WATCHMAN for Patients With Atrial Fibrillation Undergoing Transcatheter Aortic Valve Replacement
Phase: NA
Conditions: Atrial Fibrillation, Aortic Valve Stenosis
Sponsor: samir kapadia

WATCH-TAVR Clinical Study 
Protocol V4.4 
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WATCH-TAVR PROTOCOL 
 
 
 
WATCHMAN FOR PATIENTS WITH ATRIAL FIBRILLATION 
UNDERGOING TRANSCATHETER AORTIC VALVE 
REPLACEMENT 
 
 
 
 
 
Principal Investigators: Samir Kapadia MD, Martin Leon MD 
 
Sponsor: Cleveland Clinic Investigator Initiated Trial 
Funded by: Boston Scientific 
Version Number:  v4.4 
July 9 2020 
 
 
 

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Principal Investigator Protocol Approval Page 
Study Title: WATCHMAN FOR PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING TRANSCATHETER AORTIC VALVE 
REPLACEMENT 
Version: V4.4  
Study Sponsor: Cleveland Clinic Investigator Initiated Trial 
 
 
I, the undersigned, have read and approve this protocol and agree on its content. It is confirmed that the 
information and guidance given in this protocol complies with scientific principles, the guidelines of Good Clinical 
Practice.  
 
 
 
 
 
 
Principal Investigator Signature:           
 
 
7/14/20 
 
 
 
 
    Martin Leon, MD 
 
 
                     (Date) 
 
 
 
                    Columbia University Medical Center  
 
 

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INVESTIGATOR PROTOCOL AGREEMENT 
Study Title: WATCHMAN FOR PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING TRANSCATHETER AORTIC VALVE 
REPLACEMENT 
Version: V4.4 
Study Sponsor: Cleveland Clinic Investigator Initiated Trial 
 
By my signature, I  
 
Confirm that my staff and I have carefully read and understand this protocol or protocol amendment and 
are thoroughly familiar with the appropriate use of the device described herein. 
 
Agree to comply with the conduct and terms of the study specified herein and with any other study 
conduct procedures provided by the Sponsor (Cleveland Clinic).   
 
Agree to assume responsibility for the proper conduct of the study at this site. 
 
Agree not to implement deviations from or changes to the protocol or protocol amendments without 
agreement from the Sponsor (Cleveland Clinic) and prior submission to and written approval (where 
required) from the Institutional Review Board (IRB) except when necessary to eliminate an immediate 
hazard to the patients, or for administrative aspects of the study (where permitted by all applicable 
regulatory requirements).  
 
 
 
 
Investigator’s Signature 
 
Date 
 
 
 
Print Name 
 
 
 
 

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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..................................................................................................................................... 10 
PROTOCOL SUMMARY ......................................................................................................................................... 10 
1 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ...................... 14 
1.1 
Background Information .................................................................................................................... 14 
1.2 
Rationale ............................................................................................................................................. 14 
1.3 
Potential Risks and Benefits ............................................................................................................ 14 
1.3.1 
Known Potential Risks ................................................................................................... 14 
1.3.2 
Known Potential Benefits .............................................................................................. 15 
2 
OBJECTIVES AND PURPOSE .................................................................................................................. 16 
3 
STUDY DESIGN AND ENDPOINTS ......................................................................................................... 16 
3.1 
Description of the Study Design ...................................................................................................... 16 
3.2 
Primary Endpoint ............................................................................................................ 17 
3.3 
Secondary Endpoints .................................................................................................... 17 
4 
STUDY ENROLLMENT AND WITHDRAWAL ......................................................................................... 17 
4.1 
Participant Inclusion Criteria ............................................................................................................ 17 
4.2 
Participant Exclusion Criteria ........................................................................................................... 17 
4.3 
subject selection ................................................................................................................................ 18 
4.4 
Participant Withdrawal or termination ............................................................................................. 18 
5 
STUDY DEVICE ........................................................................................................................................... 19 
5.1 
Study device Description .................................................................................................................. 19 
6 
STUDY PROCEDURES AND SCHEDULE .............................................................................................. 19 
6.1 
Study Procedures/Evaluations ......................................................................................................... 19 
6.1.1 
Study procedures ........................................................................................................... 19 
6.2 
Study Schedule .................................................................................................................................. 21 
6.2.1 
Study Requirements ...................................................................................................... 21 
6.2.2 
Enrollment ....................................................................................................................... 23 
6.2.3 
Follow-up ......................................................................................................................... 24 
6.2.4 
Watchman Device Implant Pharmacologic Regimen ............................................... 25 
7 
ASSESSMENT OF SAFETY ...................................................................................................................... 26 
7.1  
Specification of Safety Parameters ................................................................................................. 26 
7.2 
Adverse event reporting .................................................................................................................... 26 
8 
CLINICALMONITORING ............................................................................................................................. 27 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 28 
9.1 
Statistical and Analytical Plans ........................................................................................................ 28 
9.2 
Statistical Hypotheses ....................................................................................................................... 28 
9.3 
Analysis POPULATIONS .................................................................................................................. 29 
9.4 
Description of Statistical Methods ................................................................................................... 29 
9.4.1 
General Approach .......................................................................................................... 29 
9.4.2 
Analysis of the Primary Endpoint ................................................................................. 29 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 30 
9.4.4 
SAMPLE SIZE ................................................................................................................ 30 
10 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................................... 31 
10.1 
Institutional Review Board ................................................................................................................ 31 
10.2 
Informed Consent Process ............................................................................................................... 31 
10.2.1 
Consent Procedures and Documentation .................................................................. 31 

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10.3 
Participant and data Confidentiality ................................................................................................ 32 
11 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 32 
11.1 
Data Collection and Management Responsibilities ...................................................................... 32 
11.2 
Study Records Retention .................................................................................................................. 32 
11.3 
Protocol Deviations............................................................................................................................ 33 
11.4 
Publication and Data Sharing Policy ............................................................................................... 33 
12 
STUDY ADMINISTRATION ........................................................................................................................ 33 
13 
LITERATURE REFERENCES.................................................................................................................... 34 
 
 
LIST OF ABBREVIATIONS 
AF: Atrial Fibrillation 
AS: Aortic Stenosis 
KCCQ: Kansas City Cardiomyopathy Questionnaire 
mRS: Modified Rankin Scale 
NIHSS: National Institute of Health Stroke Scale 
QoL: Quality of Life 
TAVR: Transcatheter Aortic Valve Replacement 
VARC: Valve Academic Research Consortium 
 
PROTOCOL SUMMARY 
Title: 
WATCHMAN for Patients With Atrial Fibrillation Undergoing Transcatheter 
Aortic Valve Replacement 
Short Title: 
WATCHMAN and TAVR 
Objectives: 
 
To evaluate the safety and effectiveness of the left atrial appendage 
occlusion with WATCHMAN Device in prevention of stroke and bleeding in 
patients with atrial fibrillation (AF) undergoing transcatheter aortic valve 
replacement (TAVR). 
Endpoints 
Primary Endpoint: Composite of all-cause mortality, stroke (ischemic and 
hemorrhagic), and bleeding (life-threatening and major) events. Secondary 
Endpoints: All-cause mortality, stroke (ischemic and hemorrhagic), bleeding 
(major and/or life-threatening as per VARC2 definitions), cardiovascular 
mortality, arterial or venous thrombosis or embolism, rehospitalization 

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related to WATCHMAN procedure or device, QoL (KCCQ) at follow-up, and 
procedural costs for both TAVR and WATCHMAN.  
Population: 
The WATCHMAN device is FDA approved for stroke prevention in patients 
with non-valvular atrial fibrillation defined as “Atrial fibrillation in the 
absence of rheumatic mitral valvular heart disease”. The current study aims 
to investigate the outcomes of implantation of the WATCHMAN device in 
patients with non-valvular AF undergoing FDA approved TAVR. 
Phase: 
IV 
Number of Sites 
enrolling participants: 
Approximately 33 US sites 
Description of Study 
Agent: 
 
Study Design: 
The WATCHMAN device is a self-expanding left atrial appendage closure 
(LAAC) device with a porous covering on the proximal face.  
Device sizes: 21 mm, 24 mm, 27 mm, 30 mm, 33 mm  
WATCH-TAVR is a prospective, multicenter, randomized event-driven 
controlled trial. Only centers with approval for commercial WATCHMAN 
implantation will be included in this trial. Subjects will be enrolled at 
approximately 33 centers in the United States. There will be approximately 
350 subjects enrolled, with 175 patients being randomized to TAVR + 
medical therapy and 175 patients randomized to simultaneous 
TAVR+WATCHMAN to accumulate the 191 primary events needed. Patients 
with non-valvular AF undergoing standard of care TAVR will be enrolled in 
the trial.  
Patients randomized to receive the WATCHMAN device will receive 
anticoagulation with warfarin and aspirin for 6 weeks after the procedure. 
After 6 weeks, the plan of care will follow WATCHMAN labeling. Patients 
randomized to the TAVR + medical therapy arm will be treated in 
accordance with standard of care with either warfarin, other 
anticoagulant/antiplatelet therapy, or no anticoagulation at the discretion 
of the treating physician.  All patients will continue to receive routine post-
TAVR  follow-up and care. 
Patients will be monitored for primary and secondary endpoints as outlined. 
Baseline information and laboratory data will be collected as described in 
the protocol. 
Selection Criteria 
 
 
Inclusion Criteria: Determination for participation in the study is based upon 
standard of care practice for assessment of TAVR & WATCHMAN eligibility.  
1. Men and Women ≥ 18 years of age 

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2. The patient meets criteria for and is eligible to undergo TAVR 
procedure 
3. The patient has documented paroxysmal, persistent, or permanent 
atrial fibrillation 
4. The patient meets the WATCHMAN labeling guidelines and is eligible 
to undergo the WATCHMAN implantation procedure 
5. The patient is eligible for short term warfarin therapy 
6. The patient or legal representative is able to understand and willing 
to provide written informed consent to participate in the trial 
7. The patient is able and willing to return for required follow-up visits 
and examinations 
Exclusion Criteria: 
1. The patient had a  stroke or TIA  within the last 6 months prior to 
enrollment 
2. Contraindication for short term anticoagulation 
3. Moderate or severe MS with mean gradient across MV >10 mm Hg 
of MVA < 1.2cm2. 
4. The patient has symptomatic carotid disease (i.e., carotid stenosis 
≥ 50% associated with ipsilateral transient or visual TIA evidenced 
by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke 
within 6 months) 
5. Prior occlusion of LAA 
6. The patient has an implanted mechanical mitral valve  
7. The patient requires long-term warfarin therapy due to:  
a. Secondary to conditions such as prior arterial embolism or 
other indications such as pulmonary embolism or deep vein 
thrombosis within the previous 6 months 
b. The patient is in a hypercoagulable state; exclude the patient if 
per medical record documentation, the patient meets any of 
the following criteria:  
• Thrombosis occurring at under 40 years age 
• Idiopathic or recurrent VTE (venous thromboembolism) 
• Thrombosis at an unusual site (cerebral veins, hepatic 
veins, renal veins, IVC, mesenteric veins)  
• Family history of VTE or of inherited prothrombotic 
disorder, recurrence/extension of thrombosis while 
adequately anti-coagulated 
8. The patient is actively enrolled in another trial of a cardiovascular 
device or an investigational drug (post-market study participation 
and registries are acceptable) 

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9. The patient is pregnant or pregnancy is planned during the course 
of the investigation if patient is of child bearing potential 
10. Any clinically significant medical condition or presence of any 
laboratory abnormality performed prior to randomization that is 
considered by the investigator to be clinically important and could 
interfere with the conduct of the study or not meeting procedure 
guidelines for TAVR or WATCHMAN  
11. The patient has a life expectancy of less than two years 
Participant Duration: 
2 Years 
 
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1 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
 
1.1 
BACKGROUND INFORMATION 
Atrial fibrillation (AF) is a common baseline comorbidity and the commonest arrhythmia in patients with aortic 
stenosis (AS) undergoing Transcatheter Aortic Valve Replacement (TAVR). AF is a known risk factor for stroke during 
or after TAVR, associated with stroke, bleeding complications, worse outcomes and increased mortality1. The TAVR 
population is at increased long-term bleeding risk, with cognitive impairment, high risk of falls, history of 
spontaneous bleeding, etc. Standard medical therapy for emboli prevention in AF, long term oral anticoagulation 
(OAC), carries risk of hemorrhagic stroke, as well as major bleeding complications2. Anti-platelets prescribed after 
TAVR, combined with OAC, worsen bleeding risk further3. Left atrial appendage closure is an alternative to OAC, 
which obviates the need for regular medication and frequent monitoring. The WATCHMAN Left Atrial Appendage 
Closure (LAAC) System is the only device that has been approved by the FDA for preventing thrombo-embolic events 
in patients with non-valvular atrial fibrillation (AF)4. Non-valvular AF is defined as atrial fibrillation in the absence of 
rheumatic mitral valvular heart disease5. The WATCHMAN device has shown improved safety compared to OAC, 
with reduced event rates for hemorrhagic stroke and major bleeding in patients receiving the implant6,7. There are 
only small reports of feasibility of the procedure8. Randomized trials with the WATCHMAN device have excluded 
patients with valvular heart disease. As a result, data on safety and efficacy of the device in TAVR patients with AF is 
lacking9. 
 
1.2 
RATIONALE 
The WATCH-TAVR study aims to investigate the safety and efficacy of the WATCHMAN device in patients with AF 
who have severe AS and are undergoing TAVR. In addition, the simultaneous procedure arm aims to combine two 
device-related procedures into one single procedure, thereby exposing the patient to only one hospitalization and 
general anesthesia, potentially reducing risks in an already elderly and frail population. The combined procedure 
also allows a common venous access to be obtained for temporary pacing and delivery of the WATCHMAN device. 
The combined procedure, OR time, TEE and fluoroscopy may reduce costs to the patient. The trial is feasible and has 
the potential to have impactful and practice changing results. 
 
1.3 
POTENTIAL RISKS AND BENEFITS 
 
1.3.1 KNOWN POTENTIAL RISKS 
Potential surgical risks associated with the WATCHMAN implant procedure are similar to those encountered peri- 
and postoperatively for many routine catheterization procedures. 
In addition to the general surgical risks, additional risks specifically associated with the WATCHMAN implant are as 
follows:   

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 
Additional surgery if the device is not placed in the correct position  
 
Allergic reaction to the implant materials  
 
Device misplacement  
 
Device embolization  
 
Device fracture or extrusion  
 
Excessive bleeding    
 
Hypertrophic scarring or thrombosed veins  
 
Inability to move or retrieve device   
Patients who receive the WATCHMAN implant should stop warfarin therapy at the 45-day follow-up visit; therefore, 
at that time, patients may be at an increased risk of stroke. Warfarin is the proven standard of care for reducing the 
risk of stroke in atrial fibrillation.   
Risks associated with long term warfarin therapy are: 
 
Fatal or nonfatal hemorrhage from any tissue or organ  
 
Bleeding which occurs when PT/INR is within the therapeutic range warrants diagnostic investigation since 
it may unmask a previously unsuspected lesion, e.g., tumor, ulcer, etc.  
 
Necrosis of skin and other tissues.  
 
See ADVERSE REACTIONS section of warfarin tablets package insert. 
 
1.3.2 KNOWN POTENTIAL BENEFITS 
The WATCHMAN device has been FDA approved to prevent thrombo-embolic events originating from the LAA. 
However trials with the WATCHMAN device have excluded any patient with an Aortic Valve Area < 1.0 cm2. In 
patients with AS, the primary site of thrombus origin has been demonstrated to be the LAA. This makes the 
WATCHMAN device potentially beneficial in stroke prevention for patients with AS. The device also has improved 
safety compared to oral anticoagulation, with less bleeding and hemorrhagic stroke rates. 
The simultaneous TAVR and WATCHMAN procedure will share anesthesia time, OR time, TEE and hospital admission 
costs. By avoiding two separate general anesthesia events, risks to the patient are reduced. Risks of bleeding 
associated with two separate intra-procedure heparinization are also avoided. 
Long term oral anticoagulation carries with it an elevated risk of bleeding. The general population of patients 
undergoing TAVR are elderly and have high frailty scores, increasing risks of bleeding further. Device based thrombo-
embolism prevention will avoid these increased bleeding risks and possibly improve quality of life. It will also obviate 
the need for regular medication, decrease drug-drug interactions in a population already on multiple medications, 
and reduce the need for regular monitoring of INR levels. 
 
 
 
 

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2 
OBJECTIVES AND PURPOSE 
The WATCH-TAVR study is designed to evaluate the safety and effectiveness of left atrial appendage occlusion with 
the WATCHMAN device in the prevention of stroke and bleeding in patients with atrial fibrillation undergoing 
transcatheter aortic valve replacement (TAVR). 
The efficacy of the WATCHMAN device has been previously demonstrated in patients with non-valvular AF who are 
eligible for warfarin therapy. Until now, trials with the WATCHMAN device have excluded patients with aortic 
stenosis (AVA <1.0cm2). There is no conclusive evidence of the benefit of the device in patients with severe AS. A 
large portion of patients with severe AS who undergo TAVR are known to have AF. This increases stroke risk 
dramatically after the procedure and is associated with worse outcomes. Standard medical therapy, i.e. 
anticoagulation is associated with increased risks of bleeding, including major bleeds and intra-cranial hemorrhage. 
There is a lack of clear consensus guidelines regarding the use of anticoagulation in AF after TAVR. In addition, many 
patients are unsuitable candidates for long term anticoagulation and need an alternative approach to stroke 
prevention. This study aims to establish the efficacy and safety of the WATCHMAN device in preventing stroke and 
bleeding in patients with AF undergoing TAVR. 
 
3 
STUDY DESIGN AND ENDPOINTS 
 
3.1 
DESCRIPTION OF THE STUDY DESIGN 
The WATCH-TAVR study is a prospective, multicenter, randomized trial to be conducted at approximately 33 centers 
in the U.S. The trial aims to enroll approximately 350 patients to accumulate the necessary 191 primary events. 
Enrollment is expected to occur over the course of 18 months. Patients will be followed up for a total of 2 years. 
Eligible patients from each investigator’s patient population shall be screened as potential candidates for the 
WATCH-TAVR study. The patient’s history and baseline clinical parameters will be reviewed and written informed 
consent to participate will be obtained. The fulfillment of all inclusion and exclusion criteria shall be assessed and 
further baseline parameters necessary prior to randomization shall be obtained. Patients will be randomized to TAVR 
procedure alone or TAVR procedure combined with the WATCHMAN procedure. Determination for participation in 
the study is based upon standard of care practice for assessment of TAVR & WATCHMAN eligibility. 
It is recommended that the procedure (TAVR or combined WATCHMAN + TAVR) should be performed within two 
weeks of randomization. All patients who receive the WATCHMAN device will follow the WATCHMAN Device Implant 
Pharmacologic Regimen (see section 6.2.4). Patients randomized to the TAVR procedure only will be treated in 
accordance with standard of care with either warfarin, other anticoagulant/anti-platelet therapy, or no 
anticoagulation at the discretion of the treating physician. All patients will continue to receive routine post-TAVR 
follow-up and care. Use of the WATCHMAN device in the TAVR only arm should be avoided during the first year, 
unless medically necessary. All enrolled study patients shall be followed up at 45 days, 6 months, 12 months and 24 
months. Follow-up beyond 1 year may be in the form of an office visit or a phone call. 
 

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Patients shall be evaluated for neurological function by NIH Stroke Scale and for modified Rankin Scale (MRS) stroke 
disability at baseline and each visit. In addition all patients who experience a Stroke or TIA will be evaluated by a 
neurologist and have brain imaging.  
 
3.2 
PRIMARY ENDPOINT 
Composite of all-cause mortality, stroke, life- threatening, and major bleeding events. 
 
3.3 
SECONDARY ENDPOINTS 
All-cause mortality, stroke (ischemic and hemorrhagic), bleeding (major and/or life-threatening as per VARC2 
definitions), cardiovascular mortality, arterial or venous thrombosis or embolism, rehospitalization related to the 
WATCHMAN procedure or device, QoL (KCCQ-12) at follow-up, and procedural costs related to the initial TAVR and 
WATCHMAN procedures. 
 
4 
STUDY ENROLLMENT AND WITHDRAWAL 
 
4.1 
PARTICIPANT INCLUSION CRITERIA 
The WATCH-TAVR study will include patients who fulfill the following criteria: Determination for participation in the 
study is based upon standard of care practice for assessment of TAVR & WATCHMAN eligibility. 
1. Men and Women ≥ 18 years of age 
2. The patient meets criteria  for and is eligible to undergo TAVR procedure 
3. The patient has documented paroxysmal, persistent, or permanent atrial fibrillation 
4. The patient meets the WATCHMAN labeling guidelines and is eligible to undergo the WATCHMAN 
implantation procedure 
5. The patient is eligible for short term warfarin therapy 
6. The patient or legal representative is able to understand and willing to provide written informed consent 
to participate in the trial 
7. The patient is able and willing to return for required follow-up visits and examinations 
 
4.2 
PARTICIPANT EXCLUSION CRITERIA 
Any patient who fulfills any of these criteria shall be excluded: 
1. The patient had a  stroke or TIA  within the last 6 months prior to enrollment 
2. Contraindication for short term anticoagulation 
3. Moderate or severe MS with mean gradient across MV >10 mm Hg or MVA < 1.2cm2. 

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4. The patient has symptomatic carotid disease (i.e., carotid stenosis ≥ 50% associated with ipsilateral 
transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke within 
6 months) 
5. Prior occlusion of LAA 
6. The patient has an implanted mechanical mitral valve  
7. The patient requires long-term warfarin therapy due to:  
a. Secondary to conditions such as prior arterial embolism or other indications such as pulmonary 
embolism or deep vein thrombosis within the previous 6 months 
b. The patient is in a hypercoaguable state; exclude the patient if per medical record documentation, 
the patient meets any of the following criteria:  
• Thrombosis occurring at a young age (i.e. less than 40 y/o)  
• Idiopathic or recurrent VTE (venous thrombo-embolism) 
• Thrombosis at an unusual site (cerebral veins, hepatic veins, renal veins, IVC, mesenteric 
veins)  
• Family history of VTE or of inherited prothrombotic disorder, recurrence/extension of 
thrombosis while adequately anticoagulated 
8. The patient is actively enrolled in another trial of a cardiovascular device or an investigational drug (post-
market study participation and registries are acceptable) 
9. The patient is pregnant or pregnancy is planned during the course of the investigation if patient is of child 
bearing potential 
10. Any clinically significant medical condition or presence of any laboratory abnormality prior to 
randomization that is considered by the investigator to be clinically important and could interfere with the 
conduct of the study or not meeting procedure guidelines for TAVR or Watchman 
11. The patient has a life expectancy of less than two years 
 
4.3 
SUBJECT SELECTION 
All patients undergoing TAVR who are in AF shall be considered as potential candidates for the trial. Patients who 
potentially fulfill the inclusion and exclusion criteria will be informed in detail about the study and invited to 
participate. Prior to any study assessments or procedures, the patient will be asked to read and sign the informed 
consent form (ICF). Patient eligibility can be determined if all inclusion and no exclusion criteria have been met, after 
which randomization may take place. 
 
4.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
All subjects have the right to withdraw from treatment or study participation without prejudice. The investigator 
can discontinue any subject at any time if medically necessary, although every effort should be made to follow the 
subjects until study completion. At a minimum, vital status on every subject should be ascertained at study 
completion. It will be documented whether or not each subject completed the clinical study.  
Reasons that a subject may discontinue participation in a clinical study are considered to constitute one of the 
following: 

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• 
Death 
• 
Subject withdrew consent 
• 
Physician decision 
• 
Lost to follow-up 
 
5 
STUDY DEVICE 
 
5.1 
STUDY DEVICE DESCRIPTION 
The WATCHMAN LAAC device is permanently implanted at or slightly distal to the LAA ostium. It is delivered using a 
standard transseptal catheterization technique in a catheterization laboratory or cardiovascular operating room 
setting. It is designed to prevent emboli from the LAA and thus prevent ischemic stroke and thromboembolism in 
patients with atrial fibrillation who are at risk for LAA thrombi. The device can be implanted during the TAVR 
procedure, potentially using the site of the temporary pacemaker for access.  
The WATCHMAN LAA Closure Technology consists of: 
 
WATCHMAN LAA Closure Device (also referred to as “WATCHMAN Device”, “WATCHMAN LAAC Device”) 
 
WATCHMAN Delivery System (consisting of Delivery Catheter and loaded Implant) 
 
WATCHMAN Access System (consisting of Access Sheath and Dilator)   
The WATCHMAN LAAC Device is the implantable component of the WATCHMAN LAAC Technology. It is composed 
of a self-expanding nitinol structure with a porous membrane on the proximal face. The implant is delivered to the 
Left Atrial Appendage by femoral venous access and transseptal puncture to enter the left atrium. 
Device sizes: 21 mm, 24 mm, 27 mm, 30 mm, 33 mm. 
 
6 
STUDY PROCEDURES AND SCHEDULE 
 
6.1 
STUDY PROCEDURES/EVALUATIONS 
6.1.1 STUDY PROCEDURES 
The time course for the trial is divided into a treatment period and follow-up period. Patients will be randomized in 
a 1:1 allocation ratio to the following treatment arms: 
 
TAVR alone (n=175) 
 
TAVR and WATCHMAN (n=175) 
Follow-up will commence once the treatment period is completed. Patients will be followed up to 2 years from 
treatment procedure completion. 

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6.2 
STUDY SCHEDULE 
 
6.2.1 STUDY REQUIREMENTS 
 
STUDY REQUIREMENTS FOR TAVR/WATCHMAN COMBINED PROCEDURE 
STUDY REQUIREMENTS TAVR/WATCHMAN COMBINED ARM 
 
Baseline 
45 days  after 
Combined 
Procedure 
(+/- 15 d) 
6 Months 
after 
Procedure 
(+/- 1 month)   
12 Months 
after 
Procedure 
(+/- 1 month) 
24 Months 
after 
Procedure1 
(+/- 1 month) 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Informed Consent 
+ 
 
 
 
 
Inclusion/Exclusion 
Criteria 
+ 
 
 
 
 
Randomization 
+ 
 
 
 
 
WATCHMAN 
Procedure 
+ 
 
 
 
 
TEE2 
+ (during 
WATCHMAN 
procedure) 
+ 
 
 
 
KCCQ-12 Score 
+ 
+ 
+ 
+ 
+ 
Vital Signs 
+ 
+ 
+ 
+ 
 
AE Monitoring 
+ 
+ 
+ 
+ 
+ 
INR 
+ 
+ 
+3 
+3 
+3 
Blood Work 
+4 
 
 
 
 
NIH Stroke Scale 
(NIHSS 
+ 
+ 
+ 
+ 
+ 
Modified Rankin 
Scale (MRS) 
+ 
+ 
+ 
+ 
+ 
Brain Image (CT or 
MRI)5 
As Required 
Neuro Assessment6 
As Required 
 
1 May be visit or phone follow up 
2 TEE During the WATCHMAN  procedure and 45 days (+/-15 days) after the WATCHMAN Procedure. Patients randomized to WATCHMAN who 
have intracardiac thrombus visualized are contraindicated from receiving the device per labeling guidelines, but will remain in the trial as intent 
to treat and should be followed for all study visits. 
3 If patient continues to be on warfarin 
4 Tests include serum creatinine, platelet count and hemoglobin level. To be obtained within 7 days of randomization/WATCHMAN procedure 
5 Required following a Stroke or TIA event including neurological assessment by a Neurologist.  
6 Neurological assessment by neurologist if a patient experiences a stroke or TIA throughout the duration of the study 
 
 
 
 
 
 
 
 
 

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STUDY REQUIREMENTS FOR TAVR PROCEDURE ALONE 
 
1May be visit or phone follow up 
2 If patient continues to be on warfarin 
3 Tests include serum creatinine, platelet count and hemoglobin level. To be obtained within 7 days of randomization and within 7 days of      
WATCHMAN (same lab may be used if 7 day criteria met) 
4 Required following a Stroke or TIA event including neurological assessment by a Neurologist.  
5 Neurological assessment by neurologist if a patient experiences a stroke or TIA throughout the duration of the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY REQUIREMENTS TAVR PROCEDURE ALONE (MEDICAL TREATMENT) ARM 
 
Baseline 
45 days  after  
TAVR 
procedure 
(+/- 15 d) 
6 Months 
after 
procedure 
(+/- 1 month)   
12 Months 
after 
procedure 
(+/- 1 month)   
24 Months after 
procedure 1 
(+/- 1 month)   
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Informed Consent 
+ 
 
 
 
 
Inclusion/Exclusion 
Criteria 
+ 
 
 
 
 
Randomization 
+ 
 
 
 
 
KCCQ-12 Score 
+ 
+ 
+ 
+ 
+ 
Vital Signs 
+ 
+ 
+ 
+ 
 
AE Monitoring 
+ 
+ 
+ 
+ 
+ 
INR 
+ 
+ 
+ 
+ 
+2 
Blood Work 
+3 
 
 
 
 
NIH Stroke Scale 
(NIHSS 
+ 
+ 
+ 
+ 
+ 
Modified Rankin 
Scale (MRS) 
+ 
+ 
+ 
+ 
+ 
Brain Image (CT or 
MRI)4 
As Required 
Neuro Assessment5 
As Required 

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23 
6.2.2 ENROLLMENT 
All Patients who are to undergo a TAVR procedure and have non-valvular AF are eligible for screening as potential 
candidates for the study. 
Patients who provide consent and satisfy all the inclusion and exclusion criteria will be eligible for randomization.  
PATIENT ENROLLMENT OVERVIEW 
 
 
 
 
 
 

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6.2.3 FOLLOW-UP 
Patients will have follow-up visits at 45 days following the TAVR procedure alone or post-WATCHMAN implant, and 
6 months, 12 months and 24 months post -procedure. During each follow-up visit (scheduled or interim), all enrolled 
patients must be evaluated for adverse events using an assessment of history and physical exam.  NIHSS Stroke 
Assessment Worksheet and MRS Stroke Assessment Worksheet should be completed at each visit. 
For patients who suffer a stroke or TIA following randomization, the following assessments should be completed: 
 
Complete evaluation by Neurologist, AND 
 
Brain Imaging (CR/MRI) 
Patients who received a WATCHMAN implant are required to undergo a TEE examination during the procedure and 
45-days post-implant. TEE imaging must be performed in accordance with standard protocol, using color Doppler 
technology and possibly ECHO contrast within the LAA to confirm the absence of blood flow AROUND and/or 
THROUGH the WATCHMAN implant. Patients randomized to WATCHMAN who have intracardiac thrombus 
visualized during the procedure are contraindicated from receiving the device per labeling guidelines, but will remain 
in the trial as intent to treat and should be followed for all study visits. 
 Completion of the following assessments must be documented on the Follow-Up Case Report Form: 
 
The presence or lack of flow in the LAA; 
 
Residual atrial septal shunt; 
 
Thrombus on the device surface;  
 
Device position 
Patients randomized to the TAVR alone group are to remain on anticoagulant/antiplatelet therapy at the discretion 
of the treating physician indefinitely if possible. If the patient is on warfarin, dosage should be adjusted such that 
patients maintain a therapeutic INR of 2.0 – 3.0. According to ACC/AHA/ESC Guidelines on Management of Patients 
with Atrial Fibrillation, INR is to be monitored per site standard of care guidelines while patients are on warfarin 
therapy. 
All patients should continue to undergo routine post-TAVR follow-up as per accepted standards of care. 
 
 
 

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6.2.4 WATCHMAN DEVICE IMPLANT PHARMACOLOGIC REGIMEN 
 
Post-procedure warfarin therapy is required in ALL patients receiving a WATCHMAN Device. Patients should be placed on 81-100 mg of aspirin 
and warfarin titrated to post-implant INR 2.0-3.0. At 45 days (±15 days) post-implant, WATCHMAN Device assessment is to be performed via TEE. 
Cessation of warfarin is at physician discretion provided that any peri-device flow demonstrated by TEE is ≤5 mm. If adequate seal is not 
demonstrated, subsequent warfarin cessation decisions are contingent on demonstrating flow ≤5 mm. At the time the patient ceases warfarin, 
the patient should begin clopidogrel 75 mg daily and increase aspirin to 300-325 mg daily. This regimen should continue until 6 months have 
elapsed after implantation. Patients should then remain on aspirin 300-325 mg indefinitely. If a patient remains on warfarin and aspirin 81 mg 
for at least 6 months after implantation, and then ceases warfarin, the patient should not require clopidogrel, but should increase aspirin to 300-
325 mg daily, which then should be continued indefinitely. 
* Timing of re-evaluation of LAA seal by TEE is per physician’s discretion and according to standard of care. 

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26 
7 
ASSESSMENT OF SAFETY 
 
7.1  
SPECIFICATION OF SAFETY PARAMETERS 
Because all of the devices and interventions for this study are FDA approved, if a subject experiences an adverse 
event that the investigator feels is related to a device or intervention, site staff should follow the standard reporting 
procedures as outlined in the manufacturer’s product labeling and/or as required by applicable country regulations. 
The Medical Monitor will review safety data for the study and provide study oversight as necessary (see Medical 
Monitor Charter for details). 
 
7.2 
ADVERSE EVENT REPORTING 
An adverse event is an untoward event that affects the patient’s health or safety. When reporting an adverse event, 
the investigator will complete the AE report form.  
Adverse experiences that require reporting include any adverse event with clinical symptoms that could possibly be 
contributed to any of the following:  
• 
The WATCHMAN device  
• 
The TAVR device 
• 
The WATCHMAN implant procedure (including pericardial effusion, device embolism, stroke) 
• 
The TAVR implant procedure (including pericardial effusion, device embolism, stroke) 
• 
Any study required procedures (i.e., clinical complications from protocol required TEE, etc.)  
The following adverse events will also be reported regardless of relationship to the device(s) or procedure(s):  
• 
Any event with an outcome of death 
• 
Stroke (ischemic and/or hemorrhagic) and TIA 
• 
Any events associated with bleeding 
• 
Arterial or venous thrombosis or embolism 
• 
Rehospitalization related to procedure or device implantation 
• 
Any potential Unanticipated Adverse Device Effects (see definition below)  
Each adverse event will be evaluated by the investigator for relatedness and seriousness.  
i) Relatedness  
The relatedness of an adverse event to the study, WATCHMAN Device, TAVR device, WATCHMAN procedures or 
TAVR procedure will be assessed by the Investigator for each submitted adverse event form.  
• 
Device Related: An adverse event that results from the presence or performance of the device or any other 
component of the system.  

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27 
• 
Procedure Related: An adverse event that occurs due to the system implantation procedure. Adverse 
events that are contributable to the anesthesia or contrast media given during the implant procedure will 
be considered procedure related.  
• 
Unknown: An adverse event that cannot be determined to have a causal relationship with either the system 
or procedure will be classified as unknown.  
• 
Not Related: An adverse event that is determined to not have a causal relationship with either the system 
or procedure.  
ii) Seriousness  
Adverse events as described above will be evaluated for serious injury. Adverse events resulting in death or serious 
injury are to be reported to the sponsor within 24 hours of learning of the event. Serious injury is an injury or illness 
that: 
• 
Is life-threatening, or 
• 
Results in permanent impairment of a body function or permanent damage to a body structure, or 
• 
Necessitates medical or surgical intervention to preclude permanent impairment of a body function or 
permanent damage to a body structure. Permanent means irreversible impairment or damage to a body 
structure or function, excluding trivial impairment or damage [21 CFR 803.3] 
 Note: Not all cosmetic damage is considered trivial.  Furthermore, a life-threatening injury meets the definition of 
serious injury, regardless of whether the threat was “temporary.”  It should also be noted that a device does not 
have to malfunction for it to cause or contribute to a serious injury. Even though a device may function properly, it 
can still cause or contribute to a death or serious injury. Caused or contributed to means that a death or serious 
injury was or may have been attributed to a medical device or that a medical device was or may have been a factor 
in a death or serious injury, including events occurring as a result of [21 CFR 803.3]: 1. Failure; 2. Malfunction; 3. 
Improper or inadequate design; 4. Manufacture; 5. Labeling; or 6. User error 
Unanticipated Adverse Device Effect (UADE)  
Per 21 CFR 812.3(s) “an unanticipated adverse device effect means 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 patients.”  
 
8 
CLINICALMONITORING 
The Sponsor or designee has ethical, legal and scientific obligations to carefully follow this study in accordance with 
established research principles and applicable regulations. The investigator, as part of his responsibilities, is expected 
to cooperate with the Sponsor or designee in ensuring that the study adheres to the protocol and GCP requirements.   
As part of a concerted effort to fulfill these obligations, monitoring will be carried out during the study in accordance 
with the Monitoring Plan set forth for this trial.   
 

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28 
 
 
 
9 
STATISTICAL CONSIDERATIONS 
 
9.1 
STATISTICAL AND ANALYTICAL PLANS 
All statistical analysis will be “intent-to-treat”, with each patient being considered as part of their randomized group 
irrespective of the actual treatment received. Patients not having an event, or lost to follow-up will be censored at 
the time of their last documented follow-up visit or phone call. 
The study is designed to demonstrate the non-inferiority of the WATCHMAN device compared to the control group, 
with regards to the primary endpoint (composite of all-cause mortality, stroke (ischemic and hemorrhagic), or 
bleeding (major and/or life-threatening)). Non-inferiority will be assessed using the 1-sided 97.5% confidence 
interval around the hazard ratio (WATCHMAN-TAVR: TAVR only).  Non-inferiority will be demonstrated if the 1-sided 
97.5% upper confidence limit for the difference in proportions is less than 1.5. If the non-inferiority objective is met, 
additional analyses to assess superiority of the WATCHMAN group to the control group will be performed. The 
composite primary endpoint will also be summarized as events per 100 patient-years of follow-up. 
For data collected at baseline, during the procedure and at follow-up, descriptive statistics will be generated. 
Continuous variables will be summarized with reporting of mean, standard deviation (SD), median, interquartile 
range (Q1, Q3) and range (minimum and maximum). General linear models will be used to compare continuous 
variables across treatment groups. Categorical variables will be summarized using counts and percentage of subjects 
and compared using the standard Chi-square statistic or Fisher’s Exact test, as appropriate. 
In general, missing data will not be imputed and will remain missing, unless otherwise indicated. 
 
 
9.2 
STATISTICAL HYPOTHESES 
The study is designed to demonstrate the non-inferiority of the WATCHMAN device compared to the control group, 
with regards to the primary endpoint (composite of all-cause mortality, stroke (ischemic and hemorrhagic), bleeding 
(major and/or life-threatening)).  
The following null hypotheses will be tested: 
 
H01:  The hazard ratio for WATCHMAN + TAVR relative to TAVR is ≥1.5 (non-inferiority) 
 
H02:  The hazard ratio for WATCHMAN + TAVR relative to TAVR is ≥1.0 (superiority) 
If H01 is rejected, then H02 will also be tested.  If the null hypothesis for non-inferiority is not rejected, H02 will not be 
tested. 

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29 
 
 
 
9.3 
ANALYSIS POPULATIONS 
Intention-to-Treat Population (ITT): The primary analysis will be based on the ITT population. All randomized 
subjects will be analyzed according to their original randomization assignment (WATCHMAN+TAVR or TAVR)  
regardless of treatment received.  
Per-protocol population: The per-protocol population is defined as patients in the WATCHMAN groups who received 
both the WATCHMAN and the prosthetic valve. In the TAVR only group, it is defined as patients who had the 
prosthetic valve placed.  
 
9.4 
DESCRIPTION OF STATISTICAL METHODS 
 
9.4.1 GENERAL APPROACH 
The ITT population will be used to analyze the primary and secondary endpoints. The non-inferiority hypothesis will 
only be tested using the primary endpoint of all-cause mortality, stroke, and major/life-threatening bleeding.   Event 
rates, hazard ratio and 95% confidence intervals and a p-value associated with the non-inferiority hypothesis will be 
provided. If the non-inferiority objective is met, a p-value for the superiority hypothesis will also be provided. 
Secondary endpoints will be summarized using event rates, hazard ratios and 95% confidence intervals.  Nominal p-
values for comparisons between treatment groups will be provided for descriptive purposes only. 
All patients should be followed until the termination of the study, regardless of adherence to the treatment strategy.  
Available information on patients lost to follow-up will be included in the analyses. Patients not reaching a primary 
endpoint by the time of study termination will be censored at their last known assessment. 
Statistical methods will be further outlined in the Statistical Analysis Plan (SAP). 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT 
The primary endpoint is the first occurrence of all-cause mortality, stroke or major/life-threatening bleeding event 
within one year following randomization. Estimates of the hazard ratio and 95% confidence intervals will be based 
on the Cox proportional hazards model, under the assumption of proportional hazards.  Comparison of cumulative 
hazard functions will be based on the log-rank test. 
The upper bound of the confidence interval will be generated from the Cox proportional hazards model with 
treatment group as a factor. 
 

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9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Secondary endpoints will include the following: 
 
Time from randomization to each component of the primary endpoint: 
o 
All-cause mortality 
o 
Any stroke 
o 
Any occurrence of major or life-threatening bleeding (as per VARC2 definition of bleeding) 
 
 
Time to death from cardiovascular causes 
 
Time to ischemic stroke 
 
Time to hemorrhagic stroke 
 
Arterial or venous thrombosis or embolism 
 
Rehospitalization related to WATCHMAN procedure or WATCHMAN device. 
 
Procedural costs related to the initial TAVR procedure and WATCHMAN device implantation. 
Analysis of time-to-event endpoints for the components will be analyzed similarly to that of the primary endpoint, 
except there will be no testing of the non-inferiority hypothesis. Point estimates and 95% confidence intervals will 
be derived from a Cox proportional model with treatment group as a factor. Descriptive frequencies of the endpoints 
and Kaplan-Meier curves will be presented. P-values may be provided for descriptive purposes, but should not be 
considered informative. The frequency of procedure related complications, device/implant failure or systemic 
embolism will be summarized with descriptive statistics. 
Costs directly related to the initial TAVR procedure and WATCHMAN device implantation will be collected.  
 
9.4.4 SAMPLE SIZE 
The WATCH-TAVR is a randomized, prospective multi-center event-driven non-inferiority study to determine the 
safety and efficacy of the WATCHMAN device in patients with non-valvular AF undergoing TAVR for aortic stenosis. 
The control group consists of patients undergoing TAVR who are on standard medical practice, with oral 
anticoagulation at the discretion of the treating physician. The treatment group will have the WATCHMAN 
implantation procedure performed simultaneously with TAVR. The primary endpoint is a composite of all-cause 
mortality, stroke, life-threatening or major bleeding. The objective of the study is to demonstrate non-inferiority of 
the TAVR plus WATCHMAN device compared to the TAVR only group. 
Data from the PARTNER1 trial, along with the SOURCE-XT10 and FRANCE-211 registries show all-cause mortality rates 
in TAVR patients with AF vary from 19-30%, stroke rates from 6-10% and major/life-threatening bleeding from 17-
22%. The PROTECT-AF trial for the WATCHMAN device in non-valvular atrial fibrillation patients reported a risk 
reduction of nearly 40% for the primary composite endpoint of stroke, systemic embolization or cardiovascular or 
unexplained death (RR 0.61, 95%CrI 0.42-1.07)4. 

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31 
The following assumptions were used to determine the sample size needed to assess the non-inferiority hypothesis 
for the composite primary endpoint of all-cause mortality, stroke or major or life-threatening bleeding: 
o 
One-sided α =0.025 
o 
Primary event rate in the control population (TAVR only) of 35% at one year 
o 
Non-inferiority margin of 1.5 
o 
Underlying hazard ratio of active to control is 1.0 
o 
Power at least 80% 
o 
Lost to follow-up rate 10% 
 
Assuming level of significance (α) to be 0.05 (or α =0.025 one-sided) and aiming for a study power (1-β) of 80%, we 
estimate 191 primary events will be needed to rule out an upper limit of the one-sided 97.5% confidence interval of 
1.5.  Assuming an enrollment  duration of 18 months, follow-up period of 24 months, and 10% drop out rate per 
annum, the minimum total sample size required is 350  (175per group).  
 
10 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
 
10.1 
INSTITUTIONAL REVIEW BOARD 
This protocol, the written informed consent form, and any materials presented to subjects shall be submitted to the 
IRB identified with this responsibility. Notification in writing of approval must come from the IRB chairman or 
secretary, to the investigator, either as a letter or as a copy of the appropriate section of the IRB meeting minutes 
where this protocol and associated informed consent form were discussed. The investigator will not participate in 
the decision. If the investigator is an IRB member, the written approval must indicate such non-participation in the 
voting session. The investigator will submit status reports to the IRB as required by the governing body. The IRB must 
be notified by the investigator in writing of the interruption and/or completion of the study; the investigator must 
promptly report to the IRB all changes in research (protocol amendments) and will not make such changes without 
IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects. In cases where 
it is necessary to eliminate immediate hazards to subjects, the IRB must then be notified of the change as per local 
requirements. The investigator is required to maintain an accurate and complete records of all written 
correspondence to and received from the IRB and must agree to share all such documents and reports with the 
Sponsor. 
 
10.2 
INFORMED CONSENT PROCESS 
 
10.2.1 CONSENT PROCEDURES AND DOCUMENTATION 
Written informed consent will be obtained from all subjects (or their guardian or legally authorized representative) 
before any study-related procedures (including any pre-treatment procedures) are performed. The investigator(s) 

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32 
has both ethical and legal responsibility to ensure that each subject (or their guardian or legally authorized 
representative) being considered for inclusion in this study is given a full explanation of the protocol. This shall be 
documented on a written informed consent form, which shall be approved by the same IRB responsible for approval 
of this protocol. Each informed consent form shall include the elements required by CRF21 part 50.25 and any 
applicable local regulations. The investigator agrees to obtain approval from the Sponsor of any written informed 
consent form used in the study, prior to submission to the IRB.  
Once the appropriate essential information has been provided to the subject and fully explained by the investigators 
(or a qualified designee) and it is felt that the subject understands the implications of participating, the subject and 
the investigator (or designee) shall sign the IRB approved written informed consent form. The subject shall be given 
a copy of the signed informed consent form, and the original shall be filed appropriately, according to the institution. 
A second copy may be filed in the subject's medical record, if allowed by the institution. 
 
10.3 
PARTICIPANT AND DATA CONFIDENTIALITY 
All information generated in this study must be considered highly confidential and must not be disclosed to any 
persons not directly concerned with the study without written prior permission from the Sponsor. However, 
authorized regulatory officials and Sponsor personnel will be allowed full access to the records.  
Only unique subject numbers in eCRFs will identify subjects. Their full names may, however, be made known to a 
product regulatory agency or other authorized official if necessary. 
 
11 
DATA HANDLING AND RECORD KEEPING 
 
11.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Data collection will be with an electronic CRFs (eCRF). All users will be trained on the technical features of the EDC 
(Electronic Data Capture) as well as the content of the eCRF by qualified personnel prior to gaining access to the 
EDC. An User ID/Password will be granted after training.  This ID is not to be shared amongst the study staff. The 
CRFs may be completed by clinical site personnel who have been authorized by the principal investigator and whose 
names are documented on the Signature Log, 
Prior to the database being locked, the investigator or designee will review, approve, and sign/date each completed 
eCRF. This signature serves as attestation of the Investigator’s responsibility for ensuring that all data entered into 
the eCRF are complete, accurate, and authentic. After the end of the trial, a copy of the CRF data will be provided to 
the site. This copy will contain the final data, an audit trail of activity on the data, and any queries and answers that 
were posted for data clarification. 
 
11.2 
STUDY RECORDS RETENTION 

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33 
All clinical sites will maintain study records for a minimum of two years after termination of the study. The 
investigator shall take responsibility for maintaining adequate and accurate hard copy source documents of all 
observations and data generated during this study, including any data clarification forms (DCFs) received from the 
Sponsor.  Such documentation is subject to inspection by the Sponsor or its agents, and/or other regulatory agencies. 
11.3 
PROTOCOL DEVIATIONS 
This study will be conducted as described in this protocol, except for an emergency situation in which the protection, 
safety, and well-being of the subject requires immediate intervention, based on the judgment of the investigator (or 
a responsible, appropriately trained professional designated by the investigator). In the event of a significant 
deviation from the protocol due to an emergency, accident, or mistake, the investigator or designee must contact 
the C5Research team within 5 days of the incident. This will allow an early joint decision regarding the subject’s 
continuation in the study. The investigator and the Sponsor will document this decision. The IRB will be informed of 
all protocol changes by the investigator in accordance with the IRB established procedure. 
11.4 
PUBLICATION AND DATA SHARING POLICY 
Publications addressing the WATCH-TAVR study will be managed by the study Steering Committee.  The scientific 
validity and timing of publications will be evaluated in order to maximize the benefits derived from the publication 
of the worldwide clinical data of the study. 
At the conclusion of the study, a multicenter abstract reporting the primary results will be prepared and presented 
at a major cardiovascular meeting.  A multicenter publication will also be prepared for publication in a reputable 
scientific journal.  We anticipate many secondary manuscripts with principal authorship drawn from members of the 
Steering Committee and Investigative sites.  For purposes of timely abstract presentation and publication, such 
secondary publications will be delegated to the appropriate principal authors, and final analyses and manuscript 
review for all multicenter data will require the approval of the Steering Committee. 
 
12 
STUDY ADMINISTRATION 
A Steering Committee consisting of academic experts who participated in the development of the protocol and/or 
will provide ongoing scientific and operational oversight to the study. This Committee will monitor progress of 
study enrollment, make recommendations to the Sponsors based on the Medical Monitor recommendations, and 
oversee the presentation and publication of the trial results. The membership, roles and responsibilities will be 
described in the SC Charter.  
 
 

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34 
13 
LITERATURE REFERENCES 
1.  
Genereux P, Cohen DJ, Mack M, et al. Incidence, predictors, and prognostic impact of late bleeding 
complications after transcatheter aortic valve replacement. J Am Coll Cardiol. 2014;64(24):2605-2615. 
doi:10.1016/j.jacc.2014.08.052. 
2.  
Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment. 
Chest. 2001;119(1 Suppl):108S-121S. http://www.ncbi.nlm.nih.gov/pubmed/11157645. 
3.  
Stepinska J, Czerwinska K, Witkowski A, et al. Risk factors for bleeding complications in patients undergoing 
transcatheter aortic valve implantation (TAVI). Cardiol J. 2013;20(2):125-133. doi:10.5603/CJ.2013.0024. 
4.  
FDA. PMA P130013: FDA Summary of Safety and Effectiveness Data SUMMARY OF SAFETY AND 
EFFECTIVENESS DATA (SSED). http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130013b.pdf. Published 
2013. Accessed August 8, 2016. 
5.  
January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with 
atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on 
Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76. 
doi:10.1016/j.jacc.2014.03.022. 
6.  
Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial 
fibrillation: a randomized clinical trial. JAMA. 2014;312(19):1988-1998. doi:10.1001/jama.2014.15192. 
7.  
Holmes DR, Reddy VY, Turi ZG, et al. Percutaneous closure of the left atrial appendage versus warfarin 
therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 
(London, England). 2009;374(9689):534-542. doi:10.1016/S0140-6736(09)61343-X. 
8.  
Attinger-Toller A, Maisano F, Senn O, et al. “One-Stop Shop”: Safety of Combining Transcatheter Aortic 
Valve Replacement and Left Atrial Appendage Occlusion. JACC Cardiovasc Interv. 2016;9(14):1487-1495. 
doi:10.1016/j.jcin.2016.04.038. 
9.  
Holmes DR, Kar S. Opening and Closing in Tandem. JACC Cardiovasc Interv. 2016;9(14):1496-1498. 
doi:10.1016/j.jcin.2016.05.034. 
10.  
Tarantini G, Mojoli M, Windecker S, et al. Prevalence and Impact of Atrial Fibrillation in Patients With 
Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: An Analysis From the SOURCE 
XT Prospective Multicenter Registry. JACC Cardiovasc Interv. 2016;9(9):937-946. 
doi:10.1016/j.jcin.2016.01.037. 
11.  
Chopard R, Teiger E, Meneveau N, et al. Baseline Characteristics and Prognostic Implications of Pre-Existing 
and New-Onset Atrial Fibrillation After Transcatheter Aortic Valve Implantation: Results From the FRANCE-
2 Registry. JACC Cardiovasc Interv. 2015;8(10):1346-1355. doi:10.1016/j.jcin.2015.06.010.