WAveCrest Vs. Watchman TranssEptal LAA Closure to REduce AF-Mediated STroke 2. A Prospective, Multicenter, Randomized, Active Controlled, Clinical Trial of the Coherex WaveCrest® Left Atrial Appendage Occlusion System Compared to the Watchman® LAA Closure Device for the Reduction in Risk of Ischemic Stroke or Systemic Embolism in Subjects With Non-valvular Atrial Fibrillation That Have an Appropriate Rationale to Seek a Non-pharmacologic Alternative to Chronic Oral Anticoagulation.
Phase: PHASE3
Conditions: Stroke
Sponsor: Coherex Medical

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
1 of 90
  
Clinical Investigational Plan for the 
WAVECREST 2 Trial
Trial Title: WAveCrest Vs. Watchman 
TranssEptal LAA Closure to REduce AF-Mediated 
STroke 2  
A prospective, multicenter, randomized, active controlled, clinical trial of the Coherex 
WaveCrest® Left Atrial Appendage Occlusion System compared to the Watchman® LAA 
Closure Device for the reduction in risk of ischemic stroke or systemic embolism in subjects
with non-valvular atrial fibrillation that have an appropriate rationale to seek a non-
pharmacologic alternative to chronic oral anticoagulation. 
SPONSOR:
Coherex Medical, Inc.
3598 West 1820 South 
Salt Lake City, Utah 84104-4959 
Telephone:  +1-801-433-9900 
Fax:  +1-801-433-9901 
Document Date: 04-DEC-2019

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
2 of 90
INVESTIGATOR SIGNATURE PAGE
Trial Name: The WAVECREST 2 Trial
Trial Title: WAveCrest Vs. Watchman TranssEptal LAA Closure to REduce AF-mediated 
STroke 2 
Protocol Number: CHX_IP014
IDE Number: G170113
A prospective, multicenter, randomized, active controlled, clinical trial of the Coherex 
WaveCrest® Left Atrial Appendage Occlusion System compared to the Watchman® LAA 
Closure Device for the reduction in risk of ischemic stroke or systemic embolism in subjects
with non-valvular atrial fibrillation that have an appropriate rationale to seek a non-
pharmacologic alternative to chronic oral anticoagulation. 
Sponsored by: Coherex Medical, Inc.
I, the Undersigned, 
Printed Name: 
Title: 
 
Address:  
 
 
 
 
acting as an Investigator in the above-mentioned trial, undertake to perform the trial in due 
compliance with the present protocol and with all applicable Regulatory, Ethical and Good 
Clinical Practices requirements, including but not restricted to the Declaration of Helsinki, Code 
of Federal Regulations Title 21, and ISO14155.  
No trial-specific tests or procedures will be undertaken prior to Institutional Review Board or 
Ethics Committee approval of the research and individual subject signature of an informed 
consent to participate in the trial. Use of the device will be in full compliance with this Clinical 
Investigational Plan and product Instructions for Use.  Reporting of adverse events and vigilance 
data will be performed in compliance with local regulatory and Food and Drug Administration 
requirements.
Signature: ______________________________     Date: _________________________  

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
3 of 90
TABLE OF CONTENTS
1. 
SYNOPSIS.......................................................................................................................... 7 
1.1 
Trial Flow Chart ........................................................................................................................................... 16 
1.2 
Trial Contacts ................................................................................................................................................ 17 
1.3 
Regulatory History ........................................................................................................................................ 18 
2. 
BACKGROUND AND JUSTIFICATION FOR CLINICAL TRIAL ....................... 18 
2.1 
Oral Anticoagulant Therapy ......................................................................................................................... 19 
2.2 
Risk-Stratification .......................................................................................................................................... 20 
2.3 
LAA Occlusion or Exclusion ......................................................................................................................... 21 
2.4 
Surgical Approaches ..................................................................................................................................... 21 
2.5 
Impetus for Percutaneous Approaches .......................................................................................................... 22 
2.6 
Percutaneous LAA Occlusion Devices .......................................................................................................... 22 
2.7 
Clinical Experience with the WaveCrest Device ........................................................................................... 24 
2.8 
Rationale to Conduct this Clinical Trial ....................................................................................................... 24 
2.9 
Justification for Choice of Control Arm ........................................................................................................ 24 
3. 
RISKS AND BENEFITS OF THE CLINICAL TRIAL ............................................. 25 
3.1 
Description of subject population ................................................................................................................. 25 
3.2 
Anticipated clinical benefits .......................................................................................................................... 25 
3.3 
Anticipated adverse events and adverse device effects .................................................................................. 26 
3.4 
Residual risks associated with the device under investigation, as identified in the risk analysis report ....... 27 
3.5 
Risks associated with participation in the clinical trial ................................................................................ 27 
3.6 
Possible interactions with concomitant medical treatments and/or concurrent medical interventions ........ 27 
3.7 
Steps that will be taken to control or mitigate the risks and study bias ......................................................... 28 
3.8 
Risk-to-benefit rationale ................................................................................................................................ 29 
4. 
PURPOSE ........................................................................................................................ 29 
4.1 
Name and Intended Use ................................................................................................................................ 29 
4.1.1 
Indications for Use ............................................................................................................................... 29 
4.2 
Scope of Trial ................................................................................................................................................ 30 
4.2.1 
Trial Size ............................................................................................................................................... 30 
4.2.2 
Duration ............................................................................................................................................... 31 
4.3 
Endpoints ....................................................................................................................................................... 31 
4.3.1 
Primary Endpoint ................................................................................................................................. 31 
4.3.2 
Secondary Effectiveness Endpoints ..................................................................................................... 31 
4.4 
Inclusion and Exclusion Criteria................................................................................................................... 31 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
4 of 90
4.4.1 
Inclusion Criteria .................................................................................................................................. 31 
4.4.2 
Exclusion Criteria ................................................................................................................................. 32 
4.4.3 
Echocardiographic Exclusion Criteria ................................................................................................... 33 
4.4.4 
Adequate Representation of Women and Minorities ......................................................................... 33 
4.5 
Subject Population ........................................................................................................................................ 34 
4.5.1 
Subject Screening................................................................................................................................. 34 
4.5.2 
Point of Enrollment .............................................................................................................................. 34 
4.5.3 
Enrollment of Medicare Beneficiaries (US Subjects Only) ................................................................... 34 
4.5.4 
Vulnerable Population ......................................................................................................................... 34 
4.5.5 
Description of the specific informed consent process ......................................................................... 35 
4.5.6 
Responsibilities .................................................................................................................................... 35 
4.5.7 
Composition ......................................................................................................................................... 35 
4.5.8 
Initial IRB/EC Approval ......................................................................................................................... 35 
4.5.9 
Annual IRB/EC Renewal ....................................................................................................................... 35 
4.6 
Informed Consent .......................................................................................................................................... 35 
4.6.1 
General Process ................................................................................................................................... 35 
4.6.2 
Informed consent will be obtained in Subjects unable to read or write ............................................. 36 
5. 
DEVICE UNDER INVESTIGATION AND CONTROL COMPARATORS .......... 37 
5.1 
Device Description ........................................................................................................................................ 37 
5.2 
Control device (Watchman LAA Occlusion System) ..................................................................................... 38 
5.3 
Device Accountability.................................................................................................................................... 39 
5.4 
Device Handling and Storage ....................................................................................................................... 39 
6. 
PROCEDURES ............................................................................................................... 40 
6.1 
Baseline Evaluation and Randomization/Roll-in........................................................................................... 40 
6.2 
Treatment Visit .............................................................................................................................................. 41 
6.3 
Implant Procedure ......................................................................................................................................... 42 
6.4 
Discharge ...................................................................................................................................................... 43 
6.5 
Follow-up Post-Discharge ............................................................................................................................ 44 
6.6 
Follow-up 45 Day Office Visit ....................................................................................................................... 44 
6.7 
3 Months Phone Follow-Up .......................................................................................................................... 46 
6.8 
Follow-up 6 Month Office Visit ..................................................................................................................... 46 
6.9 
Follow-up 1 Year Office Visit ........................................................................................................................ 47 
6.10 
Follow-up 2 Year, 3 Year, 4 Year and 5 Year Office Visits ...................................................................... 47 
6.11 
Follow-up Phone 1.5 Year, 2.5 Year, 3.5 Year and 4.5 Year .................................................................... 48 
6.12 
Unscheduled Neurology Visit ................................................................................................................... 48 
6.13 
Subject Trial Completion .......................................................................................................................... 51 
6.14 
Any Known or Foreseeable Factors that May Compromise the Outcome of the Clinical trial or the 
Interpretation of the Results .................................................................................................................................... 52 
6.15 
Criteria and Procedures for Subject Withdrawal or Discontinuation ...................................................... 52 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
5 of 90
6.16 
Lost-to-Follow-up (LTFU) ....................................................................................................................... 52 
6.17 
Early Trial termination ............................................................................................................................. 53 
7. 
COMPLIANCE TO CIP ................................................................................................ 53 
7.1 
Statement of Compliance ............................................................................................................................... 53 
7.2 
Adherence to the Clinical Investigation Plan ................................................................................................ 54 
8. 
ADVERSE EVENT, ADVERSE DEVICE EFFECTS, DEVICE DEFICIENCY .... 55 
8.1 
Definitions ..................................................................................................................................................... 55 
8.1.1 
Medical Device ..................................................................................................................................... 55 
8.1.2 
Adverse Event ...................................................................................................................................... 55 
8.1.3 
Serious Adverse Event ......................................................................................................................... 57 
8.1.4 
Adverse Device Effect (ADE) ................................................................................................................ 58 
8.1.5 
Unanticipated Serious Adverse Device Effect (USADE) ....................................................................... 58 
8.1.6 
Unanticipated Adverse Device Effect (UADE) ...................................................................................... 58 
8.1.7 
Anticipated Serious Adverse Device Effect (ASADE) ............................................................................ 59 
8.2 
Procedure for assessing, recording and reporting adverse events, device deficiencies/complaints, adverse 
device effects, serious adverse events and serious adverse device effects: ............................................................. 59 
8.3 
Subject Death ................................................................................................................................................ 60 
8.4 
Device Deficiency .......................................................................................................................................... 60 
9. 
DATA MANAGEMENT ................................................................................................ 60 
9.1 
Data Management Plan................................................................................................................................. 61 
9.2 
Document and Data Control ......................................................................................................................... 61 
9.2.1 
Traceability of documents and data .................................................................................................... 61 
9.2.2 
Recording data ..................................................................................................................................... 61 
9.2.3 
Records ................................................................................................................................................ 62 
9.3 
Record Retention ........................................................................................................................................... 63 
9.3.1 
Record Custody .................................................................................................................................... 63 
9.3.2 
Reports ................................................................................................................................................. 63 
9.3.3 
IRB/EC Records .................................................................................................................................... 64 
10. 
MONITORING ............................................................................................................... 64 
11. 
SUBJECT INFORMATION .......................................................................................... 66 
12. 
IRB/EC INFORMATION .............................................................................................. 66 
13. 
OTHER INSTITUTIONS .............................................................................................. 66 
14. 
REGULATORY INSPECTIONS .................................................................................. 66 
14.1 
Audits ........................................................................................................................................................ 66 
15. 
STATISTICAL METHODS .......................................................................................... 67 
15.1 
Analysis Plan ............................................................................................................................................ 67 
15.2 
Trial Endpoints ......................................................................................................................................... 67 
15.3 
Primary Safety Endpoint .......................................................................................................................... 68 
15.4 
Primary Effectiveness Endpoint ............................................................................................................... 68 
15.5 
Secondary Effectiveness Endpoints .......................................................................................................... 69 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
6 of 90
15.6 
Descriptive Endpoints............................................................................................................................... 70 
15.7 
Power & Adaptive Sample Size Selection ................................................................................................. 71 
15.8 
Trial Success ............................................................................................................................................. 72 
15.9 
Adjustment for Multiple Testing ............................................................................................................... 72 
15.10 
Sensitivity Analysis ................................................................................................................................... 72 
16. 
DOCUMENT RETENTION .......................................................................................... 73 
17. 
AMENDMENTS TO CLINICAL INVESTIGATIONAL PLAN .............................. 73 
18. 
TRIAL COMMITTEES ................................................................................................. 74 
18.1 
Physician Advisory Committee ................................................................................................................. 74 
18.2 
Clinical Event Committee (CEC) .............................................................................................................. 74 
18.3 
Data Monitoring Committee (DMC) ........................................................................................................ 74 
19. 
OUTSOURCING OF DUTIES AND FUNCTIONS .................................................... 75 
19.1 
Echocardiography Core Lab ...................................................................................................................... 75 
20. 
INVESTIGATION SUSPENSION OR TERMINATION .......................................... 75 
20.1 
Premature trial termination ...................................................................................................................... 75 
20.2 
Resuming the trial after temporary suspension ........................................................................................ 76 
20.3 
Trial conclusion ........................................................................................................................................ 77 
21. 
TRAINING ...................................................................................................................... 77 
21.1 
Training of Investigators and Trial Personnel ......................................................................................... 77 
22. 
PUBLICATION POLICY .............................................................................................. 78 
APPENDIX I: Acronyms and Definitions .................................................................................... 80 
APPENDIX B: CHADS2, CHA2DS2-VASc and HAS-BLED Scores ......................................... 85 
APPENDIX III: Questionnaire for Verifying Stroke-Free Status (QVSFS) ................................ 87 
APPENDIX IV: Neurologic Assessments .................................................................................... 88 
REFERENCES ............................................................................................................................. 88 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
7 of 90
1. SYNOPSIS  
Trial Title
WAVECREST 2 Trial: WAveCrest Vs. Watchman TranssEptal LAA 
Closure to REduce AF-Mediated STroke 2
Name of 
Investigational Device
Coherex WaveCrest® Left Atrial Appendage Occlusion System
Purpose
To evaluate the safety and effectiveness of the Coherex WaveCrest 
Left Atrial Appendage Occlusion System
Intended Use
The Coherex WaveCrest Left Atrial Appendage Occlusion System is a 
percutaneous transcatheter device intended to be used for closure of 
the left atrial appendage (LAA)
Design
Prospective, multicenter, randomized, active control, clinical trial of 
the Coherex WaveCrest Left Atrial Appendage (LAA) device 
compared to the Watchman® LAA device for the reduction in risk of 
ischemic stroke or systemic embolism in subjects with non-valvular 
atrial fibrillation who have an appropriate rationale to seek a non-
pharmacologic alternative to chronic oral anticoagulation (OAC).
Blinding
The following personnel will be blinded to the randomization 
assignment and treatment received:
x Neurology personnel evaluating subject, to the extent possible 
x Clinical Events Committee (CEC) that will adjudicate primary 
safety and effectiveness events, death (cardiovascular vs. non-
cardiovascular), and bleeding category 
x Investigator’s staff administering the Questionnaire for Verifying 
Stroke-Free Status (QVSFS), the modified Rankin Scale (mRS), 
and the National Institutes of Health Stroke Scale (NIHSS) 
questionnaires
Devices Used
Watchman LAA Closure Device and Delivery Sheath
WaveCrest Left Atrial Appendage Occlusion System and Delivery 
Sheath
Subject Population
7KHVXEMHFWSRSXODWLRQZLOOLQFOXGHSDUWLFLSDQWV\HDUVROG
diagnosed with non–valvular atrial fibrillation and a CHADS2 VFRUH
2 or a CHA2DS2-9$6FVFRUH3 who have an appropriate rationale to 
seek a non-pharmacologic alternative to chronic oral anticoagulation.  
Definitions
See protocol definitions in Appendix I: Acronyms and Definitions
Primary Effectiveness
Endpoint
Composite rate of ischemic stroke or systemic embolism at 24 months
Primary Safety 
Endpoint 
Composite rate of:
x
All cause death; or 
x
Procedure- or device-related complications requiring percutaneous 
or surgical intervention through 45 days post-procedure; or 
x
Major bleeding

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
8 of 90
Secondary Endpoints
x
Rate of ischemic stroke or systemic embolism with the WaveCrest 
device in comparison to the CHADS2 and CHA2DS2-VASc 
imputed risk of ischemic stroke or systemic embolism in the 
absence of anticoagulant therapy
x
Rate of /$$FORVXUHJDSPPDWGD\V
Descriptive Safety 
Endpoints 
x
Components of the composite primary safety endpoint through 45 
days post-procedure
x
The rates of stroke (all types) or pericardial effusion through 45 
days post-procedure
x
Pericardial effusion requiring surgical drainage through 7 days 
post-procedure or at hospital discharge, whichever is later
x
Device- or procedure-related Serious Adverse Events (SAEs) 
reported by site at 45 days, 6 months, and at each annual follow-up 
period 
x
All-cause mortality 45 days, 6 months, and at each annual follow-
up period 
x
Cardiovascular mortality at 45 days, 6 months, and at each annual 
follow-up period 
Descriptive 
Effectiveness 
Endpoints 
x
Primary effectiveness endpoint event rate at 6 months, 1 year, 3
years, 4 years and 5 years 
x
Composite of all stroke, systemic thromboembolism, or TIA at 45 
days, 6 months and at each annual follow-up period 
x
Landmark analysis of primary effectiveness endpoint from the 45-
day visit to the time of each annual follow-up period 
x
Landmark analysis of the incidence of ischemic stroke from 6 
months following device implantation and discontinuation of oral 
anticoagulant and dual antiplatelet therapy
x
Composite of all-cause stroke at 45 days, 6 months, and at each 
annual follow-up period 
x
Incidence of thrombus on the surface of the device at 45 days, 1 
year, and throughout all follow-up  
x
Strokes adjudicated as ischemic, hemorrhagic, or indeterminate at 
45 days, 6 months, and at each annual follow-up period 
x
Strokes adjudicated as major or minor at 45 days, 6 months, and at 
each annual follow-up period  
x
Stroke adjudicated as cardioembolic in origin at 45 days, 6 months, 
and at each annual follow-up period 
x
Freedom from oral anticoagulants after each protocol-required 
follow-up visit 
x
Number of devices used per subject 
x
Procedural success

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
9 of 90
x
Technical success
x
Device success
x
LAA Closure as determined by Echocardiography Core Lab (ECL) 
at 45 days, 6 months, and at 1 year
x
Procedure time, device duration, contrast volume used, and 
fluoroscopy time 
Inclusion Criteria
1. Documented evidence of paroxysmal, persistent, or permanent 
non-valvular atrial fibrillation
2. At least 18 years of age
3. Calculated CHADS2 VFRUHRUCHA2DS2-VASc VFRUH3  
4. Indication for warfarin therapy with an appropriate rationale to 
seek a non-pharmacologic alternative to chronic oral 
anticoagulation
5. Willing and able to comply with post-implant anticoagulation and 
antiplatelet regimen
6. Willing to participate in the required follow-up visits and tests 
7. Subject has been informed of the nature of the trial, agrees to its 
provisions and has provided written informed consent as approved 
by the Institutional Review Board/Ethics Committee (IRB/EC) at 
the site
Exclusion Criteria
1. Atrial fibrillation (AF) due to a reversible cause (e.g. 
thyrotoxicosis or post-operative)
2. Known contraindication and/or allergy to warfarin, nickel, aspirin, 
intravenous contrast, or P2Y12 inhibitors (clopidogrel, ticagrelor,
and prasugrel), which cannot be adequately pre-medicated or 
desensitized
3. Conditions other than atrial fibrillation requiring long-term 
anticoagulation therapy  
4. Contraindications to percutaneous catheterization procedures  
5. Prior surgical LAA occlusion/exclusion or implanted with LAA 
occlusion device, or any prior attempt of such procedures
6. Prior percutaneous or surgical closure of a patent foramen ovale or 
atrial septal defect 
7. Inability or unwillingness to take oral anticoagulation for 45 days 
post-procedure 
8. New York Heart Association Class IV heart failure
9. Prior cardiac transplant, history of mitral valve replacement, or 
transcatheter mitral valve intervention, or any mechanical valve 
implant

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
10 of 90
10. History of symptomatic carotid, intervertebral, or intracranial
artery occlusion or stenosis without revascularization with the 
exception of known occlusion without symptoms > 6 months  
11. Modified Rankin Scale Score 
12. Chronic resting heart rate > 110 bpm 
13. Congenital or other clinically significant cardiac anomalies 
requiring cardiac surgery or interventional repair 
14. Stroke or transient ischemic attack (confirmed by Neurologist)
within 60 days prior to enrollment 
15. Myocardial infarction within 60 days prior to enrollment
16. Sepsis or any active infection requiring oral antibiotic therapy 
within 14 days or intravenous antibiotic therapy within 30 days 
prior to enrollment 
17. Surgical or interventional cardiovascular and non-cardiovascular 
procedure including cardioversion within 30 days prior to 
enrollment or AF ablation within 60 days prior to enrollment or 
any planned general surgery or planned interventional procedure 
within 90 days after enrollment or any planned cardiac surgery
18. On renal replacement therapy, serum creatinine > 3.0 mg/dl (265 
μmol/L) or calculated creatinine clearance < 25 ml/minute
19. Thrombocytopenia (<60,000 platelets/mm3), leucopenia (white 
blood cell count < 3,000 cells/mm³), or anemia (hemoglobin 
concentration < 10 gram/deciliter)
20. Any medical disorder or psychiatric illness that would interfere 
with successful completion of the trial
21. Currently participating in an investigational drug trial or another 
device trial that has not completed the primary endpoint (trials 
requiring extended follow-up for products that are commercially 
available are not considered investigational trials).  Concurrent 
enrollment in the ACC LAAO Registry is permitted.
22. Subject belongs to a vulnerable population (see definition in 
Appendix I: Acronyms and Definitions) 
23. Any condition that would reduce life expectancy to less than 2 
years
24. Women of childbearing potential who are, or plan to become 
pregnant during the time of the trial (method of assessment per 
physician discretion)
Echocardiographic 
Exclusion Criteria
1. Estimated left ventricular ejection fraction < 30% 
2. Mitral valve stenosis defined as valve area < 1.5cm2, mean 
gradient > 6mmHg, or any mitral valve deformity consistent with 
rheumatic valvular disease

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
11 of 90
3. Aortic valve stenosis defined as valve area 1.0cm2 or mean 
gradient >30mmHg 
4. Circumferential pericardial effusion > 10mm, loculated pericardial
effusion with the largest dimension > 10 mm, or symptomatic 
pericardial effusion of any size
5. Evidence of intracardiac thrombus (including in left atrial 
appendage, left ventricle or elsewhere)
6. Cardiac tumor or myxoma  
7. Atrial septal defect that warrants closure
8. Complex atheroma in the ascending aorta or aortic arch as 
evidenced by mobile plaque. 
9. Left Atrial Appendage size and shape are unsuitable for closure 
with a WaveCrest or Watchman device
Pre-Procedure Care
The following Baseline steps are recommended to be performed within 
30 days prior to randomization but must be completed within 90 days 
prior to randomization (or within 90 days prior to treatment of roll-in 
subject): 
x
Document medical history (if not previously documented). 
x
Document appropriate rationale to seek a non-pharmacologic 
alternative therapy 
x
Perform physical exam
x
Administer Quality of Life (QoL) SF-36 questionnaire 
x
Blood work to document CBC (HGB, WBC, platelets), and serum 
creatinine with INR and pregnancy as necessary
x
CHADS2 and CHA2DS2-VASc score (see Appendix II for 
calculation of CHADS2 and CHA2DS2-VASc scores).
x
Calculate HAS-BLED score (see Appendix II for calculation of 
HAS-BLED score)
x
A trial staff member must administer the QVSFS to the subject 
(see Appendix III).
x
All subjects must undergo NIHSS and mRS.  Both must be 
administered by board-certified study Neurologist or trained and 
certified trial personnel (Appendix IV: Neurologic Assessments) 
x
If the subject has a history of stroke or TIA or if the baseline 
QVSFS score is > 0 the subject must be seen by a board-certified 
study Neurologist, including review of the following: 
o
Brain imaging (MRI unless contraindicated, then CT)  
o
If an imaging study is available following the prior stroke or 
TIA, a new study is not required per study Neurologist’s
discretion
o
Completed NIHSS & mRS

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
12 of 90
x
Perform baseline TEE. If thrombus is detected, the subject may 
undergo a 6-week course of anticoagulation followed by a repeat 
TEE.  The subject may be re-evaluated after appropriate 
anticoagulation therapy and considered for device placement 
following documentation of absence of thrombus. The timeline 
from initial screening subject to the end of thrombus treatment 
must be treated within 90 days prior to randomization - or 
treatment, for roll-in subjects. 
Post-Procedure Care
Immediately post-procedure for 45 days post-implant:
x
All subjects must have a TTE to rule out pericardial effusion prior 
to discharge.
x
Subjects receiving a Watchman device should 
begin/continue/resume warfarin therapy and aspirin per the product 
Directions for Use (DFU).  [Note: Alternative vitamin K 
antagonists (e.g., acenocoumarol or phenprocoumon) may be used 
according to geographic standard of care.] 
x
Subjects receiving a WaveCrest device are required to start 
clopidogrel 75 mg daily and 75-100 mg aspirin daily starting 12-48 
hours after the procedure (prasugrel or ticagrelor are allowable for 
clopidogrel intolerance, however, prasugrel is contraindicated in 
subjects with a history of prior stroke/TIA and both prasugrel and 
ticagrelor are contraindicated in subjects with a history of 
hemorrhagic stroke). 
45 days post-implant
x
At 45 days (+15/- 5 days) post-implant, a device assessment with 
TEE is to be performed.   
x
Warfarin cessation in the Watchman arm is per Watchman DFU
but is recommended if peri-device flow by TEE is  5mm.  If an 
adequate seal is not demonstrated, Watchman DFU 
recommendation for anticoagulation should be followed until peri-
device IORZPPLVobserved. 
x
When Watchman arm subjects stop warfarin, clopidogrel should be 
started per the product DFU. 
x
Evidence of device thrombus in either arm is recommended to be 
treated with a 6-week course of warfarin (+/- aspirin) and a repeat 
TEE.  For subjects in the WaveCrest arm, clopidogrel should be 
stopped prior to initiating anticoagulation therapy.
x
Subjects treated with the WaveCrest device with no evidence of 
device thrombus will continue dual antiplatelet therapy (DAPT) 
regardless of peri-device flow until 3 months post-implantation.
3 months post-implant

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
13 of 90
x
WaveCrest arm subjects discontinuing clopidogrel (or P2Y12 
inhibitor) must remain on 75-100mg aspirin daily indefinitely.
6 months post-implant
x
Subjects with peri-device flow >5mm at 45 days will undergo a 
TEE at 6 months. 
x
Watchman arm subjects discontinuing warfarin and clopidogrel (or 
P2Y12 inhibitor) should take daily aspirin per the Watchman DFU 
indefinitely. 
Number of Trial Sites
Up to 100 sites will participate in the trial in North America, Europe,
Australia, and Asia 
Sample Size
x
Up to 1,550 subjects will be randomized in a 1:1 ratio between the 
WaveCrest and Watchman devices. The trial design offers at least 
80% power to establish non-inferiority for the effectiveness and 
safety hypotheses across the range of possible event rates.
x
Sites will be allowed up to 5 roll-in cases (up to 2 per operator) 
prior to randomization for a total of up to 500 roll-in subjects.
x
Up to 2,050 total subjects will be enrolled
Enrollment Phase
The enrollment phase is expected to last between 2 and 3 years.
Follow-up
Evaluations 
Office follow-up: at 45 days, 6 months, 1, 2, 3, 4 & 5 years
Phone follow-up: at 3 month & 1.5, 2.5, 3.5, and 4.5 years
Transesophageal echocardiograms (TEE):  
x
45-day visit
x
6-month visit (if LAA closure is not established at 45-day visit) 
x
1-year visit
Summary of Study Assessments
Test
Screening
/Baseline
Treatment
Discharge
Office
F/U
Phone
F/U
Med Hx
X
Phys Exam
X
X
X
X
Blood work
X
QVSFS
X
X
X
QoL
X
X
Neuro eval
X
X (with stroke symptoms or QVSFS>0)*
TEE
X
X
X*
TTE
X
AE eval
X
X*
X
X
X
Med review
X
X
X
X
X
* - see additional details in Table 4 of the CIP below
Echocardiography
Core Lab
The echocardiography core lab will review all TTEs/TEEs performed 
at baseline, implant procedure (all echocardiographs), discharge, 45

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
14 of 90
days, 6 months (if applicable), and 1-year follow-up as well as all 
TTEs/TEEs conducted during neurology evaluations for closure and 
thrombus and any TTEs/TEEs conducted at outside facilities (e.g., for 
adverse events).
Neurological
Evaluations 
x
At Baseline (after enrollment, prior to randomization or 
procedure for roll-in subjects): 
o
Cerebrovascular and neurologic medical history (if not 
previously documented) 
o
QVSFS 
o
Quality of Life (QoL) questionnaire 
o
mRS/ NIHSS
o
If subject has a history of a stroke/TIA or a baseline QVSFS 
score > 0, they must be seen by a board-certified study 
Neurologist to review the following: 

Brain imaging
-
MRI preferred, CT if MRI contraindicated
-
If an imaging study following the prior neurologic 
event is available, repeat imaging is not required per 
board certified Neurologist’s discretion

Completed NIHSS & mRS
x
At study office visits and phone follow-ups, or if the subject has 
an unscheduled visit for stroke symptoms:
o
Blinded trial personnel must administer QVSFS
o
Subject-reported stroke/TIA or symptoms resulting in an 
increase in QVSFS score > 0 since subject’s most recent 
follow-up require a visit with board-certified study 
Neurologist (an Unscheduled Neurology Visit) to 
review/perform the following:   

Completed mRS & NIHSS  

Brain imaging (MRI or CT if MRI is contraindicated) 

If stroke is confirmed, appropriate neurology-guided 
evaluation is indicated to determine stroke etiology,
including the following recommended steps:
-
Cervical/neck artery imaging (CTA/MRA/carotid 
Doppler) 
-
Intracranial artery imaging (CTA/MRA/transcranial 
Doppler) 
-
24-hour cardiac monitoring 
-
TEE
-
Subject must have a mRS re-administered 90 (+/- 15) 
days after any confirmed stroke 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
15 of 90
Note: Personnel who administer mRS & NIHSS must be certified,
properly trained and blinded to subject randomization.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
19 of 90
almost any cause) that may result in multiple electrical atrial impulses.  These impulses arise 
from and travel through the atria at different times, producing disorganized, chaotic, and rapid 
atrial contractions that lead to conduction of irregular impulses to the ventricles.3 The atria 
become ineffective, dilated, and the normal flow of blood through them is significantly altered.4
Atrial fibrillation is classified as valvular and non-valvular.  Non-valvular AF refers to cases 
without rheumatic mitral valve disease, prosthetic heart valve, or valve repair.  Non-valvular AF 
can be further classified according to the AHA/ACC/ESC guidelines as paroxysmal, persistent, 
and/or permanent. Paroxysmal AF has been reported in an estimated 25 to 90% of patients with 
AF although 90% of cases of paroxysmal AF are asymptomatic and therefore the prevalence may 
not be known. 5,6,7,8,9,10
The alteration in blood flow in AF patients has adverse consequences related to a reduction in 
cardiac output and to atrial and LAA thrombus formation that can lead to systemic embolization 
including stroke. 1,11,12 Thrombus may form within the LAA perhaps because of its shape and 
trabeculations, which predispose to blood stasis.  Echocardiography and autopsy studies have 
shown that the LAA is the source of thrombi in more than 90% of non-valvular AF patients who 
experience stroke.13,14,15
Atrial fibrillation is responsible for 15% to 20% of ischemic stroke.16  AF accounts for one-
fourth of all strokes in the elderly and is responsible for 70,000 strokes per year in the United 
States (AHA statistics).  The risk of stroke in patients with non-valvular AF is approximately 5% 
per year in patients over age 76.17  Based on risk factors and treatment or the lack thereof, the 
risk of stroke can be as high as 18.2% per year in select patient populations.18
2.1 Oral Anticoagulant Therapy 
Guidelines recommend chronic anticoagulation for patients with non-valvular AF at risk of 
stroke.19,20,21 Anticoagulation therapy with the Vitamin K antagonist, warfarin, has been shown 
to lower the risk of clinical thromboembolism in virtually all patients with AF, including all 
levels of risk, and irrespective of type (paroxysmal, persistent, or chronic/permanent).22,23,24,25,26
Despite its proven efficacy, warfarin is often not well tolerated by patients and has a narrow 
therapeutic range and high risk of bleeding complications. Patients on long-term warfarin also
experience numerous drug-drug, drug-supplement, and drug-food interactions and need frequent 
international normalized ratio (INR) assessments. Only about 50% of patients who are eligible 
for long-term warfarin are treated with it.a,27,28  One review of antithrombotic therapy in high-
risk AF patients before admission for stroke (Registry of the Canadian Stroke Network) revealed 
that 29% of patients were not receiving any antithrombotic therapy, and only about one quarter 
of the 39% receiving warfarin (i.e., 10% of acute stroke patients with known AF) achieved 
therapeutic INR levels.29  In a recent large national assessment of warfarin therapy use involving 
138,319 subjects in the US and 2,683,674 INR results, the reported mean time in therapeutic 
range was only 53.7%.30  Additionally, approximately 20% of patients with AF in whom 
a Approved FDA Medication Guide found at: 
http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088578.pdf

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
23 of 90
The largest body of clinical experience on the Watchman device is from the PROTECT-AF IDE 
trial, which randomized 707 subjects with non-valvular AF in a 2:1 ratio between intervention 
(i.e., Watchman device, n = 463) and control (i.e., warfarin, n = 244).50 Subjects who received 
the intervention were required to be on warfarin for 45 days post-implant or until the LAA was 
closed followed by clopidogrel up to 6 months post-implant and aspirin indefinitely, whereas the 
control group was required to continue warfarin for the duration of follow-up.  Effectiveness was 
assessed by a primary composite endpoint of stroke, cardiovascular death or systemic embolism.  
The trial was designed to demonstrate non-inferiority of the intervention to the control group.  
Trial participants were elderly (~72 years old) with approximately 70% having CHADS2 score 
RIAt 1,065 subject-years of follow-up, the primary endpoint (composite of stroke, systemic 
embolism or cardiovascular death) event rate was 0.03 per subject-year in the intervention group 
and 0.049 per subject-year in the control group.  The trial met its endpoint, demonstrating non-
inferiority of the intervention.  However, there was a higher rate of safety events (major 
bleeding, pericardial effusion, device embolization) in the intervention group than in the control 
group, primarily due to peri-procedural complications. Additionally, there were confounding 
effects of concomitant antithrombotic use and subjects not receiving the assigned treatment as 
randomized.  The trial also enrolled some subjects who did not have a strong indication for 
warfarin (CHADS2 score = 1).  After 1,588 subject-years of follow-up, the primary effectiveness
event rates remained lower in the intervention group (0.03 per subject-year) than the control 
group (0.043 per subject-year). 51 However, the rate of primary safety events remained higher in 
the intervention group than in the control group (0.055 versus 0.036 per subject-year). A second 
IDE trial (PREVAIL) was designed to study subjects at higher risk of stroke and excluded 
subjects who were not indicated for chronic clopidogrel therapy.  The trial was designed with 2 
co-primary effectiveness endpoints and 1 co-primary safety endpoint.52 The trial enrolled 
subjects with a CHADS2 VFRUHRIRUsubjects with a CHADS2 score of 1, who also had other 
risk factors for stroke (effectively CHA2DS2-VASc = 2).  A total of 407 subjects were 
randomized (intervention: n = 269, control: n = 138).  In a Bayesian analysis, the 18-month 
primary endpoint event (composite of stroke, systemic embolism or cardiovascular death) rates 
were 0.064 in the intervention group and 0.063 in the control group.  The 18-month event rate for 
the second primary endpoint of ischemic stroke or systemic embolism beyond 7 days post-
randomization occurred at a rate of 0.0253 subject-years in the intervention group and 0.020 in 
the control group.  The third primary endpoint (composite of death, ischemic stroke, systemic 
embolism, or device or procedure-related events requiring open cardiac surgery or major 
endovascular intervention) within 7 days of randomization occurred in 2.2% of subjects in the 
intervention group.  The trial met two of the three primary endpoints (i.e., second and third 
primary endpoints).  In a pooled subject-level meta-analysis combining the PROTECT AF and 
PREVAIL datasets (recently presented at an FDA Advisory Panel meetingb), the Watchman 
device was associated with: 
x
21% reduction in the risk of the primary effectiveness endpoint (composite of stroke, 
systemic embolism or cardiovascular death) event,  
bhttp://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisory
Committee/CirculatorySystemDevicesPanel/ucm395638.htm  

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
24 of 90
x
reduced risk of disabling stroke (49%) relative to warfarin, and 
x
27% relative reduction in the risk of all-cause mortality.
The analysis also revealed comparable rates of all-cause stroke or systemic embolism (hazard 
ratio 1.02) and warfarin was associated with an approximately 2-fold relative increase in the risk 
of major bleed.   
2.7 Clinical Experience with the WaveCrest Device
The WaveCrest device was studied in the Coherex WAVECREST 1 Left Atrial Appendage 
(LAA) Occlusion Study (WAVECREST 1 Study).  One-hundred fifty-five (155) subjects were 
treated with the WaveCrest LAA occlusion device at 19 investigational sites in Europe, Australia 
and New Zealand.  Three device versions were studied: Version 1.1 (N=9), Version 1.2 (N=73), 
Version 1.3 (N=73). The study enrolled elderly subjects with an average CHADS2 Score of 2.5 
and at high risk of stroke.  More than half (65%) of enrolled subjects were contraindicated for 
anticoagulation.  Clinical results on device Version 1.3 are as follows:  procedural success was 
achieved in a majority of subjects (96%).  Procedure duration averaged 68 minutes, with 47% 
requiring no device repositioning.  On average, 1.3 devices were used (i.e., attempted) per 
subject$WGD\V/$$FORVXUHGHILQHGDVUHVLGXDOJDSPPRFFXUUHGLQRIsubjects.  
With LAA closure defined as a resLGXDOJDSPP/$$FORVXUH at 45 days was 100%.  
Pericardial effusions/tamponade occurred at a rate of 2.7%, none requiring surgical intervention, 
and there were no unanticipated adverse events or unanticipated adverse device effects.  
The WaveCrest device received the CE Mark in August 2013 and was available commercially in 
Europe in October 2013.  Procedural success was high during limited market release, with 88/92 
(96%) successful implants as of July 2014.  Pericardial effusions occurred at a rate of 3.3% 
(3/92).  There was one device embolization (1.1%).  In 2 subjects (2.2%), a thrombus was 
discovered on a follow-up TEE.  There were no procedural strokes.  In 2 subjects, there was 
damage to the inner liner of the sheath - both cases were “incidents” as defined by MEDDEV 
2.12-1 Rev 8 and warranted a Field Safety Notice (FSN) and Field Safety Corrective Action 
(FSCA) in Aug 2014.  A FSCA has resulted in modification to the Delivery Sheath liner. The 
device is described in Section 5. The related Change Notification was reviewed and approved 
July 29, 2015 and commercial use outside the United States resumed in September 2015. 
2.8 Rationale to Conduct this Clinical Trial
The WAVECREST 2 trial is intended to evaluate the safety and effectiveness of Coherex’s 
WaveCrest device in comparison with the Watchman device for the reduction in risk of ischemic 
stroke or systemic embolism in patients with non-valvular atrial fibrillation who are at increased 
risk for thromboembolism and have an appropriate rationale to seek a non-pharmacologic 
alternative to chronic oral anticoagulation.  The data from the trial will be used to support a pre-
market approval (PMA) application of the WaveCrest device in the United States.  
2.9 Justification for Choice of Control Arm
Boston Scientific’s Watchman LAA occlusion device received PMA approval on March 13, 
2015, to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients
with non-valvular atrial fibrillation who: 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
26 of 90
Specific benefits that may be associated with percutaneous LAA occlusion include reduction of 
embolic events (including possible stroke or TIA), associated with thrombus formation in the 
LAA in subjects with non-valvular atrial fibrillation.
In addition to these benefits, specific benefits that may be associated with use of the WaveCrest 
LAA Occlusion System compared to other devices used for LAA occlusion may include:
x
Enhanced LAA closure with ostial positioning
x
Reduced thrombus formation on the atrial surface of the device due to the selection of 
occluder materials
x
Improved anchor position near the point of occlusion for improved stability
x
Reduction in pericardial effusions requiring surgery due to absence of sheath and device 
manipulation deep in the LAA tissue 
3.3 Anticipated adverse events and adverse device effects
Potential adverse events specific to device placement include, but are not limited to: 
x
Device embolization, migration, misplacement or improper seal of the LAA
x
Device failure, fracture or extrusion of device components 
x
Inability to recapture, reposition, or retrieve the device requiring surgical retrieval 
x
Thrombus formation on the device surface with the risk of subsequent embolization 
x
Tissue erosion 
x
Pericardial effusion requiring intervention and cardiac tamponade 
Placement of the devices is performed using standard interventional cardiac catheterization 
techniques. Adverse events associated with these procedures include, but are not limited to: 
x
Air embolus
x
Allergic reactions
x
Anesthesia reactions
x
Apnea/shortness of breath 
x
Arrhythmia
x
Atrial septal defect
x
AV Fistula
x
Blood loss requiring transfusion 
x
Cardiac perforation
x
Contrast reaction
x
Chest pain
x
Death
x
Pulmonary vein obstruction 
x
Renal failure/insufficiency
x
Respiratory failure/hypoxia
x
Scarring/venous thrombosis 
x
Stroke/transient ischemic attack
x
Surgical repair/retrieval procedure
x
Fever
x
Groin pain 
x
Hematoma/ecchymosis
x
Hypertension; hypotension 
x
Infection and/or inflammation
including endocarditis or pericarditis
x
Myocardial infarction  
x
Perforation of vessel or myocardium 
x
Pericardial effusion
x
Pleural effusion
x
Pseudoaneurysm 
x
Pulmonary edema
x
Pulmonary embolus 
x
Tamponade 
x
Thrombus formation/embolism 
x
Vagal reactions
x
Valvular damage/insufficiency 
x
Vascular damage/ access site 
complications

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
27 of 90
This protocol requires TEEs, which may also result in adverse events including but not 
limited to the following:
x
Bleeding
x
Esophageal trauma 
x
Throat pain 
The following items should be noted pertaining to potential adverse events: 
x
All of the adverse events listed above are associated with percutaneous LAA occlusion 
and other percutaneous procedures.  There are no additional potential adverse events 
specific to LAA closure with the WaveCrest LAA Occlusion System compared to 
existing LAA occlusion devices used for similar indications.
x
Many of the adverse events listed above are possible only if the device is: (1) not used as 
specified in the Instructions for Use (IFU); (2) used by unskilled/untrained operators; (3) 
used in a non-sterile environment; or (4) used past its expiration date. The IFU for the 
Coherex LAA Occlusion System provides clear instructions on how to use the device in a 
way that minimizes identified risks and notifies the user of potential harms. 
x
Many risks associated with vascular interventional procedures are related to the condition 
of the subject and the subject’s vasculature, the subject’s overall physical health, pre-
existing medical conditions, and the clinician’s overall skill level.  These risks are 
minimized in this trial by the specific requirements of inclusion/exclusion criteria and 
cardiac anatomy, as well as careful selection and training of clinicians. 
3.4 Residual risks associated with the device under investigation, as identified in the risk 
analysis report 
Coherex Medical has conducted a risk analysis to identify potential hazards associated with use 
of the WaveCrest LAA Occlusion System and to determine how to mitigate the risks. The risk 
analysis included a review of the Use Failure Mode and Effects Analysis (FMEA), Design 
FMEA, Process FMEA, and currently published literature.  The anticipated clinical risks and 
benefits associated with the use of the WaveCrest LAA Occlusion System are described in the 
following sections.  
3.5 Risks associated with participation in the clinical trial
For subjects randomized to the Watchman device, the risks associated with participation in the 
clinical investigation are expected to be no different from those experienced in the commercial 
setting.  The methods of implantation are similar so the risks of participation in this clinical trial 
for subjects randomized to either the Watchman device or the WaveCrest device (Section 3.3)
are expected to be similar. 
3.6 Possible interactions with concomitant medical treatments and/or concurrent medical 
interventions
No interactions are expected between the WaveCrest device and concomitant medications.  
Oral anticoagulation is the standard of care to reduce the risk of stroke in people with atrial 
fibrillation. Subjects randomized to the Watchman arm should take post-implant medications 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
28 of 90
according to the product DFU.  This includes warfarin for 45 days post-implant, DAPT through 
6 months post-implant, and 300-325mg of aspirin indefinitely.  Alternative vitamin K antagonists 
(e.g., acenocoumarol or phenprocoumon) may be used according to geographic standard of care.
In the WaveCrest arm, subjects will receive clopidogrel (or ticagrelor or prasugrel) and aspirin 
for at least 3 months. The combination of these medications may be associated with an increased 
risk of bleeding as compared to the risk when only one medication is used.  Additional risks 
include: 
x
Internal bleeding 
x
Nose bleeds
x
Bruising
x
Prolonged bleeding from a cut or scrape 
x
Headache
x
Upset stomach
x
Nausea or vomiting 
x
Diarrhea
x
Fever
x
Skin rash 
x
Tissue death (necrosis) 
x
Decrease in white or red blood cells 
x
Inability to tolerate warfarin or aspirin
x
Interaction with other medications or foods 
3.7 Steps that will be taken to control or mitigate the risks and study bias
To minimize potential clinical risks to subjects participating in this clinical trial and potential 
bias in the study:  
x
Investigators selected for this trial will not have significant equity interest in Johnson & 
Johnson (parent company of Coherex Medical).  Physicians (or their spouses or 
dependent children) who receive compensation that could be affected by the outcome of 
this clinical trial or who have significant equity interest in Johnson & Johnson will not be 
selected as Investigators in this trial.  Each Investigator will complete a financial 
disclosure form before subject enrollment, and as requested by the Sponsor during trial 
conduct and at the completion of the trial.  A significant equity interest in Johnson & 
Johnson would include, for example: 
o
Any ownership interest, stock options, or other financial interest whose value 
cannot be easily determined through reference to public prices; 
o
an equity interest exceeding USD 50,000; 
o
Significant payments of other sorts, which are payments that have a cumulative 
monetary value of more than USD 25,000, EXCLUDING the costs of conducting 
the trial or other clinical trials. This could include, for example, payments made to 
the individual or the institution to support activities (i.e., a grant to fund ongoing 
research, compensation in the form of equipment, or retainers for ongoing 
consultation or honoraria). 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
29 of 90
x
Randomization will be stratified by site and CHA2DS2-VASFVFRUH4 vs. > 4. To 
ensure the randomization ratio is maintained within lower enrolling sites, randomization 
will be assigned in permuted blocks within site, and sites will not be aware of the 
randomization schedule.   
x
The QVSFS must be administered at each follow-up interval (with the exception of the 3-
month visit) by a person blinded to the subject’s randomization/implanted device and 
post-implant medication regimen. The QVSFS can be administered in person, over the 
phone, and/or at satellite clinical locations.  Blinding does not apply to baseline QVSFS 
administration. There is no special training required to administer this questionnaire. The 
Signature and Delegation of Duties Log may be used to indicate licensed hospital or 
clinic personnel who are blinded to the subject’s randomization arm or device received to 
administer the questionnaire.  Training of these personnel by the Sponsor will be 
documented in the Training Log.
x
The mRS and NIHSS will be administered to all subjects at baseline, if an increase in 
QVSFS score is observed in a subsequent visit, or if a neurology office consultation is 
indicated.  Blinding does not apply to baseline mRS/NIHSS.  Any mRS or NIHSS during 
follow-up must be administered by a person blinded to the subject’s randomization and 
implanted device, who has completed requisite training and is listed on the trial
Signature and Delegation of Duties Log or appropriately documented.  
x
The board-certified study Neurologist who will assess the subject for primary endpoints 
will be blinded to the subject’s randomization assignment and implanted device to the 
extent possible.  
x
An independent CEC will review and adjudicate events without knowledge of subject’s 
randomization assignment or implanted device. 
x
Subjects may withdraw from the trial for any reason, either voluntarily or due to lost-to-
follow-up.  Adverse events will be reported through the date of subject discontinuation. 
3.8 Risk-to-benefit rationale
Based on a review of the Use, Design, and Process FMEAs, the potential benefits of use of the 
WaveCrest LAA Occlusion System outweigh the risks. Percutaneous LAA occlusion may offer 
an alternative to physicians who are caring for subjects with AF who are at high risk for both 
bleeding and stroke.  
4.
PURPOSE
4.1 Name and Intended Use
The Coherex WaveCrest Left Atrial Appendage Occlusion System is a percutaneous 
transcatheter device intended to be used for closure of the left atrial appendage (LAA). 
4.1.1
Indications for Use
The Coherex WaveCrest Left Atrial Appendage Occlusion System is indicated in subjects who 
have all of the following: 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
30 of 90
x
Non-valvular paroxysmal, persistent, or permanent atrial fibrillation
x
LAA anatomy amenable to treatment by percutaneous techniques 
x
Risk factors for potential thrombus formation in the LAA
4.2 Scope of Trial
The WAVECREST 2 trial is a prospective, multicenter, randomized, active controlled, clinical 
trial to evaluate the safety and effectiveness of the Coherex WaveCrest Left Atrial Appendage 
(LAA) Occlusion System for the reduction in rate of ischemic stroke or systemic embolism in 
subjects with non-valvular atrial fibrillation who are at increased risk for stroke and have an 
appropriate rationale to seek a non-pharmacologic alternative to chronic oral anticoagulation.
Subjects will be randomized in a 1:1 ratio to the Treatment Arm (Coherex WaveCrest LAA 
occlusion system) or the Control Arm (Boston Scientific’s Watchman LAA occlusion system).  
Randomization will be stratified by site and CHA2DS2-VASc VFRUH4 vs. > 4.  The trial is 
designed to demonstrate that safety and effectiveness of the WaveCrest device are non-inferior to 
the Watchman device.  The subject, the implanting Investigator and catheterization laboratory 
staff will have knowledge of the assigned treatment. Trial personnel and the board-certified study 
Neurologist who will perform follow-up assessments for ascertainment of the primary 
effectiveness endpoint will be blinded to the randomization assignment and implanted device to 
the extent possible.   
An independent Clinical Events Committee (CEC) will be blinded to the treatment assignment 
and will adjudicate protocol-defined events, including primary and secondary endpoints, death 
(cardiovascular vs. non-cardiovascular), and bleeding category.  An independent Data 
Monitoring Committee (DMC) will monitor the safety of trial subjects and will review data at 
interim analyses. The DMC may provide recommendations for early regulatory filing of trial 
results upon review of interim analyses.  An independent Echocardiography Core Laboratory 
(ECL) will review transesophageal echocardiograms (TEE) to assess LAA closure and device 
thrombus and will review post-stroke TEEs to ascertain the mechanism of stroke. Transthoracic 
echocardiograms (TTE) will be assessed by the core lab to assess for post-implant pericardial 
effusion. 
4.2.1
Trial Size
Up to 1,550 subjects will be randomized and up to 500 subjects may be treated as roll-ins (total 
enrollment up to 2,050) at up to 100 investigational sites in North America, Europe, Australia
and Asia.  Up to 50% of subjects may be randomized outside the United States.  Each 
investigational site may not randomize more than 15% of the total randomized subjects.
Auxiliary sites (i.e., additional physical locations that are part of a clinical site) may be used to 
help in recruitment and follow-up activities but will not be utilized for protocol-specific 
assessments (e.g., subject consent, TEE, QVSFS, QoL, Neurological assessment, etc.), which 
will be performed only by sites that have been properly trained and have obtained the required 
IRB/EC approvals to conduct study-specific activities.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
31 of 90
4.2.2
Duration 
Enrollment is expected to last between 2 and 3 years, and the maximum follow-up duration is 5 
years, for a total possible trial duration of approximately 8 years. 
4.3
Endpoints
4.3.1
Primary Endpoint
This trial is designed to evaluate the safety and effectiveness of the Coherex WaveCrest LAA 
occlusion device to the Boston Scientific Watchman LAA occlusion device by demonstrating 
that the device is non-inferior to the Watchman Device with respect to the primary safety and 
effectiveness endpoints. If non-inferiority is demonstrated, superiority will be evaluated. 
x
The primary effectiveness endpoint is the composite rate of ischemic stroke or systemic 
embolism at 24 months. 
x
The primary safety endpoint is the composite rate of all cause death; procedure- or 
device-related complications requiring percutaneous or surgical intervention, including
embolization of a LAA closure device, drainage of pericardial effusion, or repair of 
cardiac or vascular structures through 45 days post-procedure; or major bleeding. 
4.3.2
Secondary Effectiveness Endpoints 
x
5DWHRI/$$FORVXUHGHILQHGDVDJDSRIPPDVassessed by TEE, at 45 days 
x
Incidence of ischemic stroke or systemic embolism with the WaveCrest device in 
comparison to the CHADS2 and CHA2DS2-VASc imputed risk of ischemic stroke or 
systemic embolism in the absence of anticoagulant therapy.  No claims will be made on 
this endpoint. 
4.4 Inclusion and Exclusion Criteria
4.4.1
Inclusion Criteria
Subjects must meet ALL of the following inclusion criteria to be considered eligible for the 
clinical trial.  
1. Documented evidence of paroxysmal, persistent, or permanent non-valvular atrial 
fibrillation
2. At least 18 years of age
3. Calculated CHADS2 VFRUHRU CHA2DS2-VASFVFRUH3 (See Appendix II for 
calculation of CHADS2 and CHA2DS2-VASc scores) 
4. Indication for warfarin therapy with an appropriate rationale to seek a non-pharmacologic 
alternative to chronic oral anticoagulation  
5. Willing and able to comply with post-implant anticoagulation and antiplatelet regimen
6. Willing to participate in the required follow-up visits and tests
7. Subject has been informed of the nature of the trial, agrees to its provisions and has 
provided written informed consent as approved by the IRB/EC at the site 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
32 of 90
4.4.2
Exclusion Criteria
If ANY of the following clinical exclusion criteria is met, the subject must be excluded from the 
clinical trial.
1. Atrial fibrillation (AF) due to a reversible cause (e.g. thyrotoxicosis or postoperative) 
2. Known contraindication and/or allergy to warfarin, nickel, aspirin, intravenous contrast 
or P2Y12 inhibitors (clopidogrel, ticagrelor, and prasugrel), which cannot be adequately 
pre-medicated or desensitized
3. Conditions other than AF requiring long-term anticoagulation therapy 
4. Contraindications for percutaneous catheterization procedures  
5. Prior surgical LAA occlusion/exclusion or implanted with LAA occlusion device, or any 
prior attempt of such procedures
6. Prior percutaneous or surgical closure of a patent foramen ovale or atrial septal defect  
7. Inability or unwillingness to take oral anticoagulation for 45 days post-procedure 
8. New York Heart Association (NYHA) Class IV heart failure
9. Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve 
intervention, or any mechanical valve implant
10. History of symptomatic carotid, intervertebral, or intracranial artery occlusion or stenosis 
without revascularization with the exception of known occlusion without symptoms > 6 
months 
11. mRS score 
12. Chronic resting heart rate  110 bpm 
13. Congenital or other clinically significant cardiac anomalies requiring cardiac surgery or 
interventional repair
14. Stroke or transient ischemic attack (confirmed by Neurologist) within 60 days prior to 
enrollment 
15. Myocardial infarction within 60 days prior to enrollment
16. Sepsis or any active infection requiring oral antibiotic therapy within 14 days or 
intravenous antibiotic therapy within 30 days prior to enrollment  
17. Surgical or interventional cardiovascular and non-cardiovascular procedure including 
cardioversion within 30 days prior to enrollment or AF ablation within 60 days prior to 
enrollment or any planned general surgery or interventional procedure within 90 days 
after enrollment or any planned cardiac surgery.
18. On renal replacement therapy, serum creatinine > 3.0 mg/dl (265 μmol/L) or calculated 
creatinine clearance < 25 ml/minute
19. Thrombocytopenia (<60,000 platelets/mm3), leucopenia (white blood cell count < 3,000 
cells/mm³), or anemia (hemoglobin concentration < 10 grams/deciliter)
20. Any medical disorder or psychiatric illness that would interfere with successful 
completion of the trial
21. Currently participating in an investigational drug trial or another device trial that has not 
completed the primary endpoint (trials requiring extended follow-up for products that are 
commercially available are not considered investigational trials).  Concurrent enrollment 
in the ACC LAAO Registry is permitted.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
33 of 90
22. Subject belongs to a vulnerable population (see definition in Appendix I: Acronyms and 
Definitions) 
23. Any condition that would reduce life expectancy to less than 2 years 
24. Women of childbearing potential who are, or plan to become pregnant during the time of 
the trial (method of assessment per physician discretion)
4.4.3
Echocardiographic Exclusion Criteria
The following echocardiographic exclusion criteria must be assessed prior to randomization (or 
prior to the procedure for roll-in cases). The transesophageal echocardiogram (TEE) must be 
performed up to 90 days before, including just prior to, randomization (or the procedure for roll-
in cases). If ANY of the following echocardiographic exclusion criteria is met, the subject must 
be excluded from the clinical trial.
1. Estimated left ventricular ejection fraction < 30% 
2. Mitral valve stenosis defined as valve area < 1.5cm2, mean gradient > 6mmHg, or any 
mitral valve deformity consistent with rheumatic valvular disease
3. Aortic valve stenosis defined as valve area 1.0cm2 or mean gradient >30mmHg 
4. Circumferential pericardial effusion > 10mm, loculated pericardial effusion with largest 
dimension > 10mm, or symptomatic pericardial effusion of any size
5. Evidence of intracardiac thrombus 
6. Cardiac tumor or myxoma  
7. Atrial septal defect that warrants closure
8. Complex atheroma in the ascending aorta or aortic arch as evidenced by mobile plaque
9. Left Atrial Appendage size and shape are unsuitable for closure with a WaveCrest or 
Watchman device 
4.4.4
Adequate Representation of Women and Minorities
Historically, women have been underrepresented in or excluded from many clinical studies, 
leading to lack of information for women and their physicians regarding the risks and benefits of 
many medical treatments and diagnostic procedures.  It is the Sponsor’s intent to apply the 
principles from FDA’s guidance titled Evaluation of Sex-Specific Data in Medical Device 
Clinical Studies in the WAVECREST 2 trial to ensure adequate representation of women and 
minorities.  
Atrial fibrillation affects 1-2% of the population.  The prevalence of atrial fibrillation increases 
with age, from < 0.5% at 40-50 years, to 5-15% at 80 years, with men being affected more often 
than women.20 Consistent with this, several clinical studies on LAA closure devices to date 
(PROTECT-AF, PREVAIL and WAVECREST 1) enrolled an elderly cohort (average age ~72 
years) with approximately one-third being women.  As the WAVECREST 2 trial will enroll 
subjects with CHA2DS2-VASFVFRUH3 (which gives a minimum score of 1 for women), the 
proportion of women in this trial is expected to be larger than one-third.  Thus, women are 
expected to be adequately represented in the WAVECREST 2 trial.  
In addition, the Sponsor will take the following steps to ensure adequate representation of 
women and racial or ethnic minorities in the WAVECREST 2 trial:

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
34 of 90
x
Where possible, sites will be selected where recruitment of women and racial or ethnic 
minorities can be more easily facilitated.
x
Sites will be instructed to screen all subjects who have documented non-valvular atrial 
fibrillation and reasons to avoid chronic OAC, without regard to sex or race.  
x
If allowed by national regulations, sites will offer nominal reimbursement to trial 
participants for protocol-required office follow-up visits, as laid out in the Clinical Trial 
Agreement with the Sponsor.  
Statistical analyses of the primary effectiveness and safety endpoints will be carried out to 
evaluate any interaction effect between treatment (WaveCrest or Watchman) and gender.   
4.5
Subject Population
4.5.1
Subject Screening
Sites may begin screening subjects for the trial upon receiving IRB/EC approval to initiate the 
trial.  Prior to enrollment in the trial, site personnel shall evaluate any potential candidates by 
reviewing the patient’s medical records against the inclusion and exclusion criteria and 
interviewing the candidate subject. Assessment for trial eligibility may be based on patient’s 
medical records at the site and interview with a candidate subject.  Potential subjects will be 
asked to complete the informed consent process.  
4.5.2
Point of Enrollment 
Subjects will be considered enrolled and followed from the time an informed consent form is
signed.  Subjects will be documented as a roll-in subject, a randomized subject, or a screen 
failure. Enrolled screen failures will be excluded from the randomized cohort.  Any adverse 
events in these subjects will be documented in eCRFs. Intent-to-treat will be established when 
they have completed screening, met all inclusion criteria, none of the exclusion criteria, and are 
randomized.   
4.5.3
Enrollment of Medicare Beneficiaries (US Subjects Only) 
This clinical trial will enroll Medicare beneficiaries and therefore conforms to all standards of 
Medicare coverage requirements.  Risks and benefits of the clinical trial section describe how all 
enrolled subjects, including Medicare beneficiaries, may be affected by the device under 
investigation.
Subjects enrolled in the clinical trial are expected to be consistent with the Medicare population 
based on age and as such, the trial results are expected to be applicable to the general Medicare 
population.
4.5.4
Vulnerable Population 
No subjects belonging to a vulnerable population (see definition of vulnerable population in 
Appendix I: Acronyms and Definitions) will participate in the trial.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
35 of 90
4.5.5
Description of the specific informed consent process
All IRB/ECs must comply with applicable regulations (21 CFR 56) and IDE regulations (21CFR 
812) and/or appropriate international standards (ISO 14155:2011) in reviewing and approving 
investigational device documents and processes. The informed consent process must be 
appropriately documented in compliance with IRB/EC approval conditions and applicable local 
regulatory requirements. 
4.5.6
Responsibilities
An IRB/EC shall safeguard the rights, safety, and well-being of all trial subjects.
4.5.7
Composition 
The IRB/EC shall be composed of members meeting the minimum requirements set forth in 21 
CFR 56.107 and/or any other applicable regulatory requirements.
4.5.8
Initial IRB/EC Approval 
Prior to shipment of investigational devices for this trial, the Sponsor will require documentation 
of IRB/EC approval of the CIP and any information used in the subject informed consent 
process. 
4.5.9
Annual IRB/EC Renewal
An IRB/EC shall conduct continuing review of the clinical trial at intervals appropriate to the 
degree of risk posed by the device, but not less than once per year (per applicable regulations).
4.6 Informed Consent
4.6.1
General Process
All subjects must sign and date the IRB/ EC approved informed consent prior to undergoing any 
trial-specific tests, assessments or procedures.  The Investigator or his/her authorized designee 
will conduct the Informed Consent Process. This process will include a verbal discussion with 
the subject on all aspects of the clinical trial that are relevant to the subject’s decision to 
participate in the clinical trial. The Investigator or his/her authorized designee who have been 
trained on the protocol will explain the nature and scope of the trial, potential risks and benefits 
of participation. Trial personnel must explain that agreeing to participate in the trial and signing 
an informed consent form does not guarantee trial participation. 
The subject must be provided ample time to read and understand the informed consent form and 
to consider participation in the clinical trial.  If the subject agrees to participate, the informed 
consent form must be signed and dated by the subject.  The person obtaining informed consent 
must sign, date and time the informed consent prior to conducting any trial-specific tests, 
assessments or procedures.  Additional site personnel may be required by the site’s IRB/EC to 
sign the informed consent form.  The consent process, provision of a copy to the subject, and 
date and time of consent must be documented in the subject’s medical records. 
The subject shall be provided with the informed consent form that is written in a language that is 
understandable to the subject and has been approved by the center’s IRB/EC.  Failure to obtain 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
36 of 90
informed consent from a subject prior to undergoing any trial-specific tests, assessments, or 
procedures should be reported to the Sponsor within 5 working days and to the reviewing 
center’s IRB/EC consistent with the center’s IRB/EC reporting requirements.  
Subject information may be entered only after the subject has provided informed consent. 
Subjects who are informally reviewed by the Investigator for inclusion in the trial but do not 
meet trial criteria and do not sign an Informed Consent will not be tracked. 
The informed consent will include an authorization for use and disclosure of the subject’s 
protected health information, in accordance with the Health Insurance Portability and 
Accountability Act (HIPAA) or as required per local regulations.  Subject confidentiality will be 
maintained throughout the clinical trial in a way that assures that individual subject data can be 
tracked back to the source data.  For this purpose, a unique subject identification code will be 
used that allows identification of all data reported for each subject.  Data relating to the trial may 
be made available to third parties, provided the data are treated as confidential and that the 
subject’s privacy is guaranteed. 
The informed consent for US subjects only will also request authorization for release of billing 
information specific to the subject’s participation in the study.  Specifically, the cost and 
frequency of health care utilization for the study procedure as well as any additional 
hospitalizations during the study period will be collected. This information will not be reported 
to the Food and Drug Administration as part of the IDE reporting. The hospitalization healthcare 
data to be collected will include but is not limited to: copies of the subject’s hospital bills (UB04) 
and/or any itemized hospital bills for services. Data to be collected from the UB04 or itemized 
patient bill includes: Subject admission date, discharge date, procedure date, ICD-10 diagnosis 
codes, ICD-10 procedure codes, DRG assignment, and total charges for the hospitalization by 
revenue center. The Sponsor will also collect health economic data associated with any follow up 
care for the duration of the study including any medical procedures, ER visits, or outpatient visits 
to address issues related to stroke or cardiovascular conditions. All forms must be de-identified 
prior to submission to the Sponsor. 
Sites may offer nominal reimbursement for their subjects for office follow-up visits required per 
this CIP, if allowed by national regulations, as laid out in the Clinical Trial Agreement with the 
Sponsor. 
4.6.2
Informed consent will be obtained in Subjects unable to read or write 
Informed consent will be obtained through a supervised oral process if a subject is unable to read 
or write. An independent witness will be present throughout the process. The written informed 
consent form and any other information will be read aloud and explained to the prospective 
subject and, whenever possible, either will sign and personally date the informed consent form. 
The witness also signs and personally dates the informed consent form attesting that the 
information was accurately explained, and that informed consent was freely given. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
37 of 90
5.
DEVICE UNDER INVESTIGATION AND CONTROL COMPARATORS
5.1
Device Description
The Coherex WaveCrest Left Atrial Appendage Occlusion System (“WaveCrest device”) is 
designed to occlude the left atrial appendage (LAA) and consists of the following components:  
the device, which is pre-loaded on the delivery system, and the delivery sheath which is 
packaged separately.  The device, consisting of a separate occluder and anchors, is the 
implantable component of the system.  The device is constructed from a laser-cut nitinol 
framework.  Parts of this framework are constructed with titanium components and also contain 
tantalum radiopaque markers. The occlusive membrane is composite construction.  The surface 
of the membrane that is exposed to the left atrium is covered with ePTFE and is designed to 
resist thrombus buildup.  The surface of the membrane that is exposed to the LAA consists of 
polyurethane foam, which is designed to promote rapid thrombus and tissue growth.   
Figure 1: Coherex Left Atrial Appendage Implant
The delivery system for the implant consists of a delivery catheter and a proximal control handle.  
The delivery catheter is constructed from polyurethane extrusions, stainless steel components, 
and polyester and PTFE materials that are common to medical catheter construction.  The 
proximal control handle is designed to actuate the anchors through the catheter and to detach the 
implant from the system.  The Coherex WaveCrest Left Atrial Appendage Occlusion System 
Delivery Sheath is designed to facilitate the delivery of the implant. The Delivery Sheath 
includes a dilator used for insertion.  The Delivery Sheath is designed to be used exclusively 
with the Coherex WaveCrest Left Atrial Appendage Occlusion System.
The implant is delivered percutaneously via the femoral vein through a transseptal puncture into 
the LAA.  A separate transseptal puncture system is required.  The occluder is designed to be 
unsheathed inside the ostium of the LAA.  When unsheathed, only the occlusive portion of the 
device is exposed.  The structure of this portion is very soft to reduce the risk of perforation or 
effusion.  The occluder may be positioned within the LAA to achieve optimal occlusion.  After 
positioning, the occluder is anchored in place by extending the anchors from the central hub of 
the device.  A distal injection port allows contrast to travel through the delivery system to the 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
38 of 90
distal side of the occluder to allow visualization of the position, stability and effectiveness of 
occlusion prior to release.  Anchoring and occlusion can then be assessed by TEE.  When 
anchoring and occlusion are confirmed, the implant is detached and left within the LAA.   The 
WaveCrest device implant is available in diameter sizes of 22, 27 and 32 mm. 
Devices:
Delivery Sheaths:
Coherex Catalog 
Number (EU)
Coherex Catalog 
Number
(US/AUS)
Coherex Catalog 
Number (China)
Name
Description
1530
2530
3530
60
60° distal curve
1540
2540
3540
75
75° distal curve
1541
2541
3541
90
90° distal curve
1551
2551
3551
90s
90° distal curve with superior 
tip angle
5.2 Control device (Watchman LAA Occlusion System)
The Watchman Left Atrial Appendage Closure (LAAC) System (“Watchman Device”) is 
intended to reduce the risk of thromboembolism from the left atrial appendage (LAA) in subjects
with non-valvular atrial fibrillation who:
x
Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-
VASc scores and are recommended for anticoagulation therapy;
x
Are deemed by their physicians to be suitable for warfarin; and  
x
Have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking 
into account the safety and effectiveness of the device compared to warfarin.
The Watchman device is intended for percutaneous, transcatheter closure of the left atrial 
appendage and consists of the Watchman Access System (Access Sheath and Dilator) and 
Watchman Delivery System (Delivery Catheter and Watchman Device). The Access Sheath and 
Delivery Catheter permit device placement in the left atrial appendage (LAA) via femoral 
venous access and inter--atrial septum crossing into the left atrium. The Watchman Device is a
self-expanding nitinol structure with a polyethylene terephthalate (PET) porous membrane on the 
proximal face. The device is constrained within the Delivery System until deployment into the 
LAA.
Coherex Catalog 
Number (EU)
Coherex Catalog 
Number (US/AUS)
Coherex Catalog 
Number (China)
Implant Size
1503
2503
3503
22mm
1513
2513
3513
27mm
1523
2523
3523
32mm

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
39 of 90
The device is available in five sizes from 21 to 33 mm.  Appropriate device sizing is determined 
by LAA measurements using fluoroscopy (fluoro) and transesophageal echocardiography (TEE).
The Watchman Device is designed to be permanently implanted at or slightly distal to the ostium 
(opening) of the LAA to close the appendage to inflow.  The placement procedure can be done 
under local or general anesthesia in a hospital cardiac catheterization or electrophysiology 
laboratory setting.
Newer generations of the Watchman device approved by the FDA for use in the US or approved 
at sites outside the US where the trial is being conducted may be used in the Control Arm if they 
become commercially available during the trial.
5.3
Device Accountability
Investigational devices will be shipped by the Sponsor to approved investigational sites after 
Sponsor receipt of the IRB/EC approval letter, signed Investigator Agreement and Clinical Trial 
Agreement and documentation of online device training.  Implant procedures will not be 
performed until Site Initiation and device training have been completed. Product received at 
investigational sites will be logged into a Device Tracking and Disposition Log which may be 
part of the electronic data collection system. Investigators must reconcile and retain disposition 
documentation including the date of receipt, the identification of each investigational device 
(batch number, serial number or unique code), the subject identification, the date of use, the 
location and the expiration date and final disposition. Throughout the course of the trial, the 
Device Tracking and Disposition Log will be used to track the disposition of investigational 
devices, and clinical monitors will review the log and verify against trial records and existing 
inventory at the site.  Access to investigational devices shall be controlled, and investigational 
devices shall be used only in the clinical investigation, according to this CIP, in accordance with 
Sponsor procedures, and in compliance with applicable federal and local regulations.
Investigators and trial personnel shall be trained to Sponsor procedures on device accountability. 
Coherex Medical will also maintain device accountability documenting all shipments and returns 
of investigational devices.
Sites with access to commercially available WaveCrest devices will be allowed to use those 
devices and will not be required to adhere to Investigational Device accountability as described 
above.  Information regarding any commercially available WaveCrest product used in 
procedures will be recorded in the same manner as Investigational product. 
5.4
Device Handling and Storage 
Coherex Medical requires all investigational products to be stored according to the labeling, in a 
secure area to prevent unauthorized access or use.  This will prevent non-investigational use of 
products that are provided for this trial. In some countries, commercial product that is identical 
to the Investigational Device will be used in the study and therefore does not require limited 
access.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
41 of 90
x
Perform baseline TEE. If thrombus is detected, the subject may undergo a 6-week course of 
anticoagulation followed by a repeat TEE.  The subject may be re-evaluated after appropriate 
anticoagulation therapy and considered for device placement following documentation of 
absence of thrombus. The timeline from initial screening to the end of thrombus treatment
must be within 90 days prior to randomization - or treatment, for roll-in subjects. 
x
Ensure adequate supply of Watchman and WaveCrest devices are available in inventory 
x
Notify Sponsor of upcoming randomization (or roll-in) procedure and potential implant dates 
to ensure adequate time for Sponsor to organize case support in order to meet the timelines 
required per this Clinical Investigation Plan.  Sponsor personnel will be present at each 
WaveCrest implant procedure to provide clinical support to the Investigator regarding 
instructions for use and procedural steps during the procedure.  Sponsor personnel may help 
ensure all data required per this CIP are collected but will not interpret or record any data in 
trial documents. 
Once these tasks have been completed, subjects will be randomized using the study EDC system.  
If the baseline TEE is performed immediately prior to the procedure, then randomization must 
take place as soon as the baseline TEE is completed, and the subject is deemed to meet none of 
the echocardiographic exclusion criteria.
If the site requires case support for subjects randomized to the Watchman device, arrangements 
must be made with appropriate company personnel prior to randomization in order to meet the 
timelines required per this CIP. 
For randomized subjects, the subject will be randomized through the database upon completion 
of required elements of the Baseline Visit and required entries in the database.  Designated trial
personnel will be notified of the device assignment (WaveCrest or Watchman) to which the 
subject has been randomized. 
Echocardiographic screening for roll-in subjects may be performed on the same day as the 
planned implant procedure provided the echocardiogram is completed prior to initiating vascular 
access.  The subject may be treated only if the subject continues to meet all Inclusion and none 
of the Exclusion criteria (Section 4.4).
6.2
Treatment Visit
For roll-in subjects, the Treatment Visit is recommended to occur within 90 days of enrollment 
and occurs upon initiation of vascular access for the purpose of the WaveCrest implant.
For randomized subjects, the Treatment Visit is recommended within 7 days of randomization, 
but in all cases must occur within 14 days of randomization.  At this visit, the randomized 
subject will undergo the WaveCrest or Watchman device implant procedure, as randomized.  
Absence of intracardiac thrombus must be confirmed by TEE prior to starting the implant
procedure.  If thrombus is detected, it is recommended the subject undergo a 6-week course of 
anticoagulation followed by a repeat TEE.  The subject may be re-evaluated after appropriate 
anticoagulation therapy and considered for device placement following documentation of 
absence of thrombus. The subject will remain in the same arm of the trial to which they were 
originally randomized and receive the same follow-up. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
44 of 90
x
A transthoracic echocardiogram (TTE) must be performed on all subjects to rule out a 
pericardial effusion prior to discharge. 
Note: Subjects who are not implanted with a device must NOT undergo any additional LAA 
closure procedure with any device within 45 days of the initial implant procedure, except as 
randomized.  At the discretion of the investigator, a second attempt to implant a subject as 
randomized may be made if there is reasonable medical justification to make such an attempt 
that is approved in writing by the Sponsor. All subjects, including those who fail to receive a 
device according to their randomization but who subsequently receive an alternate commercially 
available device or procedure will be followed with their initial randomization cohort according 
to an intent-to-treat analysis.  The WaveCrest device may not be used among US subjects
randomized to Watchman. 
6.5
Follow-up Post-Discharge 
Follow-up visits will be timed from the Treatment Visit.  Following discharge after Treatment 
Visit, subjects will have office visits at 45 days, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 
years.  Phone follow-up will occur at 3 months, 1.5 years, 2.5 years, 3.5 years and 4.5 years.  
Table 4 summarizes the schedule of assessments at each protocol-required follow-up visit.  All 
assessments required for each visit must be completed within the visit windows specified in
Table 5. 
If a subject has experienced stroke symptoms resulting in a QVSFS score > 0 since their most 
recent follow-up, a board-certified study Neurologist blinded to subject’s randomization and 
implanted device, to the extent possible, must evaluate the subject or otherwise provide rationale 
for why an in-person neurology visit and exam are unnecessary.  An Unscheduled Neurology
Visit must be completed within 14 days of QVSFS administration or site’s awareness of the 
onset of stroke symptoms (See Section 6.12 for details of the Unscheduled Neurology Visit). 
Subjects who undergo a procedure but are not implanted with an LAA occlusion device must 
have follow-up per this CIP, with the following exceptions: TEE is not required at follow-up, 
and antiplatelet and anticoagulant medications should be administered following pre-procedure 
regimen or administered per physician discretion.  
Note: Subjects will be followed as Intent-to-Treat. Any subject who does not receive an implant 
may not be treated with any other LAA device for 45 days.
The following sections describe the requirements for each follow-up office visit and phone 
follow-up for subjects implanted with an LAA occlusion device.   
6.6
Follow-up 45 Day Office Visit
x
Perform physical exam
x
Administer QoL questionnaire (see Quality of Life Questionnaire - SF-36) 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
45 of 90
x
Qualified trial personnel who are blinded to subject’s randomization and implanted 
device administer the QVSFS (see Appendix III: Questionnaire for Verifying 
Stroke-Free Status). If the subject has experienced symptoms resulting in a QVSFS 
score > 0 since their most recent follow-up, a board-certified study Neurologist
blinded to subject’s randomization and implanted device, to the extent possible, must 
evaluate the subject or otherwise provide rationale for why an in-person neurology 
visit and exam are unnecessary.  This Unscheduled Neurology Visit must be 
completed within 14 days of the QVSFS administration or site’s awareness of the 
onset of stroke symptoms.   (See Section 6.12 for details of Unscheduled Neurology 
Visit)
x
Perform a TEE following the Echocardiography Protocol and submit images to ECL.
x
Cessation of warfarin in the Watchman arm is at physician discretion and should be 
per the product DFU.  If the subject stops warfarin, clopidogrel should be 
administered per the product DFU. 
x
Evidence of device thrombus is recommended to be treated with a 6-week course of 
warfarin (+/- aspirin) and repeat TEE.
x
Watchman subjects who discontinue warfarin should be instructed to remain on
aspirin daily per the Watchman DFU. 
x
WaveCrest subjects must remain on dual antiplatelet therapy (DAPT) through 3 
months post-procedure. 
x
Table 3 summarizes the post-procedure anticoagulation and antiplatelet regimen for 
the duration of trial follow-up. 
Adjunctive Pharmacology Differences and Rationale 
WaveCrest subjects will receive DAPT between the point of implantation and 3 months 
post-implant (when clopidogrel can be discontinued).  This is based on prior experience 
with the WaveCrest device that suggests a low stroke rate with this regimen. Subjects 
implanted with the WaveCrest device will be instructed to continue taking 75–100 mg 
aspirin throughout the study. 
Watchman subjects are directed to take warfarin, clopidogrel, and aspirin based on that
device’s DFU  
Aspirin pharmacology studies have demonstrated maximal platelet inhibition with 50 mg 
of daily aspirin.53  The risk of gastric erosion increases as aspirin dosage 
increases.  Aspirin 75 -100 mg in the WaveCrest arm has been selected to provide 
maximal platelet inhibition while minimizing the risk of gastric erosion and aspirin 
induced gastrointestinal bleeding.
x
Record cardiac medications, including antiplatelet and anticoagulant medications
x
Record adverse events, device malfunctions and protocol deviations as appropriate

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
46 of 90
6.7
3 Months Phone Follow-Up
x
For subjects in the WaveCrest arm, if the LAA was closed at 45 days, instruct subject 
to discontinue clopidogrel but to continue aspirin at the assigned dosage. 
x
If the LAA was not closed at 45 days, clopidogrel may be continued at Investigator 
discretion until flow  5mm is noted in a subsequent TEE. 
x
Record cardiac medications, including antiplatelet and anticoagulant medications. 
x
Record adverse events, device malfunctions, and protocol deviations as appropriate. 
6.8
Follow-up 6 Month Office Visit
x
Perform physical exam
x
Administer QoL questionnaire (see Quality of Life Questionnaire - SF-36) 
x
Qualified trial personnel who are blinded to subject’s randomization and implanted 
device administer the QVSFS (see Appendix III: Questionnaire for Verifying 
Stroke-Free Status); If the subject has experienced symptoms resulting in a QVSFS 
score > 0 since their most recent follow-up, a board-certified study Neurologist
blinded to subject’s randomization and implanted device, to the extent possible, must 
evaluate the subject or otherwise provide rationale for why an in-person neurology 
visit and exam are unnecessary.  This Unscheduled Neurology Visit must be 
completed within 14 days of the QVSFS administration or site’s awareness of the 
onset of stroke symptoms.  (See Section 6.12 for details of Unscheduled Neurology 
Visit)
x
For subjects in the Watchman arm, if the LAA was closed at 45 days, clopidogrel 
may be discontinued per the product DFU but aspirin should continue per the product 
DFU. 
x
If the LAA was not closed at 45 days and the subject remains on warfarin (Watchman 
arm) or DAPT (WaveCrest arm), a TEE should be repeated at this visit.
Discontinuation of warfarin (Watchman arm) or P2Y12 inhibitor (WaveCrest arm) is 
at physician discretion but is recommended if peri-device color Doppler flow 
GHPRQVWUDWHGE\7((LVPP
x
If an adequate seal is not demonstrated, warfarin (Watchman arm) or P2Y12 inhibitor 
(WaveCrest arm) may be continued at Investigator discretion until flow < 5mm is 
noted.  Watchman subjects who continue warfarin for 6 months post-implant are not 
required to start clopidogrel but should remain on aspirin per the product DFU. 
x
Sites that routinely perform a 6-month TEE as their standard of care (SOC) may 
perform a TEE in all subjects at that site.  This is not required for sites that do not 
perform a 6-month TEE as part of their SOC.
x
Evidence of device thrombus is recommended to be treated with a 6-week course of 
warfarin (+/- aspirin) and repeat TEE.
x
Record cardiac medications, including antiplatelet and anticoagulant medications
x
Record adverse events, device malfunctions and protocol deviations as appropriate 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
47 of 90
6.9
Follow-up 1 Year Office Visit
x
Perform physical exam
x
Administer QoL questionnaire (see Quality of Life Questionnaire - SF-36) 
x
Qualified trial personnel who are blinded to subject’s randomization and implanted 
device administer the QVSFS (see Appendix III: Questionnaire for Verifying 
Stroke-Free Status); If the subject has experienced symptoms resulting in a QVSFS 
score > 0 since their most recent follow-up, a board-certified study Neurologist 
blinded to subject’s randomization and implanted device, to the extent possible, must 
evaluate the subject or otherwise provide rationale for why an in-person neurology 
visit and exam are unnecessary.  An Unscheduled Neurology Visit must be 
completed within 14 days of QVSFS administration or site’s awareness of the onset 
of stroke symptoms.  (See Section 6.12 for details of Unscheduled Neurology Visit)
x
Perform a TEE following the Echocardiography Protocol and submit images to ECL
x
If an adequate LAA seal is observed, instruct subject to remain on aspirin dosage as 
assigned daily indefinitely. Table 3 summarizes the post-procedure anticoagulation 
and antiplatelet regimen for the duration of trial follow-up. 
x
If an adequate seal is not demonstrated, warfarin (Watchman arm) or P2Y12 inhibitor 
(WaveCrest arm) may be continued at Investigator discretion and/or until flow 
5mm is noted. 
x
Evidence of device thrombus is recommended to be treated with a 6-week course of 
warfarin (+/- aspirin) and repeat TEE.
x
Record cardiac medications, including antiplatelet and anticoagulant medications
x
Record adverse events, device malfunctions and protocol deviations as appropriate 
6.10
Follow-up 2 Year, 3 Year, 4 Year and 5 Year Office Visits
At each of the above office visits: 
x
Perform physical exam
x
Administer QoL questionnaire (see Quality of Life Questionnaire - SF-36) 
x
Qualified trial personnel who are blinded to subject’s randomization and implanted 
device administer the QVSFS (see Appendix III: Questionnaire for Verifying Stroke-
Free Status). If the subject has experienced symptoms resulting in a QVSFS score > 0
since their most recent follow-up, a board-certified study Neurologist blinded to 
subject’s randomization and implanted device, to the extent possible, must evaluate 
the subject or otherwise provide rationale for why an in-person neurology visit and 
exam are unnecessary.  An Unscheduled Neurology Visit must be completed within 
14 days of QVSFS administration or site’s awareness of the onset of stroke 
symptoms. (See Section 6.12 for details of Unscheduled Neurology Visit).
x
Instruct subject to remain on daily aspirin at assigned dosage indefinitely. Table 3
summarizes the post-procedure anticoagulation and antiplatelet regimen for the 
duration of trial follow-up.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
48 of 90
x
If an adequate seal was not demonstrated at the 1-year TEE, warfarin (Watchman 
arm) or P2Y12 inhibitor (WaveCrest arm) may be continued at Investigator 
discretion. 
x
Evidence of device thrombus is recommended to be treated with a 6-week course of 
warfarin (+/- aspirin) and repeat TEE.
x
Record cardiac medications, including antiplatelet and anticoagulant medications
x
Record adverse events, device malfunctions and protocol deviations as appropriate 
6.11
Follow-up Phone 1.5 Year, 2.5 Year, 3.5 Year and 4.5 Year 
The QVSFS must be administered over the phone by blinded trial personnel (see Appendix III: 
Questionnaire for Verifying Stroke-Free Status
If the subject has experienced symptoms resulting in a QVSFS score > 0 since their most recent
follow-up, a Neurologist blinded to subject’s randomization and implanted device, to the extent 
possible, must evaluate the subject or otherwise provide rationale for why an in-person 
neurology visit and exam are unnecessary.  An Unscheduled Neurology Visit must be 
completed within 14 days of QVSFS administration or site’s awareness of the onset of stroke 
symptoms.  (See Section 6.12 for details of Unscheduled Neurology Visit)
x
Instruct subject to remain on daily aspirin at the assigned dosage indefinitely.  Table 3
summarizes the post-procedure anticoagulation and antiplatelet regimen for the 
duration of trial follow-up.
x
If an adequate seal was not demonstrated at the 1-year TEE, warfarin (Watchman 
arm) or P2Y12 inhibitor (WaveCrest arm) may be continued at Investigator 
discretion. 
x
Record cardiac medications, including antiplatelet and anticoagulant medications
x
Record adverse events, device malfunctions and protocol deviations as appropriate 
x
Query subject for adverse events or hospitalizations since last follow-up and 
document 
6.12
Unscheduled Neurology Visit
An Unscheduled Neurology Visit may be triggered by any of the following: 
x
Subject-reported stroke/TIA; 
x
QVSFS score > 0; 
x
Subject-reported symptoms; or 
x
Investigator suspects a stroke during a protocol-required office visit or phone follow-up. 
A board-certified study Neurologist blinded to subject’s randomization and implanted device, to 
the extent possible, must evaluate the following:

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
52 of 90
6.14
Any Known or Foreseeable Factors that May Compromise the Outcome of the 
Clinical trial or the Interpretation of the Results 
All foreseeable factors that may compromise the outcome have been taken into account by 
clinical trial design and well-defined subject selection criteria.
6.15
Criteria and Procedures for Subject Withdrawal or Discontinuation 
Every roll-in and randomized subject (including those who did not undergo a Treatment Visit or 
did not receive a device implant), shall remain in the trial until completion of 5-year follow-up;
however, subject participation in any clinical trial is voluntary and the subject has the right to 
withdraw at any time without penalty or loss of benefit.  Possible reasons for discontinuation 
may include but may not be limited to the following:
x
Subject refuses to continue participation in the trial
x
Subject is deceased (cause must be documented) 
x
Lost-to follow-up (defined below).  
It is the Sponsor’s intent to apply the principles from FDA’s guidance on Data Retention When 
Subjects Withdraw From FDA-Regulated Clinical Trials to the WAVECREST 2 trial so as to 
minimize bias and ensure trial integrity.  If a subject voluntarily withdraws from the trial, every 
effort must be made to obtain full information on any new or ongoing adverse events through the 
date of subject discontinuation.   
Investigators must report subject withdrawals to their respective IRB/EC as defined by their 
institution’s procedure.  If a subject withdrawal is related to the investigational device, the 
Investigator shall document the reason for subject discontinuation as related to investigational 
device and request subject’s permission to follow his/her status outside the clinical investigation. 
Subjects who discontinue participation prematurely will be included in the analysis of results (as 
appropriate) but will not be replaced.  At Sponsor’s request, the Investigator may consult public 
records, such as those establishing survival status, after subject withdrawal.  Alternatively, the 
Sponsor may contract with a subject search organization for the Investigator in order to establish 
survival status of discontinued subjects.   
6.16
Lost-to-Follow-up (LTFU)
If a subject misses two consecutive scheduled follow-up visits, trial personnel will make all 
possible attempts to contact the subject per the site’s standard of practice. If the Investigator 
concurs and at least two unsuccessful documented attempts on two different days have been 
made to contact the subject, the subject will be considered lost-to-follow-up.  The date, time and 
name of site personnel attempting to contact the subject, along with the Investigator’s concurring 
opinion must be documented in the subject’s medical records.  Upon determination that the 
subject is LTFU, a letter must be sent to the subject’s residence and a copy of the letter saved in 
the subject’s medical records. If a subject who has been considered LTFU is relocated and is 
interested in remaining in the trial, LTFU status may be revoked with documentation in the 
subject’s medical record along with the associated protocol deviation for missed visits. If a 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
53 of 90
subject relocates or moves and an Investigator is located in the general area, trial records may be 
transferred to another site and follow-up continued.
6.17
Early Trial termination
The Sponsor reserves the right to terminate the clinical trial at any stage with suitable written 
notice to the Investigators.  Possible reasons for termination are: 
x
Physician Advisory Committee makes a recommendation for early termination based 
upon input from the Data Monitoring Committee 
x
Unanticipated Adverse Device Effects (UADEs) present an unreasonable risk to subjects 
If the trial is terminated early, the Sponsor will provide a written statement to the Investigators to 
enable notification to the IRB/EC or will notify the EC directly as appropriate for OUS sites.
The Sponsor will also notify FDA and Competent Authorities (CAs), as applicable, of trial 
termination. Should the trial be terminated by the Sponsor, subjects must continue to be followed 
per routine hospital practice and device-related adverse events must be reported per the 
manufacturer’s procedures and applicable regulations.  
Should early termination occur, the Investigator shall return all clinical trial materials (including 
investigational devices) to the Sponsor. 
7.
COMPLIANCE TO CIP
7.1
Statement of Compliance
This trial will be conducted in accordance/compliance with this CIP, the most current version of 
the World Medical Association (WMA) Declaration of Helsinki, ISO14155, and any regional 
and/or national regulations, as appropriate. 
The sites will not start enrolling subjects or request informed consent from any subject prior to 
obtaining IRB/EC approval and Competent Authority approval, if applicable, execution of 
appropriate Investigator and/or site agreements, and authorization from the Sponsor in writing 
for the trial. 
In case additional requirements are imposed by the IRB/EC or Competent Authority, those 
requirements will be followed, if appropriate. If any action is taken by an IRB/EC, and 
regulatory requirements with respect to the trial, that information will be forwarded to Coherex
Medical.
As Sponsor, Coherex Medical has taken up general liability insurance in accordance with the 
requirements of the applicable local laws. Appropriate country representatives will be utilized to 
understand the requirements for the type of insurance that will be provided for subjects, such 
information will be incorporated into the informed consent, as applicable. 
If required, additional subject coverage or a trial specific insurance will be provided by the 
Sponsor as well. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
54 of 90
7.2
Adherence to the Clinical Investigation Plan
A deviation is defined as an event where the clinical Investigator, site personnel, Sponsor or 
Sponsor representative did not conduct the clinical trial according to the CIP, IRB/EC 
requirements or the Clinical Trial Agreement. The Investigator is not allowed to deviate from the 
CIP, except as specified under emergency circumstances.  
In some cases, failure to comply with the CIP may be considered failure to protect the rights, 
safety and well-being of subjects, since the non-compliance exposes subjects to unreasonable 
risks. For example, failure to adhere to the inclusion/exclusion criteria: these criteria are 
specifically defined by the Sponsor to exclude subjects for whom the device is not beneficial, 
and the use involves unreasonable risks. This may be considered failure to protect the rights, 
safety and well-being of the enrolled subject. Similarly, failure to perform safety assessments 
intended to detect adverse events may be considered failure to protect the rights, safety and well-
being of the enrolled subject. Investigators should seek minimization of such risks by adhering to 
the CIP.
Simultaneously, in the event that adhering to the CIP might expose the subject to unreasonable 
risks, the Investigator is also required to protect the rights, safety and well-being of the subject 
by intentionally deviating from the requirements of the CIP, so that subjects are not exposed to 
unreasonable risks.  
It is the responsibility of the Investigator to provide adequate medical care to a subject enrolled 
in a trial.
Investigators will inform their IRB/EC of protocol deviations in accordance with their specific 
IRB/EC reporting policies and procedures.   
Regulations require that the PI maintain accurate, complete, and current records, including 
documents showing the date of and reason for every deviation from the CIP.  Relevant 
information for each deviation will be documented.  
Regulations require Investigators obtain approval from Coherex Medical and the IRB/EC [as 
required] before initiating changes in or deviations from the protocol, except when necessary to 
protect the life or physical well-being of a subject in an emergency.  Under emergency 
circumstances, deviations from the CIP to protect the rights, safety and well-being of human 
subjects may proceed without prior approval of the Sponsor and the IRB/EC. Such deviations 
shall be documented and reported to the Sponsor and the IRB/EC as soon as possible, but no 
later than 5 working days.
Prior approval must be requested when the Investigator anticipates, contemplates, or makes a 
conscious decision to depart from the CIP, except when unforeseen circumstances are beyond the 
Investigator’s control (e.g. a subject who fails to attend a scheduled follow-up visit, a subject is 
too ill to perform a CIP-required test, etc.).  All deviations, including those beyond the 
Investigator’s control, must be reported on a CRF. 
All deviations must be reported to appropriate regulatory authorities in specified timelines (if 
appropriate). 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
55 of 90
In the event an Investigator is not compliant with this CIP, regulatory requirements or the 
Investigator Agreement, the Investigator will be notified of the non-compliance.  In the event of 
repeated non-compliance, the Sponsor will attempt to secure compliance by one or more of the 
following actions 
•
Visiting the Investigator 
• 
Contacting the Investigator by telephone 
• 
Contacting the Investigator in writing
•
Retraining of the Investigator 
Repeated non-compliance despite these steps may result in further escalation in accordance with 
the Sponsor’s procedures, including termination of the Investigator's participation in the trial. 
8.
ADVERSE EVENT, ADVERSE DEVICE EFFECTS, DEVICE DEFICIENCY
8.1
Definitions
8.1.1
Medical Device  
Any instrument, apparatus, implement, machine, appliance, implant, software, material or other 
similar or related article
x
Intended by the manufacturer to be used, alone or in combination, for human beings for one 
or more of the specific purpose(s) of 
o
Diagnosis, prevention, monitoring, treatments or alleviation of disease, 
o
Diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury, 
o
Investigation, replacement, modification, or support of the anatomy or of a 
physiological process,
o
Supporting or sustaining life, 
o
Control of conception, 
o
Disinfection of medical devices and
x
Which does not achieve its primary intended action in or on the human body by 
pharmacological, immunological or metabolic means, but which may be assisted in its 
intended function by such means 
8.1.2
Adverse Event
An adverse event is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational device or comparator.  This definition includes 
events related to the procedures involved.   
Note: Unchanged, chronic, non-worsening or pre-existing conditions are not adverse events, but 
any planned treatment or intervention/elective procedure must be reported on the Non-
AE/Planned Procedure eCRF.
The Investigator must monitor and report the occurrence of adverse events for each subject from 
the time of enrollment through all trial follow-up.  Adverse events, including the event 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
56 of 90
description, date of onset, outcome, whether or not any medication changed, or a hospitalization 
or intervention occurred, and whether the adverse event was resolved (if so, how, and date of 
resolution), must be reported on the appropriate eCRF within 2 weeks from when the 
investigator becomes aware of the event. Every effort must be made to report the underlying 
condition or unifying diagnosis for the event.  To avoid vague, ambiguous, or colloquial 
expressions, adverse events must be recorded in standard medical terminology rather than the 
subject’s words.  The eCRF must be updated as additional information on the event is received.  
In addition to reporting requirements specified in this CIP, sites must follow the Watchman 
manufacturer’s adverse event reporting requirements for subjects randomized to the Watchman 
device.   
Relatedness to Device or Procedure
Relationship of an adverse event to the investigational device (or comparator) or the procedure
will be based on assessment of temporal relationships, biologic plausibility, association (or lack 
of association) with underlying disease and presence (or absence) of a more-likely cause. Device
or procedure relationship of each adverse event will be categorized as the following: not related, 
unlikely, possible, probable, or causal relationship, as adapted from MEDDEV 2.7/3: 
1) Not related: relationship to the device or procedures can be excluded when:
x
the event is not a known side effect of the product category the device belongs to or of 
similar devices and procedures;
x
the event has no temporal relationship with the use of the investigational device or the 
procedures; 
x
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;
x
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; 
x
the event involves a body-site or an organ not expected to be affected by the device or 
procedure; 
x
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);
x
the event does not depend on a false result given by the investigational device used for 
diagnosis, when applicable;
x
harms to the subject are not clearly due to use error;
x
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. 
2) Unlikely: 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. 
3) Possible: 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/ 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
57 of 90
clinical condition or/and an effect of another device, drug or treatment). Cases where relatedness 
cannot be assessed, or no information has been obtained should also be classified as possible. 
4) Probable the relationship with the use of the investigational device seems relevant and/or the 
event cannot be reasonably explained by another cause, but additional information may be 
obtained. 
5) Causal relationship: the serious event is associated with the investigational device or with 
procedures beyond reasonable doubt when: 
x
the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures;
x
the event has a temporal relationship with investigational device use/application or 
procedures; 
x
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;
o
the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
o
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);
o
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; 
o
harm to the subject is due to error in use; 
The investigator will distinguish between adverse events related to the investigational device and 
those related to the implant procedure. An adverse event can be related both to the implant 
procedure and the investigational device.  
In some particular cases the event may be not adequately assessed because information is 
insufficient or contradictory and/or the data cannot be verified or supplemented. The investigator 
will make the maximum effort to define and categorize the event and avoid these situations. 
Where the investigator remains uncertain about classifying the event, it should not exclude the 
relatedness and classify the event as “possible”.
8.1.3
Serious Adverse Event
An adverse event that led to:
x
Death,
x
A serious deterioration in health of the subject, that either resulted in: 
o
A life-threatening illness or injury, or
o
A permanent impairment of a body structure or a body function, or 
o
An inpatient hospitalization or prolongation of existing hospitalization, or 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
58 of 90
o
A medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
x
Fetal distress, fetal death or a congenital abnormality or birth defect
Note: A planned hospitalization or treatment/elective procedure for a pre-existing condition, or a 
procedure required by this Clinical Investigation Plan, without serious deterioration in health, is 
not considered a serious adverse event (e.g., non-emergent cardioversion), but must be reported
on the Non-AE/Planned Procedure eCRF. 
SAEs must be reported to the Sponsor as soon as possible but no longer than 72 hours (or within 
the timeline specified by site’s local IRB/EC requirements, if these requirements are more 
stringent) on the appropriate eCRF from the time trial personnel became aware of the event or 
became aware that the event met the definition of a serious adverse event.  In the event that the 
eCRF database is not available, the Investigator must report the SAE to the Sponsor via email. 
The SAE must then be entered as soon as possible in the eCRF. The Investigator must report the 
SAE to the local IRB/EC according to the IRB/EC reporting requirements.
8.1.4
Adverse Device Effect (ADE)
Adverse event related to the use of an investigational medical device. ADEs must be reported on 
the appropriate eCRF (AE eCRF) within 2 weeks from when the Investigator becomes aware of 
the event. 
NOTE 1- This includes any adverse event resulting from insufficiencies or inadequacies in the 
instructions for use, the deployment, the implantation, the installation, the operation, or any 
malfunction of the investigational medical device.
NOTE 2- This includes any event that is a result of a use error or intentional misuse.
8.1.5
Unanticipated Serious Adverse Device Effect (USADE) 
A 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.  A USADE must be reported as soon 
as possible but no longer than 72 hours after becoming aware of the event, on the eCRF.
8.1.6
Unanticipated Adverse Device Effect (UADE) 
As defined in 21 CFR §812.3, unanticipated adverse device effects (UADE) are defined as 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 CIP or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. 
If an unanticipated adverse device effect occurs, the Investigator must notify Coherex Medical as 
soon as possible but no longer than 72 hours of the Investigator becoming aware of the event on 
the eCRF.  The Sponsor will notify all IRBs/ECs and all Investigators within 10 working days of 
the Sponsor’s knowledge of the event, as required by 21 CFR §812.150. Coherex Medical will 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
59 of 90
take any steps necessary to investigate the event and will be responsible for notifying FDA and 
all other participating IRBs/ECs, CAs, as appropriate, and Investigators.
8.1.7
Anticipated Serious Adverse Device Effect (ASADE)
A serious adverse device effect which by its nature, incidence, severity or outcome has been 
previously identified in the risk analysis report.  Such events must be reported on the eCRF no 
longer than within 72 hours of awareness of the event.
8.2
Procedure for assessing, recording and reporting adverse events, device 
deficiencies/complaints, adverse device effects, serious adverse events and serious 
adverse device effects: 
Safety surveillance within this trial and the safety reporting both performed by the Investigator, 
starts as soon as the subject is enrolled in this trial (date of signature of the informed consent).
The safety surveillance and the safety reporting will continue until the last investigational visit 
has been performed, the subject is deceased, the subject/Investigator concludes his/her
participation in the trial, or the subject/Investigator withdraws the subject from the trial, except 
as otherwise specified in the CIP.
All adverse event data including deaths and device deficiency data (if applicable) will be 
collected throughout the clinical trial and will be reported to the Sponsor through the EDC 
system.
Records relating to the subject’s subsequent medical course must be maintained and submitted 
(as applicable) to the Sponsor until the event has subsided or, in case of permanent impairment, 
until the event stabilizes, and the overall clinical outcome has been ascertained. Adverse events 
will be monitored until they are adequately resolved.  The status of the subject’s condition should 
be documented at each visit.  
Reportable events to the Sponsor are considered: 
x
All Adverse Device Effects
x
All Serious Adverse Events (whether or not the event is considered device- or procedure-
related and regardless the randomization group) 
x
(if applicable) device deficiencies, that could have led to a serious adverse device effect
o
if either suitable action had not been taken;  
o
if intervention had not been made or 
o
if circumstances had been less fortunate 
All above events will be reported to the Sponsor, as soon as possible, but no later than 72 hours 
of first learning of the event.
The Sponsor will ensure that all events and device deficiencies are reported to the relevant 
authorities as per regulations.  
Additional information may be requested, when required, by the Sponsor or CEC in order to 
support the reporting of AEs to regulatory authorities. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
60 of 90
The Investigator must notify the IRB/EC, if appropriate, in accordance with national and local 
laws and regulations, of the AEs reported to the Sponsor. 
8.3
Subject Death
Subject deaths must be reported as soon as possible but no later than 24 hours (or within the 
timeline specified by site’s local IRB/EC requirements, if these requirements are more stringent) 
on the appropriate eCRF from the day trial personnel become aware of the event.  Upon subject 
death, a trial completion eCRF must also be completed. Deaths will be reported as 
cardiovascular or non-cardiovascular (Appendix I: Acronyms and Definitions).  In the event 
that the eCRF database is not available the Investigator must report the SAE to the Sponsor in a 
timely fashion via email. The death must then be entered as soon as possible in the eCRF once 
the eCRF database becomes available.  The Investigator must report the death to the local 
IRB/EC according to the IRB/EC reporting requirements.  In the event of subject death within 45 
days of the implant procedure, an autopsy should be ordered, and the autopsy report submitted to 
the Sponsor. 
8.4
Device Deficiency
A device deficiency is the inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  
Note: Device deficiencies include malfunctions, use errors, and inadequate labeling. 
Device deficiencies for both arms of the study must be reported to the Sponsor within 3 working 
days (or within the timeline specified by site’s local IRB/EC requirements, if these requirements 
are more stringent) on the Device Deficiency eCRF from the day trial personnel become aware 
of the event.  In the event that the eCRF database is not available the Investigator must report the 
device deficiency to the Sponsor in a timely fashion via email.  The device deficiency must then 
be entered in the eCRF as soon as possible once the eCRF database becomes available.  
Investigational WaveCrest devices opened at the site that meet any of the above criteria should 
be returned to the Sponsor. An approved biohazardous materials container will be supplied by 
the Sponsor to return contaminated product, along with instructions to complete this process.  
Upon learning of a WaveCrest device deficiency, an investigation will be initiated by the 
Sponsor to track the handling of the device and report the results of any internal investigations 
related to the cause of the complaint. Investigation of Watchman device deficiencies should be 
coordinated with the Watchman manufacturer. 
Due to the passive nature of this device, explants are unlikely once the device is implanted. If a 
WaveCrest device is explanted for any reason, it should be returned to the Sponsor following the 
steps for returning investigational devices.  Explants related to the Watchman device should be 
coordinated with the Watchman manufacturer. 
9.
DATA MANAGEMENT
Overall, the Sponsor will be responsible for the data handling. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
61 of 90
The Sponsor and/or its affiliates will be responsible for compiling and submitting all required 
reports to governmental agencies. 
The Investigator or institution shall provide direct access to source data during and after the 
clinical investigation for monitoring, audits, IRB/EC/Head of Medical Institution review and 
regulatory authority inspections.  As required, the Investigator or institution shall obtain 
permission for direct access to source documents from the subject, hospital administration and 
national regulatory authorities before starting the clinical investigation.
9.1
Data Management Plan 
A detailed Data Management Plan (DMP) will be established to ensure consistency of the data. 
This document will include procedures used for data review, database cleaning, and issuing and 
resolving data queries. If appropriate, the DMP may be updated throughout the trial duration. All 
revisions will be tracked, and document controlled. 
Sponsor or designee will regularly perform data review and database cleaning, including issuing 
queries in accordance with the DMP.
CRF data will be captured in a validated electronic database management system.  
Only authorized site personnel will be permitted to enter the CRF data through the electronic 
data capture (EDC) system utilized by Coherex Medical. An electronic audit trail will be used to 
track any subsequent changes of the entered data.
9.2
Document and Data Control 
Documents and data shall be produced and maintained in a way that assures control and 
traceability.  As relevant, accuracy of translations shall be guaranteed and documented.  All 
documents, and subsequent versions, related to the clinical trial shall be identifiable, traceable 
and appropriately stored to provide a complete history of the clinical trial.   
Confidentiality of data shall be observed by all parties involved at all times throughout the 
clinical investigation.  All data shall be secured against unauthorized access.  The privacy of 
each subject and confidentiality of his/her information shall be preserved in reports and when 
publishing any data 
9.2.1
Traceability of documents and data
The Investigator shall assure the accuracy, completeness, legibility and timeliness of the data 
reported to the Sponsor.  Where copies of the original source document as well as printouts of 
original electronic source documents are retained, these shall be signed and dated by trial
personnel with a statement that it is a true reproduction of the original source document.  Data 
reported on eCRFs shall be derived from source documents and be consistent with these source 
documents.  Any discrepancies shall be explained in writing.  
9.2.2
Recording data
Source documents will be created and maintained by the investigational site team throughout the 
clinical trial.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
65 of 90
accurate.  Data submitted on eCRFs will be verified against source documents (medical records) 
utilizing the principles specified in FDA’s guidance on risk-based monitoring (Oversight of 
Clinical Investigations - A Risk-Based Approach to Monitoring) that will be detailed in the 
Monitoring Plan.
Clinical monitors shall be qualified through training and experience, as well as knowledge, in 
Good Clinical Practices, the CIP, the informed consent process, use of the investigational device 
and comparator, and relevant regulatory requirements.  Clinical monitors shall also be trained on 
relevant procedures to be implemented for this trial, as well as the Monitoring Plan.  Training 
shall be documented in Sponsor files. 
After enrollment has begun at the site, a Sponsor or contract monitor(s) trained to Coherex 
Medical’s clinical SOPs will conduct a monitoring visit at a frequency based on factors, such as 
subject accrual rate and observations from previous monitoring visits.  The monitor will schedule 
a visit with the appropriate site staff.
During the monitoring visit, the monitor will evaluate the trial progress, and ensure continual 
acceptability of the facility, adherence to the CIP, and maintenance of adequate records (See 
Section 9 Data Management).  Trial monitors will have access to all records necessary to 
ensure integrity of the data and will periodically review progress of the trial with the 
Investigator.  If a significant compliance issue or protocol deviation is noted, Coherex Medical
will make recommendations and take appropriate actions to resolve the situation.
Clinical monitors will write reports to document site visit activities.  Each report will include the 
following information: 
x
Date the visit took place
x
Name of the monitor who conducted the visit 
x
Name and address of the Investigator visited
x
Identification of persons contacted by the monitor 
x
Information reviewed during the visit (e.g., informed consent, source documents, 
regulatory binder, device accountability) 
x
Review of items discussed, and Action Items generated and resolved 
x
Additional Comments
In addition, contact between trial monitors and the clinical sites will be maintained by telephone, 
facsimile, electronic mail, and site visits per the request of the Investigator or at the discretion of 
Coherex Medical.
The Investigator will collaborate with the clinical monitor to schedule monitoring visits, provide 
a suitable environment for monitors to access trial-related documents and be available during 
monitoring visits.  A Visit Sign-In Log will be maintained at the site. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
66 of 90
11.
SUBJECT INFORMATION
All trial participants are provided with a 
Card regardless of the 
randomization assignment.  
12.
IRB/EC INFORMATION
Coherex Medical requests a waiver of the requirements under 21 CFR 812.35(b) for submitting 
certification of IRB/EC approval to the FDA prior to beginning the investigation at a particular 
site.  In lieu of this requirement Coherex Medical will submit an IRB/EC and Investigator list 
update in 6-month intervals.
13.
OTHER INSTITUTIONS
There are no other institutions that are part of this trial other than the investigative sites and 
designated echo core lab.
14.
REGULATORY INSPECTIONS
The Investigator and/or delegate must contact Coherex Medical immediately upon notification of 
a governmental agency inspection at the site. A clinical monitor or designee will assist the 
Investigator and/or delegate in preparing for the audit. 
An Investigator who has authority to grant access will permit authorized governmental agency 
employees, at reasonable times and in reasonable manner, to enter and inspect any establishment 
where devices are held (including any establishment where devices are used or where records or 
results are kept).
An Investigator, or any person acting on behalf of such a person with respect to the trial, will 
permit authorized governmental agency employees, at reasonable times and in reasonable 
manner, to inspect and copy all records relating to the trial.
An Investigator will permit authorized governmental agency employees to inspect and copy 
records that identify subjects, upon notice that governmental agency has reason to suspect that 
adequate informed consent was not obtained, or that reports required to be submitted by the 
Investigator, to the Sponsor or IRB/EC have not been submitted or are incomplete, inaccurate, 
false or misleading.
14.1
Audits
Audits of this clinical investigation may be conducted by the Sponsor or by third parties 
designated by the Sponsor, to evaluate compliance with this Clinical Investigation Plan, written 
procedures, and applicable regulatory requirements.    Individuals assigned to audit (“auditor”) 
shall be qualified by experience and shall be different from those responsible for or involved 
directly in the conduct of the trial.  At the end of each audit, the auditor shall prepare an audit 
report and an audit certificate verifying that the audit was conducted and submit them to the 
Sponsor. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
75 of 90
provide recommendations to the Sponsor on stopping enrollment and declaring early success.
Based on accumulating data from the trial, the DMC will recommend whether to continue, 
suspend, modify or stop the trial.  The DMC will be composed of at a minimum one statistician 
and 2 physicians.  The composition, responsibilities, frequency of DMC meetings, handling of 
emergency situations and documentation of DMC meetings will be specified in a DMC Charter.   
19.
OUTSOURCING OF DUTIES AND FUNCTIONS
The Sponsor may transfer any or all of the duties and functions related to the clinical trial,
including monitoring, to an external organization (such as a CRO or individual contractor), but 
the ultimate responsibility for the quality and integrity of the clinical trial will reside with the 
Sponsor. All requirements applying to the Sponsor will also apply to the external organization 
inasmuch as this organization assumes the clinical trial related duties and functions of the 
Sponsor. 
19.1
Echocardiography Core Lab 
An Echocardiography Core Laboratory (ECL) will be appointed by the Sponsor to assess TEEs 
for LAA closure and presence of device thrombus and TTEs for pericardial effusion post-
procedure.  The ECL will also assess post-stroke TEEs to ascertain the mechanism of stroke.  
The ECL will provide an Echocardiography Protocol and training to investigational sites.  The
responsibilities and processes to be followed by the ECL will be described in an ECL Manual of 
Operations.
20.
INVESTIGATION SUSPENSION OR TERMINATION
20.1
Premature trial termination 
The Sponsor reserves the right to stop the trial at any stage, with appropriate written notice to the 
Investigator.  
Possible reasons for early termination of the trial by the Sponsor, either at local, national or 
international level, may include, but are not limited to:
x
The device / therapy fails to perform as intended
x
Occurrence of USADE which cannot be prevented in future cases 
x
Sponsor’s decision 
x
Recommendation from DMC to Physician Advisory Committee and Sponsor 
x
Request from Regulatory bodies 
x
Request of Ethics Committee(s) 
x
Concern for subject safety and welfare
x
Failure to secure subject Informed Consent prior to any investigational activity 
x
Failure to report unanticipated adverse device effects within 10 working days to 
Sponsor and the EC, as required
x
Repeated non-compliance with this CIP or the Clinical Trial Agreement
x
Inability to successfully implement this CIP
x
Violation of the Declaration of Helsinki 2008  

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
76 of 90
x
Violation of applicable national or local laws and regulations 
x
Falsification of data, or any other breach of ethics or scientific principles 
x
Loss of or unaccounted use of investigational device inventory 
The trial will be terminated according to applicable regulations.
The Investigator may also discontinue participation in the clinical trial with appropriate written 
notice to the Sponsor. 
Should either of these events occur, the Investigator will return all documents to the Sponsor;
provide a written statement as to why the premature termination has taken place and notify the 
IRB/EC and/or the Competent Authority (if applicable). Follow-up for all enrolled subjects will 
be as per CIP requirements.
An Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in a clinical trial at the investigational sites for which they are responsible.   
If suspicion of an unacceptable risk to subjects arises during the clinical trial or when so 
instructed by the IRB/EC or regulatory authority, Coherex Medical may suspend the clinical trial
as appropriate while the risk is assessed.  Coherex Medical will terminate the clinical trial if an 
unacceptable risk is confirmed.   
Coherex Medical will consider terminating or suspending the participation of a particular 
investigational site or Investigator in the clinical trial if monitoring or auditing identifies serious 
or repeated deviations on the part of an Investigator.   
If suspension or premature termination occurs, the terminating party will justify its decision in 
writing and promptly inform the other parties with whom they are in direct communication.  The 
Investigator and Coherex Medical will keep each other informed of any communication received 
from IRB/EC or regulatory authority. 
If for any reason Coherex Medical suspends or prematurely terminates the trial at an individual 
investigational site, Coherex Medical will inform the responsible regulatory authority, as 
appropriate, and ensure that the IRB/EC are notified, either by the Investigator or by Coherex 
Medical.  If the suspension or premature termination was in the interest of safety, Coherex 
Medical will inform all other Investigators.
If suspension or premature termination occurs, Coherex Medical will remain responsible for 
providing resources to fulfill the obligations from the CIP and existing agreements for following 
up the subjects enrolled in the clinical trial, and the Investigator or authorized designee will 
promptly inform the enrolled subjects at his/her investigational site, if appropriate.
20.2
Resuming the trial after temporary suspension
When Coherex Medical concludes an analysis of the reasons for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, Coherex Medical will 
inform the Investigators, IRB/EC, or regulatory authority, where appropriate, of the rationale, 
providing them with the relevant data supporting this decision. 

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
77 of 90
Concurrence will be obtained before the clinical trial resumes from the IRB/EC or regulatory 
authority where appropriate. 
If subjects have been informed of the suspension, the Investigator or authorized designee will 
inform them of the reasons for resumption. 
20.3
Trial conclusion
The trial will be concluded when: 
x
All sites are closed AND
x
The Final Report generated by Coherex Medical or Coherex Medical has provided formal 
documentation of trial closure 
21.
TRAINING
21.1
Training of Investigators and Trial Personnel
Investigators and trial personnel who will be responsible for day-to-day activities for the trial 
must have completed GCP training per the sites standard operating procedures. Sponsor will 
provide training on the WAVECREST 2 CIP and the eCRF database.  
Additionally, Sponsor will provide training on WaveCrest device IFU to implanting physicians 
and imaging training for the implant procedure to echocardiographers assigned to the trial.  
Sponsor training on the WaveCrest implant procedure will include: 
x
an on-line self-study simulation module which will present device and procedure steps, 
x
training presentation focusing on anatomical considerations, device details and required 
procedural steps, and  
x
Table-top training with model to simulate implant procedure steps. 
Certification of implanting Investigators will be based on a competency assessment. On-site case 
support will be provided by the Sponsor for all implant procedures.  Prior to each procedure, a 
review of baseline imaging studies may be conducted by one of Sponsor’s certified clinical 
trainer with the Investigator.   
The echocardiographer will receive imaging training for the implant procedure from the Sponsor.  
The Sponsor will provide training to echocardiographers on the Echocardiography Protocol. 
A record of training activities and the completed training process will be kept in a Training Log
provided by the Sponsor. 
Table 8 describes the training modules required for the specific roles for trial personnel 
(Investigator, trial coordinator, echocardiographer and blinded trial personnel who will 
administer the QVSFS) assigned to the trial:

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
80 of 90
APPENDIX I: Acronyms and Definitions
ACRONYMS
AF
Atrial Fibrillation
CAS
Carotid artery surgery
CBC
Complete Blood Cell 
CEA
Carotid endarterectomy
CEC
Clinical Events Committee
CT
Computed tomography 
DMC
Data Monitoring Committee
EC
Ethics Committee
ECL
Echocardiography Core Lab
eCRF
Electronic Case Report Form
ePTFE
Expanded polytetrafluoroethylene
GI
Gastrointestinal
HGB
Hemoglobin
HIPAA
Health Insurance Portability and Accountability Act
IDE
Investigational Device Exemption
INR
International Normalized Ratio
IRB
Institutional Review Board
IV
Intravenous
LAA
Left Atrial Appendage
MRI
Magnetic Resonance Imaging
mRS
Modified Rankin Scale
NIH
National Institutes of Health
OAC
Oral Anticoagulant – synonymous with “anticoagulant”
NYHA
New York Heart Association
QVSFS
Questionnaire for Verifying Stroke-Free Status
TEE
Transesophageal Echocardiogram
TIA
Transient Ischemic Attack
TTE
Transthoracic Echocardiogram
WBC
White Blood Cell

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
81 of 90
DEFINITIONS
Anticoagulant
Medication used to reduce thrombogenic properties of blood regardless of mechanism or 
action (Abbreviated OAC)
Antiplatelet
Medication used to inhibit platelet aggregation (P2Y12 inhibitor; aspirin)
Atrial Fibrillation
Paroxysmal
x
AF that terminates spontaneously or with intervention within 7 days of onset.
x
Episodes may recur with variable frequency.
Persistent 
x
Continuous AF that is sustained > 7 days and < 12 months
Long-Standing 
Persistent
x
Continuous AF that is sustained > 12 months
Permanent 
x
Continuous AF that is sustained > 12 months that cannot or is not planned to be 
resolved with treatment
x
Note: For the purpose of this CIP, and for comparison to earlier LAA occlusion 
studies, permanent AF includes any subject with sustained AF 2 months without 
regard to ongoing treatment status.
Cardiac Tamponade
Compression of the heart by an accumulation of fluid or air in the pericardial sac (i.e.,
Pericardial Effusion).  Cardiac tamponade may range from asymptomatic to life-
threatening in severity and may include one or more of the following characteristics:
x
Hypotension, jugular venous distension, and/or muffled heart sounds  
x
Chest pain, palpitations, shortness of breath, or in more severe cases, dizziness, 
syncope and altered mental status
x
Pulseless electrical activity cardiac arrest
x
Pulses paradoxus (decrease in systolic blood pressure >10 mm Hg with inspiration)
x
Sinus tachycardia, low voltage, or electrical alternans on ECG
x
Enlarged cardiac silhouette on chest X-ray
x
Echocardiographic findings including pericardial effusion, right ventricular diastolic 
collapse, right atrial systolic collapse, hepatic veins indicating elevated systemic 
venous pressure, reduced left ventricular end-diastolic and end-systolic dimensions, 
reduced stroke volume & cardiac output, inspiratory bulge/bounce of the 
interventricular septum into the left ventricle, abnormal respiratory changes in 
Doppler flow velocity, and plethoric IVC
x
Requiring interventional or surgical drainage
Clinical Trial/
Clinical Study
For purposes of this trial and all related documents (i.e., Informed Consent, Clinical Trial 
Agreement, etc.) the terms trial and study are used interchangeably.
Device Duration
Time from introduction of delivery sheath to removal of delivery sheath
Left Atrial Duration
Time from transseptal puncture to removal of delivery sheath
Device Embolization
A device that has migrated from the Left Atrial Appendage to a different cardiovascular 
structure.
Device Migration
A device that has shifted from its original position to a different position in the Left Atrial 
Appendage post-

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
82 of 90
Myocardial Infarction
3rd Universal Definition
(see Thygesen, et al.
Circulation. 
2012;126:2020-2035 for 
additional details)
Acute Myocardial Infarction (AMI) - Evidence of myocardial necrosis consistent with 
acute myocardial ischemia.  Any one of the following meets MI diagnosis:
x
Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac 
troponin (cTn)] with at least one value above the 99th percentile upper reference level 
(URL) and with at least one of the following:
o
Symptoms of ischemia
o
New/presumed new significant ST-segment-T wave (ST-T) changes or new 
LBBB
o
Development of pathological Q waves in ECG
o
Imaging evidence of new loss of viable myocardium or new regional wall 
motion abnormality
o
Identification of an intracoronary thrombus by angiography or autopsy
x
Cardiac Death with symptoms suggestive of myocardial ischemia and presumed new 
ischemic ECG changes or new LBBB, but death occurred before cardiac biomarkers 
were obtained, or before cardiac biomarker values would be increased
x
For PCI-related MI or Prior MI – please see Thygesen, et al.
Procedure Duration
Time from venous puncture to removal of delivery catheter
Technical Success
x
Occlusion of the LAA
x
No device-related complications
x
No leak >5mm on color Doppler TEE
Procedural Success
x
Technical success
x
No procedure-related complications except uncomplicated (minor) device 
embolization (resolved by percutaneous retrieval during the procedure without 
surgical intervention or damage to surrounding cardiovascular structures)
Device Success
x
Device deployed and implanted in the correct position
Death
VARC II Definition54
Cardiovascular Death
Death that meets any of the following criteria:
x
Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac tamponade, 
worsening heart failure)
x
Death caused by non-coronary vascular conditions such as neurological events, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other 
vascular disease
x
Procedure-related death, including death related to complication of the procedure or 
treatment for a complication of the procedure 
x
Valve-related death including structural or non-structural valve dysfunction 
or other valve-related adverse events 
x
Sudden or unwitnessed death
x
Death of unknown cause
Non-cardiovascular 
Death
Death in which the primary cause of death is clearly related to another 
condition (e.g., trauma, cancer, suicide)
Endocarditis
Fulfillment of the Duke endocarditis criteria55
(see http://www.medcalc.com/endocarditis.html)
LAA Closure
No residual leak or if leak is present, residual gap  5mm (assessed by the 
ECL)
Major Bleeding
Bleeding Academic Research Consortium (BARC)56definition
Type 3a
Overt bleeding plus hemoglobin drop of 3 to < 5g/dL* (provided hemoglobin drop is 
related to bleed)
Any transfusion with overt bleeding

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
83 of 90
Type 3b
Overt bleeding plus KHPRJORELQGURSJG/SURYLGHGKHPRJORELQGURSLVUHODWHGWR
bleed)
Cardiac tamponade 
Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid)
Bleeding requiring intravenous vasoactive agents
Type 3c
Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, 
does include intraspinal)
Subcategories confirmed by autopsy or imaging or lumbar puncture
Intraocular bleed compromising vision
Type 4
CABG-related bleeding - Perioperative intracranial bleeding within 48 h
Reoperation after closure of sternotomy for the purpose of controlling bleeding
7UDQVIXVLRQRI5 U whole blood or packed red blood cells within a 48-h period†
Chest tube output 2L within a 24-h period
Type 5
Fatal bleeding
Major Vascular 
Complication 
Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, 
arteriovenous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, compartment 
syndrome, percutaneous closure device failure) leading to death, life-threatening or major 
bleeding, visceral ischemia, or neurological impairment
Pericardial Effusion
(PE)
The presence of an abnormal or unexpected amount (>10mm) of fluid or air in the 
pericardial space identified using echocardiography as echo-free space between the 
epicardium and parietal pericardium throughout the cardiac cycle.  For the purposes of this 
study, PEs must include one or more of the following:
1)
Be accompanied by chest pain or other clinical symptoms (see definition of Cardiac 
Tamponade)
2)
Have an increase of >10mm from baseline in either the width (circumferential) or 
largest measured dimension (loculated) by echocardiographic imaging
3)
Require percutaneous or surgical drainage
Pericardial effusions can be further characterized as follows:
-
Onset: Acute (intra-procedural), Subacute (post-procedure – 60 days), Long-term
(>60 days) 
-
Size: Mild (10mm), Moderate (11-20mm), Large (>20mm)
-
Distribution: Circumferential or Loculated
-
Hemodynamics: With or without Cardiac Tamponade or Effusive-Constrictive
-
Type: Transudate, Exudate, Hydropericardium (transudate, plasma ultrafiltrate), 
Hemopericardium (blood in pericardial space), Chylopericardium (chylous 
pericardial fluid), Pyopericardium (purulent pericardial effusion), or 
Pneumopericardium (air in the pericardium)
Residual Gap
Space between the implanted device and adjacent LAA tissue. This gap is 
measured on TEE where there is high velocity color flow and a 2d image 
showing space between implant and tissue. 
Roll-In
WaveCrest subjects enrolled prior to a site’s randomization phase who had 
vascular access attempted
Stroke/TIA
All Stroke
Any ischemic, hemorrhagic, or indeterminate stroke

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
84 of 90
Ischemic Stroke
Sudden onset neurological deficit in a vascular territory thought to be due to cerebral or 
retinal ischemia that a) lasts longer than 24 hours or b) lasts less than 24 hours and is 
associated with a neuroanatomically relevant lesion on neuroimaging or confirmed 
visualized retinal infarct.  A global (rather than focal) deficit thought to be due to anoxic 
brain injury is not considered a stroke. Ischemic stroke with hemorrhagic transformation is 
also categorized here.
Hemorrhagic Stroke
Any symptomatic intracerebral or subarachnoid hemorrhage.
TIA
Sudden onset neurological deficit in a vascular territory thought to be due to cerebral or 
retinal ischemia with resolution in less than 24 hours and without evidence of tissue injury 
on imaging or fundoscopic examination
Major Stroke
x
Any change on the mRS score > 2 points that persists at 90 days post-stroke
Minor Stroke
x
Stroke symptoms which last longer than 24 hours with evidence of tissue injury but 
which does not meet definition of Major Stroke
Stroke of 
Cardioembolic 
Origin
Using ASCOD Classification system57
Stroke will be considered cardioembolic except if there is:
x Another “potentially causal” mechanism is identified (any of A1, S1, O1, D1)
Systemic 
Thromboembolism
Any peripheral ischemic event evidenced by ischemic tissue or radiologic imaging 
evidence of perfusion deficit
Vulnerable Population
Individuals whose willingness to volunteer in a clinical trial could be unduly influenced 
by the expectation, whether justified or not, of benefits associated with participation or of 
retaliatory response from senior members of a hierarchy in case of refusal to participate
Example: individuals with lack of or loss of autonomy due to immaturity or through 
mental disability, impoverished persons, prison population, and those incapable of giving 
consent.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
87 of 90
APPENDIX III: Questionnaire for Verifying Stroke-Free Status (QVSFS)
This questionnaire has 8 questions, as follows.  At study follow-up visits, these questions need to 
be preceded by “Since your last study visit…”: 
1. Were you told by a physician that you had a stroke? 
 
Ƒ<HVƑ1R
2. Were you told by a physician that you had a TIA, mini-stroke or transient ischemic attack? 
Ƒ<HVƑ1R
3. Have you had a sudden painless weakness on one side of your body? 
Ƒ<HVƑ1R
4. Have you had sudden numbness or a dead feeling on one side of your body? 
Ƒ<HVƑ1R
5. Have you had sudden painless loss of vision in one or both eyes? 
Ƒ<HVƑ1R
6. Have you suddenly lost one half of your vision? 
Ƒ<HVƑ1R
7. Have you suddenly lost the ability to understand what people are saying? 
Ƒ<HVƑ1R
8. Have you suddenly lost the ability to express yourself verbally or in writing?  
Ƒ<HVƑ1R
QVSFS scores are obtained by giving 1 point to each “Yes” answer.  The scores range from 0 
(no questions positive) to 8 (all 8 questions positive).   

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
88 of 90
APPENDIX IV: Neurologic Assessments
Modified Rankin Scale
Refer to: http://www.strokecenter.org/wp-content/uploads/2011/08/modified_rankin.pdf  
NIH Stroke Scale
Refer to: https://stroke.nih.gov/documents/NIH_Stroke_Scale.pdf 
REFERENCES
1 Hall JE, Guyton AC; Textbook of Medical Physiology, 11th edition, copyright 2006, pp 116-22.
2 Miyasaka Y, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980-2000, and 
implications on the projections for future prevalence. Circulation 2006; 114:119-25.
3 Allessie MA, et al. Electrophysiologic Mechanisms of perpetuation of atrial fibrillation. Am J Cardiol 1996 Jan 25; 
77(3):10A-23A.
4 Ruigomez A, et al. Incidence of chronic atrial fibrillation in general practice and its treatment pattern. J Clin 
Epidemiol 2002; 55:358-63.
5 Kannel WB, Abbott RD, Savage DD, McNamara PM. Coronary heart disease and atrial fibrillation: the 
Framingham Study. AM Heart J. 1983 Aug:106(2):389-96.
6 Davidson E, Weinberger I, Rotenberg Z, Fuchs J, Agmon J. Atrial fibrillation: Cause and time of onset. Arch 
Intern Med. 1989 Feb 149:457-59.
7 Phillips S, Whisnant J, O’Fallon M, Frye R.  Prevalence of cardiovascular disease and diabetes mellitus in 
residents of Rochester, Minnesota. Mayo Clin Proc 1990 March 65:344-359.
8 Gajewski J, Singer R. Mortality in an insured population with atrial fibrillation. JAMA. 1981 Apr 
17;254(15):1504-44.
9 Takahashi N, Akira S, IMataka K, Fujii J.  Clinical features of paroxysmal atrial fibrillation. An observation of 94 
subjects. Jpn Heart J. 1981 March 22(2);143-49.
10 Israel C, Gronefeld G, Ehrlich J, Li Y, Hohnloser S.  Long-term risk of recurrent atrial fibrillation as documented 
by an implantable monitoring device, implications for optimal subject care.  J Am Coll Cardiol. 2004 Jan 
7;43(1):47-52.
11 Psaty BM, et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation 1997; 96:2455-61.
12 Singer DE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-
Based Clinical Practice Guidelines (8th edition). Chest 2004; 126:448S.
13 Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical subjects with atrial 
fibrillation Ann Thor Surg 1996; 61:755-59.
14 Aberg H. Atrial fibrillation: a study of atrial thrombus and systemic thromboembolism in a necropsy material. 
Acta Med Scand 1969; 185:373-9.
15 Stoddard MF, et al. Left atrial appendage thrombus is not uncommon in subjects with acute atrial fibrillation and a 
recent embolic event: a transesophageal echocardiographic study. J Am Coll Cardiol 1995; 25:452-9.
16 Crystal E, Connolly SJ.  Role of oral anticoagulation in management of atrial fibrillation. Heart. 2004 
Jul;90(7):813-7 
17 Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from 
five randomized controlled trials. Arch Intern Med 1994; 154(13):1449-57.  Erratum in: Arch Intern Med
18 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ.  Validation of clinical classification 
schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.  JAMA. 2001 Jun 13;285
(22):2864-70.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
89 of 90
19 January CT, et al. 2014 AHA/ACC/HRS Guideline for the management of subjects with atrial fibrillation: 
Executive Summary. J Am Coll Cardiol 2014; doi: 10.1016/j.jacc.2014.03.021.
20 Camm AJ, et al. Guidelines for the management of atrial fibrillation. Euro Heart J 2010; 31:2369-429.
21 EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion. Euro Intervention
2014; DOI: 10.4244/EIJY14M08_18
22The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the 
risk of stroke in subjects with nonrheumatic atrial fibrillation. N Engl J Med 1990; 323:1505-11.
23 Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation 1991; 84:527-39.
24 Petersen P, et al. Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic 
complications in chronic atrial fibrillation.  The Copenhagen AFASAK study. Lancet 1989; 1:175-9.
25 Ezekowitz MD, et al. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation.  
Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. N Engl J Med 1992; 327:1406-
12.
26 Connolly SJ, et al. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991; 18:349-
55.
27 Go AS, et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials 
translate into clinical practice? JAMA 2003; 290:2685-92.
28Walker AM and Bennett D. Epidemiology and outcomes in subjects with atrial fibrillation in the United States. 
Heart Rhythm 2008; 5:1365-72.
29 Gladstone DJ, et al. Potentially preventable strokes in high-risk subjects with atrial fibrillation who are not 
adequately anticoagulated. Stroke. 2009; 40:235-40.
30 Dlott JS, et al. National Assessment of Warfarin Anticoagulation Therapy for Stroke Prevention in Atrial 
Fibrillation. Circulation. 2014; 129:1407-14.
31 Fang MC, et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual 
Outcomes 2010; 3:624-31.
32 Tapson VF, et al. Antithrombotic therapy practices in US hospitals in an era of practice guidelines. Arch Intern 
Med. 2005; 165:1458-64.
33 Mant J, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial 
fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged study, BAFTA): A randomized controlled 
trial. Lancet. 2007; 370:493-503.
34 Connolly SJ, et al. Dabigratran versus warfarin in subjects with atrial fibrillation. N Engl J Med 2009; 361:1139-
51.
35 Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883-91.
36 Granger CB, et al; Apixaban versus warfarin in subjects with atrial fibrillation. N Engl J Med 2011; 365:981-92.
37 Giugliano RP, et al. Edoxaban versus warfarin in subjects with atrial fibrillation. N Engl J Med 2013; 369:2093-
104;
38 Eikelboom JW, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger 
subjects with atrial fibrillation: An analysis of the randomized evaluation of long-term anticoagulant therapy (RE-
LY) trial. Circulation 2011; 123:2363-72.
39 Southworth MR, et al. Dabigatran and Postmarketing Reports of Bleeding. N Engl J Med 2013; 368:1272-4.
40 Moore TJ, et al. Dabigatran, bleeding, and the regulators. BMJ 2014; 349 doi: 
http://dx.doi.org/10.1136/bmj.g4517.
41 Lane DA and Lip GYH. Use of the CHA2DS2-VASc and HAS-BLED scores to aid decision making for 
thromboprophylaxis in non-valvular atrial fibrillation. Circulation 2012; 126:860-5.
42 Lip GY, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation
using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest 2010; 137:263–272.
43 Pisters R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in subjects with 
atrial fibrillation: The Euro Heart Survey. Chest 2010; 138:1093-1100.
44 Nishimura RA, et al. 2014 AHA/ACC guideline for the management of subjects with valvular heart disease: a 
report of the American College of Cardiology/American Heart Association task force on practice guidelines. 
Circulation 2014 doi: 10.1161/CIR.0000000000000031  
45 Garcia-Fernandez MA, et al. Role of left atrial appendage obliteration in stroke reduction in subjects with mitral 
valve prosthesis: a transesophageal echocardiographic study. J Am Coll Cardiol 2003; 42:1253-8.

Title:
The WAVECREST 2 Trial 
Clinical Investigational Plan
Doc. #:
CHX_IP014
Rev:
H 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE 
REPRODUCED, DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN 
CONSENT OF COHEREX MEDICAL, INC.
Page:
90 of 90
46 Katz ES, et al. Surgical left atrial appendage ligation is frequently incomplete: a transesophageal 
echocardiographic study. J Am Coll Cardiol 2000; 36:468-71.
47 Kanderian AS, et al. Success of surgical left atrial appendage closure: assessment by transesophageal 
echocardiography. J Am Coll Cardiol 2008; 52:924-9.
48 Healey JS, et al. Left Atrial Appendage Occlusion Study (LAAOS): Results of a randomized controlled pilot 
study of left atrial appendage occlusion during coronary bypass surgery in subjects at risk for stroke. Am Heart J 
2005; 150:288-93.
49 Blackshear JL, et al. Thoracoscopic extracardiac obliteration of the left atrial appendage for stroke risk reduction 
in atrial fibrillation. J Am Coll Cardiol 2003; 42:1249-52.
50 Holmes DR, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of 
stroke in subjects with atrial fibrillation: a randomized non-inferiority trial. Lancet 2009; 374: 534-42.
51 Reddy VY, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in subjects with atrial 
fibrillation: 2.3 year follow-up of the PROTECT AF Trial. Circulation 2013; doi: 
10.1161/CIRCULATIONAHA.112.114389.
52 Holmes DR Jr, 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; 
64:1-12. doi: 10.1016/j.jacc.2014.04.029.
53 Mehta SR, et al.  Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes.  N Engl J Med 
2010; 363:930-942
54 Kappetein AP, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation. JACC
2012; 60: 1438-54. 
55 Durack DT et al.  New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic 
findings. Duke Endocarditis Service. Am J Med 1994; 96:200-9.
56 Mehran R, et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the 
bleeding academic research consortium. Circulation 2011; 123: 2736-47.
57 Amarenco P, et al. The ASCOD Phenotyping of Ischemic Stroke (Updated ASCO Phenotyping) Cerebrovasc Dis
2013; 36:1–5. DOI: 10.1159/000352050.
58 Jones WJ, et al. Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by Neurological History 
and Examination Stroke 2001; 32:2232-6.