Clinical trial NCT03204695
Conditions: Non-valvular Atrial Fibrillation
Keywords: Non-valvular atrial fibrillation Atrial Fibrillation Stroke Left Atrial Appendage (LAA) LAA Closure LAA Occlusion WaveCrest
Sponsor: Coherex Medical
Start date: 2017-05-29; Completion date: 2018-06-14
Enrollment: 27 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The WAVECREST PMCF Study is a prospective, non-randomized, multicenter study to confirm safety and performance of the Coherex WaveCrest Left Atrial Appendage (LAA) Occlusion System in the current medical practice setting in patients with non-valvular atrial fibrillation who are at increased risk for stroke. Up to 65 subjects may be enrolled at up to 15 study sites in Europe. Patients will be followed through 45 days post-procedure.

Detailed description:
The Coherex WaveCrest® Left Atrial Appendage Occlusion System is designed to permanently occlude the Left Atrial Appendage (LAA).

Arms: arm 1: Implant of WaveCrest® Left Atrial Appendage Occlusion System
Interventions: intervention 1: Percutaneous LAA Closure intervention 2: Anticoagulation or Clopidogrel
Intervention descriptions: intervention 1: LAA Closure with the WaveCrest LAA Occlusion System (study device) intervention 2: Subjects either continue on anticoagulation or receive clopidogrel

Protocol documents:
Prot_000.pdf: 
Title:
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #:
CHX_IP015 
Rev:
D 
 
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Clinical Investigational Plan for the 
WAVECREST Post Market Clinical Follow-Up (PMCF) Study 
CHX_IP015 
Study Title: WAVECREST PMCF Study 
A prospective, multicenter, non-randomized, post-market clinical follow-up study to confirm 
safety and performance of the Coherex WaveCrest® Left Atrial Appendage Occlusion System in 
current medical practice in patients with non-valvular atrial fibrillation 
SPONSOR: 
Coherex Medical, Inc. 
3598 West 1820 South 
Salt Lake City, Utah 84104-4959 
United States 
Telephone: +1 801-433-9900 
Fax: +PPD
NCT03204695


Title:
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #:
CHX_IP015 
Rev:
D 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.
Page: 
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WAVECREST Post Market Clinical Follow-Up Study 
CHX_IP015 
Study Title 
WAVECREST PMCF Study 
Device Name 
Coherex WaveCrest® LAA Occlusion System 
Device Number 
CE Mark Number 0123 
Clinical Investigational Plan Number 
CHX_IP015 
Revision Number 
Rev D, including administrative changes #1 and #2 
Date 
17/Jul/2018 
Study Oversight 
Sponsor 
Coherex Medical, Inc. 
3598 West 1820 South 
Salt Lake City, UT 84104 
USA 
PPD


Title:
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #:
CHX_IP015 
Rev:
D 
 
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INVESTIGATOR SIGNATURE PAGE 
Study Title: WAVECREST PMCF Study 
CHX_IP015 
A prospective, multicenter, non-randomized, post-market clinical follow-up study to confirm 
safety and performance of the Coherex WaveCrest® Left Atrial Appendage Occlusion System in 
current medical practice in patients with non-valvular atrial fibrillation 
Sponsored by: Coherex Medical, Inc. 
Document Type 
Revision 
Protocol/Exhibit Effective Date 
Administrative     
#1 
February 22, 2018 
Administrative 
#2 
July 17, 2018 
Protocol 
D 
July 17, 2018 
I, the Undersigned, 
Name: 
 
Title: 
 
Address:  
acting as an Investigator in the above-mentioned study, undertake to perform the study in due 
compliance with the present protocol and with all applicable Regulatory, Ethical and Good 
Clinical Practices requirements, including but not restricted to the latest version of the 
Declaration of Helsinki, Medical Device Directive (93/42/EEC) and EN-ISO 14155.  
No study-specific tests or procedures will be undertaken prior to Ethics Committee approval of 
the research and individual patient signature of an informed consent to participate in the study. 
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 requirements. 
Signature: ______________________________     Date: _________________________ 


Title:
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #:
CHX_IP015 
Rev:
D 
 
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TABLE OF CONTENTS 
1.0 
Summary ............................................................................................................................ 7 
2.0 
Introduction ..................................................................................................................... 11 
3.0 
Background ..................................................................................................................... 11 
3.1 
Oral Anticoagulant Therapy .......................................................................................... 12 
3.2 
Risk-Stratification ........................................................................................................... 13 
3.3 
LAA Occlusion or Exclusion .......................................................................................... 14 
3.3.1 Surgical Approaches ....................................................................................................... 14 
3.3.2 Impetus for Percutaneous Approaches ......................................................................... 15 
3.3.3 Percutaneous LAA Occlusion Devices .......................................................................... 15 
3.4 
Clinical Experience with the WaveCrest Device .......................................................... 15 
3.5 
Rationale to Conduct Clinical Study ............................................................................. 16 
4.0 
Identification of the Device ............................................................................................ 16 
4.1 
Manufacturer details ...................................................................................................... 16 
4.2 
Device Description .......................................................................................................... 17 
4.3 
Intended Indication ......................................................................................................... 18 
4.4 
Device Traceability ......................................................................................................... 18 
5.0 
Study Design .................................................................................................................... 19 
5.1 
Purpose............................................................................................................................. 19 
5.1.1 Number of subjects ......................................................................................................... 19 
5.1.2 Estimated study duration ............................................................................................... 19 
5.2 
Endpoints ......................................................................................................................... 19 
5.3 
Inclusion and Exclusion Criteria ................................................................................... 19 
5.3.1 Inclusion Criteria ............................................................................................................ 20 
5.3.2 Exclusion Criteria ........................................................................................................... 20 
5.4 
Subject Population .......................................................................................................... 20 
6.0 
Study Procedures ............................................................................................................ 20 
6.1 
Site and Investigator Selection ....................................................................................... 20 
6.2 
Training of Investigators and Study Personnel ............................................................ 21 
6.3 
Informed Consent ........................................................................................................... 21 
6.4 
Subject Selection and Screening .................................................................................... 22 
6.5 
Baseline Procedures ........................................................................................................ 22 
6.6 
Point of enrollment ......................................................................................................... 23 
6.7 
Recommended Pre-Procedure Medications ................................................................. 23 
6.8 
Implant Procedure .......................................................................................................... 24 
6.9 
Discharge ......................................................................................................................... 24 
6.10 
45-Day Office Visit (± 15 days) ...................................................................................... 25
6.11 
Unscheduled Neurologic Visit ........................................................................................ 26 
6.12 
Subject Discontinuation.................................................................................................. 27 
6.13 
Lost-to-Follow-up (LTFU) ............................................................................................. 27 
6.14 
End of Study Participation ............................................................................................. 27 
6.15 
Early Study / Site Termination ...................................................................................... 27 
7.0 
Protocol Compliance ....................................................................................................... 28 


Title:
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #:
CHX_IP015 
Rev:
D 
 
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7.1 
Statement of Compliance ............................................................................................... 28 
7.2 
Protocol Deviations and non-compliance...................................................................... 29 
8.0 
Adverse Event, Adverse Device Effect, Device Deficiency .......................................... 29 
8.1 
Adverse Event (AE) ........................................................................................................ 29 
8.2 
Serious Adverse Event (SAE) ........................................................................................ 31 
8.3 
Adverse Device Effect (ADE) ......................................................................................... 32 
8.4 
Serious Adverse Device Effect (SADE) ......................................................................... 32 
8.5 
Unanticipated Adverse Device Effect (UADE) ............................................................. 32 
8.6 
Device Deficiency ............................................................................................................ 32 
8.7 
Death ................................................................................................................................ 33 
8.8 
Reporting requirements ................................................................................................. 33 
9.0 
Monitoring ....................................................................................................................... 34 
10.0 
Data Management ........................................................................................................... 34 
10.1 
Data Handling and Record Keeping ............................................................................. 34 
10.2 
Record Retention ............................................................................................................ 35 
11.0 
Study Organization ......................................................................................................... 36 
12.0 
Amendments to the Clinical Investigational Plan ........................................................ 36 
13.0 
Statistical Methods .......................................................................................................... 36 
13.1 
Sample Size Justification ................................................................................................ 36 
13.2 
Endpoint Analysis ........................................................................................................... 37 
14.0 
Risk Evaluation ............................................................................................................... 37 
14.1 
Anticipated Clinical Benefits ......................................................................................... 37 
14.2 
Residual Risks ................................................................................................................. 38 
14.3 
Risks Associated with Participation in the Clinical Investigation .............................. 38 
14.4 
Possible Interactions with Concomitant Medications ................................................. 39 
14.5 
Steps to be Taken to Control or Mitigate Risks ........................................................... 39 
14.6 
Risk-to-Benefit Rationale ............................................................................................... 40 
14.7 
Risk Management Procedures ....................................................................................... 40 
15.0 
Publication Policy............................................................................................................ 40 
16.0 
Revision History .............................................................................................................. 40 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
Page: 
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TABLE OF APPENDICES  
 
APPENDIX I: ACRONYMS AND DEFINITIONS…………………………………………….42  
APPENDIX II: CHA2DS2-VAsc Score…………………………….……………………………46 
APPENDIX III: QUESTIONNAIRE FOR VERIFYING STROKE-FREE STATUS (QVSFS).47 
APPENDIX IV: NEUROLOGIC ASSESSMENTS…………………………………….............48 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
Page: 
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1.0 
Summary 
Study Title 
WAVECREST PMCF Study 
Name of Device 
Coherex WaveCrest® Left Atrial Appendage Occlusion System 
CE Mark Number 
CE 0123 issued August 2013 
Purpose 
To confirm safety and performance of the WaveCrest device in current 
medical practice in patients with non-valvular atrial fibrillation following 
minor system enhancements 
Study Design 
A prospective, multicenter, non-randomized, post-market clinical follow-
up study to confirm safety and performance of the Coherex WaveCrest® 
Left Atrial Appendage Occlusion System in current medical practice in 
patients with non-valvular atrial fibrillation  
Patient Population 
Patients with non-valvular atrial fibrillation who are at increased risk for 
stroke  
Study Endpoints 
Safety and performance of the WaveCrest device through 45days. 
• Composite rate of: 
o All-cause mortality 
o Pericardial effusion requiring intervention  
o Device embolization from the LAA 
o Device thrombus 
o Ischemic stroke  
• Device Success  
• Technical Success at implant 
• Procedural Success  
Inclusion Criteria 
The criteria for implant are in accordance to the current version of the 
Instructions for Use: 
1. Non-valvular paroxysmal, persistent, or permanent atrial fibrillation 
2. 18 years of age or older 
3. LAA anatomy amenable to treatment by percutaneous techniques 
4. Risk factors for potential thrombus formation in the LAA 
5. Willing to participate in the required follow-up visits and tests 
6. Subject has been informed of the nature of the study, agrees to its 
provisions and has provided written informed consent as approved by 
the EC at the study site 
Exclusion Criteria  
1. Known contraindication to percutaneous transseptal intervention 
2. Left atrial appendage anatomy or size that will not allow appropriate 
implantation of the WaveCrest Implant 
3. Intracardiac thrombus or other cardiac abnormality visualized prior to 
implant that would significantly impact procedural safety 
4. Mitral valve stenosis < 1.5 cm2 or any stenosis consistent with 
rheumatic valvular disease or history of mitral valve replacement or 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
Page: 
8 of 51 
 
repair 
5. Known contraindication and/or allergy to nickel 
6. Known active bacterial infection (i.e., sepsis, endocarditis) 
7. Any known medical condition or overall health of the subject that 
could adversely affect procedural safety or potentially prevent the 
patient from completing all study required visits and tests. 
8. Pregnant or breastfeeding women due to the risk of exposure to x-
rays and medications associated with the implant procedure.  
Number of Study 
Sites 
Up to 15 study sites will participate in the study in Europe  
Sample Size 
The sample size will include up to 65 enrolled subjects.  
Enrollment Phase 
The enrollment phase is expected to last between 18 and 20 months 
Follow-up 
Evaluations 
Office visit at 45 days. A transesophageal echocardiogram (TEE) will be 
performed at the 45-day visit.  
Clinical 
Visits/Testing 
At baseline: 
• History and physical exam (This is referring to the physical 
examination or ‘check-up’ of the patient for signs of disease or 
symptoms) 
• Blood work (including serum pregnancy test and INR if applicable) 
• Baseline transesophageal echocardiogram (TEE) (may be performed 
immediately prior to the procedure) 
• Questionnaire for Verifying Stroke-Free Status (QVSFS)  
• Patients with a history of stroke or TIA or a baseline QVSFS score > 
0: 
o Assessment by a neurologist or person qualified to perform 
neurological assessments is recommended, per physician’s 
judgment 
o Trained study personnel should administer the Modified 
Rankin Scale (Appendix IV)  
o Brain imaging (CT or MRI): results may be collected if brain 
imaging is done prior to implant as part of routine practice or 
if imaging was done at the time of the prior stroke. 
• CHA2DS2-VASc score 
 
At Procedure: 
• Follow Instructions For Use (IFU) for device implantation 
o TEE 
o Angiogram 
o Adverse event assessment 
 
At discharge: 
• Medication assessment 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
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• Adverse event evaluation 
• QVSFS Questionnaire 
 
45 Day Follow-up (± 15 days) 
• Physical exam (This is referring to the physical examination or 
‘check-up’ of the patient for signs of disease or symptoms) 
• TEE 
• Medication assessment 
• Adverse event evaluation 
• QVSFS questionnaire 
Neurological 
Assessment 
If there is any concern for stroke (at scheduled visits, QVSFS results in a 
score > 0), a visit with neurologist or physician certified to assess 
neurological status is recommended, per physician’s judgment.  
• If stroke is suspected and/or confirmed 
o Trained study personnel should administer the Modified 
Rankin Scale (Appendix IV)  
o Brain imaging (MRI, unless contraindicated, then CT): results 
may be collected if brain imaging is done as part of routine 
practice. 
• If stroke is confirmed, results of appropriate investigations done as 
part of routine practice, including transesophageal echocardiogram, to 
determine stroke etiology will be collected. 
Medication regimen 
and Post-Procedure 
Care 
• Patients on anticoagulants prior to implant may continue their pre-
procedure regimens of anticoagulation at the discretion of the 
implanting physician 
• Patients should be advised to use appropriate endocarditis antibiotic 
prophylaxis for future dental and surgical procedures for at least 6 
months post-implant   
• Patients who are not on anticoagulants  should receive clopidogrel 75 
mg per day for 90 days post implant 
• All patients should be maintained on 75 mg - 325 mg of aspirin per 
day indefinitely except those on anticoagulation.  A lower dose 
aspirin is recommended while patients are on clopidogrel.  
• Patients should have follow-up visit at 45 days and standard of care 
imaging, including TEE to assess device position and LAA closure.   
• Patients should be followed in accordance with recommendations for 
treatment of atrial fibrillation 
 
 
 




 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
Page: 
11 of 51 
 
2.0 
Introduction 
This document is a Clinical Investigational Plan (CIP) for the WAVECREST PMCF Study.  The 
WAVECREST PMCF Study is a prospective, non-randomized, multicenter study to evaluate 
safety and performance of the Coherex WaveCrest Left Atrial Appendage (LAA) Occlusion 
System in the current medical practice setting in patients with non-valvular atrial fibrillation. Up 
to 65 subjects may be enrolled at up to 15 study sites in Europe. Patients will be followed 
through 45 days post-procedure. 
The Sponsor shall maintain an updated list of participating investigators and study sites approved 
for participation by the relevant Ethics Committees (EC), which will be kept separately from the 
Clinical Investigational Plan. 
 
3.0 
Background 
Normal heart contractions begin as electrical impulses in an area of the right atrium called the 
sinoatrial node.  As an impulse travels through the atria, it produces a coordinated atrial muscular 
contraction that pumps blood through the atrioventricular (AV) valves into the ventricles.  The 
electrical impulse passes to the AV node in the muscle wall between the two ventricles, 
producing a coordinated ventricular muscular contraction that pumps blood to the lungs and the 
systemic circulation.  This orderly process is repeated billions of times in a normal lifetime.1 
 
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. 2  AF is usually 
associated with underlying heart disease (of 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, non-valvular, or lone.  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 subjects with 
AF 5 , 6 , 7 , 8 , 9although 90% of cases of paroxysmal AF are asymptomatic and therefore the 
prevalence may not be known10.  Paroxysmal AF terminates spontaneously whereas persistent 
AF is sustained for a minimum of seven days.  Persistent or paroxysmal AF, if sustained for 
greater than a year, may lead to permanent AF.The left atrial appendage (LAA) is believed to 
function as a decompression chamber during left ventricular systole and other periods when left 
atrial pressure is elevated.  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 (Crystal 2004).  AF accounts 
for one-fourth of all strokes in the elderly .  The risk of stroke in subjects with non-valvular AF is 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
Page: 
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approximately 5% per year in subjects over 76 years of age (AF investigators Arch Intern Med 
1994).  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 subjects (Gage 2001). 
 
3.1 
Oral Anticoagulant Therapy 
Guidelines recommend chronic anticoagulation for patients with non-valvular AF at risk of 
stroke.16,17,18 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).19,20,21,22,23  Despite its 
proven efficacy, warfarin is often not well tolerated by patients, and has a very 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,24,25  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. 26  In a recent large 
national assessment of warfarin therapy use involving 138,319 patients in the US and 2,683,674 
INR results, the reported mean time in therapeutic range was only 53.7%. 27  Additionally, 
approximately 20% of patients with AF in whom warfarin is recommended have a 
contraindication to warfarin (e.g., systemic or intracranial bleeding, potential for non-compliance 
with therapy, pregnancy, hypersensitivity).28,29,30 
 
Randomized trials of novel anticoagulants (NOACs) such as direct thrombin inhibitor 
(dabigatran), and direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) against warfarin 
have demonstrated a reduction in thrombotic and hemorrhagic stroke when compared with 
warfarin.31,32,33,34  NOACs have a more predictable pharmacokinetic profile than warfarin, fewer 
drug-drug and drug-food interactions, and do not require INR assessments.  NOACs have also 
generally demonstrated a significant reduction in major bleeding when compared with warfarin, 
including an important reduction in intracranial hemorrhage.  Several NOACs have received 
market approval for stroke risk reduction in non-valvular AF patients.  However, bleeding 
related to the use of NOACs remains a clinically significant issue.35,36,37  This bleeding risk 
increases with age, decreased creatinine clearance and concomitant aspirin use.35  The 
randomized NOAC trials also reported significant discontinuation rates for both NOACs and 
warfarin (>20% at 2 years).  The fundamental challenge in AF patients is long-term stroke 
prevention with no significant increased risk of major bleeding.     
 
                                                 
a Approved FDA Medication Guide found at: 
http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088578.pdf  


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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Page: 
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3.2 
Risk-Stratification 
Decision-making regarding the initiation of anticoagulant medication requires tools to predict 
both embolic and bleeding risk.  Risk stratification for embolization in patients with non-valvular 
AF can be performed using both clinical and echocardiographic parameters.  These parameters 
have been derived from both randomized trials and community cohorts.  To identify AF patients 
at risk for stroke, the Atrial Fibrillation Investigators (AFI) pooled and analyzed data from five 
randomized stroke prevention trials13,19,20,21,22 in patients with non-valvular AF.38  The resulting 
CHADS2 scoring system39,40 has until recently been recommended for use to estimate embolic 
stroke risk in AF patients.  CHADS2 is an acronym created from the first letter of five clinical 
parameters:  Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, and prior 
Stroke/TIA/Thromboembolism.  The CHADS2 score ranges from 0 to 6.  A limitation of the 
CHADS2 score is that a subset of patients with a CHADS2 score of 1 may have other risk factors 
for embolic stroke that are not accounted for.  This limitation is overcome by the use of the 
CHA2DS2-VASc score (which gives an additional point each for Vascular disease, Age 65 to 74 
years, and female Sex).41  The CHA2DS2-VASc score ranges from 0 to 9.  The CHA2DS2-VASc 
scoring system can be used to reliably identify truly low risk patients, who can be managed 
without antithrombotic therapy (i.e., patients with CHA2DS2-VASc score of 0).40  Table 1 
explains the CHADS2 and CHA2DS2-VASc scoring systems.   
 
Table 1: CHADS2 and CHA2DS2-VASc Scoring Systems 
CHADS2 
CHA2DS2-VASc 
Risk Factor 
Points 
Risk Factor 
Points 
Congestive Heart Failure 
1 
Congestive Heart Failurea 
1 
Hypertension 
1 
Hypertension 
1 
Age ≥ 75 years 
1 
Age ≥ 75 years 
2 
Diabetes Mellitus 
1 
Diabetes Mellitus 
1 
Stroke/TIA/Thromboembolism 
2 
Stroke/TIA/Thromboembolism 
2 
Maximum Score 
6 
Vascular Disease (prior myocardial 
infarction, peripheral artery disease 
or aortic plaque) 
1 
Age 65 to 74 years 
1 
Female 
1 
Maximum Score 
9 
a Heart failure with reduced ejection fraction or recent heart failure hospitalization (irrespective 
of ejection fraction) 
 
Table 2 shows stroke risks for the CHA2DS2-VASc scoring system.16 
   
 
 
 
 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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Table 2: Adjusted Stroke Rate by CHA2DS2-VASc Score 
CHA2DS2-VAsc Score 
Adjusted Stroke Rate 
(% per year) 
0 
0% 
1 
1.3% 
2 
2.2% 
3 
3.2% 
4 
4.0% 
5 
6.7% 
6 
9.8% 
7 
9.6% 
8 
6.7% 
9 
15.2% 
 
3.3 
LAA Occlusion or Exclusion 
There have been a number of developments in occlusion or exclusion of the LAA via surgical or 
percutaneous means.   
 
3.3.1 
Surgical Approaches 
Surgical ligation or amputation of the LAA has been performed almost since the inception of 
open heart surgery in the 1950s but it is only performed in patients who are undergoing cardiac 
surgery for other reasons (e.g., valve repair or replacement).  The AHA-ACC valvular heart 
disease guidelines state that ligation or amputation is commonly performed in patients with AF 
undergoing mitral valve surgery with the aim or reducing the risk of thromboembolic events.42  
Limited data suggest that the surgical approach to LAA ligation or amputation can reduce the 
risk of stroke.  In a non-randomized observational study of 205 patients who underwent mitral 
valve replacement, ligation of the LAA was performed in 58 patients.43 After an average of 
almost six years, the incidence of an embolic event in patients with LAA ligation was 
significantly lower than in patients who underwent only mitral valve replacement (3% versus 
17%, odds ratio 0.15, which fell to 0.08 if the patients with incomplete ligation were included in 
the group without ligation).  However, surgical LAA suture-based ligation may be incomplete in 
many cases, resulting in continued risk for thromboembolism from the LAA.44,45,46  Surgical 
clips and staplers are preferred approaches to surgical LAA closure.  One minimally invasive 
surgical approach is the AtriClip LAA Exclusion System (AtriCure, West Chester, OH, USA) 
implant.  This device has been approved in Europe (2009) and the United States (2010).  The 
device is indicated for the exclusion of the LAA in conjunction with other open cardiac surgical 
procedures.  In addition to open surgical approaches, thoracoscopic occlusion of the LAA using 
an endoloop snare has been described in 15 patients with chronic or intermittent AF.47  The 
procedure was successful in 14.  However, two strokes occurred in up to 60 months of follow-up 
(i.e., stroke rate 4% per year): 1 fatal stroke occurred 55 months after surgery and 1 disabling 
stroke 3 months after surgery.   
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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3.3.2 
Impetus for Percutaneous Approaches 
Although the efficacy of oral anticoagulant (OAC) therapy in stroke risk reduction has been 
proven, OACs are often not well tolerated by patients.  Indeed, many risk factors (e.g., age, prior 
stroke, hypertension) for stroke are also risk factors for bleeding on OAC.  Non-pharmacologic 
management in the form of surgical ligation or amputation and thoracoscopic occlusion are 
inconsistently effective and often require chronic anticoagulation.  Additionally, open surgical 
approaches to LAA ligation or amputation are only undertaken in patients who are undergoing 
open cardiac surgery for other reasons.  Minimally invasive catheter-based therapies are a 
desirable alternative for patients who do not have indications for open heart surgery and are 
intolerant of or contraindicated for OAC.  The recent EHRA/EAPCI expert consensus statement 
recognizes the role of catheter-based LAA occlusion, especially in patients who refuse OACs.18 
 
3.3.3 
Percutaneous LAA Occlusion Devices 
The Coherex WaveCrest® device is a catheter-based device for the percutaneous occlusion of the 
LAA.  The Watchman (Boston Scientific, Marlborough, MA, USA) and Amplatzer Cardiac Plug 
and Amulet (St. Jude Medical, St. Paul, MN, USA) are other percutaneous LAA occlusion 
devices. These devices are CE marked and available for commercial use in Europe.  Another 
percutaneous device is the LARIAT device (SentreHEART, Redwood City, CA, USA), which 
uses a combined pericardial and endocardial procedure to ligate the LAA.  This device has been 
approved in the United States through a 510(k) for soft-tissue approximation and/or ligation with 
a pre-tied polyester suture.  Because this device originally received regulatory approval as a 
ligation device, it is marketed as such; however, it is routinely and exclusively used throughout 
the world for LAA closure as a means of reducing AF mediated stroke.   
 
3.4 
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) patients 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) 
(enhancements were made to the device and user training), Version 1.3 (N=73) (enhancements 
were made to the anchor frame and delivery catheter).  The study enrolled elderly patients with 
an average CHADS2 Score of 2.5 and at high risk of stroke.  More than half (65%) the patients 
were contraindicated for anticoagulation.  Clinical results on device Version 1.3, which is the 
device which received CE mark are as follows:  procedural success was achieved in a majority of 
patients (96%).  Procedure duration averaged 68 minutes, with forty-seven percent (47%) of 
procedures requiring no device repositioning.  On average, 1.3 devices were used (i.e., 
attempted) per patient.  Pericardial effusions/tamponade occurred at a rate of 2.7% with none 
requiring surgical intervention. No safety-related events occurred after 45 days. At 45 days, LAA 
closure, defined in the study as residual gap ≤3mm, occurred in 97% of patients.  With LAA 
closure defined as residual gap ≤5mm, LAA closure rate at 45 days was 100%.  There were no 
unanticipated adverse events or unanticipated adverse device effects.   
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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Page: 
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The WaveCrest device received the CE Mark in August 2013 and became available 
commercially in Europe in October 2013.  Procedural success was high during limited market 
release, with 88/92 (96%) procedural success rate through July 2014.  Pericardial effusions 
occurred at a rate of 3.3% (3/92).  There was one device embolization (1.1%).  In 2 patients 
(2.2%), a thrombus was discovered on a follow-up TEE.  There were no procedural strokes.  In 2 
patients, there was damage to the inner liner of the Delivery Sheath. Both cases were considered 
“incidents” and warranted a Field Safety Notice (FSN) and Field Safety Corrective Action 
(FSCA) in August 2014, resulting in modification to the Delivery Sheath liner.  In addition, some 
minor enhancements were made to the device. These device enhancements were approved in a 
Change Notification to the original CE mark. 
 
3.5 
Rationale to Conduct Clinical Study 
The WAVECREST PMCF Study is intended to evaluate the safety and performance of 
Coherex’s WaveCrest LAA Occlusion System in current medical practice through 45 day 
follow-up following minor system enhancements.  Forty-five days is the recommended follow-
up period in the IFU and the recommended standard of care in clinical practice for this type of 
procedure. This timeframe provides an appropriate length of time from the implant procedure to 
capture any procedural safety-related events based on the canine study and prior clinical studies. 
Performance of the device is demonstrated by procedural and device success at implant. 
 
The WaveCrest device is passive in nature once it is deployed in the LAA. Initially the anchors 
hold the device in position, however, tissue in-growth (endothelialization) begins immediately in 
the occluder material once the device is implanted. Canine testing showed the safety and 
performance of the device modifications during the implant procedure and complete implant 
endothelialization by 30 days. The WAVECREST 1 study and the initial limited market release 
have effectively demonstrated the safety and performance profile during implant and long-term 
safety of the occluder materials in clinical use . 
 
4.0 
Identification of the Device 
 
4.1 
Manufacturer details 
The Coherex WaveCrest Left Atrial Appendage Occlusion System (“WaveCrest device”) is a CE 
marked device manufactured by  
Coherex Medical, Inc. 
3598 West 1820 South 
Salt Lake City, UT 84104 
United States of America 
 
The WaveCrest device is developed in accordance with EN: ISO13485 standard. 
 




 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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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 
distal side of the occluder to allow visualization of the position, stability and effectiveness of 
occlusion prior to release with fluoroscopy.  Anchoring and occlusion can also be assessed by 
TEE.  When anchoring and occlusion are confirmed, the implant is detached and left within the 
LAA and the Delivery Sheath along with the Delivery Catheter are removed.  The WaveCrest 
device implant is available in diameter sizes of 22, 27 and 32 mm. 
More detailed information on the device can be found in the latest version of the approved 
Instructions for Use and the updated version of the Investigator’s Brochure. 
 
4.3 
Intended Indication 
The Coherex WaveCrest Left Atrial Appendage Occlusion System is approved for use for the 
closure of the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation, who 
are at increased risk for stroke. 
 
4.4 
Device Traceability 
To ensure traceability of the WaveCrest devices used within the study, the following information 
will be documented:  
• Model and Lot number 
• Date of implant 
 
Process for order, receipt and return of the CE-marked devices is in accordance with the 
commercial process. A Patient Implant Card will be handed to each patient successfully 
implanted with the device. 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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5.0 
Study Design 
 
5.1 
Purpose 
This study is designed to confirm the safety and performance of the Coherex WaveCrest LAA 
Occlusion System in current medical practice through 45 day follow-up following minor system 
enhancements. 
 
5.1.1 
Number of subjects  
Up to 65 subjects will be enrolled in the study at up to 15 study sites in Europe.   
 
5.1.2 
Estimated study duration  
Enrollment in the study will be concluded in approximately 18 - 20 months after the first subject 
is enrolled.  Total duration including follow-up visits is expected to be 22 months.  
 
5.2 
Endpoints 
Safety and performance of the WaveCrest device through 45 days follow-up will include the 
following endpoints: 
• Composite rate of: 
• All-cause mortality 
• Pericardial effusion requiring intervention 
• Device embolization (major) 
• Device thrombus 
• Ischemic stroke  
 
• 
Device Success - Device deployed and implanted in the correct position 
 
• Technical Success at implant  
• Occlusion of the LAA 
• No device-related complications 
• 
No leak >5mm on color Doppler TEE 
 
• 
Procedural Success 
• Technical success 
• 
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) 
 
5.3 
Inclusion and Exclusion Criteria 
The criteria for implant are in conformity with the current version of the Instructions for Use of 
the CE-marked device:  
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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5.3.1 
Inclusion Criteria 
1. Non-valvular paroxysmal, persistent, or permanent atrial fibrillation 
2. 18 years of age or older 
3. LAA anatomy amenable to treatment by percutaneous techniques 
4. Risk factors for potential thrombus formation in the LAA 
5. Willing to participate in the required follow-up visits and tests 
6. Subject has been informed of the nature of the study, agrees to its provisions and has 
provided written informed consent as approved by the EC at the study site. 
 
5.3.2 
Exclusion Criteria 
1. Known contraindication to percutaneous transseptal intervention 
2. Left atrial appendage anatomy or size that will not allow appropriate implantation of the 
WaveCrest Implant 
3. Intracardiac thrombus or other cardiac abnormality visualized prior to implant that would 
significantly impact procedural safety 
4. Mitral valve stenosis < 1.5 cm2 or any stenosis consistent with rheumatic valvular disease 
or history of mitral valve replacement or repair 
5. Known contraindication and/or allergy to nickel 
6. Known active bacterial infection (i.e., sepsis, endocarditis) 
7. Any known medical condition or overall health of the subject that could adversely affect 
procedural safety or potentially prevent the patient from completing all study required visits 
and tests.  
8. Pregnant or breastfeeding women due to the risk of exposure to x-rays and medications 
associated with the implant procedure. 
 
5.4 
Subject Population 
Patients with non-valvular atrial fibrillation who are at increased risk for stroke. 
 
No subjects belonging to a vulnerable population (see definition of vulnerable population in 
Appendix I: Acronyms and Definitions) will participate in the clinical study. 
6.0 
Study Procedures 
The clinical study shall be conducted in accordance with the CIP reflecting current medical 
practices and approved IFU.  All parties participating in the conduct of the clinical study shall be 
qualified by education, training, or experience to perform their tasks and this shall be 
documented appropriately. 
The clinical study shall not commence until Coherex Medical receives written approval from the 
relevant EC of each study site as necessary. 
6.1 
Site and Investigator Selection 
Sites will be selected for this study based on the qualification and experience of the implanting 
investigator.  The implanting investigator must have had experience in transseptal puncture 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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Page: 
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procedures and percutaneous LAA closure techniques.  Intended users must have completed the 
WaveCrest Physician Training program.  Investigators must provide a financial disclosure 
statement and sign an Investigator Agreement and/or a site agreement as applicable.  Site 
selection will also depend on the availability of experienced staff to conduct clinical research.  
Study personnel will be responsible for administering the Questionnaire for Verifying Stroke-
Free Status (QVSFS).  The study site will have a neurologist or other study personnel who are 
trained to administer the Modified Rankin Scale. 
 
6.2 
Training of Investigators and Study Personnel 
Sponsor will provide training on the Clinical Investigational Plan and Case Report Form (CRF) 
completion.   
 
Additionally, Sponsor will provide training to echocardiographers assigned to the study.  
Sponsor training on the WaveCrest implant procedure will include: 
• an on-line self-study simulation module which will present device and procedure steps, 
• training presentation focusing on anatomical considerations, device details and required 
procedural steps, and  
• table-top training with model to simulate implant procedure steps. 
 
A record of training activities and the completed training process will be kept in a training log 
provided by the Sponsor. 
 
6.3 
Informed Consent 
All subjects must sign and date the EC approved informed consent prior to undergoing any 
study-specific tests, assessments or procedures.  Investigator or designated study personnel will 
explain the nature and scope of the study, potential risks and benefits of participation, and 
answer any questions from the subject.  Study personnel must explain that agreeing to participate 
in the study and signing an informed consent form does not guarantee study participation.  The 
subject must be provided ample time to read and understand the informed consent form and to 
consider participation in the clinical study.  If the subject agrees to participate, the informed 
consent form must be signed and dated by the subject.  The authorized person obtaining 
informed consent must sign, and date the informed consent prior to conducting any study-
specific tests, assessments or procedures.  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.  
Subject information may be entered in the CRF only after the subject has provided informed 
consent.  
 
Subject confidentiality will be maintained throughout the clinical study 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 study may be made available to authorized third parties, provided the data 
are treated as confidential and that the subject’s privacy is guaranteed. 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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Page: 
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A Delegation of Authority Log and a Sponsor-Representative Log will be maintained and 
updated throughout the study to indicate who the authorized persons are for each task within the 
study and for whom access to patient confidential data is authorized. 
 
6.4 
Subject Selection and Screening 
Sites may begin screening subjects for the study upon receiving EC approval.  Screening for the 
study must be performed per Inclusion and Exclusion Criteria based on medical records at the 
study site (Figure 3 below).  
 
Figure 3: Patient Screening 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.5 
Baseline Procedures 
• Document medical history 
• Perform physical exam (This is referring to the physical examination or ‘check-
up’ of the patient for signs of disease or symptoms) 
• Blood work (including INR and serum pregnancy (as necessary)) 
• CHA2DS2-VASc score (see Appendix II for calculation of CHA2DS2-VASc 
score) 
Yes 
Subject has non-valvular, 
paroxysmal, persistent or 
permanent atrial fibrillation 
No further screening to be 
performed 
No 
Obtain informed consent prior to any study specific testing 
Evaluate subject for inclusion & exclusion criteria 
Screen Failure - 
Complete CRF 
Complete CRF 
Subject meets ALL 
inclusion and 
NONE of the 
exclusion criteria? 
No 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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• A study staff member who is trained must administer QVSFS (Appendix III: 
Questionnaire for Verifying Stroke-Free Status) 
• In the event of history of stroke or TIA or QVSFS score > 0 a trained study staff 
member must administer the Modified Rankin Scale. (Appendix IV: Neurologic 
Assessments). A visit to the neurologist or physician qualified to perform 
neurologic assessment is recommended, per physician’s judgment. 
• In the event of history of stroke, brain imaging (CT or MRI) results may be 
collected if brain imaging is done prior to implant as part of routine practice or if 
imaging was done at the time of the prior stroke (at any time). 
• Perform baseline TEE (may be performed immediately prior to the procedure) 
 
6.6 
Point of enrollment 
Subjects are considered enrolled in the study when the subject has properly signed the approved 
Informed Consent. If the patient doesn’t meet all of the inclusion criteria or meets one of the 
exclusion criteria, the subject is considered a screen failure. The appropriate forms in EDC need 
to be completed. 
Subjects are considered enrolled in the study and Intent-to-Treat is established when the subject 
has properly signed the approved Informed Consent, has met all of the inclusion criteria and 
none of the exclusion criteria, and the Coherex Delivery sheath has been inserted into the 
subject’s femoral vein. 
If the device is not implanted for any reason, the patient will be considered a Failure to Implant 
and discontinued from the study.  
All adverse events as of enrollment and prior to patient discontinuation will be collected. 
 
Absence of intracardiac thrombus must be confirmed on the TEE performed during the implant 
procedure.  If thrombus is observed, the implant procedure must be postponed. The subject may 
be rescreened after the thrombus has resolved.   
 
6.7 
Recommended Pre-Procedure Medications 
Recommended pre-procedure medications are in accordance with the applicable IFU 
recommendations: 
• Anticoagulation Therapy 
Subjects on anticoagulants prior to implant may continue their pre-procedure regimens of 
anticoagulation at the discretion of the implanting physician.  Subjects currently taking 
anticoagulation for history of stroke or TIA may suspend anticoagulation 3 days prior to 
the implant procedure, at the investigator’s discretion.  If the patient has been on 
anticoagulation within 7 days of the procedure it is recommended that the patient’s INR 
is checked within 24 hours prior to implant and that the implant procedure should not be 
performed if the subject’s INR ≥ 2.0.    
• Aspirin Therapy 
Administration of aspirin one day prior to the procedure is recommended at the 
physician’s discretion.  


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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• Antibiotic Therapy 
Use of antibiotic for endocarditis prophylaxis prior to the implant procedure is 
recommended per the site’s standard of care. 
6.8 
Implant Procedure 
Follow the Coherex WaveCrest LAA Occlusion System Instructions for Use (IFU) for the 
implant procedure.   
 
• 
Perform Implant Procedure 
o Perform a transseptal puncture using standard catheterization methods. 
o A TEE should be performed prior to the procedure to determine if the anatomy is 
appropriate for implantation and to confirm the absence of thrombus in the LAA 
o Images of the LAA ostium should be taken to confirm minimum and maximum 
width measurements prior to selecting a device size. 
o The subject should be heparinized to maintain an activated clotting time (ACT) 
>250 seconds for the duration of the procedure (prior to introduction of the 
implant and until sheath is withdrawn). Bivalirudin may be used if heparin is 
contraindicated. ACT measurement is not required if bivalirudin is used.  Note: 
Bivalirudin should not be used if the INR is >2.0. 
o Confirm and record the position and stability of the implant using both 
fluoroscopy and TEE before and after device release. 
• Administer recommended post-implant medications per physician’s discretion as 
subject’s condition dictates.  
• Provide subject with Patient Implant Card (this card will provide the investigator’s 
contact information and device identification number) 
• Record antiplatelet and anticoagulant medications  
• Record adverse events, device malfunctions and protocol deviations as appropriate 
 
6.9 
Discharge 
Before the subject is discharged from hospital:  
• Administer QVSFS questionnaire 
• If there is any concern for stroke, a visit to the neurologist or physician qualified 
to perform neurologic assessment is recommended  
• Record antiplatelet and anticoagulant medications. 
• Record adverse events, device malfunctions and protocol deviations as appropriate. 
• Discharge subject on 75-325mg aspirin daily and 75mg clopidogrel. 
 
Table 4 summarizes the post-procedure anticoagulation and antiplatelet regimen. 
 
Note: Subjects who are not implanted with a device should be followed through hospital 
discharge for adverse events and appropriate CRF to be completed. 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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6.10 
45-Day Office Visit (± 15 days) 
At the 45-day office visit: 
• Perform physical exam (This is referring to the physical examination or ‘check-up’ of the 
patient for signs of disease or symptoms). 
• Study personnel must administer the QVSFS;  
• If QVSFS score > 0, a visit to the neurologist or physician qualified to perform 
neurologic assessment as soon as possible following QVSFS administration is 
recommended.  The modified Rankin stroke scales should be administered by 
trained study personnel. 
• Perform a TEE following the Echocardiography Protocol.  
• If patient has been on anticoagulation, cessation of anticoagulation is at physician 
discretion provided flow around the implant, with correlate 2D residual gap, is 
demonstrated on TEE to be ≤ 5mm.  At the time the subject stops anticoagulation 
clopidogrel 75mg daily should be started and should continue until 90 days post-implant 
(prasugrel or ticagrelor may be used in place of clopidogrel, but must not be used with 
anticoagulation).   
• Instruct subject to remain on 75 -325 mg aspirin indefinitely. Table 4 summarizes the 
post-procedure anticoagulation and antiplatelet regimen.  
• Record antiplatelet and anticoagulant medications. 
• Record protocol defined adverse events, device malfunctions and protocol deviations as 
appropriate. 
 
The schedule of assessments is listed below in Table 3. 
 
Table 3: Schedule of Assessments 
Assessment 
Screening/ 
Baseline 
Treatment Visit 
(Through discharge) 
45 Day Visit 
± 15 days 
Medical history  
X 
 
 
Physical exam* 
X 
 
X 
Pre-Procedure blood work 
X 
 
 
CHA2DS2-VASc score 
X 
 
 
TEE 
X 
X 
X 
QVSFS 
X 
X 
X 
Antiplatelet and Anticoagulant Medication 
Review 
X 
X 
X 
Adverse Event Monitoringa 
X 
X 
X 
In case QVSFS > 0 or history of stroke or suspected stroke/TIA 
Neurologic examb 
X 
 
X 
Modified Rankin Scale 
X 
 
X 
Brain Imaging (MRI – if 
contraindicated, then CT) 
Xc 
 
Xd 
a Adverse event monitoring is initiated upon vascular access with Delivery Sheath. 
b Neurologic visit/exam at baseline for history of stroke or TIA or anytime QVSFS > 0 is recommended, 
per physician’s judgment 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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c Brain imaging results may be collected if imaging is performed as part of routine practice or performed at 
time of prior stroke (at any time) 
d Brain imaging results may be collected if imaging is performed as part of routine practice  
* This is referring to the physical examination or ‘check-up’ of the patient for signs of disease or symptoms 
 
6.11 
Unscheduled Neurologic Visit 
A neurologic visit may be triggered by subject symptoms, if there is any concern for stroke (at 
scheduled visits, QVSFS results in a score > 0 or if a neurologist or a physician certified to 
assess neurological status suspects a stroke).  It is recommended that a neurologist or physician 
certified to assess neurological status examines the subject, per physician’s judgment.  
• If stroke is suspected or confirmed: 
•  Modified Rankin Scale (see Appendix IV: Neurologic Assessments) must be 
administered by trained study personnel  
• Brain imaging study (MRI, CT) results may be collected if imaging is performed 
as part of routine practice or performed at time of prior stroke (at any time).   
• If stroke is confirmed: 
• Results of appropriate investigations done as part of routine practice, including 
TEE, to determine stroke etiology, will be collected (see Appendix I: Acronyms 
and Definitions for stroke definition and etiology). 
 
Table 4: Recommended Adjunctive Antiplatelet and Anticoagulant Medication Regimen 
for Successful Device Implant (per IFU)a 
Visit 
Anticoagulation 
Aspirin 
Clopidogrel 
Discharge to 45-days if patient 
has been on anticoagulation 
prior to implant for history of 
stroke 
Yesd 
 
Per institutional 
practice b 
No 
Discharge to 90-days 
No 
Yes 
75-325mg 
Clopidogrelc 
75mg 
>90 days 
No 
Indefinitely 
No 
aFor subjects not implanted with an LAA occlusion device, antiplatelet and anticoagulant medications will be per 
physician discretion.  
bIf patient remains on anticoagulation, aspirin is not recommended 
c Prasugrel 5-10 mg QD or ticagrelor 90 mg BID may be used in place of clopidogrel in subjects unable to take 
clopidogrel (but may not be used with anticoagulation). 
d if patient remains on anticoagulation, cessation of anticoagulation remains at physician discretion if closure is 
demonstrated 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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6.12 
Subject Discontinuation 
Participation in any clinical study 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: 
• Voluntary withdrawal  
• Participation is terminated by the investigator, although the subject consented, since 
participation is no longer medically appropriate 
• Lost-to follow-up (defined below) 
 
If a patient decides to withdraw from the study, effort must be made to continue monitoring for 
adverse events even if he/she declines to continue in the study. Discuss with the patient if he/she 
agrees with phone follow-up only for the purpose of recording adverse events or non-invasive 
review of records. 
 
Subjects who discontinue participation prematurely will be included in the ITT analysis of 
results (safety and performance as appropriate) but will not be replaced.   
 
Investigators must report subject withdrawals to their respective EC as defined by their 
institution’s procedure.   
 
6.13 
Lost-to-Follow-up (LTFU) 
If a subject misses scheduled follow-up visit, and study personnel make two unsuccessful 
documented attempts to contact the subject, the subject will be considered lost-to-follow-up.    
 
6.14 
End of Study Participation 
Subjects will be considered to have ended participation in the study when they have completed 
45 day follow-up or have discontinued from the study.  The appropriate CRF must be completed 
for the subject when: 
• the subject has completed 45 day follow-up, or 
• the subject has died before follow-up is complete, or  
• the subject has requested to withdraw from the trial with no further contact or review of 
charts. 
 
6.15 
Early Study / Site Termination 
The Sponsor reserves the right to suspend or terminate the clinical study at any stage.  Possible 
reasons for termination may include, but are not limited to: 
• Slow/no inclusion of patients that could not be mitigated 
• Unanticipated Adverse Device Effects (UADEs) present an unreasonable risk to subjects  


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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If the study is terminated early, the Sponsor will provide a written statement to the investigators 
(to enable notification to the EC as applicable) and the ECs, as appropriate.   
 
Should the study 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.  
 
The Sponsor may decide to suspend or prematurely terminate a study site (eg ,non-compliance or 
unmitigated lack of enrollment). If a study site is suspended or prematurely terminated, the 
Sponsor shall inform the investigator of the termination/suspension and the reason why. Also the 
reviewing EC will be informed, as required. 
 
If an investigator voluntary decides to suspend or terminate participation, the relevant EC must 
be informed, as appropriate. 
 
Should early termination occur, the investigator shall return all clinical study materials to the 
Sponsor and maintain study documentation and patient CRFs/data files for the period of time 
required by local regulations. 
 
7.0 
Protocol Compliance 
 
7.1 Statement of Compliance 
This study will be conducted in accordance with this CIP, the Declaration of Helsinki, good 
clinical practices and applicable regulations (ICH E6 GCP, ISO 14155:2011), and the 
appropriate regional and/or national regulations.   
 
The protocol and informed consent must be approved by the appropriate EC of the respective 
study site, as appropriate. 
 
The investigator will not start enrolling subjects or requesting informed consent from any subject 
prior to obtaining EC approval.  
 
In case additional requirements are imposed by the EC, those requirements will be followed, if 
appropriate. If any action is taken by an EC, and regulatory requirements with respect to the 
study, that information will be forwarded to Coherex Medical. 
 
As Sponsor, Coherex Medical has taken up general device liability insurance in accordance with 
the requirements of the applicable legislation.  
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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7.2 Protocol Deviations and non-compliance 
A protocol deviation is defined as an instance of failure to intentionally or unintentionally follow 
the requirements of this Clinical Investigation Plan.  The investigator and study personnel will 
not deviate from the protocol for any reason except in cases of medical emergencies, when the 
deviation is necessary to protect the life or physical well-being of the subject, or to eliminate an 
apparent immediate hazard to the subject.  In such an event, the investigator will notify Sponsor 
within 24 hours by phone or in writing.   
 
In the event a protocol deviation has occurred, the appropriate CRF must be completed.   
Investigators will inform their EC of protocol deviations in accordance with their specific EC 
reporting policies and procedures.   
 
It is the investigator’s responsibility to comply with this Clinical Investigation Plan, regulatory 
requirements and the Investigator Agreement.  Evaluation of investigator compliance to this 
Clinical Investigation Plan, regulatory requirements and Investigator Agreement will be 
monitored by the Sponsor or designee.  In the event an investigator is not compliant with this 
Clinical Investigation Plan, 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 contacting the investigator (by telephone, 
email/letter, or visit).  Repeated non-compliance despite these steps may result in further 
escalation in accordance with the Sponsor’s procedures, including notification to the relevant EC 
and termination of the investigator's participation in the study.  
 
8.0 
Adverse Event, Adverse Device Effect, Device Deficiency 
 
8.1 
Adverse Event (AE) 
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 device.  This definition includes events related to the procedures 
involved.   
 
Note: Unchanged, chronic, non-worsening or pre-existing conditions are not adverse events. 
 
The investigator must monitor and report the occurrence of adverse events for each subject. 
Adverse events, including the event 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 CRF within 
2 weeks.  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 should be 
recorded in standard medical terminology rather than the subject’s words.  The appropriate CRF 
must be updated as additional information on the event is received.   


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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All events must be followed until resolution or until a stable clinical endpoint is reached. The 
medical safety officer may decide if more follow up information is needed in case the event is 
not resolved at study completion. 
 
Relatedness 
For each event, the investigator will assess relationship to the device and the implant procedure.  
Relationship of an adverse event to the device and/or implant 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 and procedure 
relationship of each adverse event will be categorized according to five different levels of 
causality, adapted from MEDDEV guideline 2.7/3 rev 3 and as defined below: 
 
• Not related: relationship to the device or procedure can be excluded when: 
o the event is not a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
o the event has no temporal relationship with the use of the device or the procedures; 
o the event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
o the event involves a body-site or an organ not expected to be affected by the device or 
procedure; 
o the 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); 
o the event does not depend on a false result given by the device used for diagnosis, 
when applicable; 
o harms to the subject are not clearly due to use error; 
o 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 event. 
 
• 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. 
 
• Possible: the relationship with the use of the device is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying or concurrent illness/ 
clinical condition or/and an effect of another device, drug or treatment). Cases were 
relatedness cannot be assessed or no information has been obtained should also be 
classified as possible. 
 
• Probable: the relationship with the use of the device seems relevant and/or the event 
cannot reasonably explained by another cause, but additional information may be 
obtained. 
 
• Causal relationship: the event is associated with the device or with procedures beyond 
reasonable doubt when: 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
THIS DOCUMENT IS THE PROPERTY OF COHEREX MEDICAL, INC. AND SHALL NOT BE REPRODUCED, 
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Page: 
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o the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
o the event has a temporal relationship with device use/application or procedures; 
o the event involves a body-site or organ that  
o the device or procedures are applied to; 
o the device or procedures have an effect on; 
o the event follows a known response pattern to the device (if the response pattern is 
previously known); 
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; 
o the event depends on a false result given by the device used for diagnosis, when 
applicable; 
o In order to establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the event. 
In general, any event that occurs within 30 days is considered related to the procedure, unless 
clear signs are available that they are not. 
 
The investigator will distinguish between adverse events related to the device and those related 
to the implant procedure. An adverse event can be related both to the implant procedure and the 
device. Complications of procedures are considered not related if the said procedures would have 
been applied to the patients also in the absence of device use/application. 
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”. 
 
8.2 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is an adverse event that: 
a) Led to death, 
b) Led to serious deterioration in health of the subject, that either resulted in: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolongation of existing hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c) Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 
The following definitions will be used for defining in-patient or prolonged hospitalizations for 
SAE classification purposes: 
• Prolonged hospitalization will be defined as prolongation of hospitalization due to 
change/worsening of patient’s clinical status 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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• 
After initial procedure, subsequent hospitalization will be defined as ≥ 24 hours in 
duration or < 24 hours with medical intravenous therapy or surgical intervention 
• A planned hospitalization or treatment 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). In case a planned 
procedure is performed after the patient is enrolled in the study without any 
complications the procedure should not be reported as an SAE, however, the procedure is 
to be reported as a non-serious event in EDC. 
 
8.3 
Adverse Device Effect (ADE) 
An adverse event related to the use of an investigational medical device. 
 
This definition includes adverse events resulting from insufficient or inadequate instructions for 
use, deployment, implantation, installation, or operation, or any malfunction of the medical 
device. 
 
This definition includes any event resulting from the use error or from intentional misuse of the 
medical device. 
8.4 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event. 
 
8.5 
Unanticipated Adverse Device Effect (UADE) 
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 risk analysis plan, or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of subjects.. 
 
If the event is not serious, not life-threatening, not related to death or not related to device or 
procedure, it should not be considered unanticipated.  
 
A UADE must be reported by the investigator to the Sponsor immediately but no later than 24 
hours of the investigator’s knowledge of the event, and to the EC per EC requirements.   
 
8.6 
Device Deficiency 
A device deficiency is the inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.   
 
Device deficiencies include malfunctions, use errors, and inadequate labeling. 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
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8.7 
Death 
Subject deaths must be reported as soon as possible but no later than 24 hours on the appropriate 
CRF from the time study personnel become aware of the event.  Deaths will be reported as 
cardiovascular or non-cardiovascular (Appendix I: Acronyms and Definitions).  The 
investigator must report the death to the local EC according to the EC reporting requirements.  In 
the event of subject death within 45 days of the implant procedure and an autopsy were 
performed, the autopsy report should be submitted to the Sponsor. 
 
8.8 
Reporting requirements  
Adverse events are reported beginning from the time the patient is enrolled until patient 
participation has ended. 
The investigator shall inform the Sponsor of all adverse events and device deficiencies as 
described in table below: 
Event Classification 
Recording Method 
Timeline 
Adverse Events, including ADE 
Complete appropriate CRF form  
As soon as possible or as per local 
regulations, but no later than 2 
weeks of site awareness 
Serious Adverse Events, including 
SADE 
Complete appropriate CRF form 
Provide all necessary documentation 
needed 
Immediately upon awareness of the 
event or became aware that the event 
met the definition of a SAE, but no 
later than 72 hours  
Death 
Complete appropriate CRF form 
Within 24 hours 
UADE 
Complete appropriate CRF form 
Immediately upon awareness of the 
event, but no later than 24 hours 
Device deficiencies 
Complete appropriate CRF form 
Within 24 hours 
 
The investigator is responsible for informing the EC of adverse events as required by local 
reporting requirements. 
The Sponsor will submit on regular basis (unless otherwise indicated by the EC or recommended 
by the Sponsor’s medical safety officer) to all participating investigators an update of reported 
events and device deficiencies occurred at the participating study site. 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant 
authorities per country specific regulations.  
The Sponsor will continue safety surveillance and safety reporting until the last follow-up visit 
has been performed, the subject is deceased, the subject/investigator concludes his participation 
in the study or the subject/investigator withdraws the subject from the study. 
 
The Sponsor is responsible for the classification of adverse events and shall review the 
investigator’s assessment of all adverse events. 
The Sponsor will determine and document in writing their seriousness and relationship to device. 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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DISTRIBUTED, DISCLOSED OR USED WITHOUT THE EXPRESS WRITTEN CONSENT OF COHEREX MEDICAL, INC.  
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8.9 Contact details 
In case of questions for reporting of adverse events, the monitor responsible for the study site 
should be contacted site or the responsible Study Safety Lead for this study: 
 
9.0 Monitoring 
Sponsor or Sponsor’s representatives will monitor the clinical study to ensure compliance with 
the Clinical Investigation Plan and applicable regulations, and accuracy of study data under 
Sponsor monitoring procedures.  Source documentation must be available to substantiate proper 
informed consent procedures, adherence to the CIP, comprehensive reporting and follow-up of 
adverse events, accurate reporting of protocol deviations, and investigational device traceability.  
Monitoring will also verify that study data submitted on CRFs are complete and accurate.  Data 
submitted on CRFs will be verified against source documents (medical records).  
 
Centralized monitoring will occur through routine internal data review.  This monitoring is 
designed to identify missing and inconsistent data, data outliers, and potential protocol deviations 
that may be indicative of site non-compliance. On site monitoring will be conducted according to 
a pre-planned monitoring plan designed by the Sponsor.  
 
The investigator will collaborate with the clinical monitor to schedule monitoring visits, provide 
a suitable environment for monitors to access study-related documents and source documents, 
and be available during monitoring visits.  A monitoring visit sign-in log will be maintained at 
the study site.      
 
10.0 
Data Management 
 
10.1 
Data Handling and Record Keeping 
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 her/his information shall be preserved in reports and when 
publishing any data.  
 
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 study shall be version-dated and 
 
PPD


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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identifiable, traceable and appropriately stored to provide a complete history of the clinical 
study.   
 
Data collection will occur using an electronic database capture system (EDC) by study personnel 
trained on the CIP and CRF. Sponsor’s expectation is for data to be entered by the study site in 
the CRF in a timely manner by authorized personnel as documented in a delegation of authority 
log.   
The investigator shall assure the accuracy, completeness, legibility and timeliness of the data 
reported to the Sponsor on the CRFs and in all required reports.  Data reported on CRFs shall be 
derived from source documents and be consistent with these source documents. Corrections to 
the CRFs will be performed by the investigator or designated study personnel. A record of study 
personnel authorized to perform CRF data entry or corrections will be maintained by the study 
site and provided to the Sponsor.  
 
Sponsor or designee will regularly perform data review and database cleaning, including issuing 
queries.    
 
Data are stored in a secure environment: the EDC application is 21 CFR part 11 compliant. 
Access to data is limited to authorized individuals.   
 
Data protection will abide by regulation (EU) 2016/679 of the European Parliament and of the 
Council of 27 April 2016 on the protection of natural persons with regard to the processing of 
personal data and on the free movement of such data. Data transfer outside the EU and to the US 
will be performed under adequate levels of protection and inspired by data transfer modalities at 
least as protective as the data protection laws within Europe. 
 
10.2 
Record Retention 
The principal investigator (PI) will maintain all clinical study documents from prior, during and 
(as specified) after the clinical study on file at the study site in accordance with local legislation 
and requirements.  
The Investigator must contact the sponsor prior to destroying or archiving off-site any records 
and reports pertaining to this study to ensure that they no longer need to be retained on-site. 
All original subject files must be stored for the longest possible time permitted by the regulations 
at the hospital, research institute, or practice in question. If archiving can no longer be 
maintained at the study site, the investigator will notify the sponsor.  
 
All data and documents will be made available upon request to the auditors mandated by the 
Sponsor to conduct audits and to relevant authorities inspectorates in case of an inspection. 
 
The sponsor will archive and retain all essential clinical study documents from prior, during and 
(as specified) after the clinical study as per requirements. 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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.  
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11.0 
Study Organization  
A Physician Advisory Committee, consisting of physicians of varying specialties (interventional 
cardiology, electrophysiology, neurology) and a Sponsor representative, will be responsible for 
oversight of the scientific and operational aspects, and reporting of trial results. The committee 
will meet as needed to review trial progress and may advise the Sponsor on potential trial 
modifications during the trial conduct phase.  The Physician Advisory Committee will also make 
recommendations regarding any publications arising from data generated from the trial. 
 
The Sponsor’s Medical Safety Officer (a physician by training) will review all adverse events 
reported within this clinical study and will provide recommendations to the Sponsor if needed. 
12.0 
Amendments to the Clinical Investigational Plan 
This CIP, and any amendment, will follow Sponsor procedures for generation, approval and 
amendment of quality system documents.  Amendments to this CIP must be submitted to the EC 
for approval (by the investigator or Sponsor, as applicable), as required by local procedures, and 
the approval documentation must be submitted to Sponsor before implementation. 
 
13.0 
Statistical Methods 
. Subject data will be summarized using listings and tables.  All critical electronic case report 
form data will be listed per subject for all enrolled subjects. For continuous variables, descriptive 
statistics will include, at a minimum, the number of observations, mean, standard deviation, 
median, minimum, and maximum. For categorical variables, the number and percentage of 
subjects will be presented.  
 
For all analyses, the baseline observation is defined as the last available measurement on or 
before the date of the implantation procedure. 
 
13.1 
Sample Size Justification 
Based on the results presented in Section 3.4 for Version 1.3 of the WaveCrest device in the 
WAVECREST 1 study and during limited market release, a total of 7 (4.2%) subjects out of 165 
implanted subjects have experienced an occurrence of the composite safety endpoint of  all-cause 
mortality, pericardial effusion requiring intervention, device embolization from the LAA, device 
thrombus, or ischemic stroke. If the expected rate of occurrence of the composite safety endpoint 
is 5%, then a sample size of 56 subjects will result in the upper bound of a two-sided exact 95% 
confidence interval being less than 15% (a clinically and statistically significant difference from 
previous experience). Assuming a drop-out rate of ten percent, total enrollment in this study will 
be at least 63 subjects (56/0.9 rounded up).  
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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13.2 
Endpoint Analysis 
The number and percentage of subjects experiencing an occurrence of the composite safety 
endpoint will be summarized at the 45-day time point. An exact 95% confidence interval will 
also be provided. Similar summaries will also be provided for the number of subjects in whom 
Device Success, Technical Success at implant, and Procedural Success are achieved. These 
summaries will be repeated at the completion of the study. 
 
The number and percentage of subjects reporting adverse events will be summarized by 
MedDRA system organ class and preferred term. Separate summaries will also be provided for 
device-related AEs and procedure-related AEs. All serious adverse events (SAEs), device-related 
SAEs, and procedure-related SAEs will also be summarized by system organ class and preferred 
term. All adverse events occurring up to the 45-day time point and then all adverse events 
occurring through the completion of the study will be summarized separately.  
 
Demographic and baseline characteristics, procedural data (duration of surgery, number of 
devices attempted, length of stay), medical history, and physical examinations, as well as other 
data collected during the study will also be presented. 
14.0 
Risk Evaluation 
Coherex Medical has conducted a risk analysis to identify potential hazards associated with use 
of the WaveCrest device 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 device are described in the following sections.     
 
14.1 
Anticipated Clinical Benefits 
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 patients 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 include: 
• Ease of use due to ostial positioning 
• Shorter procedure times 
• Evaluation of closure at implant 
• Reduced thrombus formation related to the device due to the selection of occluder 
materials 
• Improved anchor position near the point of occlusion for improved stability 
• Reduction in pericardial effusions due to absence of Sheath manipulation deep in the 
LAA tissue 
 


 
 
Title: 
WAVECREST Post Market Clinical Follow-Up 
(PMCF) Study 
Doc. #: 
 
CHX_IP015 
Rev: 
 
D 
 
 
 
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14.2 
Residual Risks 
Risks involved with the use of the WaveCrest device have been mitigated to the extent possible 
in its design, non-clinical testing, and with the training and instructions given to clinicians for its 
use; however, all risks of a clinical procedure and implantable medical device cannot be 
mitigated.  The residual risks of using the device are discussed in sections below. 
 
14.3 
Risks Associated with Participation in the Clinical Investigation 
 
For subjects, the risks associated with participation in a post-market clinical investigation based 
on approved device use and indications are expected to be no different from those experienced in 
the commercial setting.   
 
Potential adverse events specific to device placement include, but are not limited to: 
• Device embolization, migration,misplacement or improper seal of the LAA 
• Device failure, fracture or extrusion of device components 
• Inability to recapture, reposition, or retrieve the device requiring surgical retrieval 
• Thrombus formation on the device surface with the risk of subsequent embolization 
• Tissue erosion 
• 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: 
• Air embolus 
• Allergic reactions 
 
 
 
• Anesthesia reactions 
• Apnea 
• Arrhythmia 
• AV Fistula 
• Blood loss requiring transfusion 
• Cardiac perforation 
• Contrast reaction 
• Chest Pain 
• Death 
• Pulmonary vein obstruction 
• Renal failure/insufficiency 
• Scarring/venous thrombosis 
• Stroke/transient ischemic attack 
• Surgical Repair/Retrieval procedure 
 
• Fever 
• Hematoma/ecchymosis 
• Hypertension; hypotension 
• Infection including endocarditis 
• Myocardial infarction  
• Perforation of vessel or myocardium 
• Pericardial effusion 
• Pleural effusion 
• Pseudoaneurysm 
• Pulmonary edema 
• Pulmonary embolus 
• Tamponade 
• Thrombus formation/embolism 
• Vagal reactions 
• Valvular damage/insufficiency 
• Vascular 
damage/ 
access 
site 
complications 
 


 
 
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14.4 
Possible Interactions with Concomitant Medications 
 
No interactions are expected between the WaveCrest device and concomitant medications.   
 
Patients treated with the WaveCrest device will take, in due conformity with the approved device 
Instructions For Use, clopidogrel and aspirin for at least 90 days. The combination of these two 
medications may be associated with an increased risk of bleeding as compared to the risk when 
only one medication is used.  Additional risks include: 
• Internal bleeding 
• Nose bleeds 
• Bruising 
• Prolonged bleeding from a cut or scrape 
• Headache 
• Upset stomach 
• Nausea or vomiting 
• Diarrhea 
• Fever 
• Skin rash 
• Tissue death (necrosis) 
• Decrease in white or red blood cells 
• Inability to tolerate clopidogrel or aspirin 
• Interaction with other medications or foods 
 
14.5 
Steps to be Taken to Control or Mitigate Risks 
 
All of the adverse events listed in Section 14.3 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 device compared to existing LAA occlusion devices 
used for similar indications. 
 
Many of the adverse events listed above mainly occurred when the device was: (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.  
 
Many risks associated with vascular interventional procedures are related to the condition of the 
patient and the patient’s vasculature, coagulation, and renal systems, the patient’s overall 
physical health, pre-existing medical conditions, and the clinician’s overall skill level.  These 
risks are minimized in this study by the specific requirements of cardiac anatomy as well as 
careful selection and training of clinicians.  
 


 
 
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14.6 
Risk-to-Benefit Rationale 
Based on a review of the Use, Design, and Process FMEAs, and based on the CE-mark approval 
of the device and its use within the approved indication the potential benefits of use of the 
WaveCrest device outweigh the risks.   
 
14.7 
Risk Management Procedures 
Risks to subjects from participation in the study will be minimized by the following steps:   
• Implanting investigators will be trained on the investigational device, the IFU, and the 
Clinical Investigation Plan prior to participating in the study. Retraining of investigators 
will be conducted if deviations from recommended use are noted. 
• Subjects will participate in the study only upon providing consent and confirmation of 
meeting study eligibility criteria.  Subjects will have follow-up visits according to the 
schedule specified in this CIP.  Subjects participating in the study will receive antiplatelet 
and anticoagulation medications to minimize risk of thromboembolism.  
• Adverse events and adverse device effects will be reported and monitored through the 
follow-up period and ECs will be notified per the local reporting requirements.  
• Sites will be notified of unanticipated adverse device effects or other safety concerns that 
could negatively impact the safety of the subjects if such issues arise.  
• Compliance of sites to the CIP and regulatory requirements will be monitored. 
• The Medical Safety Officer will  review the adverse events. 
 
15.0 
Publication Policy 
Results of this clinical study may be submitted for publication without regard for whether the 
trial results are positive or negative.  Sponsor will be responsible for oversight of the publication 
process and will have oversight of publications of results of the trial, the Physician Advisory 
Committee may advise.   
Site-specific clinical study results may be published by Investigators in compliance with the 
Investigator Agreement and/or site agreement, as applicable.  
For more information on publication guidelines, please refer to the International Committee of 
Medical Journal Editors (ICMJE) on www.icmje.org. 
 
The study will be registered on the clinicaltrials.gov website and information will be updated on 
a regular basis as required. 
16.0 
Revision History 
 
Rev. 
Description of Change 
Revised By 
CO# 
Effective Date 
A 
Initial Release 
7 May 2015 
B 
Updated exclusion criteria to be consistent 
with IFU; minor edits 
15 May 2015 
C 
Update to be consistent with latest version 
08Feb2017 
PPD


 
 
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of IFU, updated statistical section and 
latest internal study management decisions 
 
 
 
 


 
 
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APPENDIX I: ACRONYMS AND DEFINITIONS 
 
ACRONYMS 
 
AF 
Atrial Fibrillation 
CIP 
Clinical Investigational Plan 
CT 
Computed tomography  
CRF 
Case Report Form 
EC 
Ethics Committee 
ePTFE 
Expanded poly tetra fluoro ethylene 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IV 
Intravenous 
LAA 
Left Atrial Appendage 
MRI 
Magnetic Resonance Imaging 
mRS 
Modified Rankin Scale 
NYHA 
New York Heart Association 
PMCF 
Post Market Clinical Follow-Up 
QVSFS 
Questionnaire for Verifying Stroke-Free Status 
TEE 
Transesophageal Echocardiogram 
TIA 
Transient Ischemic Attack 
VKA 
Vitamin K Antagonist 
 
 
 


 
 
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DEFINITIONS 
 
Atrial Fibrillation 
 
Paroxysmal 
• 
AF that terminates spontaneously or with intervention within 7 days of 
onset 
• 
Episodes may recur with variable frequency. 
Persistent  
• 
Continuous AF that is sustained > 7 days. 
Permanent  
• 
Continuous AF that is sustained > 12 months that cannot or is not 
planned to be resolved with treatment 
• 
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. 
Device Duration 
Time from transseptal puncture to removal of delivery catheter 
Device Embolization 
A device that has dislodged from the Left Atrial Appendage and moved 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 release 
Procedure Duration 
Time from venous puncture to removal of delivery catheter 
Device Success 
Device deployed and implanted in the correct position 
Technical Success 
• 
Occlusion of the LAA 
• 
No device-related complications 
• 
No leak >5mm on color Doppler TEE 
Procedural Success 
• 
Technical success 
• 
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) 
Death 
VARC II Definition48 
Cardiovascular 
Death 
Death that meets any of the following criteria: 
• 
Death due to proximate cardiac cause (e.g., myocardial infarction, 
cardiac tamponade, worsening heart failure) 
• 
Death caused by non-coronary vascular conditions such as neurological 
events, pulmonary embolism, ruptured aortic aneurysm, dissecting 
aneurysm, or other vascular disease 
• 
Procedure-related death, including death related to complication of the 
procedure or treatment for a complication of the procedure  
• 
Valve-related death including structural or non-structural 
valve dysfunction or other valve-related adverse events  
• 
Sudden or unwitnessed death 
• 
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 
Fulfilment 
of 
the 
Duke 
endocarditis 
criteria
49
 (see 
http://www.medcalc.com/endocarditis.html)  
LAA Closure 
No residual leak, or if leak is present no residual flow > 5mm on 


 
 
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color Doppler TEE 
Bleeding 
Bleeding Academic Research Consortium (BARC)50definition 
    Type 0 
No bleeding 
    Type 1 
Bleeding that is not actionable and does not cause the patient to seek 
unscheduled performance of studies, hospitalization, or treatment by a 
healthcare 
professional; 
may 
include 
episodes 
leading 
to 
self-
discontinuation of medical therapy by the patient without consulting a 
healthcare professional 
    Type 2 
Any overt, actionable sign of hemorrhage (e.g., more bleeding than would 
be expected for a clinical circumstance, including bleeding found by 
imaging alone) that does not fit the criteria for type 3, 4, or 5 but does meet 
at least one of the following criteria: (1) requiring nonsurgical, medical 
intervention by a healthcare professional, (2) leading to hospitalization or 
increased level of care, or (3) prompting evaluation 
    Type 3a 
Overt bleeding plus hemoglobin drop of 3 to < 5g/dL* (provided 
hemoglobin drop is related to bleed) 
Any transfusion with overt bleeding 
    Type 3b 
Overt bleeding plus hemoglobin drop ≥ 5g/dL* (provided hemoglobin drop 
is related to bleed) 
Cardiac tamponade  
Bleeding 
requiring 
surgical 
intervention 
for 
control 
(excluding 
dental/nasal/skin/hemorrhoid) 
Bleeding requiring intravenous vasoactive 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 48h 
Reoperation after closure of sternotomy for the purpose of controlling 
bleeding 
Transfusion of ≥5 units whole blood or packed red blood cells within a 48-
hour period† 
Chest tube output ≥2L within a 24-hour period 
    Type 5 
Fatal bleeding 
Major Bleeding  
Type 3 or greater as defined by Bleeding Academic Research 
Consortium (BARC) 
Major Vascular 
Complication  
Access site or access-related vascular injury (dissection, stenosis, 
perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, 
irreversible nerve injury, compartment syndrome, percutaneous closure 
device failure) leading to death, life-threatening or major bleeding, visceral 
ischemia, or neurological impairment 
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.  
Stroke/TIA 
 
All Stroke 
Any ischemic or hemorrhagic stroke 
Ischemic Stroke 
Sudden onset neurological deficit in a vascular territory thought to be due 


 
 
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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 also 
considered a stroke. Ischemic stroke with hemorrhagic transformation is 
also categorized here. 
Hemorrhagic Stroke 
Any atraumatic 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 
• Any change on the modified Rankin Scale score > 2 points that persists at 
30 days post-stroke 
Minor Stroke 
Does not meet definition of Major Stroke 
Stroke of 
Cardioembolic 
Origin 
Using ASCOD Classification system51  
Stroke will be considered cardioembolic except if there is: 
• Another “potentially causal” mechanism is identified (any of A1, S1, O1, 
D1), AND 
• The C grade is 0, 3, or 9 (unlikely since all patients have AF at implant) 
Systemic 
Thromboembolism 
Any acute vascular insufficiency or occlusion of the extremities or any 
non-CNS organ associated with clinical, imaging, surgical/autopsy 
evidence of arterial occlusion in the absence of other likely mechanism 
(e.g., trauma, atherosclerosis, or instrumentation). When there is presence 
of prior peripheral artery disease, angiographic, surgical or autopsy 
evidence is required to show abrupt arterial occlusion. 
Vulnerable 
Population 
Individuals whose willingness to volunteer in a clinical study 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. 


 
 
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APPENDIX II: CHA2DS2-VAsc Score 
 
The CHA2DS2-VAsc Score is an ischemic stroke risk stratification method in subjects with non-
valvular atrial fibrillation16.  The score assigns 1 or 2 points for each of the following risk 
factors: Congestive Heart Failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke 
or TIA or Thromboembolism, Vascular Disease, Age 65 to74 years, Female.  The score ranges 
from a minimum of 0 to a maximum of 9, with lower scores having lower risk and higher scores 
having higher risk for ischemic strokes.   Subjects in the study must have a minimum score of 2. 
 
Stroke Risk Stratification with CHA2DS2-VAsc Score 
 
Risk Factor 
Points 
Congestive Heart Failure 
1 
Hypertension 
1 
Age ≥ 75 years 
2 
Diabetes Mellitus 
1 
Stroke/TIA/Thromboembolism 
2 
Vascular Disease (prior myocardial infarction, 
peripheral artery disease or aortic plaque) 
1 
Age 65 to 74 years 
1 
Female 
1 
Maximum Score 
9 
  
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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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? 
 
□ Yes □ No  
 
2. Were you told by a physician that you had a TIA, ministroke or transient ischemic attack?  
□ Yes □ No  
 
3. Have you had a sudden painless weakness on one side of your body? 
□ Yes □ No  
 
4. Have you had sudden numbness or a dead feeling on one side of your body? 
□ Yes □ No  
 
5. Have you had sudden painless loss of vision in one or both eyes? 
□ Yes □ No  
 
6. Have you suddenly lost one half of your vision? 
□ Yes □ No  
 
7. Have you suddenly lost the ability to understand what people are saying? 
□ Yes □ No  
 
8. Have you suddenly lost the ability to express yourself verbally or in writing?  
□ Yes □ No  
 
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).   
 
Refer to Jones WJ, et al.52 for further details. 


 
 
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APPENDIX IV: NEUROLOGIC ASSESSMENTS 
 
 
Modified Rankin Scale 
Refer to http://www.strokecenter.org/wp-content/uploads/2011/08/modified_rankin.pdf  
 
 
 


 
 
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44 Katz ES, et al. Surgical left atrial appendage ligation is frequently incomplete: a transesophageal 
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45 Kanderian AS, et al. Success of surgical left atrial appendage closure: assessment by transesophageal 
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50 Mehran R, et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report 
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52 Jones WJ, et al. Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by 
Neurological History and Examination Stroke 2001; 32:2232-6. 
 
 

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Biosense Webster Inc. 
STATISTICAL ANALYSIS PLAN (SAP) 
Study Title: WAVECREST PMCF Study 
Protocol Number: CHX_IP015 Revision D 
 SAP Version: 
  Date: 
 Version 1.0 
  05JUL2022 
NCT03204695




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Table of Contents 
 
1.0 
REVISION HISTORY .............................................................................................................. 4 
2.0 
INTRODUCTION .................................................................................................................... 5 
 
Study Objectives ................................................................................................................... 5 
 
Study Design Overview ......................................................................................................... 5 
3.0 
STUDY ENDPOINTS ............................................................................................................... 5 
4.0 
SUBJECT DISPOSITION ........................................................................................................ 6 
5.0 
ANALYSIS SETS ..................................................................................................................... 6 
 
Intention-to-Treat (ITT) Analysis Set .................................................................................. 6 
 
As-Treated Analysis Set ........................................................................................................ 6 
6.0 
GENERAL STATISTICAL CONSIDERATIONS .................................................................. 6 
 
Summary Statistics ............................................................................................................... 6 
 
Reporting of Numerical Values ............................................................................................ 6 
 
Handling of Missing Data ..................................................................................................... 7 
 
Statistical Software ............................................................................................................... 7 
7.0 
STATISTICAL METHODS ..................................................................................................... 7 
 
Sample Size Justification ...................................................................................................... 7 
 
Demographics and Baseline Characteristics ........................................................................ 7 
 
Safety Endpoint .................................................................................................................... 7 
 
Clinical Performance Endpoints .......................................................................................... 8 
 
Other Safety Analysis - Adverse events (AEs) ..................................................................... 8 
 
Procedural Results ................................................................................................................ 8 
 
Protocol Deviations ............................................................................................................... 9 
 
 
 
 


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1.0 
REVISION HISTORY 
 
 
Version 
Date 
Author(s) 
List of Changes 
1.0 
05JUL2022 
 
Original Creation of Document 
 
 
 
 
 
 
 
 
PPD


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2.0 
INTRODUCTION 
This is the Statistical Analysis Plan (SAP) for the final analysis of data collected under Clinical 
Investigation Plan (CIP) CHX_IP015. This SAP describes in detail the statistical methodology and 
statistical analyses for the above-mentioned protocol. 
 
Study Objectives 
This trial is designed to confirm the safety and performance of the Coherex WaveCrest LAA 
Occlusion System in current medical practice through 45 days (± 15 days) follow-up following 
minor system enhancements.   
 
Study Design Overview 
The WAVECREST PMCF Study is a prospective, multicenter, non-randomized, post-market 
clinical follow-up study to confirm safety and performance of the Coherex WaveCrest® Left 
Atrial Appendage Occlusion System in current medical practice in patients with non-valvular 
atrial fibrillation   
Up to 65 subjects will be enrolled in the study at up to 15 study sites in Europe. 
Enrollment in the study will be concluded in approximately 18 - 20 months after the first subject 
is enrolled.  Total duration including follow-up visits is expected to be 22 months. 
3.0 
STUDY ENDPOINTS 
Safety and performance of the WaveCrest device through 45 days (± 15 days) follow-up will 
include the following endpoints:  
x Composite rate of:  
• 
All-cause mortality  
• 
Pericardial effusion requiring intervention  
• 
Device embolization (major)  
• 
Device thrombus  
• 
Ischemic stroke   
x Device Success - Device deployed and implanted in the correct position  
x Technical Success at implant   
• 
Occlusion of the LAA  
• 
No device-related complications 
• 
No leak >5mm on color Doppler TEE   
x Procedural Success  
• 
Technical success  
• 
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)  


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4.0 
SUBJECT DISPOSITION 
Subject disposition will be summarized with counts and percentages in total. Categories 
summarized will include the number of enrolled subjects (i.e., subjects who signed informed 
consent), number of screen failures, and the number completed, and discontinued, as well as 
reasons for discontinuation. The summary of disposition will also include the number and 
percentage of subjects included in each analysis set described in Section 6 below. 
5.0 
ANALYSIS SETS 
Statistical analyses will be carried out on the following analysis sets. 
 
Intention-to-Treat (ITT) Analysis Set  
The ITT analysis set consist of all subjects who signed the informed consent form, have met all of 
the inclusion criteria and none of the exclusion criteria, and the Coherex Delivery sheath has been 
inserted into the subject’s femoral vein. 
 
As-Treated Analysis Set 
The As-Treated analysis set consists of all ITT subjects who received the WaveCrest LAA 
occlusion device.   
6.0 
GENERAL STATISTICAL CONSIDERATIONS 
 
Summary Statistics  
Subject data will be summarized using listings and tables.  All critical electronic case report form 
(eCRF) data will be listed per subject for all enrolled subjects. For continuous variables, 
descriptive statistics will include, at a minimum, the number of observations, mean, standard 
deviation, median, minimum, and maximum. For categorical variables, the number and 
percentage of subjects will be presented. 
For all analyses, the baseline observation is defined as the last available measurement on or 
before the date of the implantation procedure.   
 
Reporting of Numerical Values 
Raw data will be presented with the exact precision that it was collected on the eCRF or other 
external data sources. 
The number of decimal places to display for calculated data will be determined by the scale of 
measurement.  No decimal places will be displayed if the smallest calculated value is 100; 1 
decimal place will be displayed when all calculated values are within the interval (10, 100), with 
10 being inclusive; 2 decimal places are displayed when all calculated values are within (1, 10), 
with 1 being inclusive; 3 decimal places are displayed for calculated values within (0.1, 1), with 
0.1 being inclusive; and so on for even smaller scales of measurement. 
Percentages will be reported with exactly one decimal place.  For summary statistics, means, 
medians, and confidence intervals will be displayed to one more decimal place than was 
determined above, dispersion statistics will have 2 more decimal places, and the minimum and 
maximum will be displayed to the same number of decimal places as determined by the rules 
above. Blank fields on an eCRF will be displayed as blank fields in corresponding listings. 


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Handling of Missing Data 
Unless otherwise explicitly specified, missing data will not be imputed; observed cases will be 
used in the analyses.  
 
Statistical Software 
Statistical analyses will be performed using SAS version 9.4 or higher. 
7.0 
STATISTICAL METHODS 
 
Sample Size Justification 
Based on the results presented in Section 3.4 of CIP for Version 1.3 of the WaveCrest device in 
the WAVECREST 1 study and during limited market release, a total of 7 (4.2%) subjects out of 
165 implanted subjects have experienced an occurrence of the composite safety endpoint of all-
cause mortality, pericardial effusion requiring intervention, device embolization from the LAA, 
device thrombus, or ischemic stroke. If the expected rate of occurrence of the composite safety 
endpoint is 5%, then a sample size of 56 subjects will result in the upper bound of a two-sided 
exact 95% confidence interval being less than 15%. Assuming a drop-out rate of ten percent, 
total enrollment in this study will be at least 63 subjects (56/0.9 rounded up).  
 
Demographics and Baseline Characteristics 
A minimum of the following demographic and baseline characteristics will be summarized by 
each analysis set: age at enrollment, sex, race, ethnicity, weight, height, body mass index, prior 
cardiovascular history, baseline CHADS2 score, baseline CHA2DS2-VASc score, baseline HAS-
BLED score, baseline QVSFS score, modified Rankin Scale score, congestive heart failure, 
hypertension, diabetes, previous stroke/TIA, NYHA Class, type of atrial fibrillation, time of 
onset of atrial fibrillation (summarized continuously in years as well as categorically with cut 
points of < 1 year or ≥ 1 year), left ventricular ejection fraction (LVEF), left atrial appendage 
anatomy shape and morphology, and use of antiplatelet and anticoagulation medications. 
 
Safety Endpoint 
The safety endpoint for the investigation is a composite of the following through 45 days follow-
up post implant:  
• 
All-cause mortality  
• 
Pericardial effusion requiring intervention  
• 
Device embolization (major)  
• 
Device thrombus  
• 
Ischemic stroke   
All safety events occur within the 45 days follow up visit window (up to Day 60) will be 
adjudicated by the Sponsor. The safety endpoints analysis will be based on Sponsor 
Assessment of Adverse Events data. No formal statistical inference will be made. The analysis 
will be descriptive for the ITT analysis set. The number and percentage of subjects 
experiencing any occurrence of the composite safety endpoint will be summarized assuming 
binomial distribution. The exact two-sided 95% confidence intervals will be constructed for 
the composite endpoint. A similar analytical approach will be performed for each component 
as well.  


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Clinical Performance Endpoints 
Descriptive clinical performance endpoints through 45 days (+15 days) follow-up will be 
summarized and presented as detailed below for both ITT and As-Treated analysis sets. No 
formal statistical inference will be made and the exact two-sided 95% confidence intervals will 
be constructed.    
x Device success  
Device success will be calculated as the proportion of subjects who have the device deployed 
and implanted in the correct position.  
x Technical Success 
The technical success rate will be calculated as the proportion of subjects who experience 
successful placement and release of the occluder in the LAA with LAA closure (defined as 
no leak > 5mm on color Doppler TEE) and discharge from the cardiac catheterization 
laboratory without the occurrence of device-related complications. 
x Procedural success 
The procedural success rate will be calculated as the proportion of subjects who experience 
successful placement and release of the occluder in the LAA with LAA closure (defined as 
no leak > 5mm on color Doppler TEE) and discharge from the cardiac catheterization 
laboratory without device-related complications and without  procedure-related 
complications other than minor device embolization (defined as device embolization that can 
be resolved by percutaneous technique without surgical intervention or damage to 
surrounding cardiovascular structures). 
 
 
Other Safety Analysis - Adverse events (AEs) 
Site reported adverse events (AEs) during the study will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). The number and percentage of subjects reporting adverse 
events will be summarized by MedDRA system organ class and preferred term for both ITT and 
As-Treated analysis sets. Separate summaries will also be provided for device-related AEs and 
procedure-related AEs. All serious adverse events (SAEs), device-related SAEs, and procedure-
related SAEs will also be summarized by system organ class and preferred term. All adverse 
events occurring through the 45-day (+15 days) follow-up will be summarized. 
 
Procedural Results 
The following characteristics of implant procedure, which are not study endpoints, will be 
summarized descriptively (n, mean, standard deviation, median, minimum, maximum, and 95% 
confidence interval, as appropriate) based on the As-Treated analysis set:    
x Device deployment duration, defined as the difference in minutes between time of removal of 
delivery sheath and time of transseptal puncture,  
x Procedural duration, defined as the difference in minutes between time of removal of 
delivery sheath and time of venous puncture, 
x Catheterization lab duration, defined as the difference in minutes between time patient left 
catheterization lab and time patient arrived in catheterization lab,   
x Anesthesia type, and  


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x Contrast volume 
 
 
Protocol Deviations  
All protocol deviations, including rationale for deviation, recorded during the study will be 
classified by the Sponsor as minor or major and will be listed.