Continued Access to PREVAIL (CAP2)- WATCHMAN Left Atrial Appendage (LAA) Closure Technology
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Boston Scientific Corporation

THESE DOCUMENTS ARE THE PROPERTY OF BOSTON SCIENTIFIC CORP. AND SHALL NOT BE REPRODUCED, 
DISTRIBUTED, DISCLOSED OR USED FOR MANUFACTURE OR SALE OF APPARATUS WITHOUT THE EXPRESS WRITTEN 
CONSENT OF BOSTON SCIENTIFIC CORP. 
Boston Scientific 
CAP2 Protocol 
PDM 90884521 Rev AF 
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Continued Access to PREVAIL (CAP2) 
Clinical Protocol 
 
IDE #G020312 
 
Sponsored By 
Atritech, Inc (“Atritech”) 
A Subsidiary of Boston Scientific 
5905 Nathan Lane, P222 
Plymouth, MN 55442 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. It should be held 
confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 
 
 
 
 
 
 
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Contact Information 
Role 
Contact  
Clinical Contact 
Lynnett Voshage-Stahl 
Director, CRV Clinical  
Boston Scientific Corporation  
4100 Hamline Avenue North  
St. Paul, MN 55112-5798  
Tel: 651-582-2994  
lynnett.voshage-stahl@bsci.com 
 
Clinical Contributors 
Robert Shipley, Ph.D., Clinical Program Manager 
Priya Khanchandani, Clinical Scientist 
Coordinating Principal 
Investigator 
Dr. Saibal Kar 
Cedars Sinai Medical Center 
(310) 423-3977 
8631 West Third Street 
Room 415E 
Los Angeles, CA  90048 
karsk@cshs.org 
 
Dr. Shephal Doshi 
Pacific Heart 
(310)829-7678 
2001 Santa Monica Blvd Suite 280 West 
Santa Monica, CA  90404 
skdoshi@pacificheart.com 
 
Original Release: January 12, 2012 
Current Version: December 12, 2012 
 
Revision History 
Revision Number 
Release Date 
Section 
Change 
Reason for Change 
AA 
June 25, 2012 
N/A 
Migrating Atritech 
CAP2 Protocol into BSC 
Template 
Alignment with BSC 
Clinical System SOPs 
AB 
July 2, 2012 
11.6 
Update to active clotting 
time (ACT)  
To match ACT with that 
included in the clinical 
Directions for Use 
(DFU) 
AC 
July 18, 2012 
Section 2 and 
9.3  
Clarification to the 
Exclusion Criteria 
For clarification 
AD 
July 27, 2012 
Section 5 and 
Remove reference to 
Obturator will not be 
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Revision History 
Revision Number 
Release Date 
Section 
Change 
Reason for Change 
16 
obturator 
included in CAP2 
AE 
December 12, 
2012 
7 & 10 
 
Clarify AE collection for 
screened failures  
To address FDA requests 
AF 
TBD 
11 & 21 
Added NOAC caution 
and additional Stroke 
assessments 
To address DSMB 
feedback 
 
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2. Protocol Synopsis 
Continued Access to PREVAIL (CAP2) 
Objective(s) 
To provide additional information about the safety and efficacy of the 
WATCHMAN LAA Closure Technology. 
Marketing 
Performance 
Expectation  
The WATCHMAN LAA Closure Technology is intended as an 
alternative to warfarin therapy for patients with non-valvular atrial 
fibrillation. The WATCHMAN LAA Closure Technology is designed to 
prevent embolization of thrombi that may form in the LAA, thereby 
preventing the occurrence of ischemic stroke and systemic 
thromboembolism. 
Test Device 
WATCHMAN LAA Closure Technology 
Device Sizes 
21mm, 24mm, 27mm, 30mm, 33mm 
Study Design 
This is a prospective, non-randomized, multicenter study. 
Planned 
Number of 
Subjects 
Initial cohort of 300 subjects, up to a maximum of 1500 subjects. 
Planned 
Number of 
Centers / 
Countries 
60 
Primary 
Endpoint 
Descriptive statistics will be used for baseline, procedure and follow-up 
data collected through the study. 
Follow-up 
Schedule 
Subjects will be followed at intervals of 45 days, 6 months, 12 months, 
semi-annually through 3 years, and thereafter annually through 5 years 
post enrollment. 
Study Duration 
Subjects will be followed through 5 years post enrollment. It is 
anticipated that enrollment will be conducted over a period of two years. 
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Continued Access to PREVAIL (CAP2) 
Required 
Medication 
Therapy 
Warfarin, aspirin, clopidogrel, heparin, antibiotics, as applicable and 
outlined within the protocol 
 
Key Inclusion 
Criteria 
A subject may be enrolled in the study if all of the following inclusion 
criteria are met:  
1. The subject is 18 years of age or older  
2. The subject has documented paroxysmal, persistent, or permanent 
non-valvular atrial fibrillation (i.e., the subject has not been 
diagnosed with rheumatic mitral valvular heart disease)  
3. The subject is eligible for long-term warfarin therapy  
4. The subject has a calculated CHADS2 score of 2 or greater; 
Subjects with a CHADS2 score of 1 may be included if any of 
the following apply (according to the ACC/AHA/ESC 2006 
Guidelines for the Management of Subjects with Atrial 
Fibrillation subjects requiring warfarin therapy) : 
• 
The subject is a female age 75 or older 
• 
The subject has a baseline Left Ventricular Ejection 
Fraction (LVEF) > 30% and < 35% 
• 
The subject is age 65-74 and has diabetes or coronary 
artery disease 
• 
The subject is age 65 or greater and has documented 
congestive heart failure 
5. The subject or legal representative is able to understand and 
willing to provide written informed consent to participate in the 
trial 
6. The subject is able and willing to return for required follow-up 
visits and examinations 
Key Exclusion 
Criteria 
Subjects will be excluded from the study if they meet any of the 
following criteria: 
1. The subject requires long-term warfarin therapy (i.e., even if 
the device is implanted, the subjects would not be eligible to 
discontinue warfarin due to other medical conditions requiring 
chronic warfarin therapy). Additionally, a subject with any of 
the following is excluded: 
• Thrombosis occurring at a young age (<40 years old) 
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Continued Access to PREVAIL (CAP2) 
• Idiopathic or recurrent venous thromboembolism 
• Thrombosis at an unusual site (i.e., cerebral veins, 
hepatic veins, renal veins, inferior vena cava, 
mesenteric veins) 
• Family history of venous thromboembolism or of 
inherited prothrombotic disorder 
• Recurrence or extension of thrombosis while 
adequately anticoagulated 
2. The subject is contraindicated for warfarin therapy or cannot 
tolerate long-term warfarin therapy 
3. The subject is contraindicated or allergic to aspirin 
4. The subject is indicated for antiplatelet therapy other than 
aspirin (for example, a subject indicated for clopidogrel, 
prasugrel, ticlopidine or ticagrelor due to DES is excluded 
from enrollment during the dosing regimen).  A subject 
completing a course of antiplatelet therapy may be enrolled 
after a 7 day washout period  
5. The subject had any interventional or surgical procedure 
within 30 days prior to enrollment or is planning to have an 
interventional or surgical procedure in the time between the 
WATCHMAN device implant and 45-day TEE (e.g., 
cardioversion, ablation, cataract surgery, dental surgery)  
6. The subject had a prior stroke or TIA within the 90 days prior 
to enrollment 
7. The subject has had an MI within 90 days prior to enrollment 
8. The subject has a history of atrial septal repair or has an 
ASD/PFO device 
9. The subject has an implanted mechanical valve prosthesis 
10. The subject suffers from New York Heart Association Class 
IV Congestive Heart Failure at the time of enrollment 
11. The subject has 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 
12. The subject’s AF is defined by a single occurrence of AF  
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Continued Access to PREVAIL (CAP2) 
13. The subject had a transient case of AF (i.e., secondary to 
CABG, interventional procedure, etc.) 
14. The subject’s left atrial appendage is obliterated 
15. The subject has undergone heart transplantation 
16. The subject is currently treated with antibiotics for an active 
infection   
17. The subject has a resting heart rate > 110 bpm 
18. The subject has thrombocytopenia (defined as < 70,000 
platelets/mm3) or anemia with hemoglobin concentration of < 
10 g/dl (i.e., anemia as determined by the investigator which 
would require transfusion) 
19. The subject is actively enrolled in a concurrent clinical study 
of an investigational drug or investigational device (study 
specifics may be reviewed with the sponsor prior to 
enrollment to confirm a concurrent study will not interfere 
with the outcomes of this study)   
20. The subject participated in any of the following studies: 
PROTECT AF, CAP Registry, or PREVAIL.  If the subject 
received a subject ID number for a prior WATCHMAN study, 
the subject may not be enrolled. PROTECT AF control 
subjects may be considered for participation if they have 
completed 5 year follow up 
21. The subject is pregnant or pregnancy is planned during the 
course of the investigation  
22. The subject has a life expectancy of less than two years 
23. The subject is unable to complete follow-up visits for the 
duration of the study 
 
Echo Exclusion Criteria 
A subject is excluded from the study if any of the following 
echocardiographic exclusion criteria (as assessed via TTE and TEE) are 
met: 
1. The subject has LVEF < 30% 
2. The subject has intracardiac thrombus or dense spontaneous 
echo contrast as visualized by TEE and determined by the 
echocardiographer within 2 days prior to implant 
3. The subject has an existing pericardial effusion > 2mm 
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Continued Access to PREVAIL (CAP2) 
4. The subject has a high risk patent foramen ovale (PFO) with 
an atrial septal aneurysm excursion > 15mm or length > 15mm 
5. The subject has a high risk PFO with a large shunt defined as 
early, within 3 beats or substantial passage of bubbles 
6. The subject has significant mitral valve stenosis (i.e., MV <1.5 
cm2) 
7. The subject has complex atheroma with mobile plaque of the 
descending aorta or aortic arch 
8. The subject has a cardiac tumor 
Statistical Methods 
Primary 
Statistical 
Hypothesis 
Descriptive statistics will be used for baseline, procedure and follow-up 
data collected through the study. Analyses may include, but will not be 
limited to, the following: procedural success, procedural complications, 
and incidence of stroke leading to significant disability/death 
Statistical Test 
Method 
No formal pre-specified hypotheses will be tested.  
Sample Size 
Parameters 
A sample size of up to 1500 subjects was chosen to assess incidence of 
rare events with a large degree of precision.  The table below provides the 
two-sided 95% confidence interval width assuming an event rate of 5%. 
Sample Size 
95% CI Width 
1000 
2.8% 
1250 
2.5% 
1500 
2.3% 
 
 
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3. Table of Contents 
1. 
TITLE PAGE  ........................................................................................................................ 1 
2. 
PROTOCOL SYNOPSIS .......................................................................................................... 4 
3. 
TABLE OF CONTENTS .......................................................................................................... 9 
3.1. Table of Figures ...................................................................................................... 13 
3.2. Table of Tables ....................................................................................................... 13 
4. 
INTRODUCTION ................................................................................................................. 14 
i) 
Background ............................................................................................................. 14 
ii) 
WATCHMAN Therapy ......................................................................................... 14 
iii) 
WATCHMAN Clinical Study Experience ........................................................... 14 
5. 
DEVICE DESCRIPTION ....................................................................................................... 15 
i) 
WATCHMAN Delivery System ............................................................................ 16 
ii) 
WATCHMAN Access Sheath ............................................................................... 16 
6. 
OBJECTIVES ...................................................................................................................... 16 
7. 
ENDPOINT ANALYSIS ........................................................................................................ 17 
8. 
DESIGN .............................................................................................................................. 17 
8.1. Scale and Duration ................................................................................................. 17 
8.2. Implant Procedure Training ................................................................................. 17 
8.3. Treatment Assignment .......................................................................................... 18 
8.4. Justification for the Study Design ......................................................................... 18 
9. 
SUBJECT SELECTION ......................................................................................................... 18 
9.1. Study Population and Eligibility ........................................................................... 18 
9.2. Inclusion Criteria ................................................................................................... 19 
9.3. Exclusion Criteria .................................................................................................. 20 
10. SUBJECT ACCOUNTABILITY .............................................................................................. 21 
10.1. Enrollment .............................................................................................................. 21 
10.2. Withdrawal ............................................................................................................. 23 
10.3. Subject Status and Classification .......................................................................... 23 
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11. STUDY METHODS .............................................................................................................. 23 
11.1. Data Collection ....................................................................................................... 23 
11.2. Stroke Assessments ................................................................................................ 24 
11.3. Imaging Requirements .......................................................................................... 24 
i) 
Transthoracic Echocardiogram (TTE) ................................................................ 24 
ii) 
Transesophageal Echocardiogram (TEE)............................................................ 24 
11.4. Study Candidate Baseline Screening .................................................................... 27 
11.5. Informed Consent .................................................................................................. 27 
11.6. Implant Procedure ................................................................................................. 28 
i) 
Thrombus Assessment Prior to Implant .............................................................. 28 
ii) 
Implant of the WATCHMAN Device ................................................................... 28 
iii) 
Prior to Device Release .......................................................................................... 29 
iv) 
Unsuccessful Implant Attempt .............................................................................. 29 
11.7. Medication Regimen for the Study ....................................................................... 29 
i) 
Discharge Through 45-Day TEE .......................................................................... 29 
ii) 
45-Day TEE ............................................................................................................ 29 
iii) 
6 Month Visit .......................................................................................................... 30 
11.8. Follow-up Procedures ............................................................................................ 31 
i) 
INR Monitoring ...................................................................................................... 32 
ii) 
45-Day Office Visit ................................................................................................. 32 
iii) 
6 Month Visit .......................................................................................................... 33 
iv) 
12 Month Office Visit ............................................................................................. 33 
v) 
Additional Telephone Visits-18 Months and 30 Months .................................... 34 
vi) 
Annual Visits-2,3,4,5 Years ................................................................................... 34 
11.9. Study Completion ................................................................................................... 34 
12. STATISTICAL CONSIDERATIONS ....................................................................................... 34 
12.1. Sample Size Justification ....................................................................................... 34 
12.2. Statistical Analysis ................................................................................................. 35 
13. DATA MANAGEMENT ........................................................................................................ 35 
13.1. Data Collection, Processing, and Review ............................................................. 35 
13.2. Data Retention ........................................................................................................ 36 
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14. AMENDMENTS ................................................................................................................... 36 
15. DEVIATIONS ...................................................................................................................... 36 
16. DEVICE/EQUIPMENT ACCOUNTABILITY .......................................................................... 36 
17. COMPLIANCE ..................................................................................................................... 37 
17.1. Statement of Compliance ....................................................................................... 37 
17.2. Selection of Investigators ....................................................................................... 37 
17.2.1. Delegation of Responsibility ..................................................................... 37 
17.2.2. Investigator Records .................................................................................. 37 
17.2.3. Investigator Reports ................................................................................... 38 
17.3. Institutional Review Board/ Ethics Committee ................................................... 38 
17.4. Sponsor Responsibilities ........................................................................................ 39 
17.4.1. Role of Boston Scientific Representatives ................................................ 39 
17.4.2. Sponsor Records ........................................................................................ 40 
17.4.3. Sponsor Reports ......................................................................................... 40 
17.5. Insurance ................................................................................................................. 41 
18. MONITORING ..................................................................................................................... 41 
19. POTENTIAL RISKS AND BENEFITS .................................................................................... 41 
19.1. Risks Associated with the WATCHMAN Implant & Procedure ...................... 41 
19.2. Possible Interactions with Concomitant Medical Treatments ........................... 43 
19.3. Risk Minimization Actions .................................................................................... 44 
19.4. Anticipated Benefits ............................................................................................... 44 
20. INFORMED CONSENT ......................................................................................................... 44 
21. SAFETY REPORTING .......................................................................................................... 45 
21.1. Adverse Event Reporting ...................................................................................... 45 
i) 
Adverse Event Definitions ..................................................................................... 46 
21.2. Stroke Reporting .................................................................................................... 47 
21.3. Device Thrombus ................................................................................................... 48 
21.4. Boston Scientific Device Deficiencies .................................................................... 48 
21.5. Reporting to Regulatory Authorities / IRBs / ECs / Investigators .................... 48 
22. COMMITTEES .................................................................................................................... 48 
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22.1. Safety Monitoring Process ..................................................................................... 48 
22.2. Clinical Events Committee .................................................................................... 49 
22.3. Data and Safety Monitoring Board ...................................................................... 49 
23. SUSPENSION OR TERMINATION ......................................................................................... 49 
23.1 Publication Policy ................................................................................................... 49 
24. BIBLIOGRAPHY .................................................................................................................. 50 
25. DEFINITIONS ...................................................................................................................... 52 
 
 
 
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3.1. 
Table of Figures 
Figure 5-1 WATCHMAN Device .......................................................................................... 16 
Figure 10.1-1 Subject Enrollment Overview .......................................................................... 22 
 
3.2. 
Table of Tables 
Table 4-1 U.S. Clinical Studies of the WATCHMAN Device ............................................... 15 
Table 11.3-1 Data Collection Overview ................................................................................. 26 
Table 11.7-1 Medication Regimen Post Implant .................................................................... 31 
Table 11.8-1 Visit Windows ................................................................................................... 31 
Table 12.1-1 Two-Sided Confidence Interval by Sample Size ............................................... 35 
Table 17.2.3-1 Required Investigator Reports ........................................................................ 38 
Table 17.4.3-1 Required Sponsor Reports .............................................................................. 40 
Table 25-1 Definitions ............................................................................................................ 52 
 
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4. Introduction 
i) Background 
Atrial fibrillation (AF) is one of the most common abnormal rhythm disturbances and affects 
approximately 5.5 million people worldwide, including 10% of people older than 75 years.1 
The most debilitating consequence of AF is thrombus formation from stagnant blood flow 
leading to thromboembolism and stroke.  As such, the rate of ischemic stroke attributed to 
non-valvular AF is estimated to average 5% per year which is 2-7 times that of those without 
AF2. 
Treatment with warfarin therapy for the prevention of thromboemboli originating in the left 
atrial appendage has been well documented.3,4,5 Warfarin therapy targeting an International 
Normalized Ratio (INR) between 2.0 – 3.0 is considered the gold standard treatment today 
for patients with non-valvular AF for prevention of stroke.  While warfarin has remained the 
optimum treatment for many years, there are numerous challenges with the drug, such as 
frequent need for monitoring and dosage adjustments, dietary and metabolic interactions, and 
concerns of patient compliance.  Additionally, the potential for frequent and fatal bleeding 
are high concerns for patients and caregivers and often times it is found this drug is not well 
tolerated.  
As the risk of stroke increases with age and the disability and tolerance concerns with 
available drug therapy persist, the need for permanent protection against thromboembolism 
in AF patients remains unmet.  The sponsor has been investigating the use of a permanent 
implantable device to seal off the left atrial appendage, the location where the vast majority 
of thrombi originates in AF patients.  This device may provide an alternative to warfarin 
therapy in non-valvular AF patients who require thromboembolic protection.  
ii) WATCHMAN Therapy 
The WATCHMAN® Left Atrial Appendage Closure Technology is intended for patients with 
non-valvular atrial fibrillation who require treatment for potential thrombus formation and 
are eligible for warfarin therapy. 
The implanted component of the system, hereafter referred to as the WATCHMAN device, is 
a novel device designed to prevent the embolization of thrombi that may form in the left 
atrial appendage (LAA).  The WATCHMAN device may prevent the occurrence of ischemic 
stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation (AF) 
who require treatment for potential thrombus formation.  It may also reduce the risk of life-
threatening bleeding events such as hemorrhagic stroke as seen in patients on warfarin 
therapy.  The WATCHMAN is manufactured by Atritech, a subsidiary of Boston Scientific, 
received CE Mark in October 2005 and is under IDE in the United States (U.S.).   
iii) WATCHMAN Clinical Study Experience 
Clinical evaluation of the WATCHMAN LAA Closure Technology has been ongoing since 
2002, with all U.S. studies conducted under IDE #G020312. Table 4-1 lists the clinical 
studies conducted in the U.S. with the WATCHMAN device.  The pivotal study, PROTECT 
AF, demonstrated non-inferiority of the WATCHMAN device to long-term warfarin therapy 
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for the primary efficacy endpoint of stroke, systemic embolism and cardiovascular death.  
The Pre-Market Application (PMA) was therefore submitted to FDA in August 2008.  The 
FDA requested that a second pivotal study be conducted to confirm the results of the 
PROTECT AF study.  The second pivotal study, PREVAIL, was conducted to provide 
additional information on the implant procedure and complication rates associated with the 
device.  When available, the results from the PREVAIL study will be submitted to FDA in a 
Pre-Market Application for consideration of commercial approval of the WATCHMAN 
device in the U.S.  This continued access study will permit availability of the device to 
investigators and subjects during the preparation and FDA review of the Pre-Market 
Application.  
Table 4-1 U.S. Clinical Studies of the WATCHMAN Device 
Study 
Dates of Enrollment 
Enrolled 
Subjects 
Sites 
Follow-Up 
Pilot  
(feasibility study) 
Aug 2002 – Jan 2005 
66 
8 
U.S. subjects completed 5 
years; OUS subjects ongoing 
PROTECT AF  
(pivotal study) 
Feb 2005 – Jun 2008 
800 
59 
Ongoing through 5 years 
CAP Registry 
Aug 2008 – Jun 2010 
566 
26 
Ongoing through 5 years 
PREVAIL  
(pivotal study) 
Nov 2010 – Ongoing at time 
of protocol development 
Up to 475 
Up to 50 
Ongoing through 5 years 
5. Device Description 
The WATCHMAN device is designed to be permanently implanted at or slightly distal to the 
ostium (opening) of the LAA to prevent embolization of blood clots formed within the 
trabeculated LAA.  The placement procedure can be performed under general or conscious 
sedation in a catheterization or electrophysiology (EP) laboratory setting using standard 
trans-septal technique under fluoroscopic and echocardiographic guidance.  
The WATCHMAN LAA Closure Technology is a three-component system which includes 
the WATCHMAN LAA Closure Device (WATCHMAN device), the WATCHMAN 
Delivery System and the WATCHMAN Access Sheath.  
i) WATCHMAN Device 
The WATCHMAN device is comprised of a self-expanding nitinol frame structure with 
fixation barbs around the device perimeter and a permeable polyester fabric that covers the 
atrial facing surface of the device (Figure 5-1).  The device is constrained within the 
Delivery System until deployment into the LAA.  
The WATCHMAN device is available in various sizes to accommodate a range of LAA 
ostial diameters.  The device size, measured in mm, is the diameter of the device at its 
maximum dimension in an uncompressed (fully expanded) state.  An appropriate device size 
is selected based on LAA measurements obtained utilizing Fluoroscopy and Transesophageal 
Echocardiography (TEE). 
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Figure 5-1 WATCHMAN Device 
 
ii) WATCHMAN Delivery System 
The delivery catheter consists of an inner core wire with a reinforced braided jacket that is 
connected to the deployment knob at the proximal end and a screw thread assembly at the 
distal end.  The outer sheath has an overall profile of 12F.  
The WATCHMAN device is pre-loaded and is deployed by loosening the valve on the 
Delivery System and retracting the outer sheath.  The WATCHMAN device can be partially 
recaptured and redeployed if the device is too distal.  If the device is deployed too proximal, 
it can be fully recaptured. The device is released by rotating the device deployment knob 
counter clockwise. 
iii) WATCHMAN Access Sheath 
The 14F transseptal Access Sheath is utilized to gain access to the LAA and serves as a 
conduit for the Delivery System.  The distal end of the Access Sheath is available in various 
curve styles to assist with placement of the sheath into the LAA.  Various curve styles allow 
for coaxial placement of the sheath into the LAA.  The distal tip contains a marker band for 
in situ visualization as well as sizing marker bands used to gauge if the Access Sheath is 
positioned at the appropriate depth in the LAA based on the device size selected.   
The Access Sheath and dilator are utilized to gain access to the LAA after initial transseptal 
access into the left atrium has been established.  Once the Access Sheath is positioned into 
the left atrium and the dilator has been removed, it then serves as a conduit for the Delivery 
System.  The Delivery System is introduced into the Access Sheath and the components snap 
together to act as one during device implantation.   
6. Objectives 
This Continued Access Protocol is a prospective, non-randomized, multicenter study to allow 
continued access to the WATCHMAN LAA Closure Technology during the data analysis, 
reporting and review of the PREVAIL pivotal study Pre-Market Application by FDA.   
Subjects with non-valvular AF who require treatment for potential thrombus formation, and 
are eligible for warfarin therapy, will be screened to participate in the study.  Subjects will be 
screened via review of medical history, transthoracic echocardiography (TTE) and TEE 
testing.  Once study eligibility is determined, subjects will be enrolled and implanted with the 
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WATCHMAN device.  After implant, subjects will receive warfarin therapy until TEE 
imaging has confirmed adequate sealing of the LAA.  Successfully implanted subjects will be 
followed post enrollment for assessment of adverse events at intervals of 45 days, 6 months, 
12 months, semi-annually through 3 years, and thereafter annually through 5 years.  
7. Endpoint Analysis 
Descriptive statistics will be used for baseline, procedure and follow-up data collected 
through the study. Analyses may include, but will not be limited to, the following: procedural 
success, procedural complications, and incidence of stroke leading to significant 
disability/death. Any adverse events associated with screened failures who have diagnostic 
testing to assess eligibility for the device or for device implantation, or who have medication 
changes in preparation for device implantation will be included in the analyses. 
8. Design 
This is a prospective, non-randomized, multicenter study to provide additional information 
about the safety and efficacy of the WATCHMAN LAA Closure Technology.  
This study will be conducted at up to 60 investigational sites in the U.S. and enroll an initial 
cohort of up to 300 subjects.  Incremental enrollment increases may be requested during the 
study to reach a maximum of 1500 subjects.  FDA approval will be obtained prior to 
proceeding with the next cohort of subjects.  Additionally, enrollment may terminate early if 
the device is approved for commercial use or when the PMA review is complete.  The 60 
sites will include those physicians with prior WATCHMAN experience demonstrated in the 
PREVAIL or PROTECT AF pivotal studies. 
8.1. 
Scale and Duration 
Subjects will be followed at intervals of 45 days, 6 months, 12 months, semi-annually 
through 3 years, and thereafter annually through 5 years post enrollment.   
It is anticipated that enrollment will be conducted over a period of two years.   
8.2. 
Implant Procedure Training 
Investigators in the study will be those exhibiting proficiency in the trans-septal approach 
into the left atrium. Investigators with prior WATCHMAN implant experience in the 
PROTECT AF or PREVAIL studies will not be required to repeat operator training for this 
continued access study. 
New operators must complete the WATCHMAN training program.  Operator training 
includes the following elements: 
• On-line pre-study examination 
• Interactive on-line WATCHMAN case studies 
• Case observations with an experienced WATCHMAN implanting physician 
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• Hands-on training for implanting physicians and lab staff on the WATCHMAN 
implant procedure from preparation to implantation and follow-up 
8.3. 
Treatment Assignment 
Not Applicable 
8.4. 
Justification for the Study Design 
Clinical evaluation of the WATCHMAN LAA Closure Technology has been ongoing since 
2002, with all U.S. studies conducted under IDE #G020312. The pivotal study, PROTECT 
AF, demonstrated non-inferiority of the WATCHMAN device to long-term warfarin therapy 
for the primary efficacy endpoint of stroke, systemic embolism and cardiovascular death.  
The Pre-Market Application (PMA) was therefore submitted to FDA in August 2008.  The 
FDA requested that a second pivotal study be conducted to confirm the results of the 
PROTECT AF study.  The second pivotal study, PREVAIL, was conducted to provide 
additional information on the implant procedure and complication rates associated with the 
device.  When available, the results from the PREVAIL study will be submitted to FDA in a 
Pre-Market Application for consideration of commercial approval of the WATCHMAN 
device in the U.S.  This continued access study will permit availability of the device to 
investigators and subjects during the preparation and FDA review of the Pre-Market 
Application. 
9. Subject Selection  
9.1. 
Study Population and Eligibility  
The eligibility criteria for this continued access study are the same as the PREVAIL pivotal 
study.  All subjects who present with non-valvular AF and are eligible for warfarin therapy 
will be considered for inclusion into the study.  Those subjects who fulfill the inclusion 
criteria, do not meet any of the exclusion criteria, and provide written consent will be invited 
to participate.  Qualified subjects will undergo TTE and TEE testing to further determine 
eligibility for the study.  Only subjects meeting all criteria will be enrolled.   
CHADS2 Eligibility Criteria 
The CHADS2 score will be calculated for potential subjects as a basis for inclusion into the 
study.  Subjects with a CHADS2 score of 2 or greater are permitted in the study as well as 
some subjects with a CHADS2 score of 1 as described in the Inclusion Criteria. The CHADS2 
score is calculated using the following stroke risk factors: 
• 
1 point is assigned for documented congestive heart failure (defined as having 
recent heart failure-related symptoms, within the previous 100 days, and the 
presence of moderate or severe left ventricle systolic dysfunction on 
echocardiography) 
• 
1 point is assigned for documented hypertension (systolic > 160 mmHg or 
well-controlled by anti-hypertensive medication)  
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• 
1 point is assigned for subject age of 75 years or older  
• 
1 point is assigned for diabetes  
• 
2 points are assigned for prior cerebral ischemic stroke or Transient Ischemic 
Attack (TIA) 
9.2. 
Inclusion Criteria 
A subject may be enrolled in the study if all of the following inclusion criteria are met:  
1. 
The subject is 18 years of age or older  
2. 
The subject has documented paroxysmal, persistent, or permanent non-valvular 
atrial fibrillation (i.e., the subject has not been diagnosed with rheumatic mitral 
valvular heart disease)  
3. 
The subject is eligible for long-term warfarin therapy  
4. 
The subject has a calculated CHADS2 score of 2 or greater; Subjects with a 
CHADS2 score of 1 may be included if any of the following apply (according to 
the ACC/AHA/ESC 2006 Guidelines for the Management of Subjects with Atrial 
Fibrillation subjects requiring warfarin therapy) : 
• 
The subject is a female age 75 or older 
• 
The subject has a baseline Left Ventricular Ejection Fraction (LVEF) > 
30% and < 35% 
• 
The subject is age 65-74 and has diabetes or coronary artery disease 
• 
The subject is age 65 or greater and has documented congestive heart 
failure 
5. The subject or legal representative is able to understand and willing to provide 
written informed consent to participate in the trial 
6. The subject is able and willing to return for required follow-up visits and 
examinations 
 
 
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9.3. 
Exclusion Criteria 
Subjects will be excluded from the study if they meet any of the following criteria: 
1. The subject requires long-term warfarin therapy (i.e., even if the device is 
implanted, the subjects would not be eligible to discontinue warfarin due to other 
medical conditions requiring chronic warfarin therapy). Additionally, a subject 
with any of the following is excluded: 
• Thrombosis occurring at a young age (<40 years old) 
• Idiopathic or recurrent venous thromboembolism 
• Thrombosis at an unusual site (i.e., cerebral veins, hepatic veins, renal 
veins, inferior vena cava, mesenteric veins) 
• Family history of venous thromboembolism or of inherited prothrombotic 
disorder 
• Recurrence or extension of thrombosis while adequately anticoagulated 
2. The subject is contraindicated for warfarin therapy or cannot tolerate long-term 
warfarin therapy 
3. The subject is contraindicated or allergic to aspirin 
4. The subject is indicated for antiplatelet therapy other than aspirin (for example, a 
subject indicated for clopidogrel, prasugrel, ticlopidine or ticagrelor due to DES is 
excluded from enrollment during the dosing regimen).  A subject completing a 
course of antiplatelet therapy may be enrolled after a 7 day washout period  
5. The subject had any interventional or surgical procedure within 30 days prior to 
enrollment or is planning to have an interventional or surgical procedure in the 
time between the WATCHMAN device implant and 45-day TEE (e.g., 
cardioversion, ablation, cataract surgery, dental surgery)  
6. The subject had a prior stroke or TIA within the 90 days prior to enrollment 
7. The subject has had an MI within 90 days prior to enrollment 
8. The subject has a history of atrial septal repair or has an ASD/PFO device 
9. The subject has an implanted mechanical valve prosthesis 
10. The subject suffers from New York Heart Association Class IV Congestive Heart 
Failure at the time of enrollment 
11. The subject has 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 
12. The subject’s AF is defined by a single occurrence of AF  
13. The subject had a transient case of AF (i.e., secondary to CABG, interventional 
procedure, etc.) 
14. The subject’s left atrial appendage is obliterated 
15. The subject has undergone heart transplantation 
16. The subject is currently treated with antibiotics for an active infection   
17. The subject has a resting heart rate > 110 bpm 
18. The subject has thrombocytopenia (defined as < 70,000 platelets/mm3) or anemia 
with hemoglobin concentration of < 10 g/dl (i.e., anemia as determined by the 
investigator which would require transfusion) 
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19. The subject is actively enrolled in a concurrent clinical study of an investigational 
drug or investigational device (study specifics may be reviewed with the sponsor 
prior to enrollment to confirm a concurrent study will not interfere with the 
outcomes of this study)   
20. The subject participated in any of the following studies: PROTECT AF, CAP 
Registry, or PREVAIL.  If the subject received a subject ID number for a prior 
WATCHMAN study, the subject may not be enrolled. PROTECT AF control 
subjects may be considered for participation if they have completed 5 year follow 
up 
21. The subject is pregnant or pregnancy is planned during the course of the 
investigation  
22. The subject has a life expectancy of less than two years 
23. The subject is unable to complete follow-up visits for the duration of the study 
Echo Exclusion Criteria 
A subject is excluded from the study if any of the following echocardiographic exclusion 
criteria (as assessed via TTE and TEE) are met: 
1. The subject has LVEF < 30% 
2. The subject has intracardiac thrombus or dense spontaneous echo contrast as 
visualized by TEE and determined by the echocardiographer within 2 days prior 
to implant 
3. The subject has an existing pericardial effusion > 2mm 
4. The subject has a high risk patent foramen ovale (PFO) with an atrial septal 
aneurysm excursion > 15mm or length > 15mm 
5. The subject has a high risk PFO with a large shunt defined as early, within 3 beats 
or substantial passage of bubbles 
6. The subject has significant mitral valve stenosis (i.e., MV <1.5 cm2) 
7. The subject has complex atheroma with mobile plaque of the descending aorta or 
aortic arch 
8. The subject has a cardiac tumor 
10. Subject Accountability 
10.1. Enrollment 
All adult subjects with non-valvular AF who require treatment for potential thrombus 
formation and are eligible for warfarin therapy shall initially be screened as candidates for 
the study.  Subjects receiving dabigatran or rivaroxaban prior to enrollment may be 
considered for inclusion in the study however they will be required to be treated with 
warfarin post-WATCHMAN implant. Those subjects who provide consent and meet the 
Inclusion and Clinical Exclusion Criteria will undergo an echocardiographic examination 
(TTE and TEE) to further evaluate Echo Exclusion Criteria.   
If the baseline TEE confirms the presence of any intracardiac thrombus, the subject cannot be 
enrolled in the study.  The subject may be treated with anticoagulation therapy and, after an 
appropriate period of time, return for another baseline TEE to assess evidence of intracardiac 
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thrombus and other baseline criteria.  Only when the thrombus has completely resolved is the 
subject eligible for study enrollment. 
Once a subject meets all of the entrance criteria he/she is considered enrolled at the time of 
venous access for the implant procedure and must be implanted within 2 calendar days of the 
baseline TEE. 
Figure 10.1-2 Subject Enrollment Overview 
 
Inclusion/Exclusion criteria NOT met.  
(Screen Failure) 
Inclusion/Exclusion criteria met 
Echocardiographic 
exclusion criteria 
assessed 
Baseline TTE and 
TEE  
All criteria met 
Criteria NOT met- Screen 
Failure (AEs associated with 
diagnostic testing to assess 
eligibility for the device or for 
device implantation, or 
medication changes in 
preparation for device 
implantation will be followed 
for 45 days from AE onset or 
until the AE is resolved. 
 
Anticoagulation 
therapy for thrombus 
treatment; repeat all 
required baseline 
testing and TEE. 
Patient does not 
qualify for study 
Enrollment 
Implant must occur within 2 
calendar days of baseline 
TEE 
Potential patient; Informed consent obtained 
Thrombus 
on TEE 
 Device Not 
Implanted 
Follow through 45-
day visit and/or until 
any AEs resolve 
Device Implanted 
Follow per schedule 
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10.2. Withdrawal 
Every effort should be made to retain subject enrollment for the duration of the study.  
During the informed consent process subjects should be fully informed of the risks and 
should only be enrolled if willing to fully participate in the study.  In the event a subject does 
decide to withdraw from the study, every effort should be made to obtain full information on 
any ongoing adverse events.  Subjects will be given the following withdrawal options: 
1) Telephone contact to complete some or all of the visit requirements that can be completed 
over the phone including adverse event reporting 
2) Telephone contact for adverse event reporting only 
3) No contact 
Subjects should only be considered lost to follow-up after significant effort has been made to 
contact the subject.  At a minimum there should be 3 documented telephone contact attempts 
and one certified letter sent to the subject’s last known residence. 
Subjects with unsuccessful implant attempts should be followed through the 45-day visit for 
any adverse events or followed through the resolution of existing adverse events, whichever 
is later, and then be withdrawn from the study. 
Subject withdrawal and lost to follow-up will be documented on the End of Study case report 
form.  
10.3. Subject Status and Classification 
• Consent Ineligible/Screen Failure: A subject who has signed the informed consent but 
is found to not meet the eligibility criteria, and does not undergo an implant.  
• Unsuccessful Implant Attempt: A subject who meets all the eligibility criteria, is 
considered enrolled at the time of venous access at the beginning of an implant 
attempt but does not receive an implant. If the device is not successfully implanted, 
the post procedure medication regimen will be administered per physician 
discretion.  The subject will be followed in the study through the 45-day follow-up 
visit or through resolution of any peri-procedural adverse events, whichever is later.   
• Implant: A subject who receives an implant. 
11. Study Methods 
11.1. Data Collection 
To ensure data quality and completeness, all required data will be recorded on case report 
forms (CRFs) provided by the sponsor.  Data will be entered onto electronic case report 
forms by the investigational site or designee.  Case Report Forms should be completed 
accurately and completely during and in a timely manner after any visit in the study.  The 
Principal Investigator or appointed designee must review the case report forms and sign them 
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certifying their accuracy.  Completed case report forms are to be submitted to the sponsor 
within two weeks of completion of a study visit. 
11.2. Stroke Assessments 
Three stroke assessment scales will be routinely collected at baseline and follow-up visits for 
all subjects.  These scales include the following: 
• National Institutes of Health Stroke Scale (NIHSS):  The NIHSS is an assessment 
tool which quantifies stroke related neurological deficit.  This assessment must be 
conducted in person to provide valuable information on stroke severity.  This test will 
be performed at baseline and at all office visits. It must be conducted by a neurologist 
or personnel who have a current certification to conduct the NIHSS.  
• Modified Rankin Scale (MRS): This scale assesses the severity of stroke disability 
and functional dependence of subjects. This test will be collected at baseline and all 
office and telephone follow-up visits.  The assessment must be performed by either a 
neurologist or personnel who have completed a certification for the MRS.    
• Barthel Index:  The Barthel Index quantifies a subject’s ability to perform typical 
daily functions.  This test will be collected at baseline and all office and telephone 
follow-up visits. 
11.3. Imaging Requirements 
All subjects will undergo a baseline TEE and TTE and follow-up TEE at the 45-day visit and 
12 month visits. All study required TEEs will be performed in accordance with the Imaging 
Manual. 
Copies of all protocol required TEE imaging will be saved to disk and available to the 
sponsor upon request.  Certain information from TEEs conducted during the course of the 
study, including any non-protocol required TEEs, will be captured on the study case report 
forms.  A copy of the baseline TTE imaging will be saved to disk and available to the 
sponsor upon request.   The site and subject identification number along with the subject 
initials should be clearly identified on the disks. 
i) 
Transthoracic Echocardiogram (TTE) 
All TTEs will be conducted according to the Imaging Manual.  The baseline TTE will be 
done to evaluate LVEF to confirm subject eligibility.  An LVEF value obtained from a TTE 
performed within 60 days prior to enrollment may be used.  If a significant cardiac event 
occurs after the TTE which causes a change in cardiac status [i.e., major Congestive Heart 
Failure (CHF) decompensation] the baseline TTE should be repeated prior to enrollment. 
ii) 
Transesophageal Echocardiogram (TEE) 
All TEEs will be conducted according to the Imaging Manual.  The implant TEE will allow 
the investigator to obtain proper measurements of the LAA to correctly size the device, 
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confirm device release criteria are met prior to device release, and to confirm adverse events 
have not occurred during the implant procedure (i.e., pericardial effusion). 
The 45-day and 12-month TEEs are conducted to assess flow through and around the 
WATCHMAN device and to verify there is no thrombus on the surface of the device.  As 
required by protocol, some subjects may also have a 6-month TEE if the 45-day TEE 
demonstrates inadequate seal around the device.   
Table 11.3-1 provides an overview of the data to be collected at each visit. 
 
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Table 11.3-1 Data Collection Overview 
Evaluation 
Screen 
Implant 
Post 
Follow-Up 
45 Day 
Visit 
6 
Month 
Visit 
12 Month 
Visit 
18 month 30 
month 
Telephone 
Annual 
Visits 
Informed Consent  
X 
 
 
 
 
 
 
 
Assess Inclusion/Exclusion  
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Pregnancy Testa 
X 
 
 
 
 
 
 
 
TTE 
X 
 
 
 
 
 
 
 
TEE 
Xb 
X 
 
X 
If no seal at 
45-day 
X 
 
 
Brain Imaging (CT/MRI) d 
Xc 
 
As requiredd 
As requiredd 
As requiredd 
As requiredd 
As requiredd 
As requiredd 
Serum Creatinine, Platelet 
count, Hemoglobin 
X 
 
 
 
 
 
 
 
Review Medication 
Regimen 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
 
 
X 
 
X 
 
X 
NIH Stroke Scale 
X 
 
 
X 
 
X 
 
X 
Barthel Index / Modified 
Rankin 
X 
 
 
X 
X 
X 
X 
X 
Adverse Event Monitoring 
X 
X 
X 
X 
X 
X 
X 
X 
a  For women of childbearing potential only 
b  Within 2 calendar days prior to enrollment  
c  Obtain at baseline if subject had prior stroke or TIA 
d  Brain MRI or CT required if subject suffers stroke or TIA 
e Adverse events associated with diagnostic testing to assess eligibility for the device or for device implantation, and AEs associated with medication changes in preparation for 
device implantation will be collected.  
 
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11.4. Study Candidate Baseline Screening 
After the subject informed consent document has been signed, subject eligibility will be 
determined through evaluation of the inclusion and exclusion criteria.  Only those subjects 
who provide consent and meet all of the study entrance criteria will be enrolled.  Enrollment 
is defined as the time of venous access at the beginning of an implant attempt. 
Subjects who provide informed consent but do not meet all of the study entrance criteria or 
do not have an implant attempt will be considered screening failures.  
The following will be assessed during baseline screening and documented on the baseline 
case report forms for enrolled subjects: 
• Medical and cardiac history 
• Current medical status, vital signs and AF status  
• Pregnancy test for women of child-bearing potential 
• Laboratory analysis (hemoglobin, platelet count, serum creatinine)  
• Current medication regimen for the use of antiplatelet and anticoagulation 
medications 
• Subjects with prior history of ischemic stroke, hemorrhagic stroke or TIA are 
required to have a Baseline MRI or CT obtained 
• NIH Stroke Scale, Barthel Index, and Modified Rankin Scale 
• TTE – If the subject had a TTE within 60 days prior to enrollment it will not need to 
be repeated as long as the subject did not have an appreciable difference in cardiac 
status since the TTE was performed. 
• TEE – The TEE must be completed prior to enrollment to confirm eligibility criteria.  
As this is an invasive screening procedure, it is recommended the TEE be performed 
at the end of the screening process.  Subjects will be implanted within 2 calendar days 
of the baseline TEE. 
11.5. Informed Consent 
In order to determine eligibility of a subject, the investigator needs to implement the consent 
process and verify and document the subject meets the inclusion/exclusion criteria.  Subjects 
must be informed about the investigational nature of the therapy and the potential benefits 
and risks of the WATCHMAN device prior to enrollment.  Only those subjects (or legal 
guardians) who voluntarily provide written consent to participate will be allowed to continue 
in the screening process.  A subject must receive informed consent and sign and date a 
current IRB approved consent document.  Subjects should be informed that even if they 
agree to participate in the study, the baseline screening and TEE may demonstrate they are 
not candidates for the study.  The original, signed document is to be kept with the subject’s 
file and a copy must be provided to the subject.   
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11.6. Implant Procedure 
i) Thrombus Assessment Prior to Implant 
Prior to implantation with the WATCHMAN device, the peri-procedural TEE should confirm 
there is no thrombus in the LAA or left atrium.  If thrombus is identified the subject may not 
be implanted and appropriate anticoagulation should be prescribed.  If venous access was 
achieved at the time a thrombus is detected, the subject is considered enrolled.  The subject 
may not be implanted, and will be considered an implant failure.   
If thrombus is identified prior to the implant, but without venous access, the subject will be 
considered a screening failure and may be re-screened after the thrombus has resolved. 
ii) Implant of the WATCHMAN Device 
Investigators performing the WATCHMAN implant procedure will be chosen based on their 
familiarity with and training in currently accepted trans-septal and left heart techniques.   
The decision to bridge prior to the procedure with warfarin and/or heparin will be at the 
discretion of the operator. 
Antibiotics for subacute bacterial endocarditis prophylaxis are recommended for 
administration in a single dose before the procedure as outlined in the American Heart 
Association Guideline for Prevention of Infective Endocarditis.  If the dosage of antibiotic is 
inadvertently not administered before the procedure, the dosage may be administered up to 2 
hours after the procedure.  Refer to the Guidelines for more details (Circulation 
2007;116;1736-1754 or current update). 
Subjects should be fully heparinized, per hospital policy, throughout the procedure with a 
recommended active clotting time (ACT) of 200 - 250 seconds.  An ACT should be obtained 
at least every 30 minutes throughout the procedure, or per standard practice at each 
investigative center, to ensure an appropriate ACT is maintained for the duration of the 
procedure. 
TEE imaging and fluoroscopy are required during the WATCHMAN implant procedure to 
assist the investigator to appropriately guide the WATCHMAN Access System into the 
LAA, obtain proper measurements of the LAA to correctly size the device, and to ensure that 
the device meets implant release criteria.  Intraoperative TEE imaging should be performed 
in accordance with the Imaging Manual for the collection of images.  TEE imaging will 
include at least one measurement of the maximum LAA ostium width and maximum 
appendage length to confirm measurements obtained during the baseline TEE as well as to 
ensure all post device release criteria are met during the procedure and captured on imaging. 
Implanting physicians need to be cautious of inadvertently introducing air entrapped within 
the Access Sheath.  The operator must be diligent in properly flushing the sheath to prevent 
air from becoming entrapped within the sheath and then embolizing into the systemic 
circulation. 
Reference WATCHMAN LAA Closure Technology Instructions for Use (IFU) for complete 
information on the implant procedure and appropriate device release criteria. 
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iii) Prior to Device Release 
To ensure implant release criteria have been satisfied according to the IFU for position, size, 
stability and seal complete the following:  
• Using both fluoroscopy and TEE, confirm the implant is appropriately positioned at 
or slightly distal to and spans the entire LAA opening (perform multiple contrast 
injections at multiple viewing angles).  
• Confirm appropriate implant size by measuring the deployed diameter of the implant 
in situ using fluoroscopy and/or TEE to ensure appropriate device compression 
guidelines are met.  
• Confirm acceptable implant stability by performing a gentle tug on the device 
deployment knob to ensure the implant is well anchored within the LAA.  
• Confirm via fluoroscopy and TEE that all lobes are covered by the device. 
iv) Unsuccessful Implant Attempt 
If the WATCHMAN device is not successfully implanted, the post procedure medication 
regimen (See Table 11.7-1) will be administered per physician discretion.  The subject will 
be followed in the study through the 45-day follow-up visit or through resolution of any peri-
procedural adverse events, whichever is later.  The TEE evaluation and in-office visit are not 
necessary at the 45-day visit for subjects without a device; these subjects may have a 45-day 
telephone follow-up in lieu of an office visit.  After completion of the 45-day visit and 
resolution of adverse events, the subject will be exited from the study. 
11.7. Medication Regimen for the Study 
i) Discharge Through 45-Day TEE 
Following device placement warfarin therapy should be appropriately adjusted so as to 
achieve a therapeutic INR of 2.0 – 3.0.  Implanted subjects are to be on adjusted dose 
warfarin therapy through at least the 45-day follow-up TEE.  While on warfarin therapy, 
subjects will also be prescribed 81mg aspirin.  Aspirin is necessary post device placement to 
mitigate platelet aggregation.  Subjects will remain on warfarin until the 45-day TEE 
evaluation has shown adequate seal of the LAA.   
ii) 45-Day TEE 
A TEE will be conducted at the 45-day visit to assess position and the seal around the 
perimeter of the WATCHMAN device within the LAA ostium.  Adequate LAA seal is 
defined as little or no visible residual blood flow around the margins of the WATCHMAN 
device in either a retrograde or antegrade fashion, with jet size < 5mm.   
• If the 45-day TEE shows adequate seal of the LAA with a jet around the device < 
5mm,  
o Warfarin therapy will be discontinued, 
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o Aspirin dosage will be increased to 325mg indefinitely,  
o Clopidogrel will be initiated and taken until the 6 month follow-up visit then 
discontinued, and    
o There will not be a TEE at the 6 month visit  
• If the 45-day TEE shows inadequate seal of residual LAA blood flow with a jet size > 
5mm around the margins of device, 
o The subject will remain on warfarin therapy and a 6 month TEE will be 
required to assess LAA seal,  
o Aspirin dosage will remain 81mg while the subject is on warfarin therapy, and  
o Clopidogrel will not be initiated 
iii) 6 Month Visit 
A 6 month TEE is only required for those subjects determined to have an inadequate seal at 
the 45-day TEE.   
• If the 6 month TEE shows adequate seal of the LAA with a jet around the device < 
5mm,  
o Warfarin therapy will be discontinued, and  
o Aspirin dosage will be increased to 325mg indefinitely 
• If the 6 month TEE shows inadequate seal of residual LAA blood flow with a jet size 
> 5mm around the margins of device, 
o The subject will remain on warfarin therapy until a TEE can confirm adequate 
LAA seal, and 
o Aspirin dosage will remain 81mg while the subject is on warfarin therapy 
Caution should be used if considering use of novel oral anticoagulants since this has not 
been studied in patients with a WATCHMAN device.  If anticoagulation is required for 
any reason beyond what is specified in the protocol, ensure medication labeling is 
followed; specifically that related to the abrupt discontinuation of NOACs in patients 
with non-valvular atrial fibrillation without adequate continuous anticoagulation.   
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Table 11.7-1 Medication Regimen Post Implant 
Visit Interval 
Warfarin 
Aspirin 
Clopidogrel 
Implant – 45-Day  
Yes 
Adjusted dose to 
achieve INR of 2.0 – 
3.0 
Yes 
81mg while on 
warfarin 
No 
LAA Seal per 45-Day TEE 
45-Day – 6-Month  
Stop warfarin 
Yes 
325mg recommended   
Yes, Start 
Clopidogrel 
6-Month – 5 Year 
No 
Yes 
325mg recommended   
No, Stop Clopidogrel 
at 6 month visit 
No LAA Seal per 45-day TEE 
45-Day – 6-Month  
Yes 
Yes 
81mg while on 
warfarin 
No 
6-Month – 5 Year 
Discontinue when 
LAA seal adequate 
81mg for subjects 
while on warfarin 
If no warfarin therapy, 
then adult aspirin 
(325mg) indefinitely 
No 
11.8. Follow-up Procedures 
Subjects will be followed at post-enrollment intervals of 45 days, 6 months, 12 months, semi-
annually through 3 years, and thereafter annually through 5 years or until the study is 
terminated.  A projected follow-up timeline will be provided to the site for each subject upon 
enrollment.  
A Follow-Up Case Report Form will be completed for each office and telephone visit. Table 
11.8-1 provides the visit target visit dates and visit window ranges.   
Table 11.8-1 Visit Windows 
Follow-up visit 
Target  
(days post-implant) 
Range  
 
45-Day 
45 days 
30-60 days 
6-Month 
182 days 
152-242 days 
12-Month 
365 days 
335-425 days 
18-Month 
547 days  
517-607 days 
24-Month 
730 days 
700-790 days 
30-Month 
913 days 
883-973 days 
36-Month 
1095 days 
1035-1155 days 
48-Month 
1460 days 
1400-1520 days 
60-Month 
1825 days 
1765-1885 days 
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i) INR Monitoring 
All subjects will have INR monitoring performed at a minimum of every 28 days while on 
warfarin therapy.  Warfarin dosage should be adjusted to ensure subjects are in the 
therapeutic range of 2.0 – 3.0, which is standard practice for subjects with non-valvular AF. 
It is essential that investigators discuss the importance and value of the study required INR 
monitoring schedule with study subjects.  INR values will be collected from subjects during 
follow-up visits, or directly from Coumadin Clinics, and reported by sites on the INR Log.  
While subjects are not required to have an INR during time off warfarin therapy, careful 
attention should be given to ensure compliance to the INR monitoring requirement of at least 
every 28 days once warfarin is restarted.  Early discontinuation of warfarin therapy will be 
documented and the rationale provided on the case report form. 
ii) 45-Day Office Visit 
The 45-day visit will be scheduled such that the TEE occurs within 30-60 days post implant.  
Warfarin therapy and 81mg aspirin are to be maintained through the 45-day TEE. 
During the visit a TEE will be conducted to assess the presence of LAA blood flow through 
and around the WATCHMAN device.  If the TEE evaluation indicates complete LAA seal or 
residual blood flow around the margins of the WATCHMAN device in a retrograde or 
antegrade fashion, with jet size < 5mm, the subject will discontinue warfarin therapy and 
begin adult aspirin regimen (325mg) once daily for the duration of the study, unless 
continuing on 81mg aspirin is medically necessary.  Additionally, clopidogrel must also be 
started at this time and taken until the 6-month follow-up visit.  
Alternatively, if the TEE evaluation indicates residual LAA blood flow with a jet size > 5mm 
around the margins of WATCHMAN device in either a retrograde or antegrade fashion, the 
subject should continue or reinitiate warfarin therapy until such time that LAA seal occurs or 
a jet size < 5mm around the WATCHMAN device is observed.  In this case aspirin will be 
continued at 81mg.   
Additional information collected during the 45-day visit includes the following: 
• INR values while on warfarin therapy     
• TEE to assess device position, LAA seal, thrombus on the device surface, intracardiac 
thrombus and residual atrial septal shunt – to be conducted according to the Imaging 
Manual 
• NIH Stroke Scale, Barthel Index, and Modified Rankin Scale 
• Current medical status  
• Current medication regimen  
• Adverse events experienced since implant procedure 
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iii) 6 Month Visit 
The 6 month visit will be conducted via telephone for those subjects with LAA seal or 
residual blood flow with jet size < 5mm around the margins of the WATCHMAN device at 
the 45-day TEE.  Subjects who had 45-day TEE evidence of LAA seal are expected to be on 
clopidogrel and aspirin therapy at the time of the visit.  At completion of the 6-month visit, 
clopidogrel should be discontinued and subjects should remain on adult aspirin therapy 
indefinitely.  
If a subject was unable to discontinue warfarin therapy due to jet size > 5mm at the 45-day 
TEE, the 6 month visit will be conducted via an office visit and the TEE will be repeated to 
assess seal around the WATCHMAN device.  Subjects will be eligible to discontinue 
warfarin therapy only if the 6-month TEE confirms residual flow of < 5mm around the 
device.  In this scenario, warfarin would be discontinued and an adult daily aspirin prescribed 
indefinitely; Clopidogrel therapy would not be necessary to aid in the healing process after 6 
months post implant. 
Information collected during the 6-month visit includes the following: 
• Collection of INR values for subjects who were on warfarin therapy during this time  
• TEE (if required) to assess device position, LAA seal, thrombus on the device 
surface, intracardiac thrombus and residual atrial septal shunt – to be conducted 
according to the Imaging Manual 
• Barthel Index and Modified Rankin Scale  
• Current medical status  
• Current medication regimen  
• Serious adverse events and adverse events experienced since previous visit 
iv) 12 Month Office Visit 
Subjects will complete an office visit 12 months post implant with a TEE evaluation. 
Information collected during the 12-month visit includes the following: 
• Collection of INR values for any subjects who continued on warfarin therapy beyond 
the 6 month visit  
• TEE to assess device position, LAA seal, thrombus on the device surface, intracardiac 
thrombus and residual atrial septal shunt – to be conducted according to the Imaging 
Manual 
• NIH Stroke Scale, Barthel Index, and Modified Rankin Scale 
• Current medical status  
• Current medication regimen  
• Serious adverse events and adverse events experienced since previous visit 
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v) Additional Telephone Visits-18 Months and 30 Months 
All subjects will complete a telephone visit at 18 months and 30 months. 
At the 18 and 30-month visit the following information will be collected: 
• Collection of INR values for any subjects who continued on warfarin therapy after the 
last visit  
• Barthel Index and Modified Rankin Scale 
• Current medical status  
 
• Current medication regimen  
• Serious adverse events and adverse events experienced since previous visit 
vi) Annual Visits-2,3,4,5 Years 
All subjects will complete an office visit at annual intervals.  No additional TEEs are 
required after the 12-month visit.  Information collected during the annual office visits 
includes the following: 
• Collection of INR values for any subjects who continued on warfarin therapy  
• NIH Stroke Scale, Barthel Index, and Modified Rankin Scale 
• Current medical status  
• Current medication regimen  
• Serious adverse events and adverse events experienced since previous visit 
11.9. Study Completion 
Each subject will be followed for 5 years after the implant procedure. 
12. Statistical Considerations 
An overview of the adaptive study design, sample size and statistical analysis is provided 
below.  Details on each aspect and methods for analyzing the study endpoints will be 
described in a separate Statistical Analysis Plan that will supersede this document.  
12.1. Sample Size Justification 
This is a prospective, multi-center non randomized continued access study with no formal 
pre-specified hypothesis test.  All subjects will be followed for up to 5 years or until the 
study is terminated.  Subjects enrolled in this study will be analyzed separately from the roll-
in and randomized subjects enrolled in the PREVAIL study.  
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A sample size of up to 1500 subjects was chosen to assess incidence of rare events with a 
large degree of precision.  Table 12.1-1 provides the two-sided 95% confidence interval 
width assuming an event rate of 5%. 
Table 12.1-1 Two-Sided Confidence Interval by Sample Size 
Sample Size 
95% CI Width 
1000 
2.8% 
1250 
2.5% 
1500 
2.3% 
12.2. Statistical Analysis 
Analysis will include all subjects enrolled into the study who undergo an attempted implant 
of the WATCHMAN device (i.e. undergo venous access with the intent of implanting the 
WATCHMAN device).  While no formal hypothesis tests will be performed, descriptive 
statistics will be generated for the data collected at baseline, during the procedure and at 
follow-up.  For continuous variables, the mean, standard deviation, median, range and 95% 
confidence intervals will be reported.  Confidence intervals (95%) for the difference between 
means will be used to compare groups.  For proportions, 95% confidence intervals will be 
reported.  For time-to-event analyses, all subjects not having an event or are lost to follow-up 
will be censored at the time of the last documented follow-up visit.  Analyses may include, 
but will not be limited to, the following: procedural success, procedural complications, and 
incidence stroke leading to significant disability/death. 
13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata. All changes 
made to the clinical data will be captured in an electronic audit trail and available for review 
by Boston Scientific Corporation (BSC) or its representative. The associated RAVE software 
and database have been designed to meet regulatory compliance for deployment as part of a 
validated system compliant with laws and regulations applicable to the conduct of clinical 
studies pertaining to the use of electronic records and signatures. Database backups are 
performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the EDC system and will 
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be issued to the site for appropriate response. Site staff will be responsible for resolving all 
queries in the database. 
13.2. Data Retention 
The Investigator will maintain, at the investigative site, in original format all essential study 
documents and source documentation that support the data collected on the study subjects in 
compliance with ICH/GCP guidelines.  Documents must be retained for at least 2 years after 
the last approval of a marketing application or until at least 2 years have elapsed since the 
formal discontinuation of the clinical investigation of the product. These documents will be 
retained for a longer period of time by agreement with BSC or in compliance with other local 
regulations. It is BSC’s responsibility to inform the Investigator when these documents no 
longer need to be maintained. The Investigator will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. If for any reason the 
Investigator withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change.  
14. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 
15. Deviations 
Per 21 CFR 812.150(a)(5) “The investigator shall notify the sponsor and the reviewing IRB 
of any deviation from the investigational plan to protect the life or physical well-being of a 
subject in an emergency.  Such notice shall be given as soon as possible, but in no event later 
than 5 working days after the emergency occurred”  
Except in an emergency, prior written approval to deviate from the protocol should be 
obtained from the sponsor.  Any deviation from the protocol must be recorded on the 
protocol deviation case report form and must provide the dates of and the reasons for each 
deviation. 
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including notification, center re-training, or 
discontinuation) will be put into place by the sponsor. 
16. Device/Equipment Accountability 
The sponsor will provide the WATCHMAN devices and access system to the investigator.  
These devices will be labeled as Investigational Use Only and will require special handling 
and storage controls. The devices must be kept in a secure location with restricted access.  
Devices are intended for use only by the investigator or sub-investigator(s).  The investigator 
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is responsible to track the receipt, use and disposition of all investigational devices received, 
including lot/serial number and device model number.  
WATCHMAN product associated with device deficiencies should be returned to BSC for 
analysis.  If it is not possible to return the product, the investigator should document why the 
product was not returned and the final disposition of the product.  Used product not 
associated with device deficiencies does not need to be returned to BSC but should be 
discarded according to hospital policy.  Expired product should be returned to BSC and all 
unused product will be returned to BSC at the end of the study.  Instruction for returning 
WATCHMAN product is included in the study regulatory binder. 
17. Compliance 
17.1. Statement of Compliance 
This study will be conducted in accordance with ISO 14155:2011 Clinical Investigation of 
Medical Devices for Human Subjects-Good Clinical Practice, or the relevant parts of the ICH 
Guidelines for Good Clinical Practice, ethical principles that have their origins in the 
Declaration of Helsinki, and pertinent individual country laws and regulations. The study 
shall not begin until the required approval/favorable opinion from the IRB and/or regulatory 
authority has been obtained, if appropriate. Any additional requirements imposed by the IRB 
or regulatory authority shall be followed, if appropriate. 
17.2. Selection of Investigators 
Investigators will be selected for this study based upon training and experience.  Investigators 
will have experience with the WATCHMAN device due to participation in previous 
WATCHMAN studies, PROTECT AF or PREVAIL. 
The Investigator will ensure that this study is conducted in accordance with the ethical 
principles that have their origins in the Declaration of Helsinki and that are consistent with 
GCP and applicable regulatory (local) requirements; whichever affords the greater protection 
to the subject. 
17.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, included but not limited to conducting 
the informed consent process, the investigator is responsible for providing appropriate 
training and adequate supervision of those to whom tasks are delegated. The investigator is 
accountable for regulatory violations resulting from failure to adequately supervise the 
conduct of the clinical study.  
17.2.2. Investigator Records 
The investigator is responsible for the preparation (review and signature) and retention of the 
records cited below.  Records are subject to inspection and must be retained for a period of at 
least two (2) years (or according to local regulatory requirements) after the investigation is 
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terminated or the date that the records are no longer required for purposes of supporting 
publications or regulatory submissions. 
• All significant correspondence which pertains to the investigation 
• Subjects’ case history records, including: signed subject informed consent form; all 
relevant observations; observations of adverse device events; medical history; 
completed sponsor Case Report Forms; documentation of the dates and reasons for 
any deviation from the protocol  
• Copies of Case Report Forms and clinical data 
• Signed Investigator Agreement and recent curriculum vitae, both of which also must 
be submitted to the sponsor 
• IRB approval and discourse documentation.  A copy of the IRB approval must be 
submitted to the sponsor 
17.2.3. Investigator Reports 
Table 17.2.3-1 Required Investigator Reports 
Investigator Report 
Submit To 
Description 
Unanticipated Adverse 
Device Effect (UADE) 
Sponsor, IRB 
Notification within ten working days after the investigator 
first learns of the event. 
Withdrawal of IRB 
Approval 
Sponsor 
Notification within five working days. 
Progress Report 
Sponsor, IRB 
The Investigator must submit this report at regular 
intervals, but not less than once per year. 
Deviations from 
Investigational Plan 
Sponsor, IRB 
Report of any deviation from the investigational plan to 
protect the life or physical well-being of a subject in an 
emergency.  Notification within five working days. 
Device use without 
Informed consent 
Sponsor, IRB 
Notification within five working days after the use occurs. 
Final Report 
Sponsor, IRB 
Within three months of study termination or completion. 
17.3. Institutional Review Board/ Ethics Committee 
A copy of the protocol, proposed Informed Consent form, other written subject information, 
and any proposed advertising material must be submitted to the IRB for written approval.  A 
copy of the written IRB approval of the protocol and Informed Consent form must be 
received by the sponsor before recruitment of subjects into the study and shipment of 
investigational product. 
The Investigator must submit and, where necessary, obtain approval from the IRB for all 
subsequent protocol amendments and changes to the Informed Consent form.  The 
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Investigator must notify the IRB of deviations from the protocol or SAEs and UADEs 
occurring at the site in accordance with local procedures. 
The Investigator is responsible for obtaining annual IRB approval and renewal throughout 
the duration of the study.  Copies of the Investigator’s reports and the IRB continuance of 
approval must be sent to the sponsor. 
17.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative will have access to these confidential records. Authorized regulatory personnel 
have the right to inspect and copy all records pertinent to this study. Study data collected 
during this study may be used by BSC for the purposes of this study, publication, and to 
support future research and/or other business purposes. All data used in the analysis and 
reporting of this study will be without identifiable reference to specific subject name. 
Boston Scientific will keep subjects’ health information confidential in accordance with all 
applicable laws and regulations.  Boston Scientific may use subjects’ health information to 
conduct this research, as well as for additional purposes, such as overseeing and improving 
the performance of its device, new medical research and proposals for developing new 
medical products or procedures, and other business purposes. Information received during 
the study will not be used to market to subjects; subject names will not be placed on any 
mailing lists or sold to anyone for marketing purposes.  
17.4.1. Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during implant, testing required by the protocol, 
and follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices. 
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
• Discuss a subject’s condition or treatment with a subject without the approval and 
presence of the HCP 
• Independently collect critical study data (defined as primary or secondary endpoint data) 
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• Enter data in electronic data capture systems or on paper case report forms 
17.4.2. Sponsor Records 
The sponsor will maintain the following records: 
• All correspondence which pertains to the investigation 
• Signed investigator agreements and curriculum vitae 
• System/procedure related Adverse Device Events  
• All case report forms, including samples of subject informed consents, submitted by 
the investigator; investigational plan and report of prior investigations 
• Hospital staff training and study visit reports 
• The sponsor will own and store the clinical data generated under this protocol 
17.4.3. Sponsor Reports 
Table 17.4.3-1 Required Sponsor Reports 
Sponsor Report 
Submit To 
Description 
Unanticipated Adverse 
Device Effect (UADE) 
FDA, IRB, 
Investigators 
Notification within ten working days after Sponsor first 
learns of the event. 
Withdrawal of IRB 
Approval 
FDA, IRB, 
Investigators 
Notification within five working days after receipt of 
approval withdrawal. 
Withdrawal of FDA 
Approval 
IRB and 
Investigators  
Notification will be made within 5 working days after 
receipt of the withdrawal of approval. 
Current Investigator 
List 
FDA 
At 6 month intervals. 
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Progress Report 
FDA, IRB, 
Investigators 
Sponsor must submit this report at regular intervals, but not 
less than once per year. 
Recall and Device 
Disposition 
FDA, IRB, 
Investigators 
Notification will be made within 30 working days after the 
request is made, and will include the reasons for any 
request that an investigator return, repair or otherwise 
dispose of any devices.  
Final Report 
FDA, IRB, 
Investigators 
Sponsor will notify FDA within 30 working days of the 
completion or termination of the study.  A final report will 
be submitted within 6 months after completion or 
termination. 
Device use without 
informed consent 
FDA 
Notification will be made within 5 working days after 
receipt of notice from an investigator. 
17.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
18. Monitoring 
Each clinical site will be monitored to ensure that the study is conducted in full compliance 
with the study protocol, and in accordance with the FDA Guideline for the Monitoring of 
Clinical Investigations, Good Clinical Practices, and the sponsor’s policy and procedures, 
and the study Monitoring Plan.   
Professionals qualified through training, education and experience will conduct the 
monitoring of the study.  Contact the sponsor for additional information on the people 
responsible for monitoring.  
The study may also be subject to a quality assurance audit by the sponsor or its designees, as 
well as inspection by appropriate regulatory authorities. It is important that the Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
19. Potential Risks and Benefits 
19.1. Risks Associated with the WATCHMAN Implant & Procedure 
Potential procedural risks associated with the WATCHMAN implant procedure are similar to 
those encountered peri- and postoperatively for many routine catheterization procedures.  
These include, but are not limited to, the following: 
• Air embolism  
• Allergic reaction, e.g. contrast media  
• Anemia requiring transfusion 
• Anesthesia risks and complications 
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• Arrhythmias  
• Fistula, e.g. arteriovenous 
• Cardiac perforation  
• Cardiac tamponade  
• Chest pain/discomfort  
• Complete heart block  
• Cranial bleed 
• Death 
• Endocarditis 
• Gastrointestinal bleeding 
• Groin puncture bleed 
• Hematoma  
• Hyper/Hypotension  
• Infection  
• Major bleeding requiring transfusion 
• Myocardial infarction  
• Pericardial effusion  
• Pleural effusion  
• Pneumothorax   
• Pseudoaneurysm  
• Pulmonary edema   
• Pulmonary embolism   
• Pulmonary vein obstruction   
• Renal insufficiency/failure 
• Respiratory insufficiency/failure  
• Stroke  
• Systemic embolism  
• TEE complications, e.g. esophageal injury 
• Thromboembolism  
• Thrombosis  
• Thrombosis at septal puncture  
• Transient ischemic attack (TIA)   
• Valvular damage  
• Vascular damage  
• Vasovagal reactions  
• Wound dehiscence  
Definitions of potential procedural related complications are located in Table 25-1. 
In addition to the aforementioned general risks, additional risks specifically 
associated with the WATCHMAN implant are as follows: 
• Additional surgery if the device is not placed in the correct position 
• Allergic reaction to the implant materials 
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• Atrial septal shunt or iatrogenic atrial septal defect 
• Device misplacement 
• Device embolization 
• Device fracture or extrusion 
• Excessive bleeding  
• Hypertrophic scarring or thrombosed veins 
• Infection 
• Device thrombosis 
• Inability to move or retrieve device 
• Inability to implant the device 
19.2. Possible Interactions with Concomitant Medical Treatments 
Subjects who receive the WATCHMAN device may stop Warfarin therapy as early as the 
45-day follow-up visit if they meet Warfarin cessation guidelines; therefore, at that time, 
subjects may be at an increased risk of stroke.   Warfarin is the proven standard of care for 
reducing the risk of stroke in atrial fibrillation.  The WATCHMAN device is designed to be 
used instead of Warfarin.  Thus, the absence of Warfarin may represent a risk, especially if 
the device is not effective in preventing stroke.   
From the Warfarin package insert, risks associated with Warfarin therapy include: 
• Major or fatal bleeding 
• Risk factors for bleeding include: INR > 4.0, age 65 and older, high variable 
INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular 
disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, 
concomitant drugs and long duration of warfarin therapy   
• Hemorrhage from any tissue or organ 
• Necrosis and/or gangrene of the skin or other tissues 
• Epistaxis 
• Bruising 
• Prolonged bleeding from a cut or scrape 
• Headache 
• Nausea/upset stomach 
• Vomiting 
• Diarrhea 
• Fever 
• Skin rash 
• Skin or tissue necrosis 
• Decrease in white blood cell count 
• Inability to tolerate the medication 
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19.3. Risk Minimization Actions 
Efforts have been made to minimize these risks by clearly defining the subject 
inclusion/exclusion criteria and by ensuring that the treatment and follow-up of subjects are 
consistent with current medical practices.  The WATCHMAN device is constructed of well-
known, well-characterized materials and has undergone extensive mechanical functionality 
and clinical testing. 
Investigational teams selected to conduct the study will be experienced and skilled in 
interventional cardiology and/or electrophysiology with trans-septal and left heart 
experience, will have training on the WATCHMAN LAA closure implant procedure and will 
have access to modern high technology medical facilities to conduct those procedures.   
19.4. Anticipated Benefits 
The potential benefit of implanting the WATCHMAN device is its expected ability to 
prevent thromboembolic events originating in the LAA.  The WATCHMAN device may 
protect against ischemic stroke and systemic thromboembolism.  In subjects implanted with 
the device, the elimination of Warfarin therapy may reduce bleeding complications, such as 
hemorrhagic stroke, associated with long-term anticoagulation.  Economic and subject 
benefits related to the elimination of life-long compliance to Warfarin therapy and the 
frequent blood tests and lifestyle changes associated with blood thinning medications are 
numerous.  Lastly, a device-based solution addressing the mechanism of stroke in atrial 
fibrillation subjects may prove to be simple, tolerable and cost-effective. 
20. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
all subjects or their legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local Ethics Committee and/or Regulatory authority body, as applicable. The ICF must be 
approved by the center’s IRB, or central IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative center’s IRB/EC.  Any modification requires approval from BSC prior to use of 
the form.  The ICF must be in a language understandable to the subject and if needed, BSC 
will assist the center in obtaining a written consent translation. Translated consent forms 
must also have IRB/EC approval prior to their use.  Privacy language shall be included in the 
body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
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• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study. 
The ICF shall always be signed and personally dated by the subject or legal representative 
and by the investigator or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the center and a copy of the signed and dated document and 
any other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory body 
according to their requirements (e.g., FDA requirement is within 5 working days of learning 
of such an event). Any violations of the informed consent process must be reported as 
deviations to the sponsor and local regulatory authorities, as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the protocol, a change in Principal Investigator, administrative changes, or following 
annual review by the IRB. The new version of the ICF must be approved by the IRB/EC. 
Boston Scientific approval is required if changes to the revised ICF are requested by the 
center’s IRB/EC. The IRB/EC will determine the subject population to be re-consented. 
Study personnel should explain that even if a subject agrees to participate in the study and 
signs an Informed Consent for, TEE may demonstrate that the subject is not a suitable 
candidate for the study. 
21. Safety Reporting 
21.1. Adverse Event Reporting 
For the purpose of this study an adverse event (AE) is an untoward event related to the study, 
the device, or the study procedures that affects the subject’s health or safety.  For the 
purposes of this study an Adverse Device Effect (ADE) is an adverse event related to the use 
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of the investigational medical device.  When reporting an AE or ADE, the investigator will 
indicate the diagnosis of the event and correlating signs and symptoms on the adverse event 
report.  Individual signs and symptoms and treatment/intervention/diagnostic testing should 
not be reported as separate adverse events, instead be reported as supporting documentation 
on the AE CRF.  Additionally, it is not necessary to report an underlying disease that was 
present at baseline (i.e., CHF, AF, hypertension, chronic anemia, etc.).  However, any 
increase in the severity of the underlying disease may require reporting, if at the 
determination of the investigator, it is relevant to the study.   
Adverse experiences that require reporting include any adverse event with clinical symptoms 
that could possibly be contributed to any of the following: 
• The WATCHMAN device  
• The WATCHMAN implant procedure 
• The use of study mandated medications including warfarin, clopidogrel or aspirin 
(i.e.,: gastrointestinal bleeding due to warfarin or an allergic reaction to clopidogrel) 
• Any study required procedures (i.e., clinical complications from protocol required 
TEE) 
• The following adverse events will also be reported: 
• Neurological events including, but not limited to, stroke, TIA or seizure which are not 
pre-study conditions 
• Any events possibly related to the study endpoints of stroke, systemic embolization, 
death, etc.  
• Thrombosis 
• Bleeding complications requiring intervention or transfusion of blood 
• Any potential UADE  
Each adverse event will be evaluated by the investigator for relatedness and seriousness.  
Definitions of procedural related complications are located in Table 25-1. 
i) 
Adverse Event Definitions 
Adverse events should meet the reporting requirements in the preceding section before 
consideration for reporting as serious events.   
Serious adverse events are to be reported to the sponsor within 1 business day of learning of 
the event.  A serious adverse event (SAE) is an event that:  
• Led to death  
• Led to serious deterioration in the health of the subject that: 
o Resulted in a life-threatening illness or injury, or 
o Resulted in permanent impairment of a body structure or a body function, or 
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o Required in-subject hospitalization or prolongation of existing hospitalization, 
or 
o Resulted in medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to body structure or a body function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth defect 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol, without serious deterioration in health, is not considered a serious adverse event. 
A serious adverse device effect (SADE) is an adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event.  All SAEs that could have led to a 
SADE if suitable action had not been taken or if circumstances had been less fortunate shall 
be reported as required by the local IRB or the protocol. 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the protocol or application (including a supplementary plan or application), or 
any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects.  If an adverse event is determined to meet the definition of an 
unanticipated adverse event, the sponsor will immediately conduct an evaluation.  If an 
unanticipated adverse device effect that represents an unreasonable risk for subject health or 
a product performance failure becomes apparent, immediate action will be taken and the 
appropriate authorities will be notified.  The investigator will be notified of the results of this 
evaluation.  All unanticipated device-related adverse effects will be reported to all 
investigators. 
21.2. Stroke Reporting 
In the event that a subject experiences a stroke during the course of the study, supporting 
documentation will be requested by the sponsor.  This information may include neurologist 
consultation note/s, MRI/CT imaging, radiology reports, additional NIHSS/MRS/Barthel 
Index evaluations, or statement from the investigator. In addition, a search for alternative 
causes of stroke (including hypercoagulable work-up) and TEE evaluation at the time of any 
stroke or embolic event is strongly encouraged to help better ascertain the mechanism of all 
strokes. An optimal TEE evaluation includes, where feasible based on patient status and 
technical considerations, evaluation of:  
i. 
LA thrombus  
ii. 
WATCHMAN Device Seal  
iii. 
WATCHMAN Device thrombus or pannus  
iv. 
Agitated saline contrast injection to evaluate presence of residual right to left shunt at 
the atrial level (persistence of PFO or residual puncture hole from transseptal 
catheterization for device placement)  
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v. 
Presence and grade of ascending and arch aortic atheroma 
vi. 
Presence of worsening left ventricular dysfunction, “new” regional wall motion 
abnormality or presence of LV thrombus (LVEF data may be supplemented by TTE 
where appropriate, in addition to TEE parameters above)  
21.3. Device Thrombus 
The most accurate determination of whether thrombus has formed on the surface of the 
WATCHMAN device is through TEE evaluation.  In the case of thrombus on the atrial 
facing side of the device, anticoagulation therapy should be initiated for approximately 12 
weeks or a longer period of time per hospital standard of care for treatment of thrombus.  
After the course of anticoagulation therapy a repeat TEE evaluation should be performed to 
confirm the thrombus has resolved6 
21.4. Boston Scientific Device Deficiencies 
A device deficiency is any inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety or performance.  Device deficiencies include 
malfunctions, misuse or use errors, and inadequate labeling.  All device deficiencies will be 
documented and reported to BSC on the appropriate eCRF within one business day of first 
becoming aware of the event.  Device deficiencies are not to be reported as adverse events. 
However, if there is an adverse event that results from a device deficiency, that specific event 
would be recorded on the appropriate eCRF.  If possible, the device(s) should be returned to 
BSC for analysis. Instructions for returning the investigational device(s) will be provided. If 
it is not possible to return the device, the investigator should document why the device was 
not returned and the final disposition of the device. Device deficiencies should also be 
documented in the subject’s medical record. 
21.5. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating investigators 
and regulatory authorities, as applicable. The Principal Investigator is responsible for 
informing the IRB, and regulatory authorities of UADE and SAE as required by 
local/regional regulations. 
22. Committees 
22.1. Safety Monitoring Process 
To promote early detection of safety issues, the CAP 2 CEC will provide evaluations of 
safety events. Success of this program requires dynamic collection of unmonitored data as 
soon as the event is reported. This is expedited through Boston Scientific’s Global Safety 
Office, which is responsible for coordinating the collection of information for the subject 
dossier from the centers. During regularly scheduled monitoring visits, clinical research 
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monitors will support the dynamic reporting process through their review of source document 
information. 
22.2. Clinical Events Committee 
A Clinical Events Committee (CEC) is an independent group of individuals with pertinent 
expertise that reviews and adjudicates important endpoints and relevant adverse events 
reported by study investigators. The CEC will review a safety event dossier, which may 
include copies of subject source documents provided by study centers. CEC responsibilities, 
qualifications, membership, and committee procedures are outlined in the CEC charter. The 
CECs classifications of the adverse events will be used in all study reports, evaluation of 
study endpoints and in all data analyses. 
22.3. Data and Safety Monitoring Board  
An independent Data and Safety Monitoring Board (DSMB) will be established for the 
review of data and safety parameters in the study.  The DSMB will develop a charter and 
stopping rules for the study.  The members will consist of at least four physicians in 
specialties of electrophysiology, interventional cardiology, or neurology.  At least one 
member of the committee will be a biostatistician.  
The DSMB will function in accordance with Guidance for Clinical Trial Sponsors: 
Establishment and Operation of Clinical Trial Data Monitoring Committees.  Meeting 
frequency will be determined by the DSMB to review the clinical data and assess the impact 
of adverse events.   
The DSMB will be utilized to review data from the continued access study until the time of 
commercialization of the WATCHMAN device.  
23. Suspension or Termination 
This study may be terminated at any time.  Upon completion or termination, all data and 
unused investigational devices must be returned to the sponsor 
23.1 Publication Policy 
In accordance with the Corporate Policy on the Conduct of Human Subject Research, BSC 
requires disclosure of its involvement as a sponsor or financial supporter in any publication 
or presentation relating to a BSC study or its results. In accordance with the Corporate Policy 
for the Conduct of Human Subject Research, BSC will submit study results for publication 
(regardless of study outcome) following the conclusion or termination of the study. Boston 
Scientific Corporation adheres to the Contributorship Criteria set forth in the Uniform 
Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
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assist authors and investigators in publication preparation provided the following guidelines 
are followed. 
• All authorship and contributorship requirements as described above must be 
followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy 
should be discussed with the Coordinating Principal Investigator(s) and/or 
Executive/Steering Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
24. Bibliography 
1 Hankey GJ. Non-valvular Atrial Fibrillation and Stroke Prevention.  MJA 2001; 174:234-
348. 
 
2 Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le 
Heuzey J-Y, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith 
SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, 
Page RL, Riegel B, Priori SG, Blanc J-J, Budaj A, Camm AJ, Dean V, Deckers JW, Despres 
C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL. 
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a 
report of the American College of Cardiology/American Heart Association Task Force on 
Practice Guidelines and the European Society of Cardiology Committee for Practice 
Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of 
Patients With Atrial Fibrillation). J Am Coll Cardiol 2006;48:e149 –246. 
 
3Hart RG, Pearce LA, McBride R, et al. Factors associated with ischemic stroke during 
aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical 
trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 
1999;30:1223–9. 
 
4White, Harvy D., DSc; Gruber Michael, MSc; Feyzi, Jan, MS; et.al.,  Comparison of 
Outcomes Among Patients Randomized to Warfarin Therapy According to Anticoagulant 
Control:  Results from SPORTIF III AND V.,  Archives of Internal Medicine , Feb. 12, 
2007, Vol.167., pg 239-245. 
 
5Connolly, Stuart J., Pogue Janice, MA, MSc; Eikelboom, John, MBBS, MXc, 
FRACP,FRCPA, et.al.,  Benevit of Oral Anticoagulant Over Antiplatelet Therapy in Atrial 
Fibrillation Depends on the Quality of International Normalized Ration Control Achieved 
by Centers and Countries as Measured by Time in Therapeutic Range, Circulation, 
2008;118:2029-2037. 
 
6 Krusmsdorf U. et al. Incidence and clinical course of thrombus formation on atrial septal 
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defect and patient foramen ovale closure devices in 1,000 consecutive patients.  J. Am. 
Coll. Cardiol. 2004; 43; 302-309. 
 
 
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25. Definitions  
Table 25-1 Definitions 
 
Term 
Definition 
Air embolism 
 
Allergic reaction to 
contrast media 
 
Anemia requiring 
transfusion 
 
Anesthesia risks and 
complications 
 
 
 
Arrhythmias 
 
 
AV fistula 
 
 
Cardiac 
perforation/tamponade 
 
Chest pain/discomfort 
 
Complete heart block 
 
 
Cranial bleed 
 
Death 
 
 
 
Endocarditis 
 
Gastrointestinal bleeding 
 
Groin puncture bleed 
 
 
Hematoma 
 
 
 
Hyper/Hypotension 
 
Obstruction of the circulation by air that has gained entrance to vessels 
 
A response such as rash, hives, itching, asthma, hay fever, anaphylaxis, etc., to 
contrast media 
 
A drop in hemoglobin that results in transfusion of 2 or more units of packed 
red blood cells 
 
  Complications and risks of general anesthesia include but are not limited to: 
difficulties with the lung, heart, and liver or nerve functions. Serious illness, 
additional surgery and even death may result from the complications of general 
anesthesia 
 
An alteration in rhythm of the heartbeat that requires treatment with a device or 
anti-arrhythmic medication   
 
A communication between an artery and vein in which arterial blood flows 
directly into a vein or is carried into a vein by a connecting pathway 
 
See Pericardial Effusion 
 
 
Pressure, heaviness and/or sharp pain in the chest region 
 
Also known as third-degree heart block or complete AV block, it is a condition 
in which none of the electrical impulses can reach the ventricles 
 
Asymptomatic intracranial bleed 
 
A death is defined as a cardiovascular death if the death is from a 
cardiovascular event including sudden death, MI, cardiac arrhythmia, and heart 
failure 
 
Inflammation of cardiac tissue (endocardium) 
 
Bleeding with an origin within the gastrointestinal system 
 
Bleeding or oozing of blood from the groin access site used for the implant 
procedure 
 
A mass of usually clotted blood that forms in a tissue, organ, or body space as a 
result of leakage from a blood vessel that requires additional treatment beyond 
applying pressure 
 
Elevated blood pressure exceeding 140 over 90 mmHg, or low blood pressures 
less than 90 over 50 mmHg 
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Term 
Definition 
 
Infection 
 
 
 
Major bleeding requiring 
transfusion 
 
Myocardial infarction 
 
 
 
 
 
 
 
 
 
 
 
Pericardial effusion 
 
 
 
 
 
 
 
 
Pleural effusion 
 
Pneumothorax 
 
 
Pseudoaneurysm 
 
 
Pulmonary edema 
 
Pulmonary embolism 
 
 
 
 
Pulmonary vein obstruction 
 
Renal insufficiency/failure 
 
Stroke 
 
 
The invasion of the body by pathogenic microorganisms and their 
multiplication which can lead to tissue damage and disease requiring treatment, 
e.g., endocarditis, pericarditis, sepsis 
 
Non site-specific bleeding requiring the transfusion of 2 or more units packed 
red blood cells 
 
Either one of the following criteria satisfies the diagnosis for an acute, evolving 
or recent MI:   
1)  Typical rise and gradual fall (troponin) or more rapid rise and fall 
(CK-MB) of biochemical markers of myocardial necrosis with at least 
one of the following: 
a) ischemic symptoms; 
b) development of pathological Q waves on the ECG; 
c) ECG changes indicative of ischemia (ST segment elevation or 
depression); or 
d) Coronary artery intervention (e.g. coronary angioplasty). 
2)  Pathologic findings of an acute MI 
 
Pericardial effusions are defined by the clinical therapy associated with the 
effusion. 
Pericardial Effusion:  An observed pericardial effusion not necessitating 
percutaneous drainage nor surgical repair. 
Pericardial Effusion with Tamponade:  A pericardial effusion resulting in 
percutaneous treatment/drainage. 
Cardiac Perforation:  A pericardial effusion resulting in surgical 
intervention/repair. 
 
Fluid in a pleural cavity 
 
An abnormal state characterized by the presence of gas (as air) in the pleural 
cavity 
 
Extra-vascular fluid sac without vascular wall lining but with communication 
with arterial vessel 
 
Abnormal accumulation of fluid in the lungs 
 
Embolism of a pulmonary artery or one of its branches that is produced by 
foreign matter and most often a blood clot originating in a vein of the leg or 
pelvis and that is marked by labored breathing, chest pain, fainting, rapid heart 
rate, cyanosis, shock, and sometimes death 
 
An obstruction in the pulmonary vein that can decrease blood flow to the atria 
 
50% increase in creatinine level or requiring dialysis 
 
Ischemic Stroke: Sudden onset of a focal neurological deficit with symptoms 
and/or signs persisting more than 24 hours or symptoms less than 24 hours with 
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Term 
Definition 
 
 
 
Systemic embolism 
 
 
 
 
 
Thromboembolism 
 
 
Thrombosis 
 
Thrombosis at septal 
puncture 
 
Transient ischemic attack 
(TIA) 
 
 
Valvular damage 
 
Vascular damage 
 
Vasovagal reactions 
 
 
Wound dehiscence 
CT or MRI evidence of tissue loss without hemorrhage. 
Hemorrhagic Stroke: Symptomatic intracranial hemorrhage due to any cause. 
 
Abrupt vascular insufficiency associated with clinical or radiologic evidence of 
arterial occlusion in the absence of other likely mechanisms (e.g., 
atherosclerosis, instrumentation).  In the presence of atherosclerotic peripheral 
vascular disease, diagnosis of embolism to the lower extremities requires 
arteriographic demonstration of abrupt arterial occlusion. 
 
The blocking of a blood vessel by a particle that has broken away from a blood 
clot at its site of formation 
 
The formation or presence of a blood clot within a blood vessel 
 
The formation or presence of a blood clot at the location of septal puncture 
during the implant procedure 
 
Acute focal neurological event (including focal motor deficit aphasia, difficulty 
walking, hemi sensory deficit, amaurosis fugax, blindness, or focal visual 
deficit) lasting at least 5 minutes and up to 24 hours that is imaging negative   
 
Damage to the valves within the heart 
 
Damage to the walls of the vessels 
 
A fainting or loss of consciousness response generally due to a sudden drop in 
blood pressure, syncope, or other external stimuli 
 
The parting of the sutured lips of a surgical wound typically resulting from 
infection 
 
 
 
 
 
 
 
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