AMPLATZER™ Amulet™ Left Atrial Appendage Occluder Randomized Controlled Trial
Phase: NA
Conditions: Stroke
Sponsor: Abbott Medical Devices

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 1 of 92  
 
 
 
NCT Number: 02879448 
Amulet IDE Trial 
AMPLATZER™ Amulet™ Left Atrial Appendage Occluder Randomized Controlled Trial  
Study Document No: SJM-CIP-10114 
Version C 
Date: 18-DEC-2017 
 
 
Sponsor 
 
 
             Abbott Medical 
                                                      5050 Nathan Lane North 
                                                      Plymouth, MN 55442 
                                                      USA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott. 
87173 CIP Posting Cover Page Ver B 
Template 
Page 1 of 92 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 2 of 92  
 
AMPLATZER™ Amulet™ Left Atrial Appendage Occluder  
Randomized Controlled Trial   
Clinical Investigational Plan  
 
Sponsor:  
 
 
St. Jude Medical (SJM) 
5050 Nathan Lane North 
Plymouth, MN 55442  
USA 
Main (651) 756-5400  
Fax (877) 257-2381 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 3 of 92  
 
Principal Investigator Signature Page 
AMPLATZER™ Amulet™ Left Atrial Appendage Occluder  
Randomized Controlled Trial  
Clinical Investigational Plan 
 
Version C 
Reference #: SJM-CIP-10114 
 
I have read and agree to adhere to the clinical protocol and all regulatory requirements applicable 
to conducting this clinical trial. 
 
 
Principal Investigator 
 
Printed name: 
____________________________________ 
Signature:            ____________________________________ 
Date:                    ____________________________________ 
 
 
 
 
 
 
 
 

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Table of Contents 
 
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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 8 of 92  
 
subjects will have the same data collection and follow-up 
schedule requirements as the randomized subjects. 
The randomized trial design was developed to adequately characterize 
the safety and effectiveness of the Amulet device and will include 
patients meeting inclusion criteria to include patients from the 
Medicare population. The study endpoints have been developed for 
appropriate characterization of health outcomes and the trial is 
powered under assumptions based on available scientific data (i.e. the 
sample size is adequate to answer the trial’s objectives).  
 
Note: This trial is not designed to exclusively test toxicity or disease 
pathophysiology in healthy individuals, as noted above and within the 
inclusion/exclusion criteria. 
Randomization 
1:1 between Amulet LAA occlusion device (treatment) and Boston 
Scientific LAA closure device (Control) 
Sample Size 
• 1878 subjects will be randomized at up to 150 sites 
worldwide. Up to 100 sites in the US may participate.  
• Approximately 343 additional subjects may be enrolled in 
the Roll-in Phase. Since US implanting physicians have no 
experience with the Amulet device, up to 3  roll-in subjects 
per implanter will result in approximately 343 subjects 
enrolled in the Roll-in Phase (see Section 5.2.1 for 
additional details). 
• 
 
Study 
Objective/Principal 
Purpose and 
Rationale for the 
Trial  
 
To evaluate the safety and effectiveness of the Amulet device by 
demonstrating its performance is non-inferior to the commercially 
available Boston Scientific LAA closure (LAAC) device (Control) in 
subjects with non-valvular atrial fibrillation. The trial will test whether 
the device meaningfully improves health outcomes of all enrolled 
subjects through evaluation of the safety and effectiveness primary 
endpoints. The intended patient population for this trial are those 
already indicated for the Control device; therefore, a randomized 
device-to-device comparator trial is appropriate for evaluating the 
outcomes of those with non-valvular atrial fibrillation and an 
increased risk of stroke.  Additionally, since there has been no 
prospective, randomized, device-to-device comparator trial to evaluate 
LAA closure, the results of this trial are not anticipated to duplicate 
existing knowledge or data.  
Primary Endpoints  
The trial has three primary endpoints to compare safety and 
effectiveness of the Amulet device against the Control device (see 
Appendix P for definitions): 
 
Safety 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 9 of 92  
 
• A composite of  procedure-related complications, or all-
cause death, or major bleeding through 12 months  
Effectiveness 
• A composite of ischemic stroke or systemic embolism 
through 18 months  
Mechanism of Action  
• Device closure (defined as residual jet around the device ≤ 
5 mm) at the 45-day visit documented by transesophageal 
echocardiogram (TEE/TOE) defined by Doppler flow 
Secondary Endpoints  The trial will also compare the Amulet device to the Control device 
for the following secondary endpoints: 
• A composite of all stroke, systemic embolism, or 
cardiovascular/unexplained death  through 18 months  
• Major bleeding rate  through 18 months : defined as Type 
3 or greater based on the Bleeding Academic Research 
Consortium (BARC) definition  
• A composite of  procedure-related complications, or all-
cause death, or major bleeding through 12 months 
(superiority analysis) 
• A composite of ischemic stroke or systemic embolism 
through 18 months (superiority analysis) 
• Device closure (defined as residual jet around the device ≤ 
5 mm) at the 45-day visit documented by transesophageal 
echocardiogram (TEE/TOE) defined by Doppler flow 
(superiority analysis) 
Descriptive 
 Endpoints/Outcomes 
Measures  
The randomized trial will descriptively summarize the following 
endpoints for each of the following measures:  
• Technical success rate 
• Procedural success rate 
• Device success rate 
• Number of subjects on oral anticoagulant at each follow-up 
visit  
• Procedure duration  
• Procedural complications by operator 
• Device thrombosis  
• Transient ischemic attack 
• Hemorrhagic stroke 
• Systemic embolism 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 10 of 92
 
 
 
• All-cause mortality 
• Cardiovascular mortality 
• Major bleeding, by site and severity (Major bleeding 
defined as Type 3 or greater per BARC) 
• Minor bleeding, by site and severity (Minor bleeding 
defined as Type 2 per BARC) 
Operator Training/ 
Experience and 
Facility 
Requirements  
Intended users of both the Amulet and Control devices are 
interventional cardiologists and electrophysiologists trained in 
percutaneous and transseptal procedures, who have completed 
company-specified physician training programs.  
The following are required for the implanting facility to participate in 
this trial: 
• Hospital with an established structural heart disease and/or 
electrophysiology program 
• Hospital with a cardiac catheterization lab or electrophysiology 
(EP) lab with fluoroscopy capability 
• Non-invasive imaging (i.e. transesophageal echocardiography) 
with  echocardiography support 
• Anesthesiology support for administration of general anesthesia 
specific to this procedure (as necessary) 
Inclusion Criteria  
 
To participate in the trial, subjects must meet the following inclusion 
criteria: 
1. 18 years of age or older 
2. Documented paroxysmal, persistent, or permanent non-valvular 
atrial fibrillation (AF) and the patient has not been diagnosed with 
rheumatic mitral valvular heart disease  
3. At high risk of stroke or systemic embolism defined as CHADS2 
score > 2 or a CHA2DS2-VASc score of > 3  
4. Has an appropriate rationale to seek an alternative to warfarin or 
other anticoagulation medication 
5. Deemed by investigator to be suitable for short term warfarin 
therapy but deemed unable to take long term oral anticoagulation 
following the conclusion of shared decision making (see inclusion 
criteria #6) 
6. Deemed suitable for LAA closure by a multidisciplinary team of 
medical professionals (including an independent non-
interventional physician) involved in the formal and shared 
decision- making process, and by use of an evidence-based 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 11 of 92
 
 
 
decision tool on oral anticoagulation (final determination must be 
documented in the subject’s medical record) 
7. Able to comply with the required medication regimen post-device 
implant 
8. Able to understand and willing to provide written informed 
consent to participate in the trial 
9. Able to and willing to return for required follow-up visits and 
examinations 
Exclusion Criteria  
To participate in the trial, subjects must not meet any of the following 
exclusion criteria: 
1. Requires long-term oral anticoagulation therapy for a condition 
other than atrial fibrillation  
2. Contraindicated for or allergic to aspirin, clopidogrel, or warfarin 
use 
3. Indicated for chronic P2Y12 platelet therapy inhibitor 
4. Is considered at high risk for general anesthesia, in the opinion of 
the investigator, and/or based on past adverse reaction(s) requiring 
medical intervention or which resulted in prolongation of hospital 
stay (criterion is only applicable where general anesthesia is 
planned for the study procedure) 
5. Has undergone atrial septal defect (ASD) repair or has an ASD 
closure device implanted  
6. Has undergone patent foramen ovale (PFO) repair or has a PFO 
closure device implanted 
7. Implanted with a mechanical valve prosthesis 
8. Has any of the customary contraindications for a percutaneous 
catheterization procedure (e.g. subject is too small to 
accommodate the transesophageal echocardiogram (TEE/TOE) 
probe or required catheters, or subject has active infection or 
bleeding disorder)  
9. Stroke or transient ischemic attack (TIA) within 90 days prior to 
randomization or implant procedure (as applicable) 
10. Underwent any cardiac or non-cardiac intervention or surgery 
within 30 days prior to randomization, or intervention or surgery 
is planned within 60 days after implant procedure (e.g. 
cardioversion, ablation, cataract surgery, etc.) 
11. Myocardial infarction (MI) within 90 days prior to randomization  

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 12 of 92
 
 
 
12. New York Heart Association Class IV Congestive Heart Failure 
13. Left ventricular ejection Fraction (LVEF) <30% 
14. Symptomatic carotid artery disease (defined as  >50% stenosis 
with symptoms of ipsilateral transient or visual TIA evidenced by 
amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral 
stroke); if subject has a history of carotid stent or endarterectomy 
the subject is eligible if there is <50% stenosis 
15. Reversible cause of AF (i.e. secondary thyroid disorders, acute 
alcohol intoxication, trauma, recent major surgical procedures)  
16. History of idiopathic or recurrent venous thromboembolism 
17. Left atrial appendage is obliterated or surgically ligated 
18. Thrombocytopenia or anemia requiring transfusions  
19. Hypersensitivity to any portion of the device material or individual 
components of either the Amulet or Boston Scientific LAA 
closure device (e.g. nickel allergy) 
20. Actively enrolled or plans to enroll in a concurrent clinical study 
in which the active treatment arm may confound the results of this 
trial 
21. Subject is pregnant or pregnancy is planned during the course of 
the investigation 
22. Active endocarditis or other infection producing bacteremia 
23. Subject has had a transient case of AF (i.e. never previously 
detected, provoked/induced by surgical or catheter manipulations, 
etc.)  
24. Subjects with severe renal failure (estimated glomerular filtration 
rate <30 ml/min/1.73m2) 
25. Subject whose life expectancy is less than 2 years 
26. Presence of other anatomic or comorbid conditions, or other 
medical, social, or psychological conditions that, in the 
investigator’s opinion, could limit the subject’s ability to 
participate in the clinical trial or to comply with follow up 
requirements, or impact the scientific soundness of the clinical 
trial results. 
Echocardiographic 
Exclusion 
 Criteria  
To participate in the trial, subjects must not meet any of the following 
echocardiographic exclusion criteria: 
1. Intracardiac thrombus visualized by echocardiographic imaging  
2. Existing circumferential pericardial effusion  >2mm 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 13 of 92
 
 
 
3. Significant mitral valve stenosis (i.e., mitral valve area <1.5 cm2) 
4. High risk patent foramen ovale (PFO), defined as an atrial septal 
aneurysm (excursion >15mm or length >15mm; excursion defined 
as maximal protrusion of the ASA beyond the plane of the atrial 
septum) or large shunt (early, within 3 beats and/or substantial 
passage of bubbles i.e. >20) 
5. Complex atheroma with mobile plaque of the descending aorta 
and/or aortic arch 
6. Cardiac tumor  
7. LAA anatomy cannot accommodate either a Boston Scientific 
LAAC or Amulet device, as per manufacturer’s IFU. (i.e. the 
anatomy and sizing must be appropriate for both devices in order 
to be enrolled in the trial. This is applicable to all roll-in and 
randomized subjects). 
8. Placement of the device would interfere with any intracardiac or 
intravascular structure 
Requirements for 
Suspected 
Stroke / TIA  Events 
During Follow-up 
Subjects suspected of having a TIA or stroke, or who experience any 
cognitive or behavioral changes at any time during trial participation 
must be seen by a stroke/TIA neurologist for evaluation and 
appropriate investigations must be done including neuro imaging,  
neurovascular imaging, and other tests as indicated. Every effort will 
be made to keep treating neurologists blinded to the subject’s 
treatment assignment.  
• If stroke is confirmed by neurologist: complete MRI (CT if 
MRI contraindicated) as soon as possible and within 10 
days (if possible) of event, preferably using the following 
sequences: Fluid-Attenuated Inversion Recovery (FLAIR), 
Diffusion-Weighted Imaging (DWI), Susceptibility-
Weighted Imaging (SWI), Gradient Recalled Echo (GRE) 
gradient, Apparent Diffusion Coefficient (ADC) maps  
• If ischemic stroke is confirmed through imaging, a 
TEE/TOE is required as soon as possible, but within 7 
days of the neurological imaging 
• Neurological assessments to be performed and repeated 90 
days after stroke/TIA 
Follow-up 
Requirements 
Follow-up visits will occur at pre-hospital discharge, 45 days, 3 
months (phone), 6 months, 9 months (phone), 12 months, 18 months, 
24 months, and annually by phone until 5 years. 
Testing  
Baseline 
• History and Physical  

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 14 of 92
 
 
 
• Cardiovascular and medical exam 
• Neurological exam (assessment by a neurologist for 
subjects with a history of TIA and/or stroke, per 
institutional standard of care) 
• Neurologic assessments (instruments include Modified 
Rankin Scale (mRS), Barthel Index, and National Institute 
of Health Stroke Scale (NIHSS) (must be performed by 
NIHSS- Barthel- and mRS-certified personnel) 
• Questionnaire for Verifying Stroke-Free Status (QVSFS) 
• CT/MRI for subjects with documented history of 
TIA/stroke (previous imaging done post-neurological event 
is acceptable; otherwise must be repeated after consent) 
• 12-lead ECG  
• CHADS2  and CHA2DS2-VASc Score  
• HAS-BLED Score 
• INR assessment (INR target range 2-3) if subject on 
warfarin (or other oral anticoagulants requiring INR 
assessments) 
• Medication assessment including the use of antiplatelet, 
and any anticoagulation medication  
• Pregnancy test (required for females of childbearing 
potential only) 
• EQ-5D-5L (Health Questionnaire) 
• TEE/TOE to confirm eligibility (echoes done up to 90 days 
prior to consent will be accepted as baseline) 
Note: Once a subject is randomized, the LAA implant procedure must 
occur within 14 days. 
 
Follow-up Testing: 
• Transthoracic echocardiogram (TTE) before discharge to 
check for device embolization or pericardial effusion  
• TEE/TOE at 45-day visit 
o Perform color Doppler assessment  
o If residual jet is present around the device, measure size 
of residual jet around the device 
o Confirm absence of intra-cardiac thrombus 
o If closure is not confirmed at 45-day visit, continue oral 
anticoagulation (OAC, including NOACS) (Amulet 
subjects) or warfarin* (Control subjects) until 6-month 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 15 of 92
 
 
 
TEE/TOE to assess LAA seal (closure is defined as <5 
mm residual jet flow around margins of the device) 
• TEE/TOE at 12-month visit 
• Adverse event assessment, medication assessment, and 
stroke ascertainment at each follow-up 
• Questionnaire for Verifying Stroke-Free Status (QVSFS) 
(all visits) 
• INR assessment (if subject is still on warfarin or other oral 
anticoagulants requiring INR assessments) 
• EQ-5D-5L health questionnaire at 45-day and 6-, 12-, and 
18- month visits 
*Subjects enrolled outside the US may take other 
anticoagulants/vitamin K antagonists in lieu of warfarin 
 
Medication Requirements (All Subjects) 
• Aspirin (81-100 mg) 1 day prior to implant 
Amulet Subjects (Post-Procedure) 
• Aspirin (81-100 mg) and clopidogrel OR aspirin (81-100 
mg) and OAC daily until the 45-day TEE/TOE is 
performed. An alternative to clopidogrel may be used if a 
subject is a non-responder to clopidogrel, as documented in 
the subject’s medical record/study chart.  
• If the residual flow into the LAA is > 5 mm on post-
procedure TEE/TOE, OAC therapy (if warfarin, INR of 2.0 
- 3.0) and  aspirin (81-100 mg) is required until the 45-day 
TEE/TOE is performed.  
• If at the 45-day visit, the TEE/TOE shows adequate 
closure of the LAA (residual jet < 5mm) cessation of OAC 
is required. Subjects should then begin clopidogrel 75 mg 
daily until the 6-month visit and continue  aspirin  81-100 
mg daily. Cessation of clopidogrel is required at the 6-
month visit (aspirin 81-100mg to be continued 
indefinitely). 
• If at the 45-day visit, the TEE/TOE shows inadequate 
closure of the LAA (residual jet > 5mm), the subject 
should remain on OAC and aspirin until the 6-month 
TEE/TOE is performed  
Control Subjects (Post-Procedure) 
• Aspirin (81-100 mg) + warfarin* (INR of 2.0 – 3.0) until 
TEE/TOE is performed at 45-day visit 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 16 of 92
 
 
 
• If at the 45-day visit, the TEE/TOE shows adequate 
closure of the LAA (residual jet < 5mm) cessation of 
warfarin is required. Subject should then begin clopidogrel 
75 mg daily until the 6-month visit and continue  aspirin  
81-100 mg daily.  An alternative to clopidogrel may be 
used if a subject is a non-responder to clopidogrel, as 
documented in the subject’s medical record/study chart. 
Cessation of clopidogrel is required at the 6-month visit 
(aspirin 81-100mg to be continued indefinitely). 
• If at 45-day visit, the TEE/TOE shows inadequate closure 
of the LAA (residual jet > 5mm), the subject should 
remain on warfarin and aspirin until the 6-month 
TEE/TOE is performed  
*Subjects enrolled outside the US may take other 
anticoagulants/vitamin K antagonists in lieu of warfarin 
 
Appropriate endocarditis prophylaxis is recommended for 6 months 
following device implantation for all subjects. The decision to 
continue endocarditis prophylaxis beyond 6 months is at physician’s 
discretion. 
Estimated 
Enrollment Time 
The trial may continue for up to 8 years, depending on the rate of 
enrollment and the FDA approval timeline (as applicable).  The trial is 
expected to take approximately 3 years to enroll, and each subject will 
be followed for 5 years. Follow-up visits may occur as part of a post-
approval study, should the Amulet device gain approval for 
commercial distribution prior to the subject’s 5-year visit.  
Subject 
Population/Protection 
/Compliance  
 
Subject screening will be conducted by trained study site personnel. 
Subjects that meet the inclusion criteria will be consented in 
compliance with all applicable US Federal regulations concerning the 
protection of human subjects (45 CFR Part 46, and 21 CFR Parts 50, 
54, 56, and 812), and the Declaration of Helsinki. In addition, sites 
will comply with the study protocol and any additional requirements 
imposed by the IRB, EC, or HREC in Australia. This trial will provide 
and obtain meaningful informed consent from patients regarding the 
risks associated with the study items and/or services, and the use and 
eventual disposition of the collected data. All aspects of the trial will 
be conducted according to appropriate standards of scientific integrity 
and standards mandated by CMS. Protocol deviations will be 
collected and monitored by SJM for trending. Repeated and serious 
non-compliance of an investigational site can result in site visits, 
telephone discussions with the PI, or retraining by SJM. If compliance 
is not secured, the investigator and site participation may be 
terminated.  

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 17 of 92
 
 
 
Subject Enrollment  
Subjects will be considered enrolled once the informed consent has 
been signed and the subject is randomized. The trial is expected to 
include the Medicare population, based on demographic 
characteristics and cardiovascular risk factors, thereby representing 
this patient population as part of the overall cohort. These criteria are 
not expected to have a negative effect on the recruitment or retention 
of underrepresented populations. SJM intends to implement FDA’s 
guidance on sex-specific data in medical device clinical studies to 
ensure adequate representation of women and other traditionally 
underrepresented demographic subgroups. Additionally, SJM will 
approach sites that have experience implanting Control devices 
without consideration for racial or ethnic minorities, will provide 
training to participating sites to ensure adequate representation of 
these demographic subgroups, and will regularly review screening and 
enrollment logs. Informed consent material in alternative languages 
and recruitment materials may be provided. Withdrawal rates for 
underrepresented subgroups will also be regularly reviewed by SJM, 
and compared to rates in the overall study population.  
 
As this trial will enroll Medicare beneficiaries in the US, all standards 
of Medicare coverage requirements will be followed. Results of the 
trial are expected to be generalizable to the Medicare population based 
on age and cardiovascular risk factors.  
Risks and Benefits 
The anticipated clinical benefit of LAA closure is that subjects may 
not need to be on long-term warfarin therapy and thus will not be 
exposed to complications associated with long-term warfarin therapy, 
particularly bleeding complications.  
The potential benefit of participating in this clinical trial is close 
follow-up of the subject by their treating physicians. Potential benefits 
of the Amulet device (which are being assessed in this trial) are higher 
implant success rate, higher rate of device closure, lower rate of 
complications, and lower rate of stroke than the Control device. 
Future patients with non-valvular atrial fibrillation at high risk of 
stroke may benefit from the results of this clinical trial.  
Anticipated adverse events (AEs) associated with study participation 
and device implants are similar to those of other cardiac 
catheterization procedures. There are other possible risks associated 
with the use of the required medications and testing for the trial, but 
are also no different from those prescribed outside of this clinical trial. 
The trial requires FDA approval and IRB/EC/HREC approval per site, 
trained physicians specializing in cardiac catheterization procedures, 
and will utilize a Data and Safety Monitoring Board (DSMB) as an 
independent oversight committee in an effort to minimize potential 
risks to subjects. Subjects (preoperatively and postoperatively) will be 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 18 of 92
 
 
 
under the care of a cohesive, multidisciplinary team of medical 
professionals, and procedures will be furnished in a hospital with an 
established structural heart disease and/or electrophysiology program. 
Adverse 
Events/Complaints 
Safety surveillance within this trial (and the safety reporting 
performed by the investigator) starts as soon as the subject is 
consented. Safety surveillance and safety reporting will continue until 
the last study visit has been performed, or the subject is deceased, or 
the subject concludes participation in the trial. The following types of 
adverse events will be collected for all subjects: 
• Serious adverse events 
• Device and procedure-related adverse events 
• Unanticipated adverse device effects 
In addition to reporting events to the sponsor, the investigator must 
also notify the IRB/EC/HREC, as appropriate, and in accordance with 
the national and local laws and regulations. Deaths are to be 
documented and reported to the sponsor within 10 days of becoming 
aware of the event.  
A complaint is defined as any written, electronic, or oral 
communication that alleges deficiencies related to the identity, 
quality, reliability, safety, effectiveness, or performance of a device 
after its release for distribution. All complaints for the Amulet device 
are to be submitted to SJM Postmarket Surveillance.  
Committees/Core 
Lab 
This clinical trial will utilize a Steering Committee who will advise 
SJM on trial design, trial conduct, and analysis and reporting of 
results. Additionally, the trial will have a Clinical Events Committee 
(CEC) and Data and Safety Monitoring Board (DSMB). The CEC will 
review and adjudicate AEs. The DSMB will advise SJM regarding the 
continuing safety of trial subjects and those yet to be recruited to the 
trial, as well as the continuing validity and scientific merit of the trial. 
The DSMB members will not be investigators in the trial.  
An independent echocardiography core lab will be utilized to analyze 
echo images. 
Data Management/ 
Monitoring 
SJM will be responsible for data handling and analysis, and a secure, 
validated, electronic data capture system will be utilized. Site 
monitoring will be conducted by SJM personnel in order to ensure 
accurate and complete reporting of data is occurring. As part of our 
commitment, SJM is certified to the U.S.- European Union 
Framework Agreement regarding human resources and subject 
clinical trial personal information. SJM will make every effort to 
maintain the privacy of each subject; confidentiality of subject 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 20 of 92
 
 
 
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 40 cm/s2. 
Agmon et al. found that the relative risk of ischemic stroke was 2.6 times greater in patients 
with LAA flow velocities < 20 cm/s than those with higher LAA velocities6. 
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 from 1.5% to 18.2% annually as CHADS2 scores 
increased from 1 and 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 and 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.  
Recently, new drugs (known as novel oral anticoagulant, or NOAC) have been developed 
with less dietary and pharmacological interactions than warfarin and no INR monitoring 
requirements.  Major trials such as RE-LY and ROCKET AF demonstrated that dabigatran 
and rivaroxiban 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-TIMI trial demonstrated 
both once-daily dose regimens of edoxaban were noninferior to warfarin with respect to the 
prevention of stroke or systemic embolism and were associated with significantly lower 
rates of bleeding and death from cardiovascular causes16.  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.   

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 21 of 92
 
 
 
Left atrial appendage occlusion (LAAO) is considered a viable alternative to oral 
anticoagulation (OAC) therapy for stroke prevention in patients with NVAF17-27. Published 
evidence supporting LAAO is provided in large part by the major randomized controlled 
trials PROTECT AF and PREVAIL17-20. Five-year results of PROTECT AF showed 
superiority of the WATCHMANTM device in mortality and stroke compared to optimal 
medical treatment with warfarin20.  
This clinical trial will study the Amulet device, which is St. Jude Medical’s second-
generation LAA closure device.  The first generation St. Jude Medical LAA closure device 
is the AMPLATZER Cardiac Plug (ACP) based on St. Jude Medical’s AMPLATZER 
occluder technology. The ACP device received CE Mark approval in 2008.  The ACP 
device demonstrated favorable feasibility and safety in observational studies in Europe28-29.  
Additionally, Park et al. reports the results of an investigator-initiated retrospective study to 
report on the initial European experience in patients treated with the ACP device between 
December 2008 and November 2009.  SJM’s ACP Registry results were also presented at 
EURO PCR in 2012 and 201428-29.  In addition, results from a multicenter study involving 
22 sites, 1,047 consecutive patients undergoing implant of the ACP device showed a high 
procedural success rate and a favorable outcome for the prevention of AF-related 
thromboembolism30.   
The ACP device was also evaluated under an Investigational Device Exemption (IDE) in the 
United States. The trial was set up in two phases within a combined, single protocol: a small 
feasibility phase followed by a larger pivotal phase. Initial safety evaluation in the feasibility 
phase was based on device and/or procedure-related serious adverse events (SAEs) and the 
transesophageal echo (TEE) results measuring LAA closure at 45 days post implant.  A total 
of 45 subjects were randomized (2: 1 device to control (warfarin)) between March 2010 and 
March 2011: 31 to the device group and 14 to the control group.  There were no deaths or 
unanticipated adverse device effects in the device group reported through the 45-day follow 
up for this study population. Based on review of the feasibility data, FDA determined that 
sufficient data existed to support continuation into the pivotal phase of the IDE study.  
Enrollment in the pivotal phase began in February 2013 and 52 new subjects were enrolled 
(37 device and 15 control). SJM ceased enrollment in the trial on 20 December 2013 due to 
the anticipated FDA approval and subsequent market release of a competitive LAAO device. 
The decision to stop enrollment in the ACP trial was due to the expectation that once the 
competitive LAAO device was commercially available, patients would not consent to 
participate in a randomized trial including warfarin as a control group.  The decision to stop 
enrollment was not due to safety or efficacy concerns. 
In a comparative study between the ACP and the WATCHMAN devices (40 patients each), 
Chun et al.31 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 device32-33. 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 26 of 92
 
 
 
5. Has undergone atrial septal defect (ASD) repair or has an ASD closure 
device present  
6. Has undergone patent foramen ovale (PFO) repair or has a PFO closure 
device implanted  
7. Implanted with a mechanical valve prosthesis 
8. Has any of the customary contraindications for a percutaneous 
catheterization procedure (e.g. subject is too small to accommodate the 
TEE/TOE probe or required catheters, or subject has active infection or 
bleeding disorder)  
9. Stroke or transient ischemic attack (TIA) within 90 days prior to 
randomization or implant procedure (as applicable) 
10. Underwent any cardiac or non-cardiac intervention or surgery within 30 
days prior to randomization, or intervention or surgery is planned within 60 
days after implant procedure (e.g. cardioversion, ablation, cataract surgery, 
etc.) 
11. Myocardial infarction (MI) within 90 days prior to randomization  
12. New York Heart Association Class IV Congestive Heart Failure 
13. Left ventricular ejection Fraction (LVEF) <30% 
14. Symptomatic carotid disease (defined as  >50% stenosis with symptoms of 
ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral 
hemispheric TIAs or ipsilateral stroke); if subject has a history of carotid 
stent or endarterectomy the subject is eligible if there is <50% stenosis 
15. Reversible cause of AF (i.e. secondary to thyroid disorders, acute alcohol 
intoxication, trauma, recent major surgical procedures)  
16. History of idiopathic or recurrent venous thromboembolism 
17. Left atrial appendage is obliterated or surgically ligated 
18. Thrombocytopenia  or anemia requiring transfusions  
19. Hypersensitivity to any portion of the device material or individual 
components of either the Amulet or Boston Scientific LAA closure device 
(e.g. nickel allergy) 
20. Actively enrolled or plans to enroll in a concurrent clinical study in which 
the active treatment arm may confound the results of this trial 
21. Subject is pregnant or pregnancy is planned during the course of the 
investigation 
22. Active endocarditis or other infection producing bacteremia 
23. Subject has had a transient case of AF (i.e. never previously detected, 
provoked/induced by surgical or catheter manipulations, etc.)   

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 32 of 92
 
 
 
system (delivery catheter and LAAC device). The access system and delivery system 
permit device placement in the left atrial appendage (LAA) via femoral access and 
inter-atrial septum crossing into the left atrium. The Boston Scientific device is a self-
expanding nitinol structure with a polyethylene terephthalate (PET) porous membrane 
on the proximal face. The device is constrained within the delivery system until 
deployment in the LAA. Appropriate device sizing is determined by LAA measurement 
using fluoroscopy (fluoro) and transesophageal echocardiography (TEE/TOE).  
The Boston Scientific LAAC device (WATCHMAN) is designed to be permanently 
implanted at or slightly distal to the ostium of the LAA to close the appendage to 
inflow. The placement procedure can be done under local or general anesthesia in a 
hospital catheterization or electrophysiology laboratory setting. 
In the event another Boston Scientific LAAC device becomes commercially 
available, use of the device will be allowed upon approval from FDA and SJM, 
and data captured accordingly on the eCRFs.   
Table 2 provides a comparison between the Amulet and Boston Scientific 
WATCHMAN device. 
Table 2:  Comparison of the Amulet and Boston Scientific WATCHMAN Device 
Characteristic 
Amulet  
WATCHMAN 
Manufacturer 
St. Jude Medical 
Boston Scientific 
Mechanism of 
Action 
Disc seals orifice of LAA 
Closes off distal body of LAA 
Sizes (diameter) 
16, 18, 20, 22, 25, 28, 31, and 34 mm 
21, 24, 27, 30, and 33 mm 
Delivery system 
AMPLATZER TORQVUE 45x45 (sheath 
sizes 12 Fr or 14 Fr) 
WATCHMAN Access Sheath (12 Fr) 
Required 
Medication Post-
procedure  
Aspirin (or alternate antiplatelet) at least 6 
months post-implant 
 
Clopidogrel (or alternate antiplatelet) per 
standard of care 
 
Endocarditis prophylaxis 
Warfarin* and aspirin until LAA seal ≤ 5 mm 
 
Warfarin cessation, aspirin indefinitely  
 
Clopidogrel and aspirin up to 6 months post- 
procedure 
 
Endocarditis prophylaxis 
 
*Subjects enrolled outside the US may take other 
anticoagulants/vitamin K antagonists in lieu of 
warfarin 
 
 
Availability 
US: Investigational use only  
US: FDA approved 
CE Mark 
CE Mark 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 36 of 92
 
 
 
Worldwide 
Randomized Trial
Subject Assessed 
for Inclusion / 
Exclusion Criteria
Subject Consented 
(Adverse Event Reporting 
Begins)
Screen 
Failure?
Complete 
Screening 
Log / Exit
YES
Subject 
Randomized = 
Subject Enrolled
Control implant 
procedure
Procedure must occur within 14 days 
of randomization
Amulet implant 
procedure
Subject in Follow-Up
Roll-In Procedure (up 
to 3 roll-in cases per 
US implanter allowed)
NO
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2: Study flowchart 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 37 of 92
 
 
 
7.1 
Screening/Enrollment/Baseline 
The following baseline and enrollment activities are required as part of the screening 
process.  All baseline activities should be done after informed consent is obtained, except 
where otherwise noted. 
• History and physical (may be done per standard of care up to 30 days prior to 
consent) 
• Cardiovascular and medical exam (may be done per standard of care up to 30 days 
prior to consent) 
• Neurological exam (assessment by a neurologist for subjects with a history of TIA 
and/or stroke, per institutional standard of care) 
• Neurologic assessment: Modified Rankin Scale (mRS), NIHSS, Barthel Index (must 
be performed by NIHSS-, Barthel- and mRS-certified personnel) 
• Questionnaire for Verifying Stroke-Free Status (QVSFS) 
• CT/MRI for subjects with documented history of TIA/stroke (previous imaging done 
post-neurological event per standard of care is acceptable; otherwise must be done 
after consent) 
• 12-lead ECG (may be done per standard of care up to 30 days prior to consent) 
• CHADS2 Score 
• CHA2DS2-VASc score  
• HAS-BLED score  
• INR Assessment (INR target range 2-3) if subject is taking warfarin (or other oral 
anticoagulants requiring INR assessments) 
• Medication assessment including the use of antiplatelet and anticoagulation 
medication 
• Pregnancy test (required for females of childbearing potential only) 
• EQ-5D-5L (Health Questionnaire) 
• TEE/TOE to confirm eligibility (echoes done up to 90 days prior to consent will be 
accepted as baseline) 
 
The principal investigator or delegated study personnel is responsible for screening 
potential subjects to determine subject eligibility for the trial.  Enrollment information 
(date of consent, inclusion/exclusion information, etc.) will be recorded in the subject’s 
medical record and on the Baseline and Inclusion/Exclusion eCRF.  Every effort must be 
made to submit the Inclusion/Exclusion eCRF within one week of screening. 
All subjects screened (including those who sign the informed consent) for the trial should 
be entered onto a Screening Log.  If a subject does not meet all inclusion criteria or meets 
any of the exclusion criteria, the subject cannot participate in the randomized trial.   
If a subject is consented and undergoes study-specific testing (i.e. testing that otherwise 
would not be conducted unless participating in this trial) but does not qualify for the trial, 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 40 of 92
 
 
 
 
 
Note: As an endpoint visit, the 18-month visit window is - 7/+45 days based on the date of 
 
implant procedure. 
 
7.6 
Neurological Events   
The Questionnaire to Verify Stroke-Free Status (QVSFS) is to be completed at baseline 
and at each study visit (including phone visits) to screen for presenting TIA/stroke signs 
and symptoms. A positive response to any question will trigger further evaluation and a 
neurology consult, as necessary. If a stroke or TIA is suspected, or the subject experiences 
any cognitive or behavioral changes at any time during the trial, the subject must be seen 
by a stroke/TIA neurologist for evaluation and an appropriate investigation must be 
performed, including neurovascular imaging and other tests as indicated.    
• If a stroke or TIA is suspected/confirmed by neurologist: complete an MRI (CT if 
MRI- contraindicated) as soon as possible and within 10 days (if possible) of the 
event, preferably using the following sequences: Fluid-Attenuated Inversion 
Recovery (FLAIR), Diffusion-Weighted Imaging (DWI), Susceptibility-Weighted 
Imaging (SWI), Gradient Recalled Echo (GRE) gradient, Apparent Diffusion 
Coefficient (ADC) maps  
• If ischemic stroke is confirmed through imaging, a TEE/TOE is required as soon as 
possible, but within 7 days of the neurological imaging. Echo imaging should be 
submitted to the core laboratory. 
In the event of a confirmed stroke or TIA by a stroke neurologist, neurological assessments 
(NIHSS, mRS and Barthel Index) shall be completed. Neurological assessments should be 
repeated 90 days (+/- 10 days) after the event.  
Every effort will be made to keep treating neurologists blinded to the subject’s treatment 
assignment. This will require collaboration between the study investigators and 
neurologists with respect to review of the echoes and source documentation, whenever 
possible.  
7.7 
Subject Study Completion 
When the subject’s participation in the clinical trial is complete, the subject will return to 
medical care as per physician’s recommendation. Subject participation in the roll-in phase 
and randomized trial will be considered complete upon completion of the 5-year follow-up 
visit, subject has withdrawn consent or died, or upon notification from SJM that the trial is 
completed, whichever is earlier.  
7.8 
Criteria and Procedures for Subject Withdrawal or Discontinuation 
Subjects must be informed of 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, and that withdrawal from the study will not jeopardize their future medical care or 
relationship with the investigator. Subjects will be asked to specify the reason for the 
termination, but have the right not to answer. 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 41 of 92
 
 
 
The subject’s future care will not be influenced by a decision, voluntary or otherwise, to 
withdraw from the study. All reasonable efforts should be made to retain the subject in the 
clinical trial until completion of the study. 
Reasons for subject’s withdrawal include, but are not limited to:  
• Subject withdraws consent 
• Subject is deceased (cause must be documented) 
• Subject is lost to follow-up. Subjects considered lost-to-follow-up are those who have 
missed at least one visit and cannot be reached and/or are unresponsive to attempts to 
be contacted. Attempts may include the following:  
o Phone calls to the subject from the study site personnel. Attempts to contact 
subject must be documented in the subject’s study chart and/or medical record.  
o Mailing a letter to the subject’s last known address. 
Additional requirements based on geography or IRB/EC will be followed when 
considering a subject as lost-to-follow-up.  
If a subject withdraws from the clinical trial, the site will record the subject’s reasons for 
withdrawal on a Withdrawal eCRF.  
Table 3 outlines the study visits and assessments for all enrolled subjects.  
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 42 of 92 
 
 
Table 3: Study visits and assessments  
Study Evaluation 
Baseline 
 
Procedure2 
Discharge 
 
45-day visit 
 (± 5 days) 
3-month 
visit (+ 30 
days) 
Phone 
Contact 
6-month 
visit (+ 30 
days) 
9-month 
visit 
(+ 30 days) 
Phone 
Contact 
12-month 
visit 
(±30 days) 
 
**18-
month 
24-month 
visit 
(±30 days) 
Annual 
visits 
3, 4 and 5 
years (±60 
days)  
Phone 
Contact 
Stroke 
Assessment 
Visit
Informed Consent Process 
X 
 
 
 
 
 
 
 
 
 
 
 
History & Physical 
X 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular & Medical Exam 
X 
 
 
 
 
 
 
 
 
 
 
 
Neurological exam 
X 
 
 
 
 
 
 
 
 
 
 
 
CHADS2 and CHA2DS2-VASc 
scores 
X 
 
 
 
 
 
 
 
 
 
 
 
HAS-BLED score 
X 
 
 
 
 
 
 
 
 
 
 
 
Reason for seeking an alternative 
to Warfarin/OAC therapy 
X 
 
 
 
 
 
 
 
 
 
 
 
INR assessment  
(as applicable while on 
warfarin/oral anticoagulants 
requiring INR assessments) 
X 
 
 
X 
 
X 
 
X 
X 
X 
 
X 
12-lead ECG  
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
 
 
 
 
Medication Assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MRI (CT if contraindicated) 
 
X3 
 
 
 
 
 
 
 
 
 
 
X 
Modified Rankin Scale, NIHSS 
& Barthel Index4 
X 
 
 
 
 
 
 
 
 
 
 
X 
QVSFS 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
EQ-5D-5L 
X 
 
 
X 
 
X 
 
X 
X 
 
 
 
Angiography 
 
X 
 
 
 
 
 
 
 
 
 
 
TTE 
 
 
X 
 
 
 
 
 
 
 
 
 
TEE/TOE 
X* 
X 
 
X 
 
X5 
 
X6 
 
 
 
X7 
Adverse Event Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
* Echoes performed within 90 days prior to consent will be accepted; otherwise TEE/TOE must be conducted after consent 
1 Pregnancy test for women of childbearing potential 
2 Procedure must occur within 14 days from the date of randomization. Follow-up visit windows for implanted subjects will be calculated based on the date of procedure. 
3 MRI (CT if contraindicated) is required for subjects with a documented history of TIA or stroke. Previous imaging done post-neurological event is acceptable; otherwise must be repeated 
4 Perform additional Neurological assessments after a confirmed stroke or TIA and repeat within 90 days of stroke confirmation.  
5 TEE/TOE is not required if closure was confirmed at 45 days (defined as residual jet <5mm) 
6 TEE/TOE is required for all subjects at 12 months  
7 TEE/TOE is required at stroke visit only if stroke is confirmed through MRI/CT 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 43 of 92 
 
 
**As an endpoint visit, the 18-month visit window is -7/ +45 days based on the date of implant procedure.  
Note: Subjects that are randomized but do not have a procedure or do not receive a device will be followed according to Table 3; however, medication requirements and follow-up TEE/TOEs are not 
required 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 44 of 92
 
 
 
Table 4 outlines the electronic case report forms (eCRFs) to be completed for all subjects (as 
applicable), and as per the study visit intervals.  
Table 4:  Required eCRF completion for all subjects 
Visit Interval 
Required eCRFs 
eCRF Completion Timeframe 
Baseline 
• 
Screening log 
• 
Inclusion/Exclusion 
• 
Baseline 
• 
Medication 
• 
EQ-5D-5L 
• 
QVSFS 
 
 
Procedure^ 
• 
Procedure  
• 
Medication 
• 
Health Care Utilization 
After study implant procedure 
 
^ Reminder: Procedure must occur 
within 14 days of randomization 
Discharge 
• 
Follow up  
• 
Medication 
At hospital discharge 
Follow-up 
• 
Follow up ** 
• 
Medication 
• 
EQ-5D-5L^^ 
• 
QVSFS 
 
Office visits: 45-day, 6-month, 12-
month, 18-month and 24-month 
 
Phone contact: 3-month, 9-month, 
3-year, 4-year and 5-year 
 
** Reminder: Submit TEE/TOE 
images for core lab review 
 
^^Reminder: 45-day and 6-month, 
12-month, 18-month 
Stroke Assessment 
Visit 
• 
Stroke/TIA Assessment  
• 
Adverse Event 
• 
Medication  
At the time of suspected stroke/TIA 
Adverse Event 
(“Unscheduled” 
visit) 
• 
Adverse Event 
• 
Medication 
• 
Stroke/TIA Assessment* 
At the time of occurrence or notification 
of event 
* If Stroke/TIA is suspected 
Hospitalization  
• 
Health Care Utilization 
In conjunction with implant procedure 
and reportable SAEs if hospitalization 
occurs 
Protocol Deviation 
• 
Protocol Deviation 
At the time of occurrence or notification 
of event 
Withdrawal 
• 
Subject Withdrawal 
When a subject is withdrawn from the 
study for any reason  
Death 
• 
Adverse Event 
• 
Death 
• 
Out of Service 
At the time of occurrence or notification 
of event 
N/A 
• 
Out of Service 
If a device is opened, but not 
used/implanted; at the time of subject 
death 
 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
SJM-CIP-10114 
Ver. C 
     Page 46 of 92
investigator is not allowed to deviate from the CIP, except as specified under emergency 
circumstances.   
Regulations require that the PI maintain accurate, complete, and current records, including 
documents showing the date of and reason for every deviation from the CIP. Relevant 
information for each deviation will be documented on a Deviation eCRF. The site will 
submit the eCRF to SJM.  
Regulations require investigators obtain approval from SJM and the IRB/EC/HREC (as 
required) before initiating changes in or deviations from the protocol, except when 
necessary to protect the life or physical well-being of a subject in an emergency.   
Prior approval must be requested when the PI anticipates, contemplates, or makes a 
conscious decision to depart from the CIP, except when unforeseen circumstances are 
beyond the investigator’s control (e.g. a subject who fails to attend a scheduled follow-up 
visit, a subject is too ill to perform a CIP-required test, etc.).  All deviations, including 
those beyond the investigator’s control, must be reported on an eCRF. 
To obtain approval, the principal investigator may call or email and discuss the potential 
deviation with SJM or designee prior to initiating any changes. The Investigator will notify 
SJM and the reviewing IRB/EC/HREC within 5 working days of becoming aware of the 
event: 
•
Any deviation to protect the life or physical well-being of a subject in an emergency
•
Any failure to obtain informed consent
Investigators or the designee must notify SJM as soon as possible, and complete a 
Deviation eCRF. 
The Investigator is required to adhere to local regulatory requirements for reporting 
deviations to IRB/EC/HREC (or other, as applicable). 
8.3 
Repeated and Serious Non-Compliance 
Protocol deviations will be collected and monitored by SJM for trending. In the event of 
repeated non-compliance or a one-time serious non-compliance, as determined by the 
sponsor, a clinical representative will attempt to secure compliance by one or more of the 
following actions: 
•
Visiting the investigator
•
Contacting the investigator by telephone
•
Contacting the investigator in writing
•
Retraining of the investigator
If an investigator is found to be repeatedly non-compliant with the signed agreement, the 
CIP or any other conditions of the clinical study, the sponsor will either secure compliance 
or, at its sole discretion, terminate the investigator’s participation in the clinical study. 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
SJM-CIP-10114 
Ver. C 
     Page 48 of 92
Adverse Events and Unanticipated Adverse Device Effects 
Safety surveillance within this trial (and the safety reporting performed by the 
investigator), starts as soon as the subject is consented. For all subjects, adverse events will 
be collected from the time of informed consent. Safety surveillance and safety reporting 
will continue until the last study visit has been performed, or the subject is deceased, or the 
subject concludes participation in the trial. The following types of adverse event will be 
collected for all subjects:  
•
All serious adverse events
•
All device and procedure-related adverse events
•
Unanticipated adverse device effects
In particular, the following adverse events regardless of seriousness or relatedness will be 
collected: 
•
Bleeding events through 18 months
•
Embolic events (e.g. stroke, TIA, systemic embolism) through 18 months
Investigators are responsible for promptly reporting adverse events to SJM by completing 
the Adverse Event eCRF.  Serious adverse events and unanticipated adverse device effects 
need to be reported within 10 working days after the investigator first learns of the events.  
Adverse events will be assessed by the investigator for relationship to the device and to the 
implant procedure. In the event that emergent reporting of an adverse event to the sponsor 
is necessary, clinical sites will complete an eCRF through the electronic database to report 
SAEs as soon as possible.   
Additional information may be requested by the sponsor, when required, in order to 
support AE reporting to regulatory authorities. 
The investigator must notify the IRB/EC/HREC, if appropriate, in accordance with 
national and local laws and regulations, of the AEs reported to the sponsor.   
9.3 
Subject Death 
All subject deaths are to be documented and reported to the sponsor within 10 days of 
becoming aware of the event.  A Death eCRF should be completed and include additional 
information surrounding the death and cause of death. An autopsy may be requested for 
subjects with an investigational device. Corresponding source documentation (i.e. death 
certificate, autopsy results, etc.) will be requested, as appropriate.  
9.4 
Complaints 
A complaint is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a device after it is released for distribution. All complaints should be 
submitted to SJM Postmarket Surveillance by the EPIQ on-line complaint system or on the 
EPIQ Offline form via by email to complaints_amplatzer@sjm.com. In the event that the 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 50 of 92
 
 
 
• Cardiac tamponade 
• Congestive heart failure 
• Death 
• Delivery system failure 
• Device embolization 
• Device migration 
• Device thrombus 
• Dyspepsia 
• Embolic event 
• Erosion 
• Fever 
• Foreign body embolization 
• Gastrointestinal pain and/or bleeding 
• Hypertension/hypotension 
• Hypoventilation 
• Infection 
• Multi-organ failure 
• Myocardial infarction 
• Myocardial ischemia 
• Perforation 
• Pericardial effusion 
• Peripheral thromboembolism 
• Pleural effusion 
• Renal failure/dysfunction 
• Respiratory failure 
• Respiratory insufficiency 
• Seizure 
• Sepsis 
• Septicemia 
• Significant residual flow 
• ST elevation 
• Stroke 
• Systemic embolism 
• Syncope 
• Thrombophlebitis 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 51 of 92
 
 
 
• Thrombus formation 
• Tissue damage 
• Transient ischemic attack 
• Valvular regurgitation/insufficiency 
• Vascular access site injury 
• Vessel trauma/injury 
Refer to the Boston Scientific LAAC device labeling for risks associated with the Control 
device. 
10.4 Risks Associated with Participation in the Clinical Study 
Risks associated with participation in this clinical trial are no different from the risks 
associated with undergoing LAAC implant with a commercially available transcatheter 
device.  
The risks associated with the Amulet device implant procedure are similar to those of other 
cardiac catheterization procedures.  Radiation risks associated with the procedure are 
comparable to a diagnostic catheterization procedure. 
The risks associated with the implanted Amulet device are similar to other implantable 
cardiac left atrial appendage occlusion devices.   
10.5 Possible Interactions with Concomitant Medical Treatments and/or Concurrent 
Medical Interventions 
The potential risks associated with blood thinning medicines (warfarin, other OACs, 
aspirin, and clopidogrel) include, but are not limited to:  increased bleeding time, bleeding 
from the stomach or bowels, cranial bleed, drowsiness, dizziness, headache, heartburn, 
stomach pain, loss of appetite, nausea, vomiting, hives, rash, itching, bruising, swelling, 
fast heartbeat, chest pain, infection.   
The potential risks associated with a transesophageal echocardiography (TEE/TOE) 
include, but are not limited to sore throat, bleeding, breathing or heart problems, gagging, 
vomiting, pain when swallowing, dental injury and damage or tear to esophagus.  
The risks are no different from the risks associated with medications prescribed upon 
undergoing LAAC implant with a commercially available transcatheter device. 
10.6 Steps to Control or Mitigate Risks 
To minimize potential clinical risks to subjects participating in this clinical trial: 
• This study will undergo review and approval by site Institutional Review Boards 
(IRBs) or Ethics Committees (ECs).  The IRB/EC will review all study-related 
documents such as the protocol, informed consent form, and participant recruitment 
announcements. 
• The FDA (and other competent authorities, as applicable) will review the protocol 
and informed consent form. 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 56 of 92
 
 
 
H0: p2(Amulet) – p2(Control) ≥ Δ2 
H1:  p2(Amulet) – p2(Control) < Δ2 
where Δ2 is the absolute value of the non-inferiority margin for the effectiveness endpoint.  
The null hypothesis will be tested at the 2.5% significance level and will be rejected if the 
97.5% upper confidence bound (UCB) for the difference in Amulet and Control rates is less 
than Δ2.   
The 18-month rate of ischemic stroke or systemic embolism (SE) is assumed to be 4.2% in 
each of the treatment groups based on reported rates of ischemic stroke or SE for the 
Watchman device from the PREVAIL trial44 . The non-inferiority margin, Δ2, is chosen to 
be 3.2%, which represents a relative risk of 1.76.  This non-inferiority margin allows a 
maximum 18-month event rate of 7.4% (4.2%+3.2%) for the Amulet group assuming an 
18-month event rate of 4.2% in the Control group.  An 18-month rate of 7.4% is equivalent 
to an annualized event rate of 0.051 events per patient-year assuming an exponential 
survival distribution.  The event rate of 0.051 per patient-year rate is compared to the 
expected rate for untreated atrial fibrillation.  The observed distribution of CHADS2 scores 
in the PREVAIL trial is shown in Table 4.  The Amulet IDE trial will enroll subjects with 
CHADS2 ≥ 2, therefore, the distribution of CHADS2 score is expected to be skewed 
slightly to higher CHADS2 scores, i.e., subjects at higher risk of stroke compared to 
PREVAIL subjects.  The expected rate of ischemic stroke for untreated atrial fibrillation 
for each CHADS2 score is also shown in Table 4, from which the overall ischemic stroke 
rate is calculated as 0.065 events per patient-year10.  This rate is consistent with the event 
rate predicted for untreated atrial fibrillation based on baseline CHA2DS2-VASc scores in 
the PREVAIL trial (0.069 per patient-year)45.  The event rate of 0.051 events per patient-
year is also compared with the expected event rate for patients treated with warfarin.  In an 
early trial of warfarin versus placebo, the rate of ischemic stroke or systemic embolism on 
warfarin was shown to be 0.023 events per patient-year46.  In a meta-analysis of six trials 
of warfarin compared with placebo, Hart et al estimated a stroke (ischemic or hemorrhagic) 
rate of 0.022 per patient-year (53 events in 2396 patient-years) for patients randomized to 
receive warfarin47.  The ischemic stroke/SE event rate of 0.051 per patient-year is 
approximately twice the event rate observed with warfarin treatment.  The event rate of 
0.051 per patient-year is also compared with event rates on warfarin or novel oral 
anticoagulants from recently completed randomized trials of novel anticoagulant therapies.  
Figure 3 shows that annualized rates for stroke or SE on warfarin or a novel oral 
anticoagulant range from 0.011 to 0.026 events per patient-year showed.  The ROCKET-
AF trial of rivaroxaban had the highest rate of stroke or SE, as expected, given that this 
trial had the highest mean CHADS2 score (~3.5).  The proposed non-inferiority margin 
ensures that the rate observed in the Amulet group in this trial will be at most twice the rate 
expected with oral anticoagulant therapy (warfarin or novel oral anticoagulant).   
 
 
 
Table 4. Proportion of Subjects for Each CHADS2 Score and Expected Stroke Rates for 
Untreated Atrial Fibrillation 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 57 of 92
 
 
 
CHADS2 
score 
Observed 
Proportion of 
Subjects in 
PREVAIL 
Expected 
Proportion of 
Subjects in Amulet 
IDEa  
 
(A) 
Expected Ischemic Stroke 
Rate10 per 100 patient-years 
for Untreated AF 
(Unadjusted) within 
CHADS2 score category 
(B) 
Expected Ischemic 
Stroke Rate for 
Untreated AF within 
CHADS2 score 
category 
(AxB) 
1 
0.08 
0.00 
3.0 
0.0 
2 
0.47 
0.50 
4.2 
2.1 
3 
0.25 
0.30 
7.1 
2.1 
4 
0.14 
0.14 
11.1 
1.6 
5 
0.06 
0.06 
12.5 
0.8 
6 
0.00 
0.00 
13.0 
0.0 
Total 
1 
1 
N/A 
6.5 
a All subjects in AMULET IDE trial will have CHADS2 ≥ 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3. Rate of Stroke or Systemic Embolism Per 100 Patient-Years in Randomized 
Controlled Trials of Novel Oral Anticoagulant Therapy (+/- 95% Confidence Intervals) 
 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 62 of 92
 
 
 
The hypothesis will be tested at the 2.5% significance level. If the 97.5% LCB 
for(p3(Amulet) – p3(Control)) is > 0, superiority of device closure for the Amulet 
device will be claimed.  The LCB will be calculated by the Farrington Manning 
method. The same analysis populations described for the primary device closure 
endpoint will be used to test this hypothesis. 
14.2 Justification of Clinical Investigation Design 
This trial will evaluate the safety and effectiveness of the Amulet LAAO device by 
comparing outcomes with the commercially approved Boston Scientific LAAC device.  
This is a prospective, randomized, multi-center active control trial intended to demonstrate 
non-inferiority of the Amulet LAAO device to the commercially available Boston 
Scientific LAAC device in subjects with non-valvular atrial fibrillation.   
The primary safety endpoint evaluates the incidence of both procedural and longer term 
outcomes at 12 months, and the effectiveness endpoint evaluates the incidence of ischemic 
stroke or SE through 18 months. These timepoints for evaluation of safety and 
effectiveness are adequate to demonstrate non-inferiority of the Amulet device to the 
Boston Scientific LAAC device. The safety endpoint (12 months) is designed to capture 
procedural complications and mortality or bleeding associated with the procedure or use of 
antithrombotic medications specified in the protocol.  The effectiveness endpoint is 
designed to characterize longer term device effect (18 months) as the early follow-up 
(through 6 months) is confounded by both groups receiving anticoagulant or dual 
antiplatelet medication.   
14.3 Multiplicity Adjustment 
Multiplicity adjustment for the primary and secondary endpoints will apply to hypothesis 
testing for the non-inferiority tests of three primary endpoints and the five tests of 
secondary endpoints (composite endpoint of all stroke, systemic embolism, or 
CV/unexplained death, major bleeding, superiority test of the primary safety endpoint,  
superiority test of the primary effectiveness endpoint, and superiority test of device 
closure). 
If all three primary endpoints of non-inferiority of are met, the Hochberg procedure50 will 
be used to adjust for multiple comparisons for testing secondary endpoints and superiority 
of primary endpoints described in Section 14.1.4. P values are ordered largest to smallest, 
p(1), p(2), p(3), p(4), p(5), where p(1) is the largest and p(5) is the smallest p value. 
• If all the endpoints meet statistical significance at the 0.025 level (i.e., 
p(1)<0.025), then all are considered to have passed the multiple comparisons test. 
The steps described below would not be taken. 
• Otherwise 
o The endpoint with largest p value (p(1)) is removed from consideration 
o If all the remaining 4 endpoints meet statistical significance level of 
0.025/2, then all these 4 endpoints are considered to have passed the 
multiple comparison test 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 63 of 92
 
 
 
• Otherwise 
o The endpoint with largest p value is removed from consideration 
o The evaluation is repeated as above, now using 0.025/3 
• If necessary the process repeats. The very last endpoint with the smallest p value 
(p(5)) would be evaluated at the significance level of 0.025/5. 
14.4 Secondary Analyses of Primary Endpoints 
In June 19, 2017, Abbott implemented a number of steps to improve procedural training for 
field clinical personnel and implanters in the US.  Therefore, supportive secondary analyses 
for each of the three primary endpoints will be performed excluding subjects randomized in 
the US before June 19, 2017. These analyses will involve the same analyses populations and 
methods as those employed in the primary analyses. A total of 346 subjects were randomized 
in the US prior to June 19, 2017, therefore, the sample size of 1532 (=1878-346) randomized 
subjects will provide at least 80% power for each primary endpoint in the secondary analyses 
under the assumptions described within each endpoint. Abbott understands that FDA will 
treat these analyses as supportive secondary analyses and that FDA will review the totality 
of the data in the pre-market approval application.  
14.5 Overall Sample Size 
The sample size required for evaluation of the primary safety endpoint, primary 
effectiveness endpoint, and primary endpoint of device closure are 1746, 1878,  and 1258 
randomized subjects, respectively.  The primary effectiveness endpoint requires a larger 
sample size (N=1878) and therefore determines the sample size for the randomized 
subjects in the trial. To ensure enrollment balance across study sites, no investigational site 
will be permitted to enroll more than 20% of the maximum sample size (376 subjects) 
without prior written approval of the sponsor. 
14.6 Timing of Analysis 
The analyses for the pre-market approval (PMA) application will be conducted on a dataset 
locked after all randomized subjects have had the 18-month study visit (excepting deaths, 
withdrawals and loss-to-follow-up before 18 months) or crossed the 18-month visit 
window without a visit (missed visit).  
14.7 Success Criteria 
The trial has three primary endpoints for safety, effectiveness, and device closure to 
compare safety and effectiveness of the Amulet device against the Control device.  All 
three primary endpoints must be met in order to claim comparable outcomes between the 
Amulet device and the Control device.  However, it is important to note that with 1878 
randomized subjects, the overall power to demonstrate trial success (i.e., success in all 
three primary endpoints) is 80%.  (With 1878 randomized subjects, the power for each 
individual primary endpoint is 92%, 90%, and 97%. Therefore the overall power to 
demonstrate success in all three primary endpoints is 80%=.92*.90*.97)). It is possible that 
the Amulet device achieves superiority in the endpoint of device closure, yet the primary 
effectiveness endpoint may not be met due to a differential use of OAC between the two 

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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 67 of 92
 
 
 
6. Agmon Y, Khandheria BK, Gentile F, Seward JS. Echocardiographic assessment of the 
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Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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17. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbiner M, Mullin CM, Sick 
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18. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial 
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21. Gangireddy Sr, Halperin JL, Fuster V, Reddy VY. Percutaneous left atrial appendage 
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22. Park HW, Bethencourt A, Sievert H, Santoro G, Meier B, Walsh K, Lopez-Minquez JR, 
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AMPLATZER cardiac plug in atrial fibrillation: Initial European experience. Catheter 
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23. Urena M, Rodes-Cabau J, Freixa X, Saw J, Webb JG, Freeman M, Horlick E, Osten M, 
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24. Meerkin D, Butnaru A, Dratva D, Bertrand OF, Tzivoni D. Early safety of the 
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25. Nietlspach F, Gloekler S, Krause R, Shakir S, Schmid M, Khattab AA, Wenaweser P, 
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27. Camm AJ, Lip GY, De Caterina R, Savelieve I, Atar D, Hohnloser SH, Hindricks G, 
Kirchof P: ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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guidelines for the management of atrial fibrillation.  Developed with the special contribution 
of the European Heart Rhythm Association. Eur Heart J. 2012 Nov; 33(21)-2719-47. 
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Meerkin D, Valdés M, Ormerod O, Leithäuser B. Left atrial appendage closure with 
AMPLATZER cardiac plug in atrial fibrillation: Initial European experience. Catheter 
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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. 
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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. Chun K, Bordignon S, Urban V, Perrotta L, Dugo D, Fürnkranz A, et al. Left Atrial 
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center experience. Heart Rhythm. 2013 Dec; 10(12):1792-1799. 
32. Bai R, Horton R, Di Biase L, Mohanty P, Pump A, Cardinal D, et al. Intraprocedural and 
long-term incomplete occlusion of the left atrial appendage following placement of the 
WATCHMAN device: a single center experience. J Cardiovasc Electrophysiol. 2012 
May;23(5):455-61. 
33. Viles-Gonzalez J, Kar S, Douglas P, Dukkipati S, Fledman T, Horton R, et al. The 
clinical impact of incomplete left atrial appendage closure with the Watchman Device in 
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Fibrillation) substudy. J Am Coll Cardiol. 2012 Mar 6;59(10):923-9 
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Atrial Fibrillation: The First Case in Greece. Hellenic J Cardiol. 2013 Sep-Oct 54(5):408-
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35. Freixa X, Abualsaud A, Chan J, Nosair M, Tzikas A, Garceau P, et al. Left Atrial 
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36. Gloecker S, Shakir S, Doblie, J, Khattab A, Praz F, Guerios E, Koermendy D, Stortecky 
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37. Lam S, Bertog S, Gafoor S, Vaskelyte L, Boehm P, Ho R, Franke J, Hofmann I, Sievert 
H.  Left Atrial Appendage Closure Using the Amulet Device:  An Initial Experience with 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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the Second Generation AMPLATZER Cardiac Plug.  Catheter Cardiovasc Interv. 2015 Feb 
1: 85(2):297-303. 
38. CDRH. Evaluation of sex-specific data in medical device clinical studies: Guidance for 
industry and for and drug administration staff. August, 2014. 
39. Holmes DR et al Left Atrial Appendage closure as an alternative to warfarin for stroke 
prevention in atrial fibrillation: A patient-level meta-analysis. JACC (2015). 65: 2614-23. 
40. Reddy VY et al. Left Atrial Appendage closure with the Watchman device in patients 
with a contraindication for oral anticoagulation. The ASAP study (ASA Plavix Feasibility 
Study with Watchman Left Atrial Appendage Closure Technology). JACC (2013). 61: 2551-
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41. Kefer J et al. Transcatheter left atrial appendage closure for stroke prevention in atrial 
fibrillation with Amplatzer cardiac plug: the Belgian Registry. Acta Cardiol (2013). 68:551-
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42. Tzikas A, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: 
multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention. 2015 Jan 
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43. Figure 27 from Sponsor’s Executive Summary: 2013 Boston Scientific WATCHMAN 
Left Atrial Appendage Closure Therapy Advisory Panel Meeting. 
 
44. Table 12 and Table 21 from FDA Executive Summary: 2014 Boston Scientific 
WATCHMAN Left Atrial Appendage Closure Therapy Advisory Panel Meeting. 
 
45. Figure 16 and Table 21 from Sponsor’s Executive Summary: 2014 Boston Scientific 
WATCHMAN Left Atrial Appendage Closure Therapy Advisory Panel Meeting. 
46. Stroke Prevention in in Atrial Fibrillation. Circulation. 1991 August;   84, 2.  
47. Hart, et. al. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: A 
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48. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation, New Engl 
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49. Connolly SJ et al. The Long-Term Multicenter Observational Study of Dabigatran 
Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study, Circulation, 2013; 128; 
237-243. 
50. Boersma LV, Schmidt B, Betts TR, Sievert H, Tamburino C, Teiger E et al. EWOLUTION 
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51. Hochberg (1988) A sharper Bonferroni procedure for multiple tests of significance. 
Biometrika 75(4):800-802. 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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52. Mehran R, Rao, SV, Bhatt DL.  Standardized bleeding definitions for cardiovascular 
clinical trials:  A consensus report from the Bleeding Academic Research Consortium.  
Circulation 2011 Jun 14; 123 (23):  2736-47.  
53. Tzikas A, et. al. Percutaneous left atrial appendage occlusion: the Munich consensus 
document on definitions, endpoints, and data collection requirements for clinical studies. 
Eurointervention 2016; 12; 103-111. 
54. Kappetein, P.A., et. al. Updated standardized endpoint definitions for transcatheter aortic 
valve implantation. J Am Coll Cardiol. 2012; 60: 1438-54. 
55. January, Craig T., et. al. 2014 AHA/ACC/HRS guideline for the management of patients 
with atrial fibrillation. Circulation 2014; e199. 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix A: Abbreviations 
Select or add abbreviations used 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Abbreviation 
Term 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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ACP 
AE 
AF 
ASA 
ASD 
BARC 
CA 
CABG 
CE 
CEC 
CFR 
CHF 
CIP 
CMS 
CRF 
CT 
DFU 
DMP 
DSMB 
EC 
ECG 
eCRF 
EDC 
EP 
FDA 
GP 
HREC 
IB 
ICMJE 
IDE 
IFU 
INR 
IRB 
LA 
LAA 
LAAC 
LAAO 
LVEF 
MI 
MRI 
mRS 
NA 
NIHSS 
NOAC 
NSAID 
AMPLATZER™ Cardiac Plug 
Adverse Event 
Atrial Fibrillation 
Atrial Septal Aneurysm 
Atrial Septal Defect 
Bleeding Academic Research Consortium 
Competent Authority 
Coronary Artery Bypass Graft 
Conformité Européenne 
Clinical Events Committee 
Code of Federal Regulations 
Congestive Heart Failure 
Clinical Investigational Plan 
Centers for Medicare and Medicaid Services 
Case Report Form 
Computed Tomography 
Directions for Use 
Data Management Plan 
Data and Safety Monitoring Board  
Ethics Committee 
Electrocardiogram 
Electronic Case Report Form 
Electronic Data Capture 
Electrophysiology 
Food and Drug Administration 
General Practitioner 
Human Research Ethics Committee 
Investigator Brochure 
International Committee of Medical Journal Editors 
Investigational Device Exemption 
Instructions for Use 
International Normalized Ratio 
Institutional Review Board 
Left Atrium 
Left Atrial Appendage 
Left Atrial Appendage Closure 
Left Atrial Appendage Occlusion  
Left Ventricular Ejection Fraction 
Myocardial Infarction 
Magnetic Resonance Imaging 
Modified Rankin Scale 
Not Applicable 
National Institute of Health Stroke Scale 
Novel Oral Anticoagulant 
Non-Steroidal Anti Inflammatory Drug 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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NVAF 
NYHA 
OAC 
PAS 
PET 
PFO 
PI 
PMA 
RNT 
SAE 
SAP 
SC  
SE 
SJM 
TEE/TOE 
TIA 
UCB 
US 
UADE 
WMA 
Non Valvular Atrial Fibrillation 
New York Heart Association Classification 
Oral Anticoagulation 
Post-Approval Study 
Polyethylene Terephthalate  
Patent Foramen Ovale 
Principal Investigator 
Pre-Market Approval 
Randomized Not Treated 
Serious Adverse Event 
Statistical Analysis Plan 
Steering Committee 
Systemic Embolism 
St. Jude Medical 
Transesophageal echocardiography 
Transient Ischemic Attack 
Upper Confidence Bound  
United States 
Unanticipated Adverse Device Effect 
World Medical Association 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
              Page 76 of 92
 
 
 
Appendix B: List of Clinical Investigation Sites, EC/IRB/HRECs 
A list of Clinical Investigational sites, EC/ IRB/HRECs will be kept under separate cover and is 
available upon request.  
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix C: Declaration of Helsinki 
This clinical investigation will be conducted under the guidance of the current Declaration of 
Helsinki, which can be found at the following website:  
http://www.wma.net/en/20activities/10ethics/10helsinki/.  
 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix D: Informed Consent Form Template 
The informed consent form template will be provided under separate cover. 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix E:  Report of Priors  
The purpose of the Report of Prior Investigations (RoPI) is to provide the principal investigator 
with sufficient safety or performance data from pre-clinical studies or clinical studies to justify 
human exposure to the investigational device specified in the CIP.   
The RoPI will be updated throughout the course of the clinical study as significant new 
information becomes available (e.g. a significant change in risk, etc.).  
The Report of Priors will be provided under separate cover.  
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix F: Amulet Product Labeling/Instructions for Use (IFU) 
The Amulet product labeling/IFU will be provided under separate cover. 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix G: Physician Training Plan 
The Physician training plan will be provided under separate cover.  
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix H: Case Report Forms 
The case report forms will be provided under separate cover. 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix I: Modified Rankin Scale 
 
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-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix J:  The Barthel Index 
The Barthel Index will be provided under separate cover. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix K:  CHADS2  score & CHA2DS2-VASc score 
The CHADS2 scoring system criteria is specified below: 
CHA2DS 
Score 
Congestive heart failure 
1 
Hypertension 
1 
Age > 75 
1 
Diabetes mellitus 
1 
Stroke/TIA 
2 
 
The CHA2DS2-VASc scoring system criteria is specified below: 
CHA2DS2 –VASc 
Score 
Congestive heart failure/LV dysfunction 
1 
Hypertension 
1 
Age > 75 
2 
Diabetes mellitus 
1 
Stroke/TIA/TE 
2 
Vascular disease [prior myocardial 
infarction, peripheral artery disease or 
aortic plaque] 
1 
Age 65-74 
1 
Sex category [i.e. female gender] 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix L: HAS-BLED score 
The HAS-BLED scoring system criteria is specified below:  
 
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 INRs, 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 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix M:  Bleeding Academic Research Consortium Definitions (BARC)52 
All bleeding events will be classified according to the BARC definitions. 
Bleeding  
Classified as Type 0 – 5 according to the following BARC definitions 
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 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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• Transfusion of  ≥ 5 units whole blood or packed red blood cells within a 48-hour 
period (only allogenic transfusions are considered transfusions for CABG-related 
bleeds)  
• Chest tube output ≥ 2 L within a 24-hour period 
Notes: If a CABG-related bleed is not adjudicated as at least a type 3 severity event, it will 
not be classified as a bleeding event. If a bleeding event occurs with a clear temporal 
relationship to CABG (i.e. within a 48-hour timeframe) but does not meet type 4 severity 
criteria, it will not be classified as a bleeding event.  
Type 5: Fatal bleeding 
Fatal bleeding is bleeding that directly causes death with no other explainable cause. 
BARC fatal bleeding is categorized as either definite or probable as follows: 
Type 5a: 
Probably fatal bleeding: bleeding that is clinically suspicious as the cause of death, but the 
bleeding is not directly observed and there is no autopsy or confirmatory imaging 
Type 5b: 
Definite fatal bleeding: bleeding that is directly observed (by either clinical specimen 
[blood, emesis, stool, etc.] or imaging) or confirmed on autopsy 
The site of fatal bleeding is specified as intracranial, gastrointestinal, retroperitoneal, 
pulmonary, pericardial, genitourinary, or other. 
Bleeding Academic Research Consortium (BARC) indicates fatal bleeding is meant to 
capture deaths that are directly due to bleeding with no other cause. The time interval from 
the bleeding event to the death should be considered with respect to likely causality, but 
there is no specific time limit proposed. Bleeding that is contributory but not directly causal 
to death is not classified as fatal bleeding but may be categorized as other forms of 
bleeding. Bleeding that leads to cessation of antithrombotic or other therapies may be 
contributory but again would not be classified as fatal bleeding. 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix N: Echo Acquisition Protocol 
The echo acquisition protocol will be provided under separate cover. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix O: Additional Definitions 
 
• Technical success: Exclusion of the LAA with no device-related complications and no 
leak >5mm on color Doppler TEE53 
 
• Procedural success: Technical success with no procedure-related complications, except 
for uncomplicated (minor) device embolization53 
 
• Device success: Device deployed and implanted in correct position53 
 
• Device-related complication: Adverse events which are adjudicated as device-related 
and require either an invasive surgical or percutaneous intervention. Examples of device-
related complications may include embolization requiring percutaneous/surgical 
intervention, pericardial effusion or cardiac tamponade requiring pericardiocentesis or 
surgery, device-related infection, etc. 
 
• Procedural complication: Adverse events which are adjudicated as procedure-related 
and require either an invasive surgical or percutaneous intervention. Examples of 
procedural complications may include embolization requiring percutaneous/surgical 
intervention, pericardial effusion or cardiac tamponade requiring pericardiocentesis or 
surgery, etc.  
• Major vascular complication: 54  
o Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, or 
new apical aneurysm/pseudo-aneurysm  
o Access site or access-related vascular injury (dissection, stenosis, perforation, 
rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve 
injury, compartment syndrome, percutaneous closure device failure) leading to 
death, life-threatening or major bleeding, visceral ischemia, or neurological 
impairment 
o Distal embolization (non-cerebral) from a vascular source requiring surgery or 
resulting in amputation or irreversible end-organ damage  
o The use of unplanned endovascular or surgical intervention associated with death, 
major bleeding, visceral ischemia or neurological impairment  
o Any new ipsilateral lower extremity ischemia documented by patient symptoms, 
physical exam, and/or decreased or absent blood flow on lower extremity 
angiogram  
o Surgery for access site-related nerve injury  
o Permanent access site-related nerve injury 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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• Stroke: 53 An acute episode of focal or global neurological dysfunction caused by brain, 
spinal cord, or retinal vascular injury as a result of hemorrhage or infarction. The event 
classifies as a stroke rather than a TIA based on any of the following: 
o Duration of neurological dysfunction >24 h[ours] 
o Duration of neurological dysfunction <24 h[ours] in case of imaging-documented 
new hemorrhage or infarction 
o A neurological dysfunction resulting in death 
 
• TIA: 53 Any neurological dysfunction not satisfying the above criteria for stroke, 
specifically if lasting ,24 hours without imaging-documented acute brain infarction 
 
• Systemic embolism: 53 Acute vascular insufficiency or occlusion of the extremities or 
any non-CNS 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. 
 
• AF classification55 
• Paroxysmal AF – AF that terminates spontaneously or with intervention within 7 days 
of onset. Episodes may recur with variable frequency. 
• Persistent AF – Continuous AF >7 days in duration 
• Permanent AF – AF that cannot be corrected. The term “permanent AF” is used when 
the patient and clinician make a joint decision to stop further attempts to restore and/or 
maintain sinus rhythm. Acceptance of AF represents a therapeutic attitude on the part 
of the patient and clinician rather than an inherent pathophysiological attribute of AF. 
Acceptance of AF may change as symptoms, efficacy of therapeutic interventions, and 
patient and clinician preferences evolve. 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: SJM-CIP-10114, Ver. C 
Redacted Document No: ABT-CIP-10431 
Study Name: AMPLATZER™ Amulet™ Left Atrial 
Appendage Occluder Randomized Controlled Trial 
 
SJM-CIP-10114 
Ver. C                                                                                                                        
 
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Appendix P: QVSFS 
 
The Questionnaire for Verifying Stroke-Free Status (QVSFS) will be provided under separate 
cover.