A Study to Evaluate the Safety and Effectiveness of the Left Atrial Appendage Closure Therapy Using BSJ003W for Patients With Non-valvular Atrial Fibrillation at Increased Risk of ThromboEmbolism in Japanese Medical Environment (SALUTE)
Phase: NA
Conditions: Atrial Fibrillation Non-Rheumatic
Sponsor: Boston Scientific Japan K.K.

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A Study to evaluate the safety and effectiveness of the Left atrial 
appendage closure therapy Using BSJ003W for patients with non-valvular 
atrial fibrillation at increased risk of ThromboEmbolism in Japanese 
medical environment 
 
 
SALUTE 
 
CLINICAL INVESTIGATION PLAN 
 
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Sponsored By 
Boston Scientific Japan K.K. 
4-10-2 Nakano, Nakano-ku 
Tokyo 164-0001 Japan 
 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol 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 Trial Director 
(Chiken Sokatsu-sha) 
Chizuru Oribe 
Boston Scientific Japan K.K. 
4-10-2 Nakano, Nakano-ku 
Tokyo 164-0001 Japan 
Clinical Contact 
Clinical Trial Manager 
Yutaka Gomi 
Boston Scientific Japan K.K. 
4-10-2 Nakano, Nakano-ku 
Tokyo 164-0001 Japan 
Coordinating  
Principal Investigators 
Kazutaka Aonuma, MD 
University of Tsukuba Hospital 
1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577 Japan 
 
Shigeru Saito, MD 
Shonankamakura General Hospital 
1370-1 Okamoto, Kamakura-City 
Kanagawa 2478533 Japan 
Investigational Sites 
A list of study sites is provided in Appendix. 
Clinical Trial 
Organization  
Clinical trial organization is listed in an attachment  
(Investigational sites and investigators are included.)  
 
 
 

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Original Release: Nov, 24th, 2016 

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2. Protocol Synopsis 
A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
Study 
Objective(s) 
To confirm the safety and effectiveness of the BSJ003W in Japanese 
patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese Clinical environment 
Planned 
Indication(s) for 
Use  
To reduce the risk of thromboembolism from the Left Atrial Appendage  
in patients with non-valvular atrial fibrillation who are at increased risk 
based on CHADS2 or CHA2DS2-VASc scores 
Test Device 
BSJ003W LAA Closure Technology; three-component system consisting 
of the  
• 
BSJ003W Closure Device; WATCHMAN(Gen 2.5) 
• 
BSJ003W Delivery System (Delivery Catheter and BSJ003W 
Closure Device) 
• 
BSJ003W Access System (Access Sheath and Dilator) 
Control Device 
None 
Device Sizes 
21mm, 24mm, 27mm, 30mm, 33mm 
Study Design 
This is a prospective, multi-center, single-arm study to confirm the safety 
and effectiveness of BSJ003W for Japanese subjects with non-valvular 
atrial fibrillation who are eligible for long-term anti-coagulation therapy 
to reduce the risk of stroke but who have a rationale to seek a non-
pharmacologic alternative in Japanese clinical environment. 
Planned 
Number of 
Subjects 
 1 Roll-in subject per site is required prior to enroll an analyzable subject 
at each site. One more Roll-in subject should be enrolled if necessary per 
Investigators’ or a proctor’s discretion.   
Number of analyzable patients: 40 patients. 
Maximum of 60 subjects (including 10-20 Roll-in subjects) will be 
enrolled in the study. 
Planned 
Number of 
Up to 10 investigational centers in Japan 

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A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
Investigational 
Sites 
Primary 
Endpoints 
To assess safety and effectiveness of BSJ003W, the following three 
endpoints are established as Co-Primary Endpoints: 
1. The occurrence of one of the following events between the time of 
implant and within 7 days following the procedure or by hospital 
discharge, whichever is later:  
all-cause death, ischemic stroke, systemic embolism, or device- or 
procedure- related events requiring open cardiac surgery or major 
endovascular intervention such as pseudoaneurysm repair, AV fistula 
repair, or other major endovascular repair.  
Percutaneous catheter drainage of pericardial effusions, snaring of an 
embolized device, thrombin injection to treat femoral 
pseudoaneurysm and nonsurgical treatments of access site 
complications are excluded from this endpoint. 
2. The occurrence of composite events* including stroke (all/ ischemic/ 
hemorrhagic), systemic embolism and CV death (including 
unexplained cause) . 
*All data collected up to the last patient’s 6 months follow-up visit to 
be completed.  
3. The rate of effective LAA closure* at 45 days and 6 months. Change 
in the rate between the two time points will also be analyzed.  
*The effective LAA closure is defined as peri-device flow < 5mm 
demonstrated by TEE. TEE measurements will be assessed by 
independent Core Lab. 

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A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
Secondary 
endpoints 
Safety endpoints: 
• 
The occurrence of major bleeding* at 0 – 45 days, 45 days – 6 
months, 6 months – 24 months 
*Major bleeding is defined as per BARC bleeding definition type 3 or 5 
• 
Frequency of the following bleeding events at 0 – 45 days, 45 days 
– 6 months and 6 months – 24 months: 
• 
Clinically overt non-fatal bleeding*  
• 
All bleeding events 
*Clinically overt non-fatal bleeding is defined as per BARC bleeding 
definition type 2. 
 
Effectiveness endpoints: 
• 
The occurrence of composite events* for effectiveness; stroke (all/ 
ischemic/ hemorrhagic), systemic embolism and CV death (including 
unexplained cause)  
*All data collected up to the last patient’s 12 months and 24 months 
follow-up visits to be completed.  
• 
Effective LAA closure at 12-month and its time course until then. 
• 
The occurrence of ischemic stroke or systemic embolism (excluding 
7 days after implanting or day after hospital discharge whichever is 
the later) at 6 months, 12 months and 24 months. 
Additional 
Endpoints 
Device  performance: 
• 
Technical Success defined as successful delivery and release of 
BSJ003W into the LAA including successful recapture and retrieval 
if necessary. 
 
Safety endpoints: 
• 
Occurrence of reportable adverse events 
• 
Occurrence of all-cause mortality 
 
Effectiveness endpoints: 
• 
Individual occurrence of all-cause death, ischemic stroke, 

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A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
hemorrhagic stroke, systemic embolization, cardiovascular death 
(including unexplained cause) at 6-month, 12-month and 24-month.  
• 
Warfarin discontinuation rate at 45 days, 6-month and 12-month 
• 
Severity of stroke assessed by NIH Stroke Score, Modified Rankin 
Scale Score, and Barthel Index 
 
Other endpoint: 
• 
EQ-5D 
Required 
Medication 
Therapy 
Visit 
Medication 
Implant through 45-day visit 
ASA+ Warfarin 
45-day visit through 6-month visit 
ASA+ Thienopyridine  
Following the 6-month visit 
ASA 
Warfarin therapy should be appropriately monitored and adjusted so as to 
achieve a therapeutic INR of 2.0- 3.0.  For a subject who are 70 years old 
or older, a therapeutic INR of 2.0 – 2.6 is recommended considering the 
high risk of major bleeding. Subjects should remain on warfarin until the 
45-day TEE evaluation has shown adequate seal of the LAA. If the LAA 
is not adequately sealed, the subjects should be on warfarin and Aspirin 
therapy. 
Follow-up 
Schedule 
Study procedures and follow-up visits will occur as follows: 
• 
Informed consent 
• 
Screening 
• 
BSJ003W Implant  
• 
45-day Follow-up (45 ± 15 days) 
• 
6-Month Follow-up (182 ± 30 days) 
• 
12-Month Follow-up (365 ± 30 days) 
• 
18-Month Follow-up (547 ± 60 days) 
• 
24-Month Follow-up (730 ± 60 days) 
Study Duration 
The duration of the study is expected to last approximately 3 years.  The 
duration of individual subject participation is expected to last 

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A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
approximately 2 years.   
Key Inclusion 
Criteria 
1. The subject is Japanese, over 20 years old and provides written informed 
consent to participate in the trial 
2. The subject has documented paroxysmal, persistent or permanent non-
valvular atrial fibrillation 
3. The subject has a calculated CHA2DS2-VASc score of 2 or greater and 
is recommended for long-term oral anti-coagulation therapy 
4. The subject is deemed by their physicians to be suitable for 
anticoagulant therapy and have an appropriate rationale to seek a non-
pharmacologic alternative to warfarin 
5. The subject is eligible to come off warfarin therapy if the LAA is 
sealed (i.e. the subject has no other conditions that would require 
warfarin therapy). 
Key Exclusion 
Criteria 
1. The subject has a prior stroke (ischemic or hemorrhagic) or TIA 
within the 90days prior to consent 
2. The subject has had a MI either non-ST elevation or ST elevation MI 
within 90days prior to consent with or without intervention 
3. The subject had or is planning to have any cardiac (e.g. cardioversion, 
coronary angiogram, percutaneous coronary intervention, cardiac 
ablation, etc.) or non-cardiac invasive or surgical procedure (e.g. 
cataract surgery, endoscopy, etc.) within 30 days prior or 45 days 
after the BSJ003W implant 
4. The subject has a history of atrial septal repair or has an ASD/PFO 
device 
5. The subject has an implanted mechanical valve prosthesis in any 
position  
6. The subject currently NYHA class IV CHF 
7. The subject is contraindicated to aspirin 
8. The subject is contraindicated or seriously allergic to thienopyridine  
9. The subject is of childbearing potential and is, or plans to become 
pregnant during the time of the study (method of assessment upon 
study physician’s discretion) 
10. The subject is not able and willing to return for required follow-up 

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A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
visits and examinations 
11. Subjects who are currently enrolled in another investigational study 
(of which primary endpoint follow-up have not been completed yet). 
12. The subject has other reason not to be eligible for this study per 
investigators’ discretion. 
ECHO 
Exclusion 
Criteria 
 
1. The subject has LVEF < 30%. 
2. The subject has intracardiac thrombus visualized by TEE within 2 
days prior to implant. 
3. The subject has an existing pericardial effusion with a circumferential 
echo-free space > 5mm, and/or the patient has signs/symptoms of 
acute or chronic pericarditis, and/or there is evidence (clinically or 
echocardiographically) of tamponade physiology.  
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, and/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 and/or aortic arch. 
8. The subject has a cardiac tumor. 
Multiple 
Interventions 
During Index 
Procedure 
No concomitant procedures are to be performed at the time of the 
BSJ003W implant procedure. This includes, but is not limited to, cardiac 
ablation procedures, transcutaneous valve procedures, cardioversions, 
pacemaker or ICD generator change, etc. 
Statistical Methods  
Statistical 
consideration 
and Sample size 
justification 
The primary safety endpoint event rate observed in the PREVAIL study 
was 2.2%.  Based on the PREVAIL data only, the exact 95% upper 
confidence bound for this rate is 4.4%.  An additional margin of 5.6% is 
added to this upper confidence bound to create a performance target of 
10.0.  In order to maintain >=95% probability that the observed estimate 
from this study is lower than the performance target of 10.0%, 40 subjects 
are required.   
The expected primary effectiveness endpoint rate is 99.3%.  Based on this 
expected rate, and the number of subjects in the PREVAIL study with 6-
month TEEs, the corresponding exact 95% lower confidence bound is 
97.3%.  An additional margin of 3.3% is subtracted from this lower 

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A study to confirm the safety and effectiveness of the BSJ003W in 
Japanese patients with non-valvular atrial fibrillation at increased risk of 
thromboembolism in Japanese clinical environment 
confidence bound to create a performance target of 94.0%.  Accounting 
for 10% attrition to 6-month TEE follow-up, 40 subjects are required to 
maintain >=95% probability that the observed estimate from this study is 
higher than the performance target of 94.0%.  
Statistical Test 
Method 
Similarities of this study results will be evaluated with foreign pivotal 
study results. 
Roll-in patients’ data will be evaluated separately from the data of those 
patients enrolled after the Roll-in patients and will not be included in the 
endpoint analysis. 
 
 

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3. Table of Contents 
2. 
PROTOCOL SYNOPSIS .......................................................................................................... 4 
3. 
TABLE OF CONTENTS ........................................................................................................ 11 
4. 
INTRODUCTION ................................................................................................................. 16 
4.1. Background ............................................................................................................. 16 
5. 
DEVICE DESCRIPTION ....................................................................................................... 17 
5.1. Medical Equipment Description ........................................................................... 17 
5.1.1. 
BSJ003W Access System (Access Sheath and Dilator) ........................ 17 
5.1.2. 
BSJ003W Delivery System and with Pre-loaded LAAC Device ......... 18 
5.2. Indications for Use ................................................................................................. 20 
5.3. Device Labeling ...................................................................................................... 20 
6. 
STUDY OBJECTIVES .......................................................................................................... 20 
7. 
STUDY ENDPOINTS ............................................................................................................ 21 
7.1. Primary Endpoint .................................................................................................. 21 
7.2. Secondary Safety Endpoint ................................................................................... 21 
7.3. Secondary Effectiveness Endpoint ....................................................................... 21 
7.4. Additional analysis ................................................................................................. 22 
8. 
STUDY DESIGN .................................................................................................................. 22 
8.1. Scale and Duration ................................................................................................. 22 
8.2. Treatment Assignment........................................................................................... 23 
8.2.1. 
Treatment ................................................................................................... 23 
8.3. Justification for the Study Design ......................................................................... 23 
9. 
SUBJECT SELECTION ......................................................................................................... 24 
9.1. Study Population and Eligibility ........................................................................... 24 
9.2. Inclusion Criteria ................................................................................................... 24 
9.3. Exclusion Criteria .................................................................................................. 25 
9.4. Echo Exclusion Criteria ......................................................................................... 26 
10. SUBJECT ACCOUNTABILITY .............................................................................................. 26 

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10.1. Point of Enrollment ................................................................................................ 26 
10.2. Withdrawal ............................................................................................................. 26 
10.3. Subject Status and Classification .......................................................................... 27 
10.3.1. Screen Failure ............................................................................................ 27 
10.3.2. Attempt ...................................................................................................... 27 
10.3.3. Implant ....................................................................................................... 27 
10.4. Enrollment Controls .............................................................................................. 28 
11. STUDY METHODS .............................................................................................................. 29 
11.1. Data Collection ....................................................................................................... 29 
11.2. Informed Consent .................................................................................................. 30 
11.3. Screening Visit ........................................................................................................ 30 
11.4. LAA Imaging .......................................................................................................... 31 
1. 
Transthoracic Echocardiogram (TTE) ................................................................ 31 
2. 
Transesophageal Echocardiogram (TEE)............................................................ 31 
a. 
Stroke or Systemic Embolism TEE ...................................................................... 31 
b. 
Device Thrombus TEE .......................................................................................... 32 
11.5. Implant Procedure ................................................................................................. 32 
11.6. Study Medication Regimen (for subjects classified as Implant) ........................ 33 
11.7. Stroke Assessments ................................................................................................ 35 
11.8. QoL Assessments: EQ-5D...................................................................................... 35 
11.9. Follow-up Procedures at 45 days .......................................................................... 36 
11.9.1. For Subjects classified as Implants ............................................................ 36 
11.9.2. For Subjects classified as Attempts ........................................................... 36 
11.10. 
Office Visit Follow-up (6-month and 12-month)................................... 37 
11.11. 
Office visit Follow-Up (18-month and 24-month) ................................. 37 
11.12. 
Study Exit ................................................................................................. 38 
11.13. 
Source Documents ................................................................................... 39 
12. STATISTICAL CONSIDERATIONS ....................................................................................... 39 
12.1. Primary Safety Endpoints ..................................................................................... 39 
12.1.1. Statistical Hypotheses ................................................................................ 39 
12.1.2. Sample Size ............................................................................................... 40 
12.1.3. Statistical Methods ..................................................................................... 40 
12.2. Primary Efficacy Endpoints .................................................................................. 40 

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12.2.1. Hypotheses ................................................................................................. 40 
12.2.2. Sample Size ............................................................................................... 40 
12.2.3. Statistical Methods ..................................................................................... 40 
12.3. General Statistical Methods .................................................................................. 41 
12.3.1. Analysis Sets .............................................................................................. 41 
12.3.2. Control of Systematic Error/Bias ............................................................... 41 
12.3.3. Number of Subjects per Investigative Site ................................................ 41 
12.3.4. Data Analyses ............................................................................................ 41 
12.3.5. Other Endpoints/Measurements ................................................................. 41 
12.3.6. Interim Analyses ........................................................................................ 41 
12.3.7. Subgroup Analyses .................................................................................... 41 
12.3.8. Justification of Pooling .............................................................................. 42 
12.3.9. Multivariable Analyses .............................................................................. 42 
12.3.10. Other Analyses ........................................................................................... 42 
12.3.11. Changes to Planned Analyses .................................................................... 42 
13. DATA MANAGEMENT ........................................................................................................ 42 
13.1. Data Collection, Processing, and Review ............................................................. 42 
13.2. Data Retention ........................................................................................................ 42 
13.3. Core Laboratories .................................................................................................. 43 
14. AMENDMENTS ................................................................................................................... 43 
15. DEVIATIONS ...................................................................................................................... 43 
16. DEVICE/EQUIPMENT ACCOUNTABILITY .......................................................................... 44 
17. COMPLIANCE ..................................................................................................................... 45 
17.1. Statement of Compliance ....................................................................................... 45 
17.2. Investigator Responsibilities ................................................................................. 45 
17.2.1. Delegation of Responsibility ..................................................................... 46 
17.3. Institutional Review Board ................................................................................... 47 
17.4. Sponsor Responsibilities ........................................................................................ 47 
17.4.1. Role of Boston Scientific Representatives ................................................ 48 
17.5. Insurance ................................................................................................................. 48 
18. MONITORING ..................................................................................................................... 48 
19. POTENTIAL RISKS AND BENEFITS .................................................................................... 49 

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19.1. Anticipated Adverse Events and Risks Associated with the Study Device(s) ... 49 
19.2. Risks associated with Participation in the Clinical Study .................................. 50 
19.3. Possible Interactions with Concomitant Medical Treatments ........................... 50 
19.4. Risk Minimization Actions .................................................................................... 50 
19.5. Anticipated Benefits ............................................................................................... 51 
19.6. Risk to Benefit Rationale ....................................................................................... 51 
20. SAFETY REPORTING .......................................................................................................... 51 
20.1. Reportable Events by investigational site to Boston Scientific .......................... 51 
20.2. Definitions and Classification ............................................................................... 52 
20.3. Relationship to Study Device(s) ............................................................................ 54 
20.4. Investigator Reporting Requirements .................................................................. 56 
20.5. Boston Scientific Device Deficiencies .................................................................... 57 
20.6. Reporting to Regulatory Authorities / IRBs / Investigators .............................. 57 
20.7. CEC (Clinical Events Committee) Adjudication Events .................................... 57 
20.7.1. Stroke Reporting Documentation Recommendations ............................... 58 
20.7.2. All Bleeding Events Reporting Documentation Recommendations ......... 58 
20.8. Device Thrombus ................................................................................................... 58 
20.9. Death Reporting ..................................................................................................... 59 
21. INFORMED CONSENT......................................................................................................... 59 
22. COMMITTEES .................................................................................................................... 61 
22.1. Safety Monitoring Process ..................................................................................... 61 
22.2. Clinical Event Committee ..................................................................................... 61 
23. SUSPENSION OR TERMINATION ........................................................................................ 61 
23.1 Premature Termination of the Study ................................................................... 61 
23.1.1 
Criteria for Premature Termination of the Study ....................................... 61 
23.2 Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval ................................................................................................................. 62 
23.3 Requirements for Documentation and Subject Follow-up ................................. 62 
23.4 Criteria for Suspending/Terminating a Study Site ............................................. 62 
24. PUBLICATION POLICY ....................................................................................................... 62 
25. BIBLIOGRAPHY .................................................................................................................. 64 

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26. ABBREVIATIONS AND DEFINITIONS .................................................................................. 66 
26.1. Abbreviations ......................................................................................................... 66 
26.2. Definitions ............................................................................................................... 67 
26.2.1. Stroke/TIA definitions ............................................................................... 67 
26.2.2. Classification of Bleeding events .............................................................. 69 
27. APPENDICES ...................................................................................................................... 70 
27.1. Clinical Trial Organization ................................................................................... 70 
 
 
 

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4. Introduction 
4.1. 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 1years. 
Prevalence of AF in Japan in 2005 was 0.56% (0.72 million people) and it is expected to 
increase over 1% in 2050 with aging population. The most debilitating consequence of non-
valvular artrial fibrillation (NVAF) is thrombus formation from stagnant blood flow leading 
to thromboembolism and stroke. In cardiogenic stroke, an abrupt closure of cerebral artery 
from floating thrombus could cause severe ischemia with large infarction. Patient condition 
could be more serious than those who have Lacunar or atheroma stroke and patient care 
could be an serious issue. The rate of ischemic stroke attributed to NVAF 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 thromboembolism originating in the 
left atrial appendage by assessing its risk through CHADS2 and CHA2DS2-Vasc  has been well 
documented in Japanese/US/EU guidelines of AF treatment 3-5. While warfarin has remained 
the optimum treatment, there are numerous challenges with the drug. It is a big concern for 
patients and their care takers not to be able to completely avoid fatal bleeding and other 
bleeding events with ill prognosis due to its pharmacological effect. HAS-BLED score, 
therefore, is proposed to predict such bleeding during anticoagulation therapy which has been 
used in the Japanese/US/EU guidelines and proper management is recommended.  
Warfarin has relatively narrow therapeutic range, and frequent need for monitoring and 
dosage adjustments, good daily patient compliance, tolerance and dietary and metabolic 
interactions are concerned.  Bleeding is especially concerned in Japan and only 50% patients 
with CHADS2   of more than 2 and it is reported that even if treated with Warfarin, low dose 
tend to be administered2.   
Currently available alternatives to warfarin are the direct oral anticoagulants (DOACs), 
which include dabigatran, rivaroxaban, apixaban, and edoxaban. Unlike warfarin, DOACs 
can be administered without the need for monitoring, have fewer food and drug interactions.  
However, bleeding risk is not completely avoidable even with DOAC, risk of bleeding is 
increased with age, weight and renal function10-12,  and patient tolerance and compliance as 
with Warfarin are still concerned.  Non-pharmacological therapy alternative to oral 
anticoagulation therapy, therefore, is necessary. Symptomatic AF patients with intolerance to 
pharmacological therapy are treated with catheter ablation. However, in addition to 
complications associated with high frequency ablation/cryotherapy and it is difficult to apply 
them to elderly or CHF patients, and their indication is limited since results is not always 
optimal for persistent or permanent AF. Furthermore, long term effect, stroke prevention and 
improvement of prognosis have not been clearly identified.     
The sponsor has developed the BSJ003W Left Atrial Appendage Closure (LAAC) Device, 
a permanent implantable device to seal off the left atrial appendage, the location where more 
than 90% of thrombi in atrium originate in NVAF patients.  Safety and effectiveness of 
BSJ003W in NVAF patients who need reduction of thromboembolic events were evaluated 
in foreign clinical trials with Warfarin as a control. As a result, non-inferiority to Warfarin in 

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reduction of thromboembolism was confirmed, discontinuation of Warfarin reduced the risk 
of hemorrhagic stroke and bleeding events and cardiovascular death (including unexplained 
cause) was found to be reduced more than Warfarin14-18.  In comparison with Warfarin, 
BSJ003W was able to reduce cardiovascular death by 56% whereas DOAC reduced 12%, 
and therefore, BSJ003W may also be more beneficial to those NVAF patients who are 
eligible for the device as far as DOAC is concerned.  BSJ003W can provide an alternative to 
NVAF patients who require thromboembolic protection and especially with history of 
bleeding and cerebral infarction, high risk of bleeding, incompliance with anticoagulation, 
continuous administration of anticoagulation is considered not appropriate due to their 
medical history, renal function and/or liver function and high risk of trauma from 
occupational conditions or life style,.  
5. Device Description 
5.1. Medical Equipment Description 
The BSJ003W LAA Closure Technology featuring BSJ003W consists of the BSJ003W 
Access System (which consists of the Access Sheath and Dilator Figure 1) and the BSJ003W 
Delivery System (which consists of the Delivery Catheter and the pre-loaded BSJ003W 
Closure Device, Figure 2). The BSJ003W Access System and BSJ003W Delivery System 
permit device placement in the LAA via femoral venous access and crossing the inter-atrial 
septum into the left atrium. The placement procedure can be done under local or general 
anesthesia in a catheterization laboratory.  
5.1.1. BSJ003W Access System (Access Sheath and Dilator) 
The 14F (12F Inner Diameter) transseptal Access Sheath is utilized to gain access to the 
LAA and serves as a conduit for the BSJ003W Delivery System. The distal end of the Access 
Sheath is available in three different curve styles to assist with placement of the sheath into 
the LAA. These curve styles allow for coaxial placement of the sheath into the LAA. The 
distal tip of the Access Sheath 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 Closure 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, the Access Sheath 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. 
 

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Figure 1: BSJ003W Access System (Access Sheath/Dilator) 
 
 
5.1.2. BSJ003W Delivery System and with Pre-loaded LAAC Device 
The BSJ003W Closure Device is comprised of a self-expanding nitinol frame structure with 
fixation anchors around the Closure Device perimeter and a permeable polyester fabric that 
covers the atrial facing surface of the Closure Device (Figure 2). The Closure Device is 
constrained within the Delivery Catheter until deployment in the LAA. 
The BSJ003W Closure (Gen 2.5) Device is available in 5 sizes from 21 to 33 mm.  Closure 
Device selection is determined by LAA measurements using fluoroscopy (fluoro) and 
transesophageal echocardiography (TEE) (Table 5-1). The BSJ003W Closure Device is 
designed to be permanently implanted at or slightly distal to the ostium (opening) of the LAA 
to trap potential emboli before they exit the LAA. 
 
Figure 2: BSJ003W Closure Device 
 

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Table 5- 1 Device size and applicable LAA size  
BSJ003W 
Device size 
Maximum LAA 
ostium 
Diameter at 
maximally 
crimpped(20%) 
Diameter at 
minimally 
crimpped(8%) 
21 mm 
17-19 mm 
16.8 mm 
19.3 mm 
24 mm 
20-22 mm 
19.2 mm 
22.1 mm 
27 mm 
23-25 mm 
21.6 mm 
24.8 mm 
30 mm 
26-28 mm 
24.0 mm 
27.6 mm 
33 mm 
29-31 mm 
26.4 mm 
30.4 mm 
The Delivery Catheter for BSJ003W 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 BSJ003W Closure Device is pre-loaded into a Delivery Catheter and is deployed by 
loosening the valve on the Delivery System and retracting the outer sheath. The BSJ003W 
Closure Device can be partially recaptured and redeployed if the device is too distal. If the 
Closure Device is deployed too proximal, it can be fully recaptured. The Closure Device is 
released by rotating the device deployment knob counter clockwise. 
 
Figure 1  BSJ003W delivery system (delivery catheter and closure device )  
 
 

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5.2. Indications for Use 
The BSJ003W Closure Device is indicated for left atrial appendage (LAA) closure therapy to 
reduce the risk of ischemic stroke and systemic embolism in patients with non-valvular atrial 
fibrillation. 
 
Contraindications 
Do not use the BSJ003W Closure Device if: 
1. 
Intracardiac thrombus is visualized by TEE echocardiographic imaging. 
2. 
An atrial septal defect repair or closure device or a patent foramen ovale 
repair or closure device is present. 
3. 
The LAA anatomy will not accommodate a Closure Device (refer to the 
BSJ003W Closure Device Selection guide in the BSJ003W DFU).  
4. 
The patient has a known hypersensitivity to any portion of the device material 
or the individual components (see Device Description in the BSJ003W DFU) 
such that use of the BSJ003W Closure Device is contraindicated.  
5. 
Any of the customary contraindications for other percutaneous catheterization 
procedure (e.g. patient size too small for TEE probe or required catheters) or 
conditions (e.g., active infection, bleeding disorder) is present. 
6. 
There are contraindications to the use of warfarin, aspirin, or thienopyridine   
5.3. Device Labeling 
The study Manual of Operations includes the Instructions for Use (IFU) for the BSJ003W 
LAA Closure Technology. The study devices are labeled which will include the following 
information. Packaging will include peelable, self-adhesive labels for each unit shipped.  
• CAUTION: Clinical trial use only 
• Study device ID 
• Lot number 
• Expiration (use by) date (labeled as month/year, device not to be used after the last day of 
the indicated month) 
• Storage condition (if applicable) 
• Sponsor name and address 
6. Study Objectives 
To confirm the safety and effectiveness of BSJ003W in Japanese patients with non-valvular 
atrial fibrillation at increased risk of thromboembolism in Japanese Clinical environment 

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7. Study Endpoints 
7.1. Primary Endpoint 
1. The occurrence of one of the following events between the time of implant and 
within 7 days following the procedure or by hospital discharge, whichever is later:  
all-cause death, ischemic stroke, systemic embolism, or device- or procedure- 
related events requiring open cardiac surgery or major endovascular intervention such 
as pseudoaneurysm repair, AV fistula repair, or other major endovascular repair.  
Percutaneous catheter drainage of pericardial effusions, snaring of an embolized 
device, thrombin injection to treat femoral pseudoaneurysm and nonsurgical 
treatments of access site complications are excluded from this endpoint. 
 
2. The occurrence of composite events* including stroke (all/ ischemic/ hemorrhagic), 
systemic embolism and CV death (including unexplained cause) . 
*All data collected by the last patient’s 6 months follow-up visit to be completed.  
 
3. The rate of effective LAA closure* at 45 days and 6 months. Change in the rate 
between the two time points will also be analyzed. 
*The effective LAA closure is defined as peri-device flow < 5mm demonstrated by 
TEE. TEE measurements will be assessed by independent Core Lab. 
7.2. Secondary Safety Endpoint 
• 
The occurrence of major bleeding* at 0 – 45 days, 45 days – 6 months, 6 months – 24 
months 
*Major bleeding is defined as per BARC bleeding definition type 3 or 5 
• 
Frequency of the following bleeding events at 0 – 45 days, 45 days – 6 months and 6 
months – 24 months: 
Clinically overt non-fatal bleeding*  
All bleeding events*Clinically overt non-fatal bleeding is defined as per BARC bleeding 
definition type 2. 
 
7.3. Secondary Effectiveness Endpoint 
• 
The occurrence of composite events* including stroke (all/ ischemic/ hemorrhagic), 
systemic embolism and CV death (including unexplained cause)  
*All data collected up to last patient’s 12 months and 24 months follow-up visits to be 
completed.  

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• 
Effective LAA closure at 12-month and its time course until then. 
• 
The occurrence of ischemic stroke or systemic embolism (excluding 7 days after 
implanting or day after hospital discharge whichever is the later) at 6 months, 12 months 
and 24 months. 
 
7.4. Additional analysis 
Device performance: 
• 
Technical Success defined as successful delivery and release of BSJ003W into the LAA 
including successful recapture and retrieval if necessary. 
 
Safety endpoints: 
• 
Occurrence of reportable adverse events 
• 
Occurrence of all-cause mortality 
 
Effectiveness endpoints: 
• 
Individual occurrence of all-cause death, ischemic stroke, hemorrhagic stroke, systemic 
embolization, cardiovascular death (including unexplained cause) at 6-month, 12-month 
and 24-month.  
• 
Warfarin discontinuation rate at 45 days, 6-month and 12-month 
• 
Severity of stroke assessed by NIH stroke score, Modified Rankin scale and Barthel 
Index 
 
Other endpoint: 
• 
EQ-5D 
 
8. Study Design 
This is a prospective, multi-center, single-arm study. 
8.1. Scale and Duration 
This study will be conducted at up to 10 centers and enroll maximum of 60 patients in Japan.  
Of the potential 60 subjects, 10-20 subjects will be Roll-in and 40 will be enrolled as 
analyzable subjects.  Sites are required to enroll at least one Roll-in subject prior to 
enrollment of analyzable subjects. Two Roll-in subjects are allowed to be enrolled by the 
decision of proctor or investigator if needed. The use of Roll-in subjects will allow 
physicians to gain experience with the BSJ003W implant procedure prior to beginning 
enrollment of analyzable subjects.   

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Once screening is completed and BSJ003W is implanted, a subject will be followed at 45 
days, 6 months, 12 months, 18 months and 24 months after the study procedure.  
Screening 
(Baseline) 
Follow-up 
45-day 
12-month 
24-month 
Day 0 
6-month 
Implant 
IC 
ASA 
OAC 
+ ASA 
DAPT 
18-month 
 
Figure 8.1-1: Study Design 
 
8.2. Treatment Assignment 
The study is designed to enroll subjects that meet all inclusion and no exclusion criteria. 
8.2.1. Treatment 
Refer to Section 5.0 for study device information and available sizes. 
8.3. Justification for the Study Design 
Safety and Effectiveness of BSJ003W in NVAF patients who need thromboembolic event 
prevention have been confirmed through results of foreign pivotal clinical studies using 
Warfarin therapy as their controls, i.e. non-inferior to Warfarin in prevention of 
thromboembolic events and superiority in prevention of hemorrhagic stroke and bleeding 
events by Warfarin discontinuation, and furthermore reduction of cardiovascular events 
(including unexplained death) more than Warfarin.  (Refer to Section 5.0) 
Objective of this study is to confirm safety and effectiveness of BSJ003W in Japanese 
medical environment when it’s implanted in Japanese NVAF patients and confirm similarity 
of the study results to those from foreign pivotal clinical studies, and therefore, prospective 
single arm design was considered appropriate.   
To evaluate safety, collect peri-procedural adverse events related to the procedure, and to 
evaluate expected effectiveness of BSJ003W action, composite endpoints of thromboembolic 
events and LAA closure rate will be confirmed.   
Not only in PREVAIL study but also in other studies associated with anti-coagulation 
therapy, rate of thromboembolic events have been observed for two years, and so long term 
follow-up of safety and effectiveness in this study will be also evaluated for two years after 
BSJ003W implantation in the study procedure.  
 

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9. Subject Selection  
9.1. Study Population and Eligibility  
Any subject, who meets all the inclusion criteria, does not meet any of the exclusion criteria, 
and who provides written informed consent may be enrolled in the study. The subjects 
selected for participation will be from the investigators’ general subject population. The 
investigator has the responsibility for screening all potential subjects and selecting those who 
meet study inclusion criteria and do not meet any of the exclusion criteria as described in 
sections 9.2 and 9.3.  There are additional Echo exclusion criteria (section 9.4) that must be 
met.   
9.2. Inclusion Criteria 
Subjects who meet all of the following inclusion criteria (see Table 9.2-1) may be given 
consideration for inclusion in this clinical investigation.  
Table 9.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
1. The subject is Japanese, over 20 years old and provides written 
informed consent to participate in the trial 
2. The subject has documented paroxysmal, persistent or permanent non-
valvular atrial fibrillation 
3. The subject has a calculated CHA2DS2-VASc score of 2 or greater and 
is recommended for long-term oral anti-coagulation therapy 
4. The subject is deemed by their physicians to be suitable for 
anticoagulant therapy and have an appropriate rationale to seek a non-
pharmacologic alternative to warfarin 
5. The subject is eligible to come off warfarin therapy if the LAA is 
sealed (i.e. the subject has no other conditions that would require 
warfarin therapy). 
 
 
 
 

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9.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 9.3-1) will be excluded from this 
clinical study. 
Table 9.3-1: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
1. The subject has a prior stroke (ischemic or hemorrhagic) or TIA within 
the 90days prior to consent 
2. The subject has had a MI either non-ST elevation or ST elevation MI 
within 90days prior to consent with or without intervention 
3. The subject had or is planning to have any cardiac (e.g. cardioversion, 
coronary angiogram, percutaneous coronary intervention, cardiac 
ablation, etc.) or non-cardiac invasive or surgical procedure (e.g. cataract 
surgery, endoscopy, etc.) within 30 days prior or 45 days after the 
BSJ003W implant 
4. The subject has a history of atrial septal repair or has an ASD/PFO device 
5. The subject has an implanted mechanical valve prosthesis in any position  
6. The subject currently NYHA class IV CHF 
7. The subject is contraindicated to aspirin 
8. The subject is contraindicated or seriously allergic to thienopyridine  
9. The subject is of childbearing potential and is, or plans to become 
pregnant during the time of the study (method of assessment upon study 
physician's discretion) 
10. The subject is not able and willing to return for required follow-up visits 
and examinations 
11. Subjects who are currently enrolled in another investigational study (of 
which primary endpoint follow-up have not been completed yet). 
12. The subject has other reason not to be eligible for this study per 
investigators' discretion. 
 
 
 
 

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9.4. Echo Exclusion Criteria 
After informed consent and prior to or at the onset of procedure a TTE/TEE is performed.  
These additional exclusion criteria must be evaluated for each subject.  If any of the Echo 
exclusion criteria are met, then the subject will be withdrawn from the study and will be 
classified as “INTENT” subject. 
Table 9.4-1: Echo Exclusion Criteria 
Echo 
Exclusion 
Criteria 
1. The subject has LVEF < 30%. 
2. The subject has intracardiac thrombus visualized by TEE and determined 
by the echocardiographer within 2 days prior to implant. 
3. The subject has an existing pericardial effusion with a circumferential 
echo-free space > 5mm, and/or the patient has signs/symptoms of acute or 
chronic pericarditis, and/or there is evidence (clinically or 
echocardiographically) of tamponade physiology  
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 and/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 and/or aortic arch. 
8. The subject has a cardiac tumor 
 
10. Subject Accountability 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) shall be accounted for and documented. Until informed consent is 
signed by a patient, any study required tests and procedures must not be done.  
10.1. Point of Enrollment 
One Roll-in subject will be enrolled before analyzable subject will be enrolled at each site. If 
necessary per discretion of investigators and/or proctor, one more Roll-in subject can be 
enrolled at the site. 
Subjects who meet the eligibility criteria, who have signed and dated the Informed Consent 
Form and a vascular access is inserted in the body are considered enrolled in the study.  Each 
site should start enrolling analyzable subjects once enrollment of Roll-in subject is completed 
at each site. Enroll subjects once eligibility criteria are confirmed.     
10.2. Withdrawal 
If a subject withdraws from the clinical investigation, the reason(s) shall be reported. If such 
withdrawal is due to problems related to investigational device safety or performance, the 

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investigator shall ask for the subject’s permission to follow his/her status/condition outside of 
the clinical study.   
10.3. Subject Status and Classification 
10.3.1. Screen Failure 
A subject who signs informed consent, but does not meet clinical eligibility criteria or does 
not undergo a vascular access inserted into the body in order to implant the device is 
considered a screen failure.  Screen failure subjects do not count towards the enrollment 
ceiling and will not be used for the primary analysis. Additionally, these subjects will be 
included in a sensitivity analysis. The original signed Informed Consent must be maintained 
in the site and the following forms must be completed: 
• Informed Consent Information, Screening Information, Inclusion Criteria, Exclusion 
Criteria, Echo Exclusion Criteria, Demographics 
10.3.2. Attempt 
A subject who signs informed consent, meets all eligibility criteria (per Section 9.2, 9.3, and 
9.4 of this Protocol) and has had a vascular access inserted into the body in order to implant 
the device, but eventually does not receive a BSJ003W Closure Device will be classified as 
“Attempt.”  Attempt subjects will be followed for 45 days from the time of the implant 
attempt and adverse events will be collected up to the point of subject withdrawal.  Attempt 
subjects count towards the enrolment ceiling and will be used for analyses of the endpoints.  
The original signed Informed Consent must be maintained in the site and the applicable case 
report forms until 45 days visit must be completed 
The date at which the “End of Study” form has been completed will be considered as the 
point of subject withdrawal.  
10.3.3. Implant 
A subject who is successfully implanted with the BSJ003W Closure Device will be classified 
as an “Implant.” These subjects are followed in accordance with the follow-up schedule and 
included in all study analyses.  All applicable case report forms per the protocol must be 
completed. The original signed Informed Consent and any relevant documentation must be 
maintained in the site. 
 
 

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Figure 2: Subject Status and Data Collection Flow Chart 
10.4. Enrollment Controls 
Subject enrollment into the BSJ003W Japan Study will be discontinued upon enrollment of g 
40 non-roll-in subjects with the BSJ003W Closure Device. The single site ceiling is up to 8 
subjects. Beyond the limit, sponsor and site will communicate to enroll more subjects. 
Investigational sites will be notified when the enrollment goal is close to being reached and 
once enrollment is complete. 
 
 
Informed consent 
obtained 
LAA echo 
criteria met? 
Implant of BSJ003W 
NO 
YES 
Device implanted 
Device not implanted 
Follow-up according to 
protocol schedule 
Withdrawal 
(Attempt) 
All clinical criteria met? 
YES 
NO 
Duration not to 
exceed 30 days 
Withdrawal 
(Screen failure) 

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11. Study Methods 
11.1. Data Collection 
Table 11- 1 documents the information that will be requested at each visit. 
For all IMPLANT subjects (successfully received the BSJ003W Closure Device) all visits 
are required, as defined in Table 11-1.For subjects classified as ATTEMPT, all visits up to 
and including the 45 day visit are required. The TEE is not required for these subjects. 
Table 11-1: Data Collection Schedule 
Procedure/Assessment 
Screeni
ng 
Impl
ant 
Follow-up Visits 
45-Day 
(± 15 Days) 
Visite 
6-Month  
( 180 days ± 
15 Days) 
Visit 
12 months 
(365 days ± 
30 Days) 
Visit 
18 months 
(540 days 
± 60 Days) 
Visit 
24 Month 
(730 days ± 
60 Days) 
Visit 
Informed consent form, 
including informed consent 
signature date 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Physical assessment 
X 
 
X 
X 
X 
X 
X 
Medical history 
X 
 
 
 
 
 
 
Transthoracic 
echocardiogram (TTE)a 
X 
 
 
 
 
 
 
Transesophageal 
echocardiogram (TEE) 
Xb  
X 
Xc 
X 
X 
 
 
Brain Imaging (MRI/CT) 
As 
requiredd 
 
As requiredd 
As requiredd 
As requiredd 
As requiredd 
As requiredd 
Anticoagulant and 
antiplatelet medications 
X 
 
X 
X 
X 
X 
X 
Modified Rankin Scale 
X 
 
X 
X 
X 
X 
X 
NIH Stroke Scale 
X 
 
X 
X 
X 
X 
X 
Barthel Index 
X 
 
X 
X 
X 
X 
X 
Device and implant details 
 
X 
 
 
 
 
 
Adverse event/ Device 
Deficiency monitoring 
 
Xg 
X 
X 
X 
X 
X 
eGFR and proteinuria 
X 
 
 
 
 
 
 
EQ-5D 
X 
 
 
X 
X 
X 
X 
aAn LVEF value obtained from a TTE performed within 90 days prior to consent may be used.  If a significant 
cardiac event occurs after the TTE which causes a change in cardiac status [i.e., major CHF decompensation] 
the baseline TTE must be repeated prior to enrollment 
b  Must be performed within 2 days prior to the study procedure or can be done at the study procedure but before 
implant of BSJ003W 
c For Attempt, no TEE is required 
d Obtain MRI/CT required if subject had prior stroke or TIA. A MRI or CT performed within in 90 days prior 
to consent may be used. 
eFor Attempt subjects the visit can be performed in office.  For subjects classified as implant an office visit is 
required. 
g Adverse event/ Device deficiency monitoring  is started from the time when subjects enter a catheterization suite 
or an operating room for BSJ003W procedure. 

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11.2. 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. Informed 
consent is required from all subjects prior to the subject’s participation in the study. The 
subject should be given ample time to consider participation and ask questions if necessary. 
An IRB-approved informed consent form must be signed and personally dated by the subject. 
The original, signed document is to be kept with the subject’s file and a copy must be 
provided to the subject. The informed consent process must be documented by the person 
obtaining consent and the documentation must be placed in the site.  
11.3. Screening Visit 
Subjects selected for participation in this study should be from the investigator’s general non-
valvular atrial fibrillation population.  Each investigator is responsible for screening all non-
valvular atrial fibrillation subjects and selecting those who are appropriate for inclusion. 
Subjects who meet the eligibility criteria as per 9.2, 9.3 and 9.4, and have signed and dated 
the Informed Consent Form are considered enrolled. The implant visit must occur within 30 
days of consent. 
The following will be assessed at the Baseline visit and documented on the Baseline case 
report forms for enrolled subjects: 
• Demographics and medical history 
• Physical assessment including vital signs (Height,  Body weight, Blood Pressure and 
Heart rate) 
• Current medication regimen for the use of antiplatelet and anticoagulation 
• Modified Rankin Scale (MRS), NIH Stroke Scale (NIHSS) and Barthel Index (BI) 
• Subjects with prior history of ischemic stroke, hemorrhagic stroke or TIA are 
required to have a Baseline MRI or CT obtained  (up to 90 days prior to consent if no 
prior measurement is available) 
• Transesophageal echocardiogram (TEE) prior to implant 
• Transthoracic Echocardiogram (TTE) (up to 90 days prior to consent or if no prior 
measurement is available) 
• eGFR (serum creatinine up to 6 months before consent or at enrollment if no prior 
measurement is available) 
• Protenuria (dipstick protein-dichotomized as urine dipstick protein none/trace vs. 1+ 
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• EQ-5D 
11.4. LAA Imaging 
After informed consent, all subjects will undergo an enrollment TEE and TTE.   
All study required TEEs will be performed by protocol trained individuals and in accordance 
with the Imaging Manual.  Copies of the TEE’s will be sent to the Echo Core Lab per the 
Imaging Manual. Copies of all protocol required TEE imaging will be saved to disk media 
and available to the sponsor upon request.  Certain information from TEEs conducted during 
the course of the study will be captured on the study case report forms.  The site and subject 
identification number should be clearly identified on the media provided. 
Certain information from TTEs conducted during the course of the study will be captured on 
the study case report forms.  
1. 
Transthoracic Echocardiogram (TTE) 
The enrollment TTE will be done to evaluate LVEF to confirm subject eligibility.  An LVEF 
value obtained from a TTE performed within 90 days prior to consent 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 must be repeated 
prior to enrollment. 
2. 
Transesophageal Echocardiogram (TEE) 
All protocol required TEEs will be performed by protocol trained individuals and in 
accordance with the Imaging Manual.  The Enrollment TEE will determine that all inclusion 
and exclusion criteria are met and must occur within 2 days prior to the implant.  It may also 
occur on the same day as implant. The implant TEE will allow the investigator to obtain 
proper measurements of the LAA to correctly size the device, confirm device release criteria 
are met prior to device release, and confirm adverse events have not occurred during the 
implant procedure (i.e., pericardial effusion). 
The 45-day, 6-month and 12-month TEEs are conducted to assess flow through and around 
the BSJ003W Closure Device and to verify there is no thrombus on the surface of the device.  
Adequate LAA seal is defined as little or no visible residual blood flow around the margins 
of the BSJ003W Closure Device in either a retrograde or antegrade fashion, with jet size ≤ 
5mm.  
a. Stroke or Systemic Embolism TEE 
In the event that a subject experiences a stroke or SE during the course of the study, 
supporting TEE documentation will be requested by the sponsor in an attempt to search for 
causes of stroke or embolic event.  It is strongly encouraged to help better ascertain the 
mechanism of all strokes and SE. An optimal TEE evaluation includes, where feasible based 
on subject status and technical considerations, evaluation of:  

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i. 
LA thrombus – size, location, mobility, etc. 
ii. 
BSJ003W Closure Device seal or presence (and measurement) of peri-device flow 
iii. 
BSJ003W Closure Device thrombus or pannus – size, location, mobility, etc. 
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)  
v. 
Presence, location 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/substituted by TTE where appropriate, in addition to TEE parameters 
above) 
b. Device Thrombus TEE 
The most accurate determination of whether thrombus has formed on the surface of the 
BSJ003W Closure 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 resolved. Cessation of anticoagulation after this timepoint is at the 
discretion of the investigator. 
11.5. Implant Procedure 
The implant visit must occur within 30 days of consent.  The implant procedure should be 
performed using standard of care methods established by the investigational center (e.g. 
sterile technique, personnel requirements, etc.).  Implantation of the BSJ003W Closure 
Device should only be performed with support of a proctor and a Field Clinical Specialist 
and by physicians trained in percutaneous and trans-septal procedures who have completed 
the BSJ003W physician training program. Refer to the BSJ003W Directions for Use (DFU) 
for detailed instructions regarding the implantation and use of the BSJ003W Closure Device. 
Information collected during the implant procedure includes the following: 
• BSJ003W Closure Device usage information 
• Access System(s) usage information 
• Device Release Criteria 
• Device Deficiencies 

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• Adverse events experienced since previous visit 
11.6. Study Medication Regimen (for subjects classified as Implant) 
Protocol-required concomitant medications must be reported in the eCRF from the time of 
the enrollment visit through the 2 year follow-up. Information pertaining to the use of oral 
anticoagulants, thienopyridine and aspirin, including dose changes, medication interruptions, 
and medication cessation, must be documented. (See Figure 3). 
1 Day Prior to Implant
Begin aspirin
Day of Implant
Anticoagulation during the study procedure is 
decided at investigator’s discretion
Continue aspirin and start warfarin to adjust INR to 
2.0-3.0 or 2.0-2.6 recommended for >70 years old. 
Continue till 45 day FU
45 Days Post-Implant
TEE
Is LAA seal <5mm?
Cease warfarin and continue aspirin
Add thienopyridine
6-Month Post-Implant
TEE
Is LAA seal <5mm?
Continue warfarin (adjust INR 
appropriately) and aspirin
Continue warfarin (adjust INR 
appropriately) and aspirin
Cease thienopyridine and continue 
aspirin
Cease warfarin, if continued
12-Month Post-Implant
TEE
Is LAA seal <5mm?
Pharmacologic regimen after this 
will be decided at investigator’s 
discretion
No
Yes
No
No
If still continued, cease warfarin
 and continue aspirin
Yes
Yes
 
Figure 3: BSJ003W Closure Device Implant Pharmacologic Regimen 

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▪ Implant through 45-Day TEE 
  Implanted subjects should be on adjusted dose warfarin therapy through at least the 45-day 
follow-up TEE.  While on warfarin therapy, subjects should also be prescribed aspirin. 
Warfarin therapy should be appropriately adjusted so as to achieve a therapeutic INR of 2.0 – 
3.0, monitored per standard of care.  For a subject who are 70 years old or older, a 
therapeutic INR of 2.0 – 2.6 is recommended considering the high risk of major bleeding.  
▪ 45-Day Visit 
A TEE will be conducted at the 45-day visit to assess position and the seal around the 
perimeter of the BSJ003W Closure Device within the LAA ostium.  Adequate LAA seal is 
defined as little or no visible residual blood flow around the margins of the BSJ003W 
Closure 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:  
• Warfarin therapy should be discontinued, 
• Aspirin should be continued indefinitely, and 
• Thienopyridine should be initiated, taken for 6-months post-implant, and then 
discontinued.  
If the 45-day TEE shows inadequate seal of residual LAA blood flow with a jet size > 5mm 
around the margins of device, 
• The subject should remain on warfarin and aspirin therapy.  
• Thienopyridine should not be initiated. 
 
▪ 6-Month Visit 
A TEE will be conducted at the 6-Month visit.If the 45-day or 6-Month TEE shows adequate 
seal of the LAA:  
• Warfarin therapy should be discontinued (If continuously prescribed after 45 days) 
• Thienopyridine should be discontinued 
• Aspirin should be continued indefinitely 
If the 6-month TEE shows inadequate seal of residual LAA blood flow with a jet size > 5mm 
around the margins of device, 
• The subject should remain on warfarin and aspirin therapy.  
• Thienopyridine should not be initiated. 
 

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▪ 12-Month Visit 
If the 45-day, 6-Month or 12-Month TEE shows adequate seal of the LAA:  
• Aspirin should be continued indefinitely  
If the 12-Month TEE shows inadequate seal of the LAA, anticoagulation and antiplatelet 
therapy after the 12-Month is at the discretion of the investigator. 
Caution:  
1. Use of direct oral anticoagulants (DOACs) in this study is not recommended since this has 
not been studied in subjects with a BSJ003W Device.  If anticoagulation is required for 
any reason beyond what is specified in the protocol, ensure medication labeling is 
followed, specifically labeling related to the abrupt discontinuation of DOACs in subjects 
with non-valvular atrial fibrillation without adequate continuous anticoagulation. 
2. No antiplatelet drug other than Aspirin was administered for long term in a clinical study, 
and therefore, no other antiplatelet drug but Aspirin is recommended in this study after 6 
months post-implant. If administration of any antiplatelet drug like thienopyridine is 
required other than Aspirin, ensure medication labeling is followed. 
 
11.7. Stroke Assessments 
The Modified Rankin Scale (MRS) score and the Barthel Index score will be routinely 
collected at screening and follow-up visits for all subjects and at 90 (+/- 10) days following a 
stroke or TIA event.  This scale assesses the severity of stroke disability and functional 
dependence of subjects. This test will be collected at baseline and all office follow-up visits.  
The assessment must be performed by either a neurologist or personnel who have completed 
a certification for the MRS. 
The NIH Stroke Scale (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 all office follow-
up visits and if possible, following stroke. It must be conducted by a neurologist or personnel 
who have a current certification to conduct the NIHSS. 
11.8. QoL Assessments: EQ-5D 
The EQ-5D will be collected at baseline, at 6 months, 12 months, 18 months and 24 months 
office follow-up visits.   
 
 
 

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11.9. Follow-up Procedures at 45 days 
11.9.1. For Subjects classified as Implants 
Subjects successfully implanted with the BSJ003W Closure Device, “IMPLANT”, will 
complete an office visit 45-days post-implant with a TEE evaluation. Information collected 
during the 45-day visit includes the following: 
TEE (as described in Section 11.5) 
MRS, NIHSS and BI 
Current medication regimen for the use of antiplatelet and anticoagulation 
medications (as described in Section 11.7)  
Physical assessment including vital signs  (Body weight, Blood Pressure and 
Heart rate) 
Device-,procedure- and/or study-related adverse events, including device 
deficiencies experienced since previous visit 
Stroke, SE and/or Thrombus TEE, if needed 
Brain MRI or CT required if subject suffers stroke or TIA 
Adverse events including device deficiencies experienced since previous visit 
 
11.9.2. For Subjects classified as Attempts 
Subjects who were NOT successfully implanted with the BSJ003W Closure Device will 
complete an office visit 45-days post procedure. Information collected during the 45-day visit 
for “ATTEMPT” subjects includes the following: 
Adverse events including device deficiencies experienced since previous visit 
TEE is not required for these subjects 
 
 
 

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11.10. 
Office Visit Follow-up (6-month and 12-month) 
Information collected during the 6months and 12 months visit includes the following: 
TEE  
MRS, NIHSS and BI 
Current medication regimen for the use of antiplatelet and anticoagulation 
medications ( as described in Section 11.7)  
Physical assessment  including vital signs  (Body weight, Blood Pressure and 
Heart rate) 
Adverse events including device deficiencies experienced since previous visit 
Stroke, SE and/or Thrombus TEE, if needed 
Brain MRI or CT required if subject suffers stroke or TIA 
EQ-5D 
 
11.11. 
Office visit Follow-Up (18-month and 24-month) 
“IMPLANT” subjects will complete an office visit 18 months and 24 months post implant.  
Information collected during this visit includes: 
MRS, NIHSS and BI 
Current medication regimen for the use of antiplatelet and anticoagulation 
medications (as described in Section 11.6) 
Physical assessment including vital signs  (Body weight, Blood Pressure and 
Heart rate) 
Adverse events including device deficiencies experienced since previous visit 
Stroke, SE and/or Thrombus TEE, if needed 
Brain MRI or CT required if subject suffers stroke or TIA 
EQ-5D 
 
 
 

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11.12. 
Study Exit 
Once a study subject has exited the study, their participation in the study has ended.  
Appropriate eCRFs are completed indicating the status of the subject (i.e., end of study form).  
The table below provides information on the appropriate eCRF’s to complete. 
 
Type of Study Exit 
Date to Use 
Form(s) to complete 
Subject withdrawal 
Date of subject 
withdrawal 
End of Study form 
Adverse Event  (resolve/close any AE’s) 
Subject Lost to Follow-
up 
Date subject was last 
seen in office 
End of study 
Adverse Event  (resolve/close any AE’s) 
Subject Death 
Date of Death 
Adverse Event (only one) with fatal 
outcome, resolve/close other AE’s 
End of Study Form 
Complete all protocol 
visits 
Date of last study visit 
End of Study Form 
Adverse Event (resolve/close any AE’s) 

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11.13. 
Source Documents 
Original source documents should be maintained, when available. Where copies of the original 
source document as well as printouts of original electronic source documents are retained, it is 
required that the copies be signed and dated by a member of the investigation site team with a 
statement that it is a true reproduction of the original source document. 
Table 11.13-1: Source Documentation Requirements 
Requirement 
Disposition 
Signed Informed Consent, patient charts including 
nursing records and catheterization record, lab results, 
study device accountability record, photographic 
negatives, radiographs and other hospital records, kept 
at the investigational sites, laboratories and medico-
technical departments involved in the study. 
Kept at investigational sites 
Data if directly documented in the eCRF; e.g. 
relationship of AE to study device(s), index procedure 
and anticipatedness assessment of ADEs, will be 
considered source data for the study. 
In the eCRF 
 
12. Statistical Considerations 
To discuss similarity of outcomes of this study and the foreign pivotal studies, working 
hypothesis was developed. 
Data collected from Roll-in patients will not be included in the following endpoint analysis 
and will be analyzed separately from those data collected from patients enrolled after 
completion of the Roll-in. 
12.1. Primary Safety Endpoints 
Primary safety endpoint is the occurrence of one of the following events between the time of 
implant and within 7 days following the procedure or by hospital discharge, whichever is 
later:  
all-cause death, ischemic stroke, systemic embolism, or device- or procedure- related events 
requiring open cardiac surgery or major endovascular intervention such as pseudoaneurysm 
repair, AV fistula repair, or other major endovascular repair.  
Percutaneous catheter drainage of pericardial effusions, snaring of an embolized device, 
thrombin injection to treat femoral pseudoaneurysm and nonsurgical treatments of access site 
complications are excluded from this endpoint. 
Similarities of this study results will be evaluated with foreign pivotal study results. 
12.1.1. Statistical Hypotheses 
Not applicable. 

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12.1.2. Sample Size  
The primary safety endpoint event rate observed in the PREVAIL study was 2.2% and an 
additional margin was added to create a performance target of less than 10.0%. Considering  
that 1-2 events may occur by chance, equal or more than 40 subjects will allow at least 3 
events or more to occur and with  >=95% probability, observed estimate from this study is 
lower than the performance target .   
 
12.1.3. Statistical Methods 
Each event will be evaluated individually and occurrence rate and 95% CI will be calculated.  
12.2. Primary Efficacy Endpoints 
Primary efficacy endpoints are the occurrence of composite events including stroke (all/ 
ischemic/ hemorrhagic), systemic embolism and CV death (including unexplained cause) and 
the rate of effective LAA closure at 45 days, 6 months and change in rate between the two 
time points.  
12.2.1. Hypotheses 
Not applicable. 
12.2.2. Sample Size  
A performance target of an effective LAA closure rate of this study, 94.0%, was created by 
considering an additional margin with 99.3% of the effective LAA closure rate observed in 
PROTECT AF and PREVAIL studies.  Accounting for 10% attrition to 6-month TEE follow-
up, 40 subjects are required to maintain >=95% probability that the observed estimate from 
this study is higher than the performance target of 94.0%. This will allow up to 2 patients 
whose LAA may not be effectively closed for any reasons at 6 months. 
Meantime, sample size of 40 patients were established taken into consideration that 10% of 
pivotal study sample size was reasonable from standpoint of the study feasibility and 
similarity comparison of outcomes of this study and the pivotal studies. 
12.2.3. Statistical Methods 
The occurrence of composite events including stroke (all/ ischemic/ hemorrhagic), systemic 
embolism and CV death (including unexplained cause) as well as effective LAA closure rate 
will be calculated and similarities of this study results will be evaluated with foreign pivotal 
study results. All data collected up to the last patient’s 6 month follow-up completion will be 
used for the analysis. 
 
 

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12.3. General Statistical Methods 
12.3.1. Analysis Sets 
Roll-in patients’ data will be evaluated separately from the data of those patients enrolled 
after the Roll-in patients. 
Intension-to-Treat( ITT)  subjects are included in primary analysis for primary safety and 
efficacy endpoints as well as secondary endpoints and other endpoints. In addition, Implant 
subjects alone will be evaluated as needed as reference.    
ITT: A subject who signs informed consent and regardless of the study device implanted or 
not, being enrolled into the study. IMPLANT and ATTEMPT subjects are included in ITT. 
12.3.2. Control of Systematic Error/Bias 
Selection of subjects for enrollment will be made from the Investigator’s usual subject load. 
All subjects meeting the eligibility criteria and having signed the ICF will be eligible for 
enrollment in the study. To control for the potential bias that could be introduced via sponsor 
classification of adverse events, a Clinical Events Committee (CEC) will adjudicate 
important endpoints and relevant adverse events. 
12.3.3. Number of Subjects per Investigative Site 
To avoid any center effect and bias, one center will not be authorized to enroll more than 
20% of the 40 subjects (n = 8) per this protocol. Further enrollment will require advance 
agreement from sponsor. 
12.3.4. Data Analyses 
Baseline and other results will be analyzed descriptively with continuous variables (mean, 
standard deviation, number of patients, minimum, maximum, etc) and discrete values 
(frequency table and percentage).  
12.3.5. Other Endpoints/Measurements  
Descriptive statistics will be used for other endpoints. 
12.3.6. Interim Analyses  
Interim analysis is not planned. 
Initial analysis is planned at the last patient’s 6 month follow-up completion and the second 
analysis at 12 month follow-up completion. Final analysis is planned once all follow-ups 
(24month follow-up) required by the study are completed.  
12.3.7. Subgroup Analyses 
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12.3.8. Justification of Pooling 
Not applicable. 
12.3.9. Multivariable Analyses 
Univariate and multivariate analyses will be performed to assess predictors for Primary 
safety endpoint, primary efficacy endpoint and secondary endpoint. Details of the analysis 
will be included in Statistical Analysis Plan. 
12.3.10. Other Analyses 
Descriptive analysis will be used for other analysis. 
12.3.11. Changes to Planned Analyses 
Any changes to the planned statistical analyses will be documented in an amended Statistical 
Analysis Plan approved prior to the change. Changes from the planned statistical methods 
after completion of the statistical analysis will be documented in the clinical study report 
along with a reason for the deviation. 
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 EDC System. All changes 
made to the clinical data will be captured in an electronic audit trail and available for review 
by the sponsor 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 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, head of medical institution and founder of the IRB will maintain all 
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collected on study subjects in compliance with GCP guidelines. The documents must be 
retained until the date of the marketing application approval or until 3 years have elapsed 
since the formal discontinuation or completion of the clinical investigation of the device, 
whichever is longer. 
These documents will be retained for a longer period of time by agreement with sponsor. If 
for any reason the Investigator and Site withdraw responsibility for maintaining these 
essential documents, custody must be transferred to an individual who will assume 
responsibility. The Investigator and Site will take measures to ensure that these essential 
documents are not accidentally damaged or destroyed. Sites are required to inform Boston 
Scientific in writing where paper or electronic files are maintained in case files are stored off 
site and are not readily available. 
The Sponsor must maintain necessary essential documents for 5 years from the date of the 
marketing application approval or until 3 years have elapsed since the formal discontinuation 
of the clinical investigation of the device, whichever is longer. If Re-Evaluation is applicable 
and requires more than 5 years to complete, the sponsor must maintain the essential 
documents until its completion. 
13.3. Core Laboratories 
An independent core laboratory will be utilized to review TEE imaging collected at protocol 
required time points during the study. All interpretations of TEE imaging for purposes of 
subject care will be conducted by each site’s investigator and/or echocardiographer. The 
Core Lab will not be utilized as a means of reference for subject management decisions. 
Imaging will be collected by each study site according to the Imaging Protocol and submitted 
to the Core Lab for review. The Core Lab will provide Boston Scientific with summary of 
results for reporting purposes and associated study endpoint analyses. 
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 IRB approval of the 
revised protocol must be obtained prior to implementation. 
15. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An 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, and those deviations which affect 
the scientific integrity of the clinical investigation. Such notice shall be given as soon as 
possible, but no later than 5 working days after the emergency occurred.  

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All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using eCRF. Sites may also be 
required to report deviations to the IRB, per local guidelines and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
 
16. Device/Equipment Accountability 
The investigational devices shall be securely maintained, controlled, and used only in this 
clinical study. Vender will be used to track subjects and device allocations during the study.  
The sponsor shall keep records to document the physical location of all investigational 
devices from shipment of investigational devices from BSC or designated facility to the 
investigation sites until return or disposal. 
Records shall be kept by the vender to document the physical location and conditions of 
storage of all investigational devices.  
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the investigational devices, which shall include the 
following 
• Date of receipt 
• Identification of each investigational device (batch number or unique code) 
• Expiry date, as applicable 
• Date or dates of use 
• Subject identification 
• Date on which the investigational device was returned/explanted from subject, if 
applicable 
• Date of return (and number) of unused, expired, or malfunctioning investigational 
devices/equipment, if applicable. 
Current sponsor processes will be used to track subjects and investigational device during the 
study. Upon completion of enrollment into the study, or as directed by the sponsor, all 
unused investigational devices must be returned to the sponsor. 
 

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17. Compliance 
17.1. Statement of Compliance 
This study will be conducted in accordance with Japan Medical Device GCP, ethical 
principles that have their origins in the Declaration of Helsinki, Pharmaceutical and Medical 
Device act, local regulations and this protocol. The study shall not begin until the required 
approval from the IRB and an acceptance of Chiken Todoke by regulatory authority have 
been obtained. Any additional requirements imposed by the IRB or regulatory authority shall 
be followed, if appropriate.  
17.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation plan, 
Japan Medical Device GCP, Pharmaceutical and Medical Device act, ethical principles that 
have their origins in the Declaration of Helsinki, any conditions of approval imposed by the 
reviewing IRB, and local laws and regulations, whichever affords the greater protection to 
the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign or name and seal the Protocol Signature page or 
Protocol agreement documenting his/her agreement to conduct the study in accordance 
with the protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the eCRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to sponsor, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
• Report to the IRB and regulatory authorities any SAEs and device deficiencies that could 
have led to a SADE and potential/USADE or UADE, if required by the national 

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regulations or this protocol or by the IRB, and supply BSC with any additional requested 
information related to the safety reporting of a particular event. 
• Maintain the device accountability records and control of the device, ensuring that the 
investigational device is used only by authorized/designated users and in accordance with 
this protocol and instructions/directions for use. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the IRB when performing auditing activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
17.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal 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.  

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17.3. Institutional Review Board 
Prior to gaining Approval-to-Enroll status, the investigational site will provide to the sponsor 
documentation verifying that their IRB is registered according to regulatory requirements.   
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. Prior approval must also be obtained for other materials related to 
subject recruitment or which will be provided to the subject. 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by IRB requirements. Copies of the Investigator’s reports and the IRB 
continuance of approval must be provided 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 including, but not limited to Contract Research Organization (CRO) 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’ identifiable 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.  
The clinical trial organization including study sites is provided as an attachment to this 
protocol. BSC may utilize contract research organizations (CROs) or other contractors to act 
as their representative for carrying out designated tasks. Responsibilities for these entities are 
defined in the applicable contracts or agreements. Contact information for the CROs is 
provided as an attachment to this protocol. 
The sponsor is responsible for providing the appropriate training about the study device 
implanting procedure to investigators.  
These training may include the following; 
• Overview of the study device 
• Overview of the implant procedure 
• Tips and size selection 
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• Proctoring 
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 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). 
• Enter data in electronic data capture systems or on paper case report forms. 
 
17.5. Insurance  
BSC will obtain proof and type of insurance coverage for subjects in the study. 
18. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 

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19. Potential Risks and Benefits 
19.1. Anticipated Adverse Events and Risks Associated with the Study 
Device(s)  
The following anticipated adverse events (AE) have been identified for this study. Potential 
procedural risks associated with the BSJ003W implant procedure are similar to those 
encountered peri- and post-operatively for many routine catheterization procedures. 
• Table 19-1: Anticipated Adverse Events 
• Air embolism 
• Airway trauma 
• Allergic reaction to contrast 
media/medications or device materials 
• Altered mental status 
• Anemia requiring transfusion 
• Anesthesia risks 
• Angina 
• Anoxic encephalopathy 
• Arrhythmias 
• Atrial septal defect  
• AV fistula  
• Bruising, hematoma or seroma 
• Cardiac perforation  
• Chest pain/discomfort  
• Confusion post procedure 
• Congestive heart failure 
• Contrast related nephropathy  
• Cranial bleed 
• Death 
• Decreased hemoglobin 
• Deep vein thrombosis 
• Device embolism 
• Device fracture 
• Device thrombosis 
• Edema 
• Excessive bleeding 
• Fever 
• Groin pain 
• Groin puncture bleed 
• Hematuria 
• Hemoptysis 
• Hypotension 
• Hypoxia 
• Improper wound healing 
• Inability to reposition, recapture, or retrieve the 
device 
• Infection / pneumonia  
• Interatrial septum thrombus 
• Intratracheal bleeding 
• Major bleeding requiring transfusion  
• Misplacement of the device / improper seal of the 
appendage / movement of device from 
appendage wall 
• Myocardial erosion 
• Nausea 
• Oral bleeding 
• Pericardial effusion / tamponade 
• Pleural effusion 
• Prolonged bleeding from a laceration 
• Pseudoaneurysm  
• Pulmonary edema 
• Renal failure 
• Respiratory insufficiency / failure  
• Stroke – Ischemic  
 Stroke – Hemorrhagic 
•  Surgical removal of the device 
• Systemic embolism 
• TEE complications (throat pain, bleeding, 
esophageal trauma) 
• Thrombocytopenia 
• Thrombosis 
• Transient ischemic attack (TIA) 
• Valvular damage 
• Vasovagal reactions 

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19.2. Risks associated with Participation in the Clinical Study 
Subjects who receive the BSJ003W Closure 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 and other oral anticoagulants are the 
most frequently utilized modality for reducing the risk of stroke in atrial fibrillation.  The 
BSJ003W Closure Device is designed to be used instead of warfarin.  The absence of an oral 
anticoagulant may represent a risk, especially if the device is not effective in preventing 
stroke. 
19.3. Possible Interactions with Concomitant Medical Treatments 
Refer to the warfarin, aspirin and thienopyridine package insert. 
19.4. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
BSC will minimize risks of enrolled subjects by evaluating cause of the risks with 
experiences obtained from BSJ003W clinical studies and sales. Furthermore, minimization of 
the above mentioned risks should be tried through the following ways: 
Target population of the study is those patients with high risk of stroke, and therefore, 
measures should be taken to prevent stroke by appropriately control the biggest risk factor of 
the stroke, blood pressure, in accordance with Japanese Guideline for the Management of 
Stroke (2015)20. On the other hand, per Guidelines for management of anticoagulant and 
antiplatelet therapy in cardiovascular disease (JCS 2009）21, gastrointestinal bleeding from 
low dose Aspirin increases with age, and the target population of Aspirin treatment is older 
generation, and therefore, it is important to monitor gastrointestinal complications in order 
for Aspirin to be administered safely.   
• 
Complete risk assessment of the study device before the study initiation per 
ISO14971 
• 
Conduct safety test of BSJ003W using canine model to confirm safety and vascular 
compatibility  
• 
Select investigators who understand risk, clinical indication and basic principal of 
percutaneous and trans-septal technique through the study device training. 
• 
Clearly define inclusion and exclusion criteria so that only those patients who are 
eligible for the study to enroll. 
• 
Align treatment and follow-up of subjects to the current medical practice. 
• 
Safety evaluation process based on the threshold established in advance. 

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19.5. Anticipated Benefits 
No direct subject benefit is expected from this study. Subjects enrolled in this study will 
receive the same clinical care as subjects who are routinely implanted with a BSJ003W 
Closure Device and not enrolled in this study. However, results from the data collected 
during this study may improve the management of BSJ003W subjects in the future; therefore, 
the subjects enrolled in this study may also benefit at a later stage.  
The potential benefit of implanting the BSJ003W Closure Device is its expected ability to 
prevent thromboembolic events originating in the LAA.  The BSJ003W Closure 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. 
19.6. Risk to Benefit Rationale 
Risk management activities, including Hazard Analyses (HA) and Failure Mode Effects 
Analyses (FMEA), have been performed on the BSJ003W Closure Device to identify and 
analyze known and foreseeable hazards and reasonably foreseeable sequences or 
combinations of events that could result from using this product and the risks associated with 
each hazard.  Mitigations have been implemented in the design, processes, and/or labeling 
and directions for use of the product to reduce the residual risk of each hazard as necessary 
and practicable.  The HA has been reviewed and approved and the remaining risks are 
acceptable when weighed against the intended benefits to the subject. 
In addition, investigational teams selected to conduct the study will be experienced and 
skilled in interventional cardiology and/or electrophysiology with transseptal and left heart 
experience, will have completed the BSJ003W Physician Training program and will have 
access to modern high technology medical facilities to conduct those procedures. 
20. Safety Reporting 
20.1. Reportable Events by investigational site to Boston Scientific 
Any Adverse Event required by the protocol, experienced by the study subject after informed 
consent and once considered enrolled in the study (as defined in study subject classification 
section), whether during or subsequent to the procedure, must be recorded in the eCRF. 
In accordance with requirements of the protocol (see Table 20.2-1 for AE definitions), it is 
the responsibility of the investigator to assess and report to BSC any event which occurs in 
any of following categories: 

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• All Serious Adverse Events 
• All Investigational Device Deficiencies  
• Unanticipated Serious Adverse Device Effects 
• Unanticipated Adverse Device Effects 
• New findings/updates in relation to already reported events 
• All Device Related Adverse Events 
• All Study Procedure Related Adverse Events 
• Adverse Events related to BSJ003W (device thrombus, embolization, erosion, etc.)... 
• All Bleeding Events regardless of relationship to the BSJ003W 
• All Strokes (regardless of cause), Transient Ischemic (TIA) and Systemic Embolism 
regardless of relationship to the BSJ003W 
• All serious adverse events, including: death of all cause (cardiovascular, non-
cardiovascular, and unknown)  
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency.  
Underlying diseases are not reported as AEs unless there is an increase in severity of 
frequency during the course of the investigation.  
Death should not be reported as an AE, but should only be reflected as an outcome of 
ONE(1) specific SAE (see table 20-2) 
In-patient hospitalization is defined as the subject being admitted to the hospital, with the 
following exceptions. 
• A hospitalization for a purpose of tests or a hospitalization that is uncomplicated and 
elective/planned (i.e., planned prior to enrollment) does not have to be reported as an 
SAE. 
• If AEs occur during an elective/planned (i.e., planned prior to enrollment) 
hospitalization after enrollment, the complications and AEs must be reported as AEs 
or SAEs if they meet the protocol-specified definitions. 
Refer to Section 18 for the known risks associated with the study device(s). 
20.2. Definitions and Classification 
Adverse event definitions are provided in Table 20.2 1. Administrative edits were made to 
combine the definitions from GCP, Order for Enforcement of the Pharmaceutical and 
Medical Device Affairs Law of serious adverse event from ISO 14155-2011 for clarification 
purposes. 

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Table 20.2-1: Adverse Event Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: GCP,Article 2 Part 20  
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274  
Ref: ISO 14155:2011  
 
 
Any untoward or unintended disease or injury or untoward clinical signs 
(including an abnormal laboratory finding) occurrence in subjects, users or 
other persons on whom the investigational medical device have been used 
whether or not related to the investigational device.  
NOTE 1: This definition includes events related to the investigational 
medical device. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274 
Ref: ISO 14155:2011 
 
 
Adverse event related to the use of an investigational medical device 
An event that is suspected of being caused by the use of an investigational 
medical device or a communicable disease suspected of being caused by its 
use.  
NOTE 1: This definition includes any adverse events resulting from 
insufficientcies or inadequatecies in the instructions for use, the deployment, 
the implantation, the installation  or operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 
Note3: The definition of “an event that is suspected of being caused by the 
use of an investigational medical device” refers to event is other than that 
whose cause and effect relationship with the investigational medical device 
can be denied, and includes that whose cause and e effect relationship is 
uncertain. 
Note 4: The definition of “a communicable disease that is suspected of being 
caused by its use” refers to the suspected contamination of the 
investigational medical device with biological ingredients by pathogen. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155:2011 
 
Adverse event that: 
• Led to death, 
•  Led to  serious deterioration in the health of the subject, as defined by 
either 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient hospitalization or prolonged hospitalization , or 
o medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the Clinical Investigation Plan, without serious 
deterioration in health, is not considered a serious adverse event. 
Serious Adverse Device Effect 
(SADE) 
 
Adverse device effect that resulted in any of the consequences characteristic 
of a serious adverse event. 
Serious adverse effect that is suspected of being caused by the use of an 

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Table 20.2-1: Adverse Event Definitions 
Term 
Definition 
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274  
Ref: ISO 14155:2011 
investigational medical device or serious communicable disease suspected 
of being caused by its use. 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
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 investigational plan 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. 
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref:GCP, Article 28 Part 2 and 
3 
Ref: ISO 14155:2011 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in the 
risk analysis report. 
Device Deficiency 
 
Order for Enforcement of the 
Pharmaceutical and Medical 
Device Law, Article 274)  
Ref: ISO 14155:2011 
An inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 
 
20.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device or procedure. See 
criteria in Table 20.3-1:  

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Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to AE 
Classification 
Description 
Not Related 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to or of similar 
devices and procedures; 
- the event has no temporal relationship with the use of the investigational device or the procedures; 
- the serious event does not follow a known response pattern to the medical device (if the response 
pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase of the 
level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the device or procedure; 
the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment or other risk 
factors); 
- the event does not depend on a false result given by the investigational device used for diagnosis, 
when applicable; harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be met at the same 
time, depending on the type of device/procedures and the serious event. 
Unlikely 
Related 
The relationship with the use of the device seems not relevant and/or the event can be reasonably 
explained by another cause, but additional information may be obtained. 
Possibly 
Related 
The relationship with the use of the investigational device is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying or concurrent illness/ clinical 
condition or/and an effect of another device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
Probably 
Related 
The relationship with the use of the investigational device seems relevant and/or the event cannot 
reasonably explained by another cause, but additional information may be obtained. 
Causal 
Relationship 
The serious event is associated with the investigational device or with procedures beyond 
reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or of similar devices 
and procedures; 
- the event has a temporal relationship with investigational device use/application or procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the response pattern 
is previously known); 
- the discontinuation of medical device application (or reduction of the level of activation/exposure) 
and reintroduction of its use (or increase of the level of activation/exposure), impact on the serious 
event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an effect 
of another device, drug or treatment) have been adequately ruled out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the investigational device used for diagnosis, when 
applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious event. 

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20.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 20.4-1. 
Note: The “become aware date” for an event that requires reporting per the protocol is the date 
that investigator or trained study staff are notified of the event. 
Table 20.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline pre-market studies* 
Unanticipated Adverse device 
Effect(UADE)/Unanticipated 
Serious Adverse Device 
Effect (USADE) 
Complete AE eCRF page with 
all available new and updated 
information.  
• Within 1 business day of first becoming aware of 
the event. 
• Terminating at the end of the study 
Serious Adverse Event (SAE) 
Complete AE eCRF page with 
all available new and updated 
information.  
• Within 3 calendar days of first becoming aware 
of the event or as per local/regional regulations.  
• Reporting required through the end of the study 
Provide all relevant source 
documentation (unidentified) 
for reported event upon request 
of the sponsor 
• At request of sponsor 
Serious Adverse Device 
Effects (SADE) 
Complete AE eCRF page with 
all available new and updated 
information. 
• Within 3 calendar days of first becoming aware 
of the event or as per local/regional regulations.  
• Reporting required through the end of the study 
Provide all relevant source 
documentation (unidentified) 
for reported event 
• When documentation is available 
Device Deficiencies 
(including but not limited to 
failures, malfunctions, and 
product nonconformities) 
Note:  Any Investigational 
Device Deficiency that might 
have led to a serious adverse 
event if a) suitable action had 
not been taken or b) 
intervention had not been 
made or c) if circumstances 
had been less fortunate is 
considered a reportable event. 
Complete CRF fields/pages with 
all available new and updated 
information.  
Provide all relevant source 
documentation (unidentified) 
for reported event upon request 
of the sponsor 
• Within 3 calendar days of first becoming aware 
of the event.  
• Reporting required through the end of the study 
Adverse Event (AE) including 
Adverse Device Effects 
(ADE) 
 
Complete AE eCRF page, 
which contains such information 
as date of AE, treatment of AE 
resolution, assessment of 
seriousness and relationship to 
the device.  
• In a timely manner  (e.g. Recommend within 10 
business days) after becoming aware of the 
information 
• Reporting required through the end of the study 
 
Abbreviations: AE=adverse event; CRF=case report form; IDE=Investigational Device Exemption; * Please note that 
pre-market studies are clinical studies with investigational devices or with medical devices that bear the regulatory 
approval and are not being used for the same approved indications. 

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20.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the manufacturer) 
will be documented and reported to BSC. 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 failures and malfunctions should 
also be documented in the subject’s medical record. 
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not adverse events. However, an adverse event that results from a 
device failure or malfunction, would be recorded as an adverse event on the appropriate 
eCRF. 
Any Device Deficiency that might have led to a serious adverse event if a) suitable action 
had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
20.6. Reporting to Regulatory Authorities / IRBs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
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. 
20.7. CEC (Clinical Events Committee) Adjudication Events 
As an Independent CEC will be adjudicating events for this study, appropriate medical 
records from investigative sites must be sent to Boston Scientific.   
Events which require source documents include: 
• 
Stroke (all causes)  
• 
TIA 
• 
All deaths throughout the study 
• 
Systemic embolism 
• 
Major open cardiac and/or endovascular surgery through 7 days or hospital discharge 
(whichever is later) 
• 
Major bleeding defined by BARC 3 or 5 
• 
Clinically overt non-fatal bleeding defined by BARC 2 
• 
Other events, at the discretion of Boston Scientific 
 

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20.7.1. Stroke Reporting Documentation Recommendations 
In the event that a subject experiences a stroke or SE 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 subject status and technical considerations, evaluation of:  
• LA thrombus – size, location, mobility, etc. 
• BSJ003W Device Seal or presence (and measurement) of peri-device flow 
• BSJ003W Device thrombus or pannus – size, location, mobility, etc. 
• 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)  
• Presence and grade of ascending and arch aortic atheroma 
• Presence of worsening left ventricular dysfunction, “new” regional wall motion 
abnormality 
or 
presence 
of 
LV 
thrombus 
(LVEF 
data 
may 
be 
supplemented/substituted by TTE where appropriate, in addition to TEE parameters 
above)  
20.7.2.  All Bleeding Events Reporting Documentation Recommendations 
In the event that a subject experiences all bleeding events during the course of the study, 
supporting documentation including a statement from the investigator will be requested by 
the sponsor.   
20.8. Device Thrombus 
The most accurate determination of whether thrombus has formed on the surface of the 
BSJ003W 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 resolved. Cessation of anticoagulation after this time point is at the 
discretion of the investigator.  

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20.9. Death Reporting 
• A subject death that occurs during the study should be reported to Boston Scientific 
as soon as possible and, in any event, within 3 calendar days of center notification. 
The center’s IRB must be notified of any deaths in accordance with that center’s IRB 
policies and procedures. 
Source documentation of death will include a detailed narrative (death letter) that 
provides detailed information describing the circumstances surrounding the death and 
is signed by the principal Investigator or authorized co-Investigator. For any 
information which may be unknown, the investigator must still address the relevant 
area in the detailed death narrative.  A death narrative in the local language is 
acceptable. The death narrative must include all of the following, if available: 
• Date and time of death 
• Place death occurred 
• Immediate cause of death 
• Whether the death was related to the investigational device or clinical 
investigation, procedure, or patient condition 
• Whether or not the death was witnessed 
• Whether the subject had any Transient Ischemic Attack/Stroke/Bleeding prior to 
the death 
• Any other circumstances surrounding the death 
• Approximate time interval from the initiating event to death (temporal course) 
• Investigator or co-Investigator signature and date 
Any information listed above that is unavailable or unknown must be specified as 
unavailable or unknown, as applicable, in the narrative. Also submit the following 
documentation: 
• A copy of the relevant medical records from enrollment to death, this will include  
H & P, consults, test results, operative reports, and/or progress notes from the 
hospital chart and clinic chart 
• Death certificate (if available) 
• Autopsy report (if applicable) 
 
21. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her 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, Japan Medical Device GCP, Pharmaceutical and 

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Medical Device act, and Regulatory authority body. The ICF must be accepted by BSC or its 
delegate (e.g. CRO), and approved by the site’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 site’s IRB.  Any modification requires acceptance from BSC prior to use of the 
form.  The ICF must be in a language understandable to the subject. 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 at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• 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 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/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 site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form. Signatures can be 
replaced by printed name and seal of appropriate individuals. 
Failure to obtain subject consent will be reported by BSC to the applicable regulatory body 
according to their requirements. Any violations of the informed consent process must be 
reported as deviations to the sponsor, the site and/or its IRB, 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 applicable laws, 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. Acceptance by Boston Scientific is required if changes to the revised ICF are requested 
by the site’s IRB. The IRB will determine the subject population to be re-consented. 

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22. Committees 
22.1. Safety Monitoring Process 
To promote early detection of safety issues, Boston Scientific reviews adverse events and 
device deficiencies per the Safety Plan. Events are reviewed with BSC Safety Office and 
success of this program requires dynamic collection of unmonitored data as soon as the event 
is reported. This is expedited through BSC’s Global Safety Office, which is responsible for 
coordinating the collection of information for the subject dossier from the centers and core 
laboratories. During regularly scheduled monitoring visits, clinical research monitors will 
support the dynamic reporting process through their review of source document information. 
22.2. Clinical Event Committee 
A Clinical Events Committee (CEC) is an independent group of individuals with pertinent 
expertise that reviews and adjudicates important events for inclusion into the primary and 
secondary endpoints.  The events that the CEC will review for this study are the primary and 
secondary endpoint events and include: all stroke, TIA, all-cause death, systemic embolism, 
device and/or procedure-related events which resulted in open cardiac/endovascular surgery 
and all bleeding events including major bleeding.  Any additional event which the BSC 
Safety Office feels requires the review of an independent committee may also be sent.  The 
CEC will review a safety event dossier, which may include copies of subject source 
documents provided by study centers and confirm inclusion of the event into the primary and 
secondary endpoints.   CEC responsibilities, qualifications, membership, and committee 
procedures are outlined in the CEC charter. Name and address of CEC are included in the 
attachment of this protocol.  
23. Suspension or Termination 
23.1 Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or administrative reasons and reasons 
related to protection of subjects.  Investigators, the sites and regulatory authorities will be 
notified in writing in the event of study termination. 
23.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue development of the 
device. 

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23.2 Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval 
Any investigator or IRB in the WATCHMAN Japan Study may discontinue participation in 
the study or withdrawal approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated IRBs and regulatory authorities, as applicable, 
will be notified in writing in the event of these occurrences. 
23.3 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB and regulatory authorities, as applicable, will be notified. Detailed information on how 
enrolled subjects will be managed thereafter will be provided.  
In the event an IRB terminates participation in the study, participating investigators, 
associated IRBs and regulatory authorities, as applicable, will be notified in writing. Detailed 
information on how enrolled subjects will be managed thereafter will be provided by Boston 
Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled 
subjects will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
23.4 Criteria for Suspending/Terminating a Study Site 
Boston Scientific Corporation reserves the right to stop the inclusion of subjects at a study 
site at any time after the study initiation visit if the site has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of site participation, all study devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IRB and regulatory authorities, as applicable, will be notified. 
All subjects enrolled in the study at the site will continue to be followed per the investigator’s 
standard of care for subjects. The Principal Investigator at the site must make provision for 
these follow-up visits unless BSC notifies the investigational site otherwise. 
24. Publication Policy 
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. 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 

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(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 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.  
 
 

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25. Bibliography 
1. Colilla S, Crow A, Petkun W, et al. Estimates of current and future incidence and prevalence of atrial 
fibrillation in the U.S. adult population. The American journal of cardiology. 2013;112(8):1142-7.  
2. Inoue H, Fujiki A, Origasa H, et al. Prevalence of atrial fibrillation in the general population of Japan: 
An analysis based on periodic health examination. International Journal of Cardiology. 2009;137:102-
107. 
3. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation 
4. Guidelines for Pharmacotherapy of Atrial Fibrillation( JCS 2013) 
5. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with 
EACTS 
6. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus 
warfarin in subjects with atrial fibrillation. The New England journal of medicine. 2009;361(12):1139-
51. Doi: 10.1056/NEJMoa0905561. PubMed PMID: 19717844. 
7. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in 
nonvalvular atrial fibrillation. The New England journal of medicine. 2011;365(10):883-91. Doi: 
10.1056/NEJMoa1009638. PubMed PMID: 21830957. 
8. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus 
warfarin in subjects with atrial fibrillation. The New England journal of medicine. 2011;365(11):981-
92. Doi: 10.1056/NEJMoa1107039. PubMed PMID: 21870978. 
9. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus 
warfarin in subjects with atrial fibrillation. The New England journal of medicine. 2013;369(22):2093-
104. Doi: 10.1056/NEJMoa1310907. PubMed PMID: 24251359. 
10. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L. Newly identified events in the RE-LY 
trial. The New England journal of medicine. 2010;363(19):1875-6. Epub 2010/11/05. Doi: 
10.1056/NEJMc1007378. PubMed PMID: 21047252. 
11. Hart RG, Diener HC, Yang S, Connolly SJ, Wallentin L, Reilly PA, et al. Intracranial hemorrhage in 
atrial fibrillation subjects during anticoagulation with warfarin or dabigatran: the RE-LY trial. Stroke. 
2012;43(6):1511-7.  
12. FDA Drug Safety Communication: Update on the risk for serious bleeding events with the 
anticoagulant Pradaxa (dabigatran) FDSC. http://wwwfdagov/Drugs/DrugSafety/ucm326580htm. 
13. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with 
atrial fibrillation. Ann Thorac Surg. 1996 Feb;61(2):755-9. 
14. Reddy VY, Doshi SK, Sievert H, Buchbinder M, Neuzil P, Huber K, et al. Percutaneous left atrial 
appendage closure for stroke prophylaxis in subjects with atrial fibrillation: 2.3-Year Follow-up of the 
PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Subjects with 
Atrial Fibrillation) Trial. Circulation. 2013;127(6):720-9.  
15. Rhythm H. The Heart Rhythm Society’s 34th Annual Scientific Sessions. 2013  
16. Reddy VY, Holmes D, Doshi SK, Neuzil P, Kar S. Safety of percutaneous left atrial appendage 
closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Subjects 
with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation. 
2011;123(4):417-24.  
17. Holmes DR, Jr., Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective Randomized 
Evaluation of the Watchman Left Atrial Appendage Closure Device in Subjects With Atrial Fibrillation 
Versus Long-Term Warfarin Therapy: The PREVAIL Trial. J Am Coll Cardiol. 2014;64(1):1-12.  
18. Reddy VY, Möbius-Winkler S, Miller MA, et al. Left atrial appendage closure with the Watchman 
device in patients with a contraindication for oral anticoagulation. J Am Coll Cardiol 2013;61:2551-6. 
19. Chai-Adisalsopha C, Hillis C. Isayama T, et al. Mortality outcomes in patients receiving direct oral 
anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb 
Haemost. 2015 Nov;13(11)2012-20. 
20. Japanese Guidelines for the management of stroke 2015 

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21. Guidelines for management of anticoagulant and antiplatelet therapy in cardiovascular disease(JCS 
2009). 
 
 
 

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26. Abbreviations and Definitions  
26.1. Abbreviations 
Abbreviations are shown in Table 26.1-1.   
Table 26.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse device effect 
AE 
Adverse event 
AF 
atrial fibrillation 
ASA 
acetylsalicylic acid 
ASD 
atrial septal defect 
BI 
Barthel Index 
CEC 
clinical event committee 
CHADS2 
scoring system used to identify subjects in need of anticoagulation (congestive 
heart failure, hypertension, age≥75years, diabetes, previous stroke [doubled]) 
CHA2DS2-VASc 
complemental scoring system used to identify subjects in need of 
anticoagulation (congestive heart failure, hypertension, age≥75y [doubled], 
diabetes, previous stroke [doubled], vascular disease, age65-74y, sex category) 
CHF 
Congestive heart failure 
CRF 
Case report form 
DAPT 
Double Antiplatelet Therapy 
DOAC 
Direct oral anticoagulant 
EU 
European Union 
FDA 
Food and Drug Administration 
eGFR 
(estimated) glomerular filtration rate 
ICF 
Informed consent form 
INR 
international normalized ratio 
IRB 
Institutional Review board 
ITT 
intention-to-treat 
LAA 
left atrial appendage 
LVEF 
left ventricular ejection fraction 
MRS 
Modified Rankin Scale 
MV 
Mitral valve 
NIHSS 
NIH stroke score 
NVAF 
non-valvular atrial fibrillation 
PFO 
patent foramen ovale 
PG 
performance goal 
PMA 
premarket approval 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
TEE 
transesophageal echocardiogram 
TIA 
transient ischemic attacks 
TTE 
transthoracic echocardiogram 

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Table 26.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ADE 
Adverse device effect 
AE 
Adverse event 
UADE 
Unanticipated adverse device effect 
USADE 
Unanticipated serious adverse device effect 
26.2. Definitions 
26.2.1. Stroke/TIA definitions 
Broad definitions: 
Neurological deficit: An acute episode of a focal or global neurological deficit with at 
least one of the following: 
• 
Change in the level of consciousness 
• 
Hemiplegia 
• 
Hemiparesis 
• 
One-sided numbness or sensory loss 
• 
Dysphasia or aphasia 
• 
Hemianopia 
• 
Amaurosis fugax 
• 
Any other neurological signs or symptoms consistent with stroke 
 
In addition, there are no other readily identifiable non-stroke cause for the clinical 
presentation (e.g., brain tumor, trauma, infection, hypoglycemia, peripheral lesion, 
pharmacologic influences), to be determined by or in conjunction with the designated 
neurologist.  
 
Stroke: Stroke is defined by either one of the following: 
• 
Duration of focal or global neurological deficit >24 h. 
• 
Duration of focal or global neurological deficit <24 h in case of imaging-documented 
new hemorrhage or infarct. 
• 
A neurological deficit resulting in death;  
 
Transient ischemic attack: A TIA is defined by any neurological deficit not satisfying the 
above criteria for stroke, specifically a deficit lasting <24 h without imaging-documented 
new hemorrhage or infarct. . 
 
 
Stroke diagnostic criteria:  
• Rapid onset of a focal or global neurological deficit with at least one of the following: 
change in level of consciousness, hemiplegia, hemiparesis, numbness or sensory loss 
affecting one side of the body, dysphasia or aphasia, haemianopia, amaurosis fugax, 
or other neurological signs or symptoms consistent with stroke;  
• Duration of a focal or global neurological deficit ≥24 h; OR, 24 h, if therapeutic 
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angioplasty); OR available neuroimaging documents a new haemorrhage or infarct; 
OR the neurological deficit results in death  
• No other readily identifiable non-stroke cause for the clinical presentation (e.g. brain 
tumor, trauma, infection, hypoglycaemia, peripheral lesion, pharmacological 
influences) 
• Confirmation of the diagnosis by at least one of the following: 
o Neurology or neurosurgical specialist 
o Neuroimaging procedure (MR or CT scan or cerebral angiography) 
o Lumbar puncture (i.e. spinal fluid analysis diagnostic of intracranial 
haemorrhage) 
 
 
 

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Stroke Types: 
Ischemic: An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal 
infarction 
Hemorrhagic: 
• intracerebral: rapidly developing clinical signs of neurological dysfunction 
attributable to a focal collection of blood within the brain parenchyma or ventricular 
system that is not caused by trauma. 
• subarachnoid:  rapidly developing signs of neurological dysfunction and/or headache 
because of bleeding into the subarachnoid space (the space between the arachnoid 
membrane and the pia mater of the brain or spinal cord), which is not caused by 
trauma. 
Silent infarction: Imaging or neuropathological evidence of CNS infarction, without a 
history of acute neurological dysfunction attributable to the lesion. 
Stroke caused by cerebral venous thrombosis: Infarction or hemorrhage in the brain, spinal 
cord, or retina because of thrombosis of a cerebral venous structure. Symptoms or signs 
caused by reversible edema without infarction or hemorrhage do not qualify as stroke. 
Not otherwise specified: an episode of acute neurological dysfunction presumed to be caused 
by ischemia or hemorrhage, persisting ≥ 24 hours or until death, but without sufficient 
evidence to be classified as one of the above 
(from Kappetein, A.P., et al., J Am Coll Cardiol, 2012. 60(15): p. 1438-54) 
26.2.2. Classification of Bleeding events 
In response to the need to develop, disseminate, and ultimately adopt standardized bleeding 
end-point definitions for subjects receiving antithrombotic therapy, the Bleeding Academic 
Research Consortium (BARC) convened in February 2010 at the US Food and Drug 
Administration (FDA) headquarters in White Oak, MD. BARC effort brought together 
representatives from academic research organizations, the FDA, the National Institutes of 
Health, and pharmaceutical and cardiovascular device manufacturers and independent 
physician thought leaders in the field of cardiovascular disease to develop consensus 
bleeding definitions that would be useful for cardiovascular clinical trials. Application of 
these definitions is recommended for both clinical trials and registries:  
 
Type 0: 
No bleeding 
Type 1: 
Bleeding that is not actionable and does not cause the subject to seek unscheduled 
performance of studies, hospitalization, or treatment by a health-care professional; 
may include episodes leading to self-discontinuation of medical therapy by the 
subject without consulting a health-care professional. 
Type 2: 
Any overt, actionable sign of hemorrhage (e.g., more bleeding than would be 
expected for a clinical circumstance, including bleeding found by imaging alone) that 
does not fit the criteria for type 3, 4, or 5 but does meet at least one of the following 
criteria: 
• requiring nonsurgical, medical intervention by a health-care professional, 

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• leading to hospitalization or increased level of care, or 
• prompting evaluation 
Type 3: 
Type 3a: 
o Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL* (provided hemoglobin 
drop is related to bleed) 
o Any transfusion with overt bleeding 
Type 3b: 
o Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop is 
related to bleed), 
o Cardiac tamponade, 
o Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid), 
o Bleeding requiring intravenous vasoactive agents 
Type 3c: 
o Intracranial hemorrhage (does not include microbleeds or hemorrhagic 
transformation, does include intraspinal), 
o Subcategories confirmed by autopsy or imaging or lumbar puncture, 
o Intraocular bleed compromising vision. 
Type 4: 
• CABG-related bleeding, 
• Perioperative intracranial bleeding within 48 h, 
• Reoperation after closure of sternotomy for the purpose of controlling bleeding 
• Transfusion of ≥ 5 U whole blood or packed red blood cells within a 48-h period, 
• Chest tube output more than or equal to 2L within a 24-h period 
Type 5: 
Fatal bleeding 
Type 5a: 
Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious 
Type 5b: 
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation 
 
(from Circulation. 2011; 123(23): 2736-47) 
27. Appendices 
27.1. 
Clinical Trial Organization 
In the following cases, special sentences must be described in the protocol according to Japan 
GCP and GCP manual (article 7 of Japan Medical Device GCP). 
 
Investigational device affords no intended clinical benefit to the subjects 
 
Informed consent is expected to be difficult to obtain from subject 
 
Life-saving clinical trial in an emergency situation, when the clinical trial is planned to 
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obtained and the legally acceptable representative of the prospective subject cannot be 
reached for informed consent