21 
6.6 
Sponsor Representatives ...................................................................................................... 21 
6.7 
Subject Study Completion ..................................................................................................... 21 
6.8 
Subject Withdrawal ............................................................................................................... 21 
 
Compliance Statements ................................................................................................................. 22 
 
Serious Adverse Events, Serious Adverse Device Effects, Deaths and Device Deficiencies ....... 22 
8.1 
Serious Adverse Events ........................................................................................................ 22 
8.1.1 
Serious Adverse Device Effect .......................................................................................... 23 
8.1.2 
Assessing, recording and reporting serious adverse events, serious adverse device 
effects, and device deficiencies/complaints ................................................................................... 23 
8.1.3 
Subject death .................................................................................................................... 24 
8.2 
Device Deficiency/Complaint Handling ................................................................................. 24 
 
Data Management ......................................................................................................................... 24 
9.1 
Data Management Plan ........................................................................................................ 24 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 5 of 59 
 
9.2 
Document and Data Control.................................................................................................. 25 
9.2.1 
Document and data traceability ......................................................................................... 25 
9.2.2 
Recording data .................................................................................................................. 25 
 
Risks and Benefits .................................................................................................................... 25 
10.1 
Anticipated Clinical Benefits .................................................................................................. 25 
10.2 
Anticipated Adverse Events and Adverse Device Effects ..................................................... 25 
10.3 
Risks ...................................................................................................................................... 25 
10.4 
Risk to Benefit Rationale ....................................................................................................... 25 
10.5 
Residual Risks Associated with the Device .......................................................................... 25 
10.6 
Steps to Control or Mitigate Risks ......................................................................................... 26 
 
Clinical Events Committee (CEC) ............................................................................................. 26 
 
Monitoring .................................................................................................................................. 26 
 
Regulatory Inspections .............................................................................................................. 26 
 
Statistical Methods .................................................................................................................... 26 
14.1 
Primary Endpoints ................................................................................................................. 26 
14.1.1 
Primary Effectiveness Endpoint 1: ................................................................................ 26 
14.1.2 
Primary Effectiveness Endpoint 2: ................................................................................ 27 
14.1.3 
Primary Safety Endpoint: .............................................................................................. 27 
14.2 
Secondary Endpoint .............................................................................................................. 28 
14.2.1 
Analysis method ............................................................................................................ 28 
14.2.2 
Analysis population ....................................................................................................... 28 
14.3 
Descriptive Endpoints/Outcomes Measures ......................................................................... 28 
14.4 
Compromising Factors .......................................................................................................... 29 
 
Document Retention ................................................................................................................. 29 
 
Amendments to the Clinical Protocol ........................................................................................ 29 
 
Outsourcing of Sponsor Duties and Functions ......................................................................... 30 
 
Investigation Suspension or Termination .................................................................................. 30 
18.1 
Premature Termination ......................................................................................................... 30 
18.2 
Study Conclusion .................................................................................................................. 31 
 
Publication Policy ...................................................................................................................... 31 
 
Bibliography............................................................................................................................... 32 
Appendix A: Abbreviations .................................................................................................................... 35 
Appendix B: Protocol Revision History ................................................................................................. 36 
Appendix C: Declaration of Helsinki ...................................................................................................... 37 
Appendix D: List of Clinical Investigation Sites and Ethics Committees ............................................... 38 
Appendix E: Sample Informed Consent ................................................................................................ 39 
Appendix F: Case Report Forms .......................................................................................................... 53 
Appendix G: Modified Rankin Scale (mRS) .......................................................................................... 54 
Appendix H: Major Bleed classification/definition ................................................................................. 55 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 6 of 59 
 
Appendix I: Cardiovascular Mortality Definition .................................................................................... 57 
Appendix J: Definitions of Potential Adverse Event .............................................................................. 58 
 
 
 
TABLE OF TABLES 
Table 1: Model numbers and key dimensions of the AMPLATZER LAA Occluders 
and delivery system .............................................................................................................. 15 
Table 2: Study visits and assessments (subjects who are implanted with an 
AMPLATZER LAA Occluder) .............................................................................................. 18 
Table 3: CHA2DS2-VASc score ........................................................................................... 20 
Table 4: HAS-BLED score ................................................................................................... 20 
 
 
TABLE OF FIGURES 
Figure 1: The AMPLATZER Cardiac Plug and key components ........................................ 15 
Figure 2: AMPLATZER Amulet Occluder key components ................................................. 15 
Figure 3: Study flowchart for subject screening, consent, enrollment and follow-up ...... 17 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 7 of 59 
 
1 
Synopsis 
Name of Study 
AMPLATZER™ LAA Occluder Post Approval Study 
Study Sponsor 
Abbott 
Device 
Description: Abbott’s transcatheter, self-expanding AMPLATZER™ LAA 
Occluders are made of nitinol mesh and a polyester patch. The lobe has 
stabilizing wires placed within the left atrial appendage (LAA) and a disc (to 
cover the LAA orifice) connected to the lobe by a central waist.  The 
AMPLATZER™ Cardiac Plug™ and the AMPLATZER™ Amulet™ LAA 
Occluders are currently available in the following sizes: 
Sizes (lobe diameter):  
• 
16, 18, 20, 22, 24, 26, 28 and 30 mm for the AMPLATZER™ Cardiac 
Plug™ 
• 
16, 18, 20, 22, 25, 28, 31 and 34 for the AMPLATZER™ Amulet™ 
 
Future generation AMPLATZER™ LAA Occluders may be used in the study 
upon approval by Health Canada.  
 
Delivery System: AMPLATZER TorqVue™ 45x45 (sheath sizes 9,10,12,13 
and 14 Fr)  
Indications for Use 
Abbott’s AMPLATZER™ LAA Occluders are intended to prevent thrombus 
embolization from the left atrial appendage (LAA) in patients who have non-
valvular Atrial Fibrillation (AF).  The device may be considered for use in 
patients who have a high risk of stroke and bleeding and are deemed by their 
physician to have an appropriate rationale to seek a non-pharmacologic 
alternative to long term anticoagulants.  
Study Objective 
To compile real world outcome data on the use of the AMPLATZER LAA 
Occluder in subjects with non-valvular atrial fibrillation. 
Study Design 
This is a non-randomized multicenter study on patients who have undergone 
a procedure to implant an AMPLATZER LAA Occluder or will undergo an 
implant of an AMPLATZER LAA Occluder. 
Randomization 
Non-randomized 
Sample Size 
This study, and other AMPLATZER LAA Occluder post approval studies 
collecting similar data, will contribute to the overall sample size of 1000 
subjects for analysis of study endpoints.  Up to 100 sites worldwide will 
participate in this study. 
Primary Endpoints  
This study has three primary endpoints: 
• 
Efficacy Endpoint 1: The occurrence of the composite of stroke 
(including ischemic or hemorrhagic), systemic embolism, or 
cardiovascular or unexplained death at 24 months from the time of 
enrollment 
• 
Efficacy Endpoint 2: The occurrence of ischemic stroke or systemic 
embolism at 24 months from the time of enrollment 
• 
Safety Endpoint: The occurrence of one of the following events 
between the time of implant and within 7 days of the procedure or by 
hospital discharge, whichever is later: all-cause death, ischemic 
stroke, systemic embolism, or device or procedure-related events 
requiring open cardiac surgery or major endovascular repair  
Secondary Endpoint 
Comparison of the observed rate of ischemic stroke at 24months with the 
CHA2DS2-VASc predicted rate. 
Descriptive 
Endpoints/Outcomes 
Measures  
The following endpoints will be summarized descriptively:  
• 
Oral anticoagulant use over time 
• 
Device closure at the 2 month visit 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 8 of 59 
 
• 
Procedural success  
• 
Technical success 
• 
Procedure duration  
• 
Device thrombosis  
• 
Transient ischemic attack 
• 
Death  
• 
Major bleeding 
Enrollment Criteria 
Prospective Enrollments 
Patients in whom an AMPLATZER LAA Occluder device is intended to be 
implanted  
Retrospective Enrollments 
Patients who underwent an AMPLATZER LAA Occluder implant attempt after 
the device was approved in the applicable geography 
 Clinical Follow-up 
Visits/Testing  
Subjects will be followed through 2 years post implant. 
Required Testing for Prospective Enrollments 
• 
Baseline evaluation: Informed consent, history and physical, 
pregnancy testing for women of childbearing age, CHA2DS2-VASc 
score, HAS-BLED score, modified Rankin Scale, medication 
assessment 
• 
Procedure: Transesophageal echocardiogram (TOE), angiogram, 
adverse event assessment 
• 
Post procedure/Pre-Discharge: Transthoracic echocardiogram 
(TTE), medication assessment, adverse event assessment 
• 
2M (+/- 45 days): TOE, medication assessment, adverse event 
assessment 
• 
6M (+/- 4 weeks): Phone contact follow-up for medication 
assessment, adverse event assessment 
• 
12M (+/- 6 weeks):  Medication assessment, adverse event 
assessment 
• 
2yrs (+/- 12 weeks): Medication assessment, adverse event 
assessment 
• 
Interim/unscheduled visits: per physician discretion 
 
Retrospectively enrolled subject data collection will include adverse events 
and standard of care (SOC) echo data previously collected by the site. 
Protocol required follow up visits will begin upon subject consent 
Suspected 
Stroke / TIA   
Requirements  
• 
Subjects suspected of a stroke should be seen by a stroke/TIA 
neurologist for evaluation and appropriate baseline neurological 
testing (i.e. magnetic resonance imaging (MRI), computed 
tomography (CT) 
• 
Modified Rankin Scale 
• 
TOE or ICE should be conducted within 7 days of confirmation of 
stroke to verify the presence of device related thrombus 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 9 of 59 
 
1.1 Study Contacts 
Clinical Department, LAA Program 
Abbott 
Global Clinical Affairs  
5050 Nathan Lane North 
Plymouth, MN  55442  
USA 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 10 of 59 
 
 
Introduction 
This document is a clinical investigational plan for St. Jude Medical’s AMPLATZER™ Cardiac Plug™ 
and AMPLATZER™ Amulet™ Left Atrial Appendage (LAA) Occluders (these devices are referred to 
as “AMPLATZER LAA Occluder”).  The study is a post-approval study to compile real world outcome 
data on the use of AMPLATZER LAA occluders in patients with non-valvular atrial fibrillation who are 
at increased risk for stroke and systemic embolism.  This is a worldwide study intended to fulfill Health 
Canada’s post-approval requirements for the device.  Future generation AMPLATZER™ LAA 
Occluders may be used in the study upon approval by Health Canada. A patient who was either 
implanted or had an attempt to implant with an AMPLATZER LAA Occluder may be retrospectively 
enrolled in the study if the device was approved in the applicable geography at the time of the 
procedure. 
 
 Background and Justification  
Atrial fibrillation (AF) is the most common sustained heart rhythm disorder1.  During AF there are 
multiple simultaneous waves of contractions, which spread in a chaotic manner through both atria.  
This arrhythmia results in rapid, uncoordinated contractions, which decrease the blood pumped 
through the atria.  The loss of mechanical efficiency during AF leads to insufficient contractions in the 
left atrium (LA)2.  Stagnation of blood flow in the LA leads to hypercoagulability and thus increases the 
risk for thrombus formation in the LA or left atrial appendage (LAA).  Approximately 90% of all the 
thrombi in subjects with non-valvular AF (NVAF) forming in the LA originate in the left atrial 
appendage3.  The thrombus formation, in turn exposes the patient to thromboembolic events. 
Echocardiographic risk factors for LAA thrombus formation include echocardiographic evidence of 
decreased LAA flow velocity and spontaneous echo contrast within the left atrium and left atrial 
appendage4,5.  The normal flow pattern of the LAA is the ejection of blood from the appendage 
following atrial contraction at a velocity greater than 40cm/s2.  Agmon et al. found that the relative risk 
reduction of ischemic stroke was 2.6 times greater in patients with LAA flow velocities <20cm/s2 than 
those with higher LAA velocites6. 
Non-valvular AF patients have been assessed to determine the risk of stroke based on the presence 
of independent risk factors.  In a study by Gage et al. the CHADS2 index was shown to be a tool to 
predict the risk of stroke in subjects with AF7.  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 patients who 
were not treated with anti-thrombotic agents had an increased risk of stroke ranging from 1.9% to 
18.2% as CHADS2 scores increase from 0 to 6. 
A study by Go et al. reviewed outcome data (11,526 patients) in a large primary care setting and 
confirmed that thromboembolic risk increases progressively with CHADS2 score8.  The study also 
noted that oral anticoagulation with warfarin reduces the risk of stroke in most patients with the 
exception of those at lowest risk (CHADS2 score of zero) and highest risk (CHADS2 >5) for stroke.  
The more recently developed CHA2DS2-VASc risk assessment scheme9, which identifies truly low risk 
subjects, assigns two points to age >75 years and previous stroke, TIA or thromboembolism and one 
point each to congestive heart failure or left ventricular dysfunction, hypertension, diabetes, vascular 
disease, age between 65-74 years and female sex.  A recent validation10 of these risk schemes in 
more than 90,000 patients without oral anticoagulation (OAC) but on aspirin showed annual ischemic 
stroke rates ranging from 0.6% in CHA2DS2-VASc = 1 to 4.8% in CHA2DS2-VASc = 4, and more than 
12% for CHA2DS2-VASc = 9. 
In a meta-analysis conducted by Andersen et al., warfarin was found to be superior to aspirin and 
placebo in reducing the risk of systemic embolism in subjects with NVAF11.  Hart et al. reported that 
adjusted dose warfarin reduces stroke by 64% (6 trials) and antiplatelet agents reduce stroke risk by 
22%12.  The study also reported that risk of intracranial hemorrhage was doubled with adjusted-dose 
warfarin compared with aspirin. 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 11 of 59 
 
Recently, new drugs (known as novel oral anticoagulant, or NOAC) have been developed with less 
dietary and pharmacological interactions than warfarin and less stringent requirements for frequent 
INR monitoring.  Major trials such as RE-LY and ROCKET AF demonstrated that dabigatran and 
rivaroxaban are non-inferior to warfarin in the prevention of stroke or systemic embolism13, 14.  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 fibrillation15.  
The ENGAGE AF-TIMI16 trial demonstrated both once daily dose regimens of Edoxaban were non-
inferior to warfarin with respect to the preventions of stroke or systemic embolism and were 
associated with significantly lower rates of bleeding and death from cardiovascular causes17.  A 
number of characteristics that increase a patient’s risk for stroke also increase the patient’s risk for 
bleeding; therefore an alternative to warfarin and NOAC drugs is needed. 
Left atrial appendage occlusion (LAAO) is considered a viable alternative to oral anticoagulation 
(OAC) therapy for stroke prevention in patients with NVAF15-25.  Published evidence supporting LAAO 
is provided in large part by the major randomized controlled trials PROTECT AF and PREVAIL15-18.  
Five-year results of PROTECT AF showed superiority of the WATCHMAN™ device in mortality and 
stroke reduction compared to optimal medical treatment with warfarin18. 
The AMPLATZER Cardiac Plug demonstrated favorable feasibility and safety in observational studies 
in Europe26-28.  Additionally, Park et al. reported the results of an investigator-initiated retrospective 
study to report on the initial European experience in patients treated with the AMPLATZER Cardiac 
Plug device between December 2008 and November 2009.  SJM’s AMPLATZER Cardiac Plug 
Registry results were also presented at EURO PCR in 2012 and 201429-30.  In addition, results from a 
multicenter study involving 22 sites and 1047 consecutive patients undergoing implant of the 
AMPLATZER Cardiac Plug device showed a high procedural success rate and a favorable outcome 
for the prevention of AF related thromboembolism31. 
In a comparative study between the AMPLATZER Cardiac Plug and the WATCHMAN devices (40 
patients each), Chun et al.32 found the devices to perform similarly.  The rate of successful 
implantation achieved with the ACP device was greater than with the WATCHMAN device (100% vs. 
95%) although the difference was not statistically significant.  TEE at follow-up revealed a significantly 
higher incidence of residual peri-device flow (jet > 5 mm) for the WATCHMAN device compared to the 
ACP device, although this was not associated with an increased incidence of thromboembolic events.  
This finding is consistent with other reports on the ACP device33. 
In conclusion, percutaneous LAAO devices have emerged as an alternate option for stroke reduction 
in non-valvular AF patients at high risk for stroke. 
*See Appendix A for a listing of abbreviations used throughout this document 
 
 Study Design 
4.1 Purpose 
The AMPLATZER LAA Occluders are transcatheter, self-expanding nitinol devices intended for 
use in preventing thrombus embolization from the LAA.  The purpose of this study is to compile 
real world outcome data on the use of an AMPLATZER LAA Occluder in subjects with non-
valvular atrial fibrillation (NVAF). 
4.2 Study Design and Scope 
The AMPLATZER LAA Occluder devices will be clinically evaluated through this post approval 
study.  This is a multicenter, non-randomized observational post-approval study in subjects who 
meet one of the following criteria: 
 
Prospective Enrollments 
Patients in whom an AMPLATZER LAA Occluder device is intended to be implanted   
 
Retrospective Enrollments 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 12 of 59 
 
Patients who underwent an AMPLATZER LAA Occluder implant attempt after the device was 
approved in the applicable geography 
 
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 
This study, and other AMPLATZER LAA Occluder post approval studies collecting similar 
data, will contribute to the overall sample size of 1000 subjects for analysis of study 
endpoints.  Up to 100 sites worldwide, will participate in this study.  
 
 
 
  
4.2.3 Enrollment period and study duration 
 
 
  
4.3 Endpoints 
4.3.1 Primary endpoints 
This study has three primary endpoints:  
1. Efficacy Endpoint 1: The occurrence of the composite of stroke (including ischemic or 
hemorrhagic), systemic embolism and cardiovascular or unexplained death at 24 
months 
2. Efficacy Endpoint 2: The occurrence of ischemic stroke or systemic embolism at 24 
months 
3. Safety Endpoint: The occurrence of one of the following events between the time of 
implant and within 7 days of the procedure or by hospital discharge, whichever is later: 
all cause death, ischemic stroke, systemic embolism, or device or procedure-related 
events requiring open cardiac surgery or major endovascular repair* 
* NOTE: Percutaneous catheter drainage of pericardial effusion, snaring of an embolized device, 
thrombin injection to treat femoral pseudoaneurysm and nonsurgical treatments of access site 
complications will not be included in the assessment of the third primary endpoint. 
4.3.2 Secondary endpoint 
The secondary endpoint is a comparison of the observed rate of ischemic stroke at 24 months 
with the CHA2DS2-VASc predicted rate. 
4.3.3 Descriptive Endpoints/Outcomes Measures 
The following endpoints will be summarized using descriptive statistics. 
• 
Oral anticoagulant use over time 
• 
Device closure 
o 
Defined as residual jet around the device < 5mm at the 2-month visit 
documented by transoesophageal echocardiogram (TOE)  
• 
Procedure success 
o 
Procedural success-defined as implantation of the AMPLATZER LAA Occluder 
with no serious adverse events prior to hospital discharge 
• 
Technical success 
o 
Technical success-defined as delivery and release of the AMPLATZER LAA 
Occluder. 
• 
Procedure duration 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 13 of 59 
 
• 
Device thrombosis 
• 
Transient Ischemic Attack 
• 
Death 
• 
Major bleeding defined as Type 3 or greater based on the Bleeding Academic Research 
Consortium (BARC -  Appendix H: Major Bleed classification/definition) 
 
4.4 Enrollment Criteria 
This study will enroll patients in whom an AMPLATZER LAA Occluder device is either intended 
to be implanted or underwent an implant attempt after the device was approved in the 
applicable geography 
All patients who sign the informed consent will be assigned a study identification number and 
this will be recorded on a baseline 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. 
4.5 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 Institutional Review Board (IRB) or ethics committee (EC).  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 IRB/EC requirements.  
A template of the informed consent form is provided in Appendix E: Sample Informed Consent. 
Any changes to the informed consent must be approved by Abbott prior to ethics committee 
review and approval.  
A subject cannot be consented for the study prior to IRB/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 IRB/EC.   
The subject is enrolled in the study when consent has been obtained and vascular access 
initiated, (prospective), or when consent is obtained after a subject underwent a study device 
implant attempt that may have been successful or unsuccessful (retrospective). Failure to 
obtain informed consent from a subject must be reported to the Sponsor within 5 working days 
and to the reviewing center’s IRB/EC according to the IRB/EC’s reporting requirements.  
 Device  
5.1 Device Descriptions 
The AMPLATZER Cardiac Plug (ACP) (Figure 1) and AMPLATZER  Amulet Occluder (Figure 
2)  are constructed from a nitinol mesh and consist of a lobe and a disc connected by a central 
waist.  These devices are percutaneous transcatheter devices intended to prevent thrombus 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 14 of 59 
 
embolization from the left atrial appendage (LAA) in patients who have non-valvular atrial 
fibrillation. These devices may be considered for use in patients who have a high risk of stroke 
and bleeding and are deemed by their physician to have an appropriate rationale to seek a non-
pharmacologic alternative to long term anticoagulants.   
Depending on the device, 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 secured to the device using polyester thread.  A platinum/iridium thread is 
attached to the nitinol braid. 
Accessories packaged with the AMPLATZER LAA Occluder device include the loader, loading 
cable, loading cable vise, delivery cable, delivery cable vise, and hemostasis valve.   
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 17 of 59 
 
Figure 3: Study flowchart for subject screening, consent, enrollment and follow-up 
 
  

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 18 of 59 
 
Table 2: Study visits and assessments (subjects who are implanted with an AMPLATZER LAA 
Occluder) 
 
  
 
 
 
 
 
 
 
 
  
 
  
 
Follow up visit timing begins from the date of the procedure for both prospective and retrospective 
enrollments. 
 
The electronic Case Report Forms (eCRFs) to be completed for enrolled subjects per the study visit 
intervals are: 
• 
Baseline – Baseline, Enrollment, Modified Rankin Scale, Medication, and Echo  
• 
Procedure – Procedure, Echo, Medication  
• 
Discharge, 2M, 6M, 12M and 24M – Follow-up, Echo (as required), Medication  
• 
Unscheduled visit - Follow-up, Medication, Echo (as required)  

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 19 of 59 
 
For retrospective enrollments, the applicable Baseline, echo, and adverse events CRFs should be 
retrospectively completed based on information from the subject’s medical records. Retrospective 
data should include any adverse events from the date of implant or attempted implant. Protocol 
required follow up visits will begin after the subject’s trial enrollment date. 
 
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 
▪ 
Stroke/TIA Assessment eCRF 
▪ 
Echo eCRF 
▪ 
Modified Rankin Scale (Appendix G: Modified Rankin Scale (mRS) (complete 90 days 
after confirmed stroke) 
Suspected stroke or TIA 
▪ 
Prospective enrollment: If a stroke or TIA is suspected, the subject should be seen by a 
neurologist or neurosurgeon for evaluation and appropriate neurological testing (CTA 
(computed tomography angiography) or MRA (magnetic resonance angiography). If a 
stroke is confirmed, a TOE is required as soon as possible, but no later than 7 days to 
confirm device placement, LAA flow parameters and presence/absence of device-
related thrombus. See Section 8.1 for further details. 
▪ 
Retrospective enrollment: If a previous stroke or TIA was suspected, any neurologic 
evaluation data including neurological testing and echo imaging should be submitted 
through the Stroke/TIA Assessment eCRF and any previous AEs due to the suspected 
stroke or TIA should be submitted according to Section 8.1. 
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 
▪ 
TOE (optional if a TOE is performed on the day of procedure) 
▪ 
Modified Rankin Scale 
▪ 
Medication assessment 
▪ 
CHA2DS2-VASc score: 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 20 of 59 
 
Table 3: 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 
 
• HAS-BLED score: 
Table 4: 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, 
enrollment criteria, etc.) will be recorded in the subject’s hospital records and on the Baseline 
eCRF.  For prospective subjects, the Baseline eCRF should be submitted within one week of 
signing the informed consent form. Baseline eCRFs for retrospectively enrolled subjects will 
capture data before attempted implant, collected from their medical history. 
For prospective subjects, if a subject does not meet criteria for AMPLATZER LAA Occluder 
implant, the subject cannot participate in the study.  The Baseline eCRF (consented screen 
failure), as applicable, must be completed and the subject should be withdrawn.  If the subject 
was enrolled (i.e. consented and vascular access initiated), but does not get a device implanted 
due to anatomy or other reason, the Baseline, Procedure, and Withdrawal eCRFs should be 
completed.  
Serious adverse events will be reported from the time vascular access was initiated to the time 
the subject concludes the study.  Adverse Event eCRFs should be completed, as applicable.  
 
6.2 Implant/Procedure/Post-Procedure 
Refer to the IFU for procedural and post-procedural instructions.  
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 21 of 59 
 
6.3 Attempt to treat 
Subjects who are consented, in whom vascular access for the AMPLATZER LAA Occluder was 
initiated, but the device was not implanted, will be considered “Attempt to Treat”.  The subject 
will be followed for 7 days or until discharge, whichever is later. Retrospectively enrolled 
subjects will include “Attempt to Treat” subjects; AEs that occurred within 7 days following the 
implant attempt or by discharge, whichever was later, will be captured. 
 
6.4 Scheduled Follow-ups 
Required follow-up visits for subjects who are prospectively implanted with an AMPLATZER 
LAA Occluder will be at 2 months, followed by a 6-month telephone follow-up, and 12 and 24-
month follow-up visits.  For retrospective subjects, follow-up visits after enrollment will be 
conducted per protocol, and will be based on the date of implant. However, all AEs from the 
time of the implant procedure will be collected. Refer to Table 2 for required follow-up testing 
and assessments. Subjects in whom vascular access is initiated for an AMPLATZER LAA 
Occluder, but the device is not implanted, will be considered “Attempt to Treat” and will be 
followed for 7 days until discharge, whichever is later. 
 
6.5 Unscheduled Visits  
If an unscheduled visit occurs, a Follow-up eCRF should be completed to capture data collected 
at the visit as well as pertinent additional eCRFs (medication, echo, and adverse event 
assessments as applicable).  
In the event of a confirmed stroke, a TOE is required as soon as possible, but no later than 7 
days after the stroke.  The Stroke/TIA assessment, modified Rankin Scale, and Echo eCRFs 
should be completed and applicable imaging submitted to the Sponsor.  Ninety (90) days after 
the event, the Stroke/TIA assessment and mRS should be repeated and applicable eCRFs 
submitted to the sponsor.  
 
6.6 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 Abbott 
and/or authorized designees according to the International Organization for Standardization 
(ISO) 14155 for post market studies, and applicable Abbott standard operating procedures and 
work instructions.  Qualified monitors will ensure investigators comply with this clinical protocol 
and ISO 14155 post market requirements.  
Sponsor representatives will periodically request source documents, resolution of 
discrepancies, submission of echocardiography imaging etc. for data cleaning and reporting 
purposes.  
 
6.7 Subject Study Completion 
Subjects will complete their participation in the study at the 2-year follow-up visits and will return 
to receiving medical care per their physician’s recommendations. 
 
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 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 22 of 59 
 
investigator.  Subjects will be asked to specify the reason for their termination, but have the 
right not to answer. 
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 dies (adverse events leading to death must be documented on an Adverse 
Event eCRF) 
▪ 
Subject did not have a successful implant and does not have a study device implanted 
(subjects who had an unsuccessful implant, the withdrawal date should be at 7 days 
post-implant attempt) 
▪ 
Subject is ‘lost to follow up’ (a subject will be considered “lost to follow-up” after a 
minimum of 2 attempted phone calls and a letter to the subject from study site 
personnel.  Attempts to contact subject must be documented in the subject’s study 
chart and/or medical record.  If phone attempts are unsuccessful, a letter should be 
sent to the subjects last known address) 
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, and any regional and/or 
national regulations and will be compliant to these International Standards and any regional and 
national regulations, as appropriate. 
The investigator will not enroll subjects or obtain informed consent from any subject prior to obtaining 
EC approval and authorization from the Sponsor in writing for the study.  For prospective enrollments, 
the subject must sign the study informed consent form prior to implant procedure.  
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 the Sponsor. 
As the Sponsor, Abbott has taken general liability insurance in accordance with the requirements of 
applicable local laws. Appropriate Abbott 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 
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: 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 23 of 59 
 
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 
 
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 vascular access has been initiated. The safety 
surveillance and the safety reporting will continue until the last visit has been performed, the 
subject is deceased, or the subject withdraws 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/complaints will be 
reported per country reporting timeline requirements using the standard process per country 
regulations. 
For any serious adverse event (including deaths) and any serious adverse device effect, the 
investigator shall notify the Sponsor within 3 calendar days of the investigator’s awareness of 
the event and provide the Sponsor with all necessary documentation needed.  
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 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) 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant 
authorities per country specific regulations.  
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 24 of 59 
 
8.1.3 Subject death 
All subject deaths with all necessary documentation needed are to be reported to the Sponsor 
within 3 calendar days upon the investigator’s awareness of the event. The Sponsor must 
report the death (classified as a serious adverse event) to the National Competent Authorities  
(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.  
Abbott 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.   
 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 
Canada, Europe and/or any other worldwide regulatory authority in support of a market-approval 
application. 
Abbott respects and protects personally identifiable information that is collected or maintained. As part 
of its commitment, Abbott is certified to the U.S. - European Union Framework and PIPEDA-Canada 
privacy act. 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 Abbott. 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 Abbott. Only authorized site personnel will be permitted to enter the 
data through the electronic data capture (EDC) system deployed by Abbott. An electronic audit 
trail will be used to track any subsequent changes of the entered data. 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 25 of 59 
 
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 
duration of 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.  
 
 Risks and Benefits  
10.1 Anticipated Clinical Benefits 
Patients suitable to receive the AMPLATZER LAA Occluder should be deemed by their 
physician to have an appropriate rationale to seek an alternative to pharmocologic therapy such 
as the inabilty to tolerate long term anticoagulants.  The AMPLATZER LAA Occluder is intended 
to be an alternative long term stroke prophylaxis when long term anticoagulation therapy is 
unacceptable.  The potential benefit of participating in this clinical study are close follow-up of 
the subejct by their treating physicians. 
 
10.2 Anticipated Adverse Events and Adverse Device Effects 
Anticipated adverse events and adverse device effects may occur during and after the 
AMPLATZER LAA Occluder implant procedure.  Serious adverse event definitions are provided 
in Section 8.  Refer to IFU for a complete list of potential anticipated serious adverse events. 
 
10.3 Risks 
The risks associated with the AMPLATZER LAA Occluder are no different from the risks 
associated with undergoing implant of an LAA Occluder with other commercially available 
transcatheter devices.  
 
10.4 Risk to Benefit Rationale 
Risks associated with participating in this clinical study are no different from risks associated with 
undergoing LAAO implant with a commercially available transcatheter device.  A potential benefit 
of participation in this clinical study may be close follow-up of the subject by their treating 
physicians. 
 
10.5 Residual Risks Associated with the Device 
The AMPLATZER Left Atrial Appendage Occluder device is market approved in all the 
countries where the study will be conducted.  The risk profile of the LAA Occluder device 
implant procedure is described in the IFU, and Section 8 of this protocol.  Risks associated with 
participating in this clinical study are no different from risks associated with undergoing LAAO 
implant with a commercially available transcatheter device. 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 26 of 59 
 
10.6 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 principal 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.  Any 
additional risk is mitigated with vigilance reporting for a licensed product. 
 Clinical Events Committee (CEC) 
A CEC will be responsible for providing an independent adjudication of study endpoints as outlined in 
the CEC Charter. 
 Monitoring  
It is the responsibility of Abbott 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 study-specific 
monitoring plan. 
Prior to beginning the clinical investigation, the Sponsor will contact the investigator or designee to 
discuss the clinical investigation and data requirements. A designated monitor will periodically review 
the subject records and associated source documents.  The investigator shall make subject and study 
records available to the clinical monitor for monitoring. 
Additionally, centralized monitoring may 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.   
 Regulatory Inspections 
The investigator and/or delegate should contact SJM as soon as possible 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 
 
 
 
14.1 Primary Endpoints 
There are three primary endpoints, two effectiveness endpoints and one safety endpoint. 
14.1.1 Primary Effectiveness Endpoint 1: 
Primary effectiveness endpoint 1 is the occurrence of the composite of stroke (including ischemic 
or hemorrhagic), systemic embolism, or cardiovascular or unexplained death at 24 months. 
Hypothesis: 
Ho: λ1 ≥ 9.6%   

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 27 of 59 
 
Ha: λ1 < 9.6%, 
where  λ1 is the rate of primary composite endpoint 1 at 24 months. 
Analysis Methods: 
Kaplan-Meier analysis will be used to estimate the event rate of at 24 months (731 days post 
implant).  The 97.5% upper confidence bound for the event rate must be less than 9.6% in order 
to declare success. 
 
 
 
Analysis Population: 
Subjects in this study who receive an implant of the AMPLATZER LAA Occluder will be included 
in the analysis. 
14.1.2 Primary Effectiveness Endpoint 2: 
Primary effectiveness endpoint 2 is the occurrence of the composite of ischemic stroke or 
systemic embolism at 24 months. 
Hypothesis: 
Ho: λ2 ≥ 6.6%   
Ha: λ2 < 6.6%, 
where λ2 is the rate of primary composite endpoint 2 at 24 months. 
 
Analysis Methods: 
Kaplan-Meier analysis will be used to estimate the rate of event at 24 months (731 days post 
implant).  The 97.5% upper confidence bound for the event rate must be less than 6.6% in order 
to declare success. 
 
 
 
Analysis Population: 
Subjects in this study who receive an implant of the AMPLATZER LAA Occluder will be included 
in the analysis. 
 
14.1.3 Primary Safety Endpoint: 
The primary safety endpoint is the occurrence of one of the following events between the time of 
implant and within 7 days of the procedure or by hospital discharge, whichever is later: All-cause 
death, ischemic stroke, systemic embolism, or device or procedure related events requiring open 
cardiac surgery or major endovascular repair (percutaneous catheter drainage of pericardial 
effusion, snaring of an embolized device, thrombin injection to treat femoral pseudoaneurysm, 
and nonsurgical treatments of access site complication  will not be included in the assessment of 
the third primary endpoint). 
Hypothesis: 
Ho: P ≥ 2.66%   
Ha: P < 2.66%, 
where P is the proportion of subjects experiencing a primary safety event within 7 days of the 
procedure or by hospital discharge, whichever is later. 
 
Analysis Methods: 
The proportion of subjects experiencing a primary safety endpoint will be estimated.  The 97.5% 
upper confidence bound for the proportion of subjects experiencing a safety event will be 
calculated using the exact binomial method. The 97.5% upper confidence bound for the 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 28 of 59 
 
proportion must be less than 2.66% in order to declare success.  
 
 
Analysis Population: 
Subjects who undergo an implant attempt with the AMPLATZER LAA Occluder will be included.  
An attempt is defined as a subject in whom vascular access has been initiated. 
 
14.2 Secondary Endpoint 
The secondary endpoint is a comparison of the observed rate of ischemic stroke at 24 months 
with the CHA2DS2-VASc predicted rate. 
14.2.1 Analysis method 
 
 
 
 
 
 
  
14.2.2 Analysis population 
The analysis will include subjects who receive an implant of an AMPLATZER LAA Occluder. 
14.3 Descriptive Endpoints/Outcomes Measures 
The following endpoints will be summarized using descriptive statistics. 
Oral anticoagulant use over time: 
The count and proportion of subjects using oral anticoagulants will be summarized at scheduled 
follow-up visit.  Subjects who are implanted with the AMPLATZER LAA Occluder will be included 
in this analysis. 
Device closure: 
The number and proportion of subjects in whom device closure is achieved at the 2-month visit 
will be summarized.  Device closure is defined as residual jet around the device < 5mm at the 2-
month visit documented by transesophageal echocardiogram (TOE). Subjects who are implanted 
with the AMPLATZER LAA Occluder and in whom device closure is assessed will be included in 
this analysis. 
Procedure duration: 
Procedure duration will be summarized using descriptive statistics including mean, standard 
deviation, median and range.  Procedure duration is defined as the time from the device 
delivery/device sheath is inserted into the vasculature until delivery sheath removed.  Subjects 
who are attempted to be implanted with the AMPLATZER LAA Occluder, or have been 
retrospectively enrolled will be included in this analysis. 
Procedure success: 
The count and proportion of subjects with a successful implant will be summarized.  A successful 
implant procedure is defined as implantation of the AMPLATZER LAA Occluder during the 
procedure with no serious adverse device effect prior to hospital discharge. Subjects who are 
attempted to be implanted with the AMPLATZER LAA Occluder will be included in this analysis. 
Technical success: 
The count and proportion of subjects with a successful implant will be summarized.  Technical 
success is defined as delivery and release of the AMPLATZER LAA Occluder. Subjects who are 
attempted to be implanted with the AMPLATZER LAA Occluder (introduction of the 
delivery/device sheath into the vasculature) will be included in this analysis. 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 29 of 59 
 
Device Thrombosis: 
The count and proportion of subjects with a device thrombus will be summarized.  Subjects 
implanted with an AMPLATZER LAA Occluder will be included in this analysis. 
Transient Ischemic Attack: 
Kaplan-Meier analysis will be used to estimate the rate of transient ischemic attack (TIA).  
Subjects who are attempted to be implanted with the AMPLATZER LAA Occluder, or have been 
retrospectively enrolled will be included in this analysis. 
All Cause Death: 
Kaplan-Meier analysis will be used to estimate the rate of death.  Subjects who are attempted to 
be implanted with the AMPLATZER LAA Occluder, or have been retrospectively enrolled will be 
included in this analysis. 
Major Bleeding: 
Kaplan-Meier analysis will be used to estimate the rate of major bleeding events.  Major bleeding 
is defined as Type 3 or greater based on BARC. Subjects who are attempted to be implanted 
with the AMPLATZER LAA Occluder, or have been retrospectively enrolled will be included in 
this analysis. 
Reporting: 
The following data will be summarized and reported annually to Health Canada. 
• 
Investigator sites and enrollment status 
• 
Demographic and baseline characteristics 
• 
Serious Adverse Events 
• 
Procedural results (procedure success, implanted device size, procedure duration) 
• 
Device closure rates 
• 
Oral anticoagulant use 
 
14.4 Compromising Factors 
This is an observational post approval study evaluating real-world outcomes in subjects 
undergoing implant with an AMPLATZER LAA Occluder.  The study endpoints and analysis 
populations will appropriately characterize safety of the procedure and long-term effectiveness of 
the device.  There are no known or foreseeable factors that may compromise the outcome of the 
clinical investigation or the interpretation of results. 
 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, or 2 years following study 
completion, whichever is longer duration.  
 Amendments to the Clinical Protocol 
Study related documents such as, protocol, eCRFs ( 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 30 of 59 
 
Appendix F: Case Report Forms) informed consent form (Appendix E: Sample Informed Consent) 
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 protocol, the subject’s informed consent form and amendment notification will be submitted for 
review and approval by the local IRB/EC and regulatory authorities (as applicable). The version 
number and date of amendments will be documented (Appendix B: Protocol Revision History). 
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 the external organization inasmuch as this organization assumes the clinical study related 
duties and functions of the Sponsor. 
 Investigation Suspension or Termination 
18.1 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. 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
. 
 
Page 31 of 59 
 
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. 
 
18.2 Study Conclusion 
The study will be concluded when: 
▪ 
All sites are closed AND 
▪ 
The final report generated by Abbott has been provided to sites or Abbott has provided 
formal documentation of study closure 
 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 AMPLATZER LAA Occluder Post Approval 
Study shall be subject to review and release of the Sponsor’s publication committee, which shall 
confer with the site regarding such publication. 
Publication guidelines will be followed according to the International Committee of Medical Journal 
Editors (ICMJE).  This study will also be posted on ClinicalTrials.gov and results will be posted on 
ClinicalTrials.gov as required. 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 32 of 59 
 
 Bibliography  
1. Fuster V, Ryden LE, Cannom D.  ACC/AFA/ESC Guidelines for the management of subjects 
with atrial fibrillation.  A report of the American College of Cardiology/American Heart 
Association task force on practice guidelines and the European Society of Cardiology 
Committee for practice guideline (writing committee to revise the 2001 Guidelines for 
management of subjects with atrial fibrillation).  Am Coll Cardol.  2006 48:e149. 
2. Ostemayer SH, Reisman M, Kramer PH, Matthews RV, Gray WA, Block PC, Omran H, 
Bartorelli AL, et al.  Percutaneous left atria appendage occlusion (PLAATO SYSTEM) to 
prevent stroke in high risk subjects with non-rheumatic atrial fibrillation: results from the 
international multicenter feasibility trials.  J AM Coll Cardiol.  2005 Jul 5; 46 (1): 9-14. 
3. Blackshear JL, Odell JA.  Appendage obliteration to reduce stroke in cardiac surgical subjects 
with atrial fibrillation.  Ann Thorac Surg.  1996; 61:755-9. 
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. Agmon Y, Khandheria BK, Gentile F, Seward JS. Echocardiographic assessment of the left 
atrial appendage. J Am Coll Cardiol. 1999; 34; 1867-1877. 
7. 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. 
8. Go AS, Hylek EM, ChangY, 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. 
9. Lip G, Nieuwlaat R, Pisters R, Lane D, Crijns H.  Refining clinical risk stratification for 
predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based 
approach: the Euro Heart Survey on atrial fibrillation.  Chest.  2010;137:263-72. 
10. Friberg l, Rosenqvist M, Lip G.  Evaluation of risk stratification schemes for ischaemic stroke 
and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort 
study.  Eur Heart J.  2012 (33): 1500-1510. 
11. 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 
12. 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. 
13. 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. 
14. 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. 
15. 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 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 33 of 59 
 
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.  
16. 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.  
17. 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. 
18. 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. 
19. 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. 
20. 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. 
21. 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. 
22. 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. 
23. 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. 
24. 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. 
25. 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. 
26. 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. 
27. 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. 
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 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 34 of 59 
 
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 occlusion European multicentre post market observational study. Presented at 
EURO PCR May 2014. 
31. 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). 
32. Chun K, Bordignon S, Urban V, Perotta L, Dugo D, Furnkranz A, et al.  Left Atrial Appendage 
Closure Followed by Six weeks Antithrombotic Therapy – a Prospective Single Center 
Experience.  Heart Rhythm.  2013(10):1792-1799. 
33. Gloecker S, Shakir S, Doblie J, Khattab A, Praz F, Guerios E, Koermendy D, Stortecky S, et 
al.  Early results of First versus Second generation AMPLATZER Occluders for Left Atrial 
Appendage Closure in Patients with Atrial Fibrillation.  Clinical Research in Cardiology.  2015: 
Published online March 2015. 
34. Figure 17 from Sponsor’s Executive Summary/ Circulatory System Devices Panel Meeting: 
2014 Boston Scientific WATCHMANTM Left Atrial Appendage Closure Technology for Patients 
with Non-Valvular Atrial Fibrillation. 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 36 of 59 
 
Appendix B: Protocol Revision History 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 37 of 59 
 
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-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 38 of 59 
 
Appendix D: List of Clinical Investigation Sites and Ethics Committees 
 
  
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 39 of 59 
 
Appendix E: Sample Informed Consent 
 
 
_ 
_ 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 40 of 59 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 41 of 59 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
Page 44 of 59 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 45 of 59 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
. 
 
Page 46 of 59 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 47 of 59 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
    
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
    
 
  
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 48 of 59 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
 
   
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
   
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 49 of 59 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 50 of 59 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
Page 51 of 59 
 
 
 
l 
 
, 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
Page 52 of 59 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 53 of 59 
 
Appendix F: Case Report Forms 
 
  
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 54 of 59 
 
Appendix G: 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-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 55 of 59 
 
Appendix H: Major Bleed classification/definition 
 
*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 
 
 
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: 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 56 of 59 
 
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.  
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 57 of 59 
 
Appendix I: Cardiovascular Mortality Definition 
 
Cardiovascular 
Mortality 
▪ Death resulting from an acute myocardial infarction 
(MI), sudden cardiac death, death due to heart 
failure (HF), death due to stroke, death due to 
cardiovascular (CV) procedures, death due to CV 
hemorrhage, and death due to other CV causes. 
 
 
 

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 58 of 59 
 
Appendix J: Definitions of Potential Adverse Event 
 
▪ 
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 Appendix I   
▪ 
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.  

 
Study Document No: SJM-CIP-10122 Ver. C 
Study Name: AMPLATZER™ LAA Occluder Post 
Approval Study 
 
Clinical Investigation Plan 
 
 
 
 
Page 59 of 59 
 
o 
Hemorrhagic Stroke: an acute episode of focal or global cerebral or spinal 
dysfunction caused by intraparenchymal, intraventricular, or subarachnoid 
hemorrhage 
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