Conditions: Post-Operative Atrial Fibrillation
Keywords: Left Atrial Appendage Anticoagulation CHA2DS2- VASc HASBLED
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 562
Healthy volunteers: no

Brief summary:
Patients without a documented history of Atrial Fibrillation (AF) and will undergo a valve or Coronary Artery Bypass Graft (CABG) procedure with direct visual access to the Left Atrial Appendage (LAA) will be eligible to participate. Patients enrolled will be randomized 2:1 (2 with AtriClip to 1 without AtriClip. Subjects who develop Post-operative Atrial Fibrillation (POAF) and receive the AtriClip will be followed for 365 days post index procedure.

Detailed description:
Patients without a documented history of AF but who present with a CHA2DS2- VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex category) of =\> 2 and HASBLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) of =\> 2 and will undergo a valve or CABG (structural heart) procedure with direct visual access to the LAA will be eligible to participate based upon the inclusion and exclusion criteria defined in this protocol. Up to 2000 patients will enroll at up to 40 sites and will be randomized 2:1 (2 with AtriClip to 1 without AtriClip. Subjects who not develop Post-operative Atrial Fibrillation (POAF) will be followed for 30 days for safety. Subjects who develop POAF and receive the AtriClip will be followed for 365 days post index procedure.

Arms:
arm 1: LAA Exclusion with AtriClip®: AtriClip® is used per label and is not experimental. arm 2: Medical Management: Standard of Care Oral Anticoagulation Therapy at the discretion of the Investigator.

Interventions: intervention 1: AtriClip® Gillinov-Cosgrove™ LAA Exclusion Systems intervention 2: Anticoagulation Therapy
Intervention descriptions: intervention 1: None intervention 2: Anticoagulation Therapy- Standard of Care at the discretion of the Investigator.

Protocol document:
Prot_SAP_000.pdf: 
 
 
Study Number: CP2015-2 
CONFIDENTIAL 
Page 1 of 48 
Record: Clinical Study Protocol 
 
 
Version date: 15Feb2017/ Rev: H 
 
AtriCure, Inc. 
7555 Innovation Way 
Mason, Ohio 45040 
 
 
ATLAS Study 
CLINICAL STUDY PROTOCOL 
Study Number:  CP2015-2 
 
Version date: 15Feb2017 / Rev: H 
 
 
Regulatory Classification: 
Check One: 
 IDE 
 Exempt 
 Post-Market Surveillance 
 Other        
  
Name of Finished Product(s): 
AtriClip® Gillinov-Cosgrove™ LAA Exclusion Systems   
[AtriClip FLEX (ACH2), AtriClip Long (LAA), or AtriClip 
Standard (ACH1)] 
 
Sponsor’s Medical Monitor: 
  
  
 
 
 
 
 
 
 
 
 
This study will be performed in compliance with the 21 CFR Parts 11 (Electronic Records; Electronic 
Signatures), 50 (Protection of Human Subjects), 56 (Institutional Review Boards), and 803 (Medical Device 
Reporting), International Conference on Harmonization (ICH) Guideline E6 for Good Clinical Practice 
(GCP); Declaration of Helsinki; Health Insurance Portability and Accountability Act (HIPAA) regulations; 
and Applicable state and local laws and regulations.  
 
CONFIDENTIALITY STATEMENT 
This document is a confidential communication of AtriCure, Inc.  The recipient agrees that no unpublished 
information contained herein will be published or disclosed without prior written approval of AtriCure, Inc. 
except that this document may be disclosed to appropriate IRB or Ethics Committees or duly authorized 
representatives of the U.S. Food and Drug Administration or other responsible regulatory authorities under 
the condition that they are requested to keep it confidential.  It should be held confidential and maintained 
in a secure location.  It should not be copied or made available for review by any unauthorized person or 
firm. 
 


 
 
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Version date: 15Feb2017/ Rev: H 
 
INVESTIGATOR SIGNATURE PAGE 
I have read, understood, and agree to: 
 
Ensure that the requirements for obtaining informed consent are met; 
 
Conduct the clinical study in accordance with this protocol, including applicable local/state laws 
and regulations; 
 
Adhere to the publication policy of AtriCure, as stated in the Clinical Study Agreement (CSA), for 
data collected during this study; 
 
Ensure that all associates, colleagues, and employees assisting in the conduct of the study are 
informed of their obligations in meeting the above commitments; 
 
Complete all Case Report Forms and study documentation and relevant imaging assessments (as 
required) promptly to the Sponsor, AtriCure, Inc., or its authorized representatives; 
I will ensure that the IRB review complies with governmental requirements and will be responsible for the 
initial and continuing review and approval of the clinical investigation.  I also agree to promptly report to 
the IRB all changes in the research activity and all unanticipated problems involving risks to human subjects 
or others.  Additionally, I will not make any changes in the research without sponsor and IRB approval of 
an amended protocol, except where necessary to eliminate apparent immediate hazards to human subjects. 
 
I agree to comply with all other requirements regarding the obligation of clinical investigators and all other 
pertinent requirements of the sponsor and government agencies. 
 
Investigator Signature:  I have read and understood the contents of this protocol.  I agree to follow and 
abide by the guidelines set forth in this document. 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 
Please scan, email or fax this signed off page to: 
 
 
 
 
 
  
 
PLEASE RETAIN THE ORIGINAL IN YOUR STUDY RECORDS. 
 




 
 
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CLINICAL STUDY PROTOCOL SYNOPSIS 
Protocol Name: 
ATLAS Study 
Protocol Number: 
CP2015-2 
Protocol Title: 
AtriClip® Left Atrial Appendage Exclusion Concomitant to Structural Heart 
Procedures (ATLAS) 
Name of Finished 
Product(s): 
AtriClip® Gillinov-Cosgrove® LAA Exclusion Systems [AtriClip FLEX (ACH2), 
AtriClip Long (LAA), or AtriClip Standard (ACH1)] 
Development Phase: 
Exempt, post market 
Study Design: 
This is a prospective, multicenter, randomized (2:1), unblinded pilot study. 
Indication of Device: 
All medical devices used during this study are cleared for commercial distribution and 
are to be used in accordance with approved product labeling. 
 
The AtriClip LAA Exclusion System is indicated for the occlusion of the left atrial 
appendage, under direct visualization, in conjunction with other open cardiac surgical 
procedures.  Direct visualization, in this context, requires that the surgeon is able to 
see the heart directly, without assistance from a camera, endoscope, etc., or any other 
viewing technology. This includes procedures performed by sternotomy (full or 
partial) as well as thoracotomy (single or multiple). 
Objective(s): 
The objective(s) of this trial are to:  
1. Compare impact of POAF among two randomized treatment arms; 
patients with POAF and surgical LAA closure (using AtriClip Gillinov-
Cosgrove LAA Exclusion Systems) versus patients with POAF and no 
surgical LAA closure. 
2. Evaluate Healthcare resource utilization [i.e. Hospital length of stay 
(LOS), emergency room and/or hospital re-admissions, and costs 
associated with specific adverse events that may be related to atrial 
fibrillation]. 
3. Evaluate long-term outcomes of LAA closure with AtriClip in patients at 
risk of developing POAF. 
Number of Subjects 
(Planned): 
Up to 2000 subjects will be randomized into this study.  
Sites: 
Up to 40 sites  
Patient Population: 
Patients without a documented history of AF but who present with a CHA2DS2- VASc 
of > 2 and HASBLED of > 2 and will undergo a valve or CABG (structural heart) 
procedure with direct visual access to the LAA will be eligible to participate based 
upon the inclusion and exclusion criteria defined in this protocol.    


 
 
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Inclusion Criteria: 
Patients satisfying the following criteria will be considered the screening population 
and will be eligible for participation: 
1. Age > 18 years male or female. 
2. Scheduled for any non-mechanical valve and/or CABG (structural heart) 
procedure where direct access to the LAA is expected. 
3. No documented preoperative AF.  
4. CHA2DS2-VASc score of > 2.  
5. HASBLED score of > 2. 
6. Acceptable surgical candidate, including use of general anesthesia. 
7. Willing and able to provide written informed consent. 
8.  Female patients must be of non-child bearing potential, or have a negative 
pregnancy test within 7 days prior to index procedure. 
9. Must be willing and able to return for scheduled follow-up visits. 
Exclusion Criteria: 
Patients satisfying the following criteria will not be eligible for participation: 
1. Redo cardiac surgery. 
2. Mechanical heart valve or other anticipated or current requirement for 
anticoagulation therapy during the post-operative (30 day) period.   
3. Hypercoagulability conditions that may confound the study.  
4. Ejection Fraction < 30. 
5. Left Atrium > 6 cm. 
6. Severe Diastolic Dysfunction.   
7. Requires anticoagulation therapy. 
8. Any known reason that the patient would be unable to tolerate post-surgical 
anticoagulants. 
9. Patient had a stroke/cerebrovascular accident (CVA) within previous 30 days 
prior to signing informed consent. 
10. Any medical condition or finding for which the Investigator used medical 
discretion to determine the subject should be excluded. 
11. Patient is currently or has participated in a clinical study in the last 30 days 
prior to signing informed consent.  Participation in survey clinical studies with 
no treatment is not an exclusion criterion. 
12. Patient has a condition that, in the opinion of the investigator, may jeopardize 
the patient’s well-being, the soundness of this clinical study, or could interfere 
with provision of informed consent, completion of tests, therapy, or follow-
up. 
Intra-Operative 
Exclusion Criteria 
 
Patients satisfying the following criteria will not be eligible for participation: 
1. Presence of thrombus in the left atrium or LAA. 
2. LAA tissue is deemed friable or has significant adhesions (as evaluated by the 
surgeon) near or on the LAA making AtriClip placement overly risky.  


 
 
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3. Left atrial appendage is outside the range of manufacturer’s recommendations 
- width < 29mm or > 50mm. 
4. Direct visualization access is not available for AtriClip placement. 
5. Any medical condition or finding for which the Investigator used medical 
discretion to determine the subject should be excluded. 
Study Duration:  
Anticipated subject duration will be approximately 365-days post index procedure (+/- 
30 days). 
Study Endpoints: 
 
Endpoints: 
1. Perioperative complications associated with AtriClip placement. [Defined as: 
stroke, major bleeding that requires re-operation and/or transfusion of > 2 U 
packed red blood cells (PRBC) within any 24-hour period during the first 2 
days’ post-index procedure, myocardial infarction (MI), or death.] 
2. Intraoperative successful exclusion of LAA. [Defined as no (0 mm) flow 
between LAA and LA and < 5 mm LAA remnant by intraoperative TEE with 
Doppler.] 
3. Composite event rates between the group of subjects diagnosed with POAF 
(AtriClip vs no AtriClip) through 365-days post index procedure and between 
the group of subjects not diagnosed with POAF (AtriClip vs no AtriClip) 
through 30 days’ post index procedure.  Events to be evaluated include: 
Thromboembolic & Hemorrhagic Events such as cerebrovascular accident 
(CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic 
stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding 
event. 
4. Composite event (listed above) rates through 365-days post index procedure 
for all AtriClip patients, regardless of whether the patient develops POAF. 
5. Healthcare resource utilization variance between groups as related to the 
composite events above.  [Specifically hospital length-of-stay (LOS), 
reoperation for bleeding, neurologic consults for stroke or TIA, emergency 
department (ED) visits, and hospital readmissions.] 
 
 
 
 
 


 
 
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TABLE OF CONTENTS 
 
Page 
INVESTIGATOR SIGNATURE PAGE ..................................................................................... 2 
SPONSOR SIGNATURES ....................................................................................................... 3 
CLINICAL STUDY PROTOCOL SYNOPSIS............................................................................ 4 
KEY PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS ........................................ 9 
SCHEDULE OF ASSESSMENTS .......................................................................................... 10 
ETHICS ............................................................................................................................... 11 
STUDY ADMINISTRATIVE STRUCTURE ........................................................................... 13 
1.0 
INTRODUCTION .................................................................................................. 13 
2.0 
STUDY OBJECTIVES............................................................................................ 16 
3.0 
STUDY ENDPOINTS ............................................................................................. 17 
4.0 
INVESTIGATIONAL PLAN................................................................................... 18 
4.1 
Overall Study and Design – Subject Disposition Diagram ......................................... 18 
4.2 
Selection of Study Population .................................................................................. 19 
4.2.1 
Recruitment ............................................................................................................ 19 
4.2.2 
Enrollment ............................................................................................................. 20 
4.2.3 
Inclusion Criteria .................................................................................................... 20 
4.2.4 
Exclusion Criteria ................................................................................................... 20 
4.2.5 
Intra-Operative Exclusion Criteria .......................................................................... 21 
4.2.6 
Removal of Subjects from Study .............................................................................. 21 
4.2.7 
Follow-up for Early Terminated Subjects ................................................................ 22 
5.0 
PROCEDURE ........................................................................................................ 22 
5.1 
General Description ................................................................................................ 22 
5.2 
Left Atrial Appendage (LAA) Exclusion (Index Procedure) ...................................... 23 
5.2.1 
No AtriClip arm ...................................................................................................... 23 
5.2.2 
AtriClip arm ........................................................................................................... 23 
5.3 
Post-Surgical Follow-up Anticoagulation Therapy.................................................... 24 
6.0 
IDENTITY OF STUDY DEVICES .......................................................................... 24 
6.1 
Product Accountability............................................................................................ 25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.0 
DATA MANAGEMENT AND INTEGRITY ............................................................ 29 
8.1 
Data Completion and Record Keeping ..................................................................... 29 
8.1.1 
Source Documents ................................................................................................... 29 
8.1.2 
Data Collection ....................................................................................................... 30 
8.1.3 
Data Correction ...................................................................................................... 31 
8.1.4 
Investigator Regulatory Binder ............................................................................... 31 


 
 
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8.1.5 
Study Correspondence ............................................................................................ 31 
8.1.6 
Data Privacy ........................................................................................................... 31 
8.1.7 
Record Retention, Inspection, and Custody .............................................................. 31 
8.1.8 
Medical Dictionary Coding ...................................................................................... 32 
8.1.9 
Data Quality Assurance ........................................................................................... 32 
8.1.10 
Investigator Training - Protocol Specific Training .................................................... 32 
8.1.11 
Monitoring ............................................................................................................. 32 
8.2 
Changes to Protocol, Protocol Deviations and Protocol Amendments ........................ 33 
8.2.1 
Changes to Protocol ................................................................................................ 33 
8.2.2 
Protocol Deviations ................................................................................................. 33 
8.2.3 
Protocol Amendments ............................................................................................. 34 
9.0 
STATISTICAL METHODS .................................................................................... 34 
9.1 
Clinical Study Objective .......................................................................................... 34 
9.2 
Study Endpoints ..................................................................................................... 34 
9.3 
Healthcare resource utilization ................................................................................ 35 
9.4 
Sample Size and Power............................................................................................ 35 
9.5 
Randomization ........................................................................................................ 36 
9.6 
Analysis Populations ............................................................................................... 36 
9.7 
Analysis of Study Endpoints .................................................................................... 36 
9.7.1 
Effectiveness and Health Economic Analysis ............................................................ 36 
9.7.2 
Safety Analysis ........................................................................................................ 37 
9.8 
Detailed Analysis Plan ............................................................................................. 37 
10.0 
Safety Monitoring ................................................................................................... 37 
10.1 
Adverse Events ....................................................................................................... 38 
10.1.1 
Definition of an Adverse Event ................................................................................ 38 
10.2 
Serious Adverse Events ........................................................................................... 38 
10.2.1 
Definition of a Serious Adverse Event ...................................................................... 38 
10.2.2 
Subject Death ......................................................................................................... 38 
10.2.3 
Adverse Event Classification ................................................................................... 38 
10.2.4 
Reporting Adverse and Serious Adverse Events ....................................................... 39 
11.0 
PRODUCT COMPLAINTS .................................................................................... 39 
11.1 
Medical Device Reporting and Product Complaints .................................................. 39 
11.2 
Source of Product Complaint Data .......................................................................... 40 
12.0 
STUDY OVERSIGHT ............................................................................................ 40 
12.1 
Independent Oversight ............................................................................................ 40 
13.0 
Appendices ............................................................................................................. 42 
APPENDIX 1 - EQ-5D-5L QUESTIONNAIRE ........................................................................ 42 
APPENDIX 2 - RISK/BENEFIT ASSESSMENT ...................................................................... 47 
 
 
 


 
 
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KEY PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS 
Acronyms/Abbreviation 
Terms 
AE 
Adverse Event 
AC 
Anticoagulant 
AF 
Atrial Fibrillation  
CPT 
Current Procedural Terminology  
CRA 
Clinical Research Associate 
CVA 
Cerebrovascular Accident 
CABG 
Coronary Artery Bypass Graft 
DRG 
Diagnosis-related Group 
eCRF 
Electronic Case Report Form 
ED 
Emergency Department 
EQ 
EuroQol  or European Quality of Life 
LOS 
Length of Stay 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal  
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
IFU 
Information for Use 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
LAA 
Left Atrial Appendage 
MDR 
Medical Device Reporting 
OAC 
Oral Anticoagulant 
PI 
Principal Investigator 
POAF 
Post-operative Atrial Fibrillation 
PET 
Polyethylene Terephthalate 
PE 
Physical Exam 
PRBC 
Packed Red Blood Cells 
SAE 
Serious Adverse Event 
SAS 
Science Analysis System 
SOC 
Standard of Care 
SOP 
Standard Operating Procedures 
PHI 
Protected Health Information 
STS 
Society of Thoracic Surgeons 
PROM 
Predicted Risk of Mortality 
QS 
Quality Systems 
TEE 
Transesophageal Echocardiogram (graphy) 
TIA 
Transient Ischemic Attack 
VAS 
Visual Analog Scale 




 
 
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ETHICS 
Institutional Review Board 
The study will be conducted in accordance with the ethical principles that have their origins in the 
Declaration of Helsinki. 
 
The study protocol, any protocol amendments, Informed Consent Form (ICF), any ICF amendments, and 
if applicable, any other written information provided to the subjects e.g., subject recruitment advertising, 
will be reviewed and approved by an or Institutional Review Board (IRB) prior to implementation of any 
procedures required solely for the purposes of this study.  Each Investigator must obtain IRB approval prior 
to consent of the first subject. 
 
Prior to site initiation, a signed copy of the IRB approval letter identifying the study and site is required to 
be submitted to the sponsor signifying study approval. 
 
Each Investigator must also maintain continuous IRB approval.  Documentation of approval and renewals 
must be provided to the Sponsor, and filed on site in the Investigator’s Regulatory Binder.  Additionally, 
amendments to the protocol will be submitted for review before implementation except when necessary to 
eliminate apparent immediate hazards to a subject.  IRB approval is required to implement protocol 
amendments or to resume a suspended clinical investigation. 
 
The occurrence of serious or unanticipated Adverse Events (AEs) during the study must be reported to the 
IRB. 
 
Applicable Regulations 
Regulations are to be followed as applicable including: 21 CFR Parts 11 (Electronic Records; Electronic 
Signatures), 50 (Protection of Human Subjects), 56 (Institutional Review Boards), and 803 (Medical Device 
Reporting); All surgical products used in this study are commercially available and will be used within 
current labeling and indications for use.  Consequently, this study is not investigational and is exempt from 
21CFR Part 54 (Financial Disclosure by Clinical Investigators) and 21CFR Part 812 (Investigational Device 
Exemptions) with the exception of 21CFR812.119 (Disqualification of a Clinical Investigator); 
International Conference on Harmonization (ICH) Guideline E6 for Good Clinical Practice (GCP); 
Declaration of Helsinki; Health Insurance Portability and Accountability Act (HIPAA) regulations; and 
Applicable state and local laws and regulations. 
 
Subject Information and Consent 
This informed consent process applies to participation in the study only (i.e., this process does not include 
consent required for structural heart surgery).  The surgeon will obtain the Institution’s standard informed 
consent for surgery.   
 
In compliance with FDA regulations, no subject shall be enrolled in an investigation without provision of 
adequate informed consent.  The Principal Investigator is responsible for ensuring that each subject enrolled 
in the study is given adequate informed consent.  Failure to obtain and properly document this process is in 
violation of the US Code of Federal Regulations, the Declaration of Helsinki, and this study protocol. 
The ICF must have the approval of the IRB.  While some institutions may request for modification of the 
ICF to satisfy specific institutional requirements, the use of a modified or unique ICF is permitted if it meets 
the requirement of 21 CFR Part 50 and is approved by the Sponsor.  Informed consent of all subjects must 
be documented on an ICF in the primary language of the subject.  All translated consent forms need IRB 


 
 
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approval.  Eligible U.S. subjects should also sign the Health Insurance Portability & Accountability Act 
form, if not combined with the ICF. 
 
The Investigator or designee shall carry out the Informed Consent process on those subjects meeting the 
eligibility criteria.  The informed consent process involves the following: giving a subject adequate 
information concerning the study, providing adequate opportunity (time) for the subject to consider all 
available options, responding to the subject’s questions, ensuring that the subject has comprehended this 
information and finally, obtaining the subject’s consent to participate in this study.  All subjects in this 
study should be completely informed about the purpose, risks, benefits, and other pertinent details of this 
study.  The informed consent process is careful to avoid the perception of any coercion or undue influence 
on, or inducement of, the subject to participate, and does not waive or appear to waive the subject's legal 
rights.  The ICF is presented in native, non-technical language that is understandable to the subject.  The 
ICF ensures important new information is provided to new and existing subjects throughout the clinical 
investigation.  
 
The Informed Consent process is finalized by completion of the ICF.  Following the explanation of the 
study intent, the Investigator or designee shall offer to answer any of the subject’s questions.  If the subject 
then agrees to participate, his or her willingness must be documented via signatures of the ICF. 
 
This document must be signed and dated by the subject prior to any study related procedures or enrollment.  
No dates should be pre-populated, or completed by someone other than the person providing the signature.  
The subject will be provided a copy of the signed informed consent document. 
 
During a subject's participation in the study, the subject will sign and date any amendment(s) to the 
informed consent document and a copy of the signed document will be provided to them. 
 


 
 
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STUDY ADMINISTRATIVE STRUCTURE 
This study is sponsored by AtriCure, Inc. and will be conducted in the US, under a single protocol approved 
by an IRB for each site prior to implementation at the study site.   
 
The Principal Investigators (PI) at the study sites are board-certified cardiothoracic surgeons qualified by 
education, experience and training to assume responsibility for the conduct of this study.   
 
An Electronic Data Capture (EDC) system will be utilized by study site personnel to transfer study data 
from source records (medical records and/or source document worksheets) onto common electronic case 
report forms (eCRFs). The EDC system is a web-based, secure electronic software and is compliant with 
national and international GCP data protection/data privacy and electronic record/electronic signature (e.g., 
21 CFR Part 11) regulatory requirements. 
 
Serious Adverse Events (SAEs) and product quality problems (for products used during the index 
procedure), including potential and actual product use errors suspected to be associated with the use of a 
Food and Drug Administration (FDA) regulated drug, biologic, medical device or dietary supplement used 
during the course of this study will be reported by the PI to applicable authorities including the: 1) Sponsor 
(AtriCure); 2) IRB; 3) respective manufacturer(s); and/or 4) FDA via MedWatch Online Voluntary 
Reporting Process or Medical Device Reporting (MDR) as appropriate. 
 
1.0 INTRODUCTION 
The traditional standard of care for patients with POAF is oral anticoagulation (OAC) therapy as 
prophylaxis of thromboembolic events.   Recent clinical literature from Gallego et al (Gallego, Relation of 
the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and mortatlity in 
anticoagulated patients with atrial fibrillation., 2012) suggests that the risk of major bleeding exceeds the 
risk of thromboembolic events in AF patients at a HAS-BLED score of > 3.  Gallego et al. also reported 
that patients with low CHADS score (e.g., 0 – 1) have lower major bleeding risk than those patients with 
CHADS >=2. Although Gallego et al. focused on HAS-BLED > 3, the study recruited 800 (83%) and 740 
(77%) patients with HASBLED>=2 and CHADS>=2, respectively. In fact, 472 (49%) of the patients 
recruited in the study had a HASBLED score of 2. Other peer-reviewed research from Tung et al (Tung, 
2015)  identifies that the highest risk for major bleeding occurs within the first 30 days of initiating OACs.  
Therefore, this study focuses entirely on a subset of patients that are vulnerable to both initiation of OACs 
as well overalls risks of OAC therapy.   
Literature and current practice reinforce the fact that this subset of high risk AF patients are not routinely 
being started on OACs.  In a recent meta-analysis from Lip et al (Lip, Underuse of Oral Anticoagulation in 
AF, A systematic review, 2010), looking at high risk patients (defined as those with a CHADS > 2) only 
39% of AF patients in the U.S. were on OAC therapy. 
This study intends to monitor a subset of patients with specific risk factors where both the risk of 
thromboembolic events and major bleeding intersect resulting in significant clinical equipoise both in 
literature and in current “real life” clinical practice. 
Use of the AtriClip device may eliminate the nidus for AF-related thrombi originating in the Left Atrial 
Appendage.   While not the focus of this study it is believed that this may contribute favorably to the primary 
composite endpoint of major bleeding, stroke and TIA.  This research may begin to better inform clinical 
practice for those treating these high risk patients and continue to ascertain the risk of major bleeding vis-


 
 
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à-vis the risk of thromboembolic events in AF patients at a HAS-BLED score >=2. 
 
Need for Treatment in ATLAS 
Postoperative atrial fibrillation (POAF) and related stroke/TIAs impact mortality, morbidity and QOL for 
patients undergoing structural heart disease procedures.    Oral anticoagulation (OAC) therapy is typically 
indicated for stroke prophylaxis in patients with POAF.   Risk factors identified by HAS-BLED scoring of 
>2 present an increased risk for bleeding creating clinical equipoise between the risk/benefit of stroke/TIA 
risk and clinically significant bleeding.  Initiation of anticoagulation therapy for POAF patients is reported 
to increase hospital length of stay by 2-5 days.  Exclusion of the Left Atrial Appendage in patients with 
Atrial Fibrillation is believed to reduce the potential for thrombus formation within the Left Atrial 
Appendage which is the site of a majority (90%) of all thrombi identified in patients examined with an AF 
related stroke (Blackshear, 1996).   
 
The 2006 ACC/AHA Guidelines recommended removal of the Left Atrial Appendage to reduce the 
potential for stroke during cardiac (structural heart) procedures for any patient with risk factors for stroke 
or postoperative atrial fibrillation when it can be done without adding risk to the primary operation.  Due 
to a lack of randomized controlled trials showing a reduction in stroke in patients with their LAA removed, 
prophylactic LAA exclusion is not routinely performed.    
 
Postoperative Atrial Fibrillation (POAF) incidence is reported to be between 30-50% depending upon 
patient demographics, procedural variables and intensity of rhythm monitoring.  Historically, POAF was 
considered to be self-terminating and confined to the postoperative hospital stay.  A recent paper from 
Joung et al (Joung, 2014), published in the American Heart Journal suggests that new-onset POAF is 
associated with a five times higher risk of future long term AF than matched patients as well as a three 
times higher mortality. 
 
In addition, POAF has been shown to have a strong association with perioperative stroke/TIA, increased 
length of hospital stay, decreased QOL and increased mortality.    A 2014 Annals paper from LaPar et al. 
(LaPar, 2014) evaluated ~50,000 patients undergoing structural heart procedures.   For patients with POAF, 
stroke incidence was 2.6% vs. 1.1% vs. in non-POAF patients at 30-day follow-up, increased ICU time of 
48 hours longer, increased hospital LOS of 3 days, and a 25% higher 30-day readmission rate.  The total 
incremental hospital costs associated with POAF was determined to be ~$9000.  Yusuf et al (Yusuf, 2014), 
reviewed data on over 100,000 cardiac surgery patients in Ontario, Canada over 10 years to examine the 
rate and predictors of early and late stroke.   New-onset POAF was one of the strongest predictors of early 
stroke with an Odd Ratio of 1.5.  Age, history of TIA/stroke, PAD, CHF, and valve surgery were also 
predictors.  The data also showed that increasing CHADS2 scores predicted increased risk of stroke or 
death among patients with AF vs. those without AF.  
 
An October 2013 JTCVS paper by Chua et al. (Chua, 2013) validated the CHADS2 scoring system as 
highly predictive for risk of POAF in CABG patients without a history of preoperative AF.  Specifically, 
patients with CHADS2 scores of >2 had a 36% risk of POAF (range of 27-100%).   
 
A more refined scoring system, the CHA2DS2-VASc score, has been validated to define the risk of stroke 
in AF patients in numerous papers.  A CHA2DS2-VASc of >2 estimates an annual risk of stroke of between 
4.5-18.2% in patients with AF.    


 
 
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Risks Associated with Initiating Anticoagulation Therapy 
Typical hospital protocol for stroke prophylaxis in patients with POAF is the initiation of anticoagulation 
therapy (AC) within 24 hours of diagnosis.   A 2009 Annals paper from (Kasirajan, 2009) et al. identified 
isolated POAF as adding 2.2 days to hospital length of stay presumably associated with normalization of 
anticoagulation therapy within therapeutic range.   The HASBLED scoring system has been validated in 
multiple studies to identify the risk of clinically significant bleeding.    HASBLED scores of >2 have an 
associated risk of bleeding of between 4.1-19.6% annually.     
A recent Circulation paper from Roldan (Rolden, 2013) et.al defined a strong correlation between bleeding 
and adverse cardiovascular events using the HASBLED scoring system.  They concluded that crude 
bleeding rates exceeded thrombotic events at HAS-BLED scores of >3.    
Azoulay (Azoulay, 2014) et al. reported that the initiation of Warfarin was associated with a 1.71 relative 
risk of AF-related stroke within the first 30 days suggesting a significant   transient hypercoagulable state 
at the start of treatment.  In a report from Ruiz-Nodar at al. (Ruiz-Nodar, 2012), they reported a major 
bleeding rate of 11.8% at one year in patients with a HAS-BLED score of > 3 in their series of patients 
undergoing coronary artery stenting procedures.    
Clinical equipoise exists regarding the initiation of anticoagulation therapy in patients with a significant 
risk of AF-related stroke as well as significant risk of bleeding related to OAC therapy. 
Evidence suggests that the risk of major bleeding exceeds the risk of thromboembolic events in AF patients 
with a HAS-BLED > 3 (Gallego, Relation of the HAS-BLED bleeding risk score to major bleeding, 
cardiovascular events, and mortatlity in anticoagulated patients with atrial fibrillation., 2012).  Other peer-
reviewed research identifies that the highest risk for major bleeding and ischemic stroke occurs within the 
first 30 days of initiating OACs (Tung, 2015) (Gomes, 2013).  This study focuses on patients that are 
vulnerable to both risks identified by two well established scoring strata (CHADS and HASBLED) as well 
as significantly increased risks for patients initiating OAC therapy for a complication that will largely self-
terminate within 30 days of onset.   
 
Hypothesis Testing of LAA Closure in POAF   
Dr. Cox (Cox, 1993) describes a large series of patients where a Maze procedure was performed including 
LAA surgical exclusion.   At 90 day follow up only 2/306 (.6%) patients experienced a stroke/TIA although 
37% had POAF in spite of a majority not receiving postoperative anticoagulation therapy.    
In a 2013 paper from Kim et al. (Kim, 2013); describes a series of 631 matched patients with/without LAA 
exclusion concomitant to cardiac (structural heart) procedures.  Using propensity analysis, 260 subjects 
with postoperative AF were analyzed evaluating incidence of stroke/TIA.   In the LAA exclusion group 
there were zero (0%) stroke/TIAs in spite of a majority of these patients not receiving anticoagulation 
therapy.  Conversely there were 6% stroke/TIAs in the no LAA exclusion group (p = 0.003).  A second 
article (Viles-Gonzalez, 2012) et al.; showed a ~77% reduction in expected stroke rate in AF patients with 
a >2 CHADS2 score undergoing a percutaneous LAA closure device and contraindications to Warfarin.    
 
These papers provide preliminary evidence that LAA exclusion may potentially reduce stroke/TIA 
complications associated with POAF and that its application to patients with a significant risk of bleeding 
on OACs may have a secondary benefit in reducing bleeding complications. 
 


 
 
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Published data suggests a risk of POAF in valve and CABG patients of between 32-66% (Creswell, 1993).  
The risk of a perioperative CVA event in the POAF patient population of up to 6% (Lee, 2014) and a 2-
year rate of stroke or death of 21.2% for those with a CHADS2 score of greater than 3 (Whitlock, 2014).    
The decision to forgo placing an AtriClip in the treatment arm will be at the surgeon’s perioperative 
discretion due to overall risk of the procedure or risk associated with accessing the LAA and documented 
with a rationale on the Case Report Form (for example, excessive adhesions in the vicinity of the LAA.). 
 
The Role of ATLAS in Critically Ill Patients 
Anticoagulation therapy is considered the standard of care for stroke prophylaxis in patients with Atrial 
Fibrillation but in patients with risk factors for bleeding the risk/benefit of medical management is 
elucidated.  This study will evaluate a medical management arm vs. mechanical exclusion of the left 
appendage via an implantable device.  It is believed that the left appendage is the source for a predominant 
number of stroke causing emboli in AF patients.  It is postulated that patients receiving anticoagulation will 
incur a longer length of stay due to the initiation and normalization and maintenance of therapeutic levels 
associated with therapy.  This will also be evaluated in the study.   
 
2.0 STUDY OBJECTIVES 
 
The objective(s) of this trial are to:  
1. Compare impact of POAF among two randomized treatment arms; patients with POAF and 
surgical LAA closure (using AtriClip Gillinov-Cosgrove LAA Exclusion Systems) versus 
patients with POAF and no surgical LAA closure. 
2. Evaluate Healthcare resource utilization [i.e. Hospital length of stay (LOS), emergency room 
and/or hospital re-admissions, and costs associated with specific adverse events that may be 
related to atrial fibrillation]. 
3. Evaluate long-term outcomes of LAA closure with AtriClip in patients at risk of developing 
POAF. 
 
 


 
 
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3.0 STUDY ENDPOINTS 
 
Study Endpoints are as follows. 
1. Perioperative complications associated with AtriClip placement. [Defined as: stroke, major 
bleeding that requires re-operation and/or transfusion of > 2 U packed red blood cells (PRBC) 
within any 24-hour period during the first 2 days’ post-index procedure, myocardial infarction (MI), 
or death.] 
2. Intraoperative successful exclusion of LAA. [Defined as no (0 mm) flow between LAA and LA 
and < 5 mm LAA remnant by intraoperative TEE with Doppler.] 
3. Composite event rates between the group of subjects diagnosed with POAF (AtriClip vs no 
AtriClip) through 365 days’ post index procedure and between the group of subjects not diagnosed 
with POAF (AtriClip vs no AtriClip) through 30 days’ post index procedure.  Events to be evaluated 
include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), 
transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, 
gastrointestinal (GI) bleeds, or other major bleeding event. 
4. Composite event rates through 365-days post index procedure for all AtriClip patients, regardless 
of whether the patient develops POAF. 
5. Healthcare resource utilization variance between groups as related to the composite events above.  
[Specifically hospital length-of-stay (LOS), reoperation for bleeding, neurologic consults for stroke 
or TIA, emergency department (ED) visits, and hospital readmissions.] 
 


 
 
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4.0 INVESTIGATIONAL PLAN 
 
4.1 
Overall Study and Design – Subject Disposition Diagram 
 


 
 
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Overall Study and Design – Description 
All patients who undergo a valve or CABG (structural heart) procedure with direct visual access to the 
LAA will be eligible to participate based upon consent and evaluation of the inclusion and exclusion criteria 
defined in this protocol.    
 
The target patient population includes patients at risk of POAF based on the CHA2DS2-VASc and 
HASBLED scoring.  
 
Patient must meet all inclusion/exclusion criteria (including intra-operative exclusion criteria) before 
enrollment or randomization.     
 
During the planned structural heart procedure, the intra-operative exclusion criteria will be assessed.  If any 
intra-operative exclusion criteria are met, the subject will be a screen fail and will not be enrolled or 
randomized.     
 
To execute randomization, at the time of enrollment, subjects will be assigned a sequential identification 
number at each site and a corresponding sealed envelope which will be opened in the operating room to 
reveal the treatment group.  Subjects will be randomized 2:1 (2 with AtriClip® to 1 with no AtriClip®).  
Randomization sequences will be generated by the AtriCure Statistician and will be stratified by site.  The 
subject population will be randomized using a blocking scheme for each surgeon to ensure equal and 
balanced treatment group allocations and to avoid bias with respect to known or unknown subject variables 
that could affect the outcome of this study. 
 
Post-index procedure, all subjects will be monitored per the hospital standard of care processes for POAF.   
 
Four (4) treatment arms result: 
 
Surgery with AtriClip (POAF diagnosed / Institution SoC anticoagulation therapy) 
 
Surgery with AtriClip (No POAF) 
 
Surgery with no AtriClip (POAF diagnosed / Institution SoC anticoagulation therapy) 
 
Surgery with no AtriClip (No POAF) 
 
Subjects will be assessed for AEs related to the placement of the AtriClip and will be instructed to notify 
the PI of any AEs that occur during the study.  All subjects that develop POAF during the hospital stay will 
be followed for approximately 1 year (365 days) post index procedure. In addition, all the subjects in the 
AtriClip group that do not develop POAF will also be followed for 365-days post index procedure. 
4.2 
Selection of Study Population 
4.2.1 
Recruitment 
All patients who meet the inclusion criteria will be tracked on a Screening Log.  Patients will be provided 
the IRB approved ICF and will have the opportunity to read, understand, and have their questions answered 
prior to signing the ICF.  If the patient agrees to participate in the study and signs consent, the ICF will be 
completed.  The subject must sign and date the ICF prior to any study-specific procedures being performed.  
The person reviewing the ICF with the subject will also sign and date the ICF.  The subject will be given a 
copy of the signed ICF to keep. 
 


 
 
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 All subjects who sign the ICF will be documented on a paper Screening and Enrollment Log.  Only subjects 
enrolled into the study will be entered into the EDC. 
4.2.2 
Enrollment 
Patients are considered enrolled in the study once they have met Inclusion/Exclusion (including intra-
operative exclusion) criteria and are randomized. 
4.2.3 
Inclusion Criteria 
Patients satisfying the following criteria will be considered the screening population and will be eligible for 
participation: 
1. Age > 18 years male or female. 
2. Scheduled for any non-mechanical valve and/or CABG (structural heart) procedure where direct 
access to the LAA is expected. 
3. No documented preoperative AF.  
4. CHA2DS2-VASc score of > 2  
5. HASBLED score of > 2 
6. Acceptable surgical candidate, including use of general anesthesia. 
7. Willing and able to provide written informed consent. 
8. Female patients must be of non-child bearing potential, or have a negative pregnancy test within 7 
days prior to index procedure 
9. Willing and able to return for scheduled follow-up visits. 
4.2.4 
Exclusion Criteria 
Patients satisfying the following criteria will not be eligible for participation: 
1. Redo cardiac surgery. 
2. Mechanical heart valve or other anticipated or current requirement for anticoagulation therapy 
during the post-operative (30 day) period.   
3. Hypercoagulability conditions that may confound the study.  
4. Ejection Fraction < 30. 
5. Left Atrium > 6 cm. 
6. Severe Diastolic Dysfunction.   
7. Requires anticoagulation therapy. 
8. Any known reason that the patient would be unable to tolerate post-surgical anticoagulation 
therapy. 
9. Patient had a stroke/cerebrovascular accident (CVA) within previous 30 days prior to signing 
informed consent. 
10. Any medical condition or finding for which the Investigator used medical discretion to determine 
the subject should be excluded. 


 
 
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11. Patient is currently or has participated in a clinical study in the last 30 days prior to signing informed 
consent.  Participation in survey clinical studies with no treatment is not an exclusion criterion. 
12. Patient has a condition that, in the opinion of the investigator, may jeopardize the patient’s well-
being, the soundness of this clinical study, or could interfere with provision of informed consent, 
completion of tests, therapy, or follow-up. 
4.2.5 
Intra-Operative Exclusion Criteria 
Prior to randomization subjects must also meet the following intra-operative criteria.  (If criteria are not 
met, the subject will be a screen fail and will not be eligible to be randomized into the study.)  
1. Presence of thrombus in the left atrium or LAA. 
2. LAA tissue is deemed friable or has significant adhesions (as evaluated by the surgeon) near or on 
the LAA making AtriClip placement overly risky.  
3. Left atrial appendage is outside the range of manufacturer’s recommendations - width < 29mm or 
> 50mm. 
4. Direct visualization access is not available for AtriClip placement. 
5. Any medical condition or finding for which the Investigator used medical discretion to determine 
the subject should be excluded.  Any medical condition or finding for which the Investigator used 
medical discretion to determine the subject should be excluded. 
4.2.6 
Removal of Subjects from Study 
In accordance with the Declaration of Helsinki and the Code of Federal Regulations, a subject has the right 
to withdraw from the study at any time for any reason without prejudice to his/her future medical care by 
the physician or the institution.  Should a subject (or subject’s legally authorized guardian/representative) 
decide to withdraw; all efforts will be made to collect and report the final visit observations as thoroughly 
and timely as possible.  Subjects who withdraw from the study will not be replaced. 
The primary reason for early termination and the date of termination will be recorded in the electronic case 
report form.  Reasons may include: 
Investigator Decision 
If the subject experiences an adverse event and the Principal Investigator or Medical Monitor 
believes it is in their best interest to discontinue participation in the study, they will be withdrawn 
from the study. 
Lost to Follow-up 
When contact with the subject has been lost without completing the final visit assessment, and 
every attempt to contact has failed, the subject will be considered lost to follow-up.  Final 
documentation regarding all attempts to contact the subject requesting their return for the final 
visit should be documented. 
Withdrawal of Consent 
The subject withdraws consent for participation in the study.  Any method of contact with the 
subject in which they state they no longer want to participate in the study specific activities 


 
 
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constitutes withdrawal of consent.  When possible the reason for withdrawal will be documented. 
Site Termination or Study Termination 
A site or study may be terminated.  When this occurs all subjects at the site will be withdrawn and 
documented as early termination.  Reasons for site or study termination may include, but are not 
limited to the following: 
 
Administrative Concerns (e.g., inadequate subject enrollment, Investigator/institution non-
compliance, change of business strategy, etc.); 
 
Safety Issues, including those due to non-compliance, which substantially affect the risk to 
benefit ratio of the study subjects at a site or for the study as a whole; 
 
Regulatory Body Mandate(s) 
 
Other (which may include): 
 
Protocol deviation, noncompliance or violation 
 
Sponsor recommendation 
 
Device/index procedure failure 
 
Death 
4.2.7 
Follow-up for Early Terminated Subjects 
In the event that a subject is eligible, enrolled, and randomized into the study but must early terminate either 
prior to the index procedure (AtriClip placement) or even after the index procedure; the subject will be 
followed for 30 days for safety purposes.   
5.0 PROCEDURE 
5.1 
General Description 
Individual centers and investigators will be selected based upon their expertise in the targeted structural 
heart disease procedures (non-mechanical Mitral Valve Repair/Replacement, Aortic Valve 
Repair/Replacement, and Coronary Artery By-Pass procedures) as well as proficiency in AtriClip 
placement. 
The term index procedure refers only to the placement/non-placement of the AtriClip (dependent on 
randomization). All procedures leading up to and after the placement of the AtriClip are considered part 
of the structural heart procedure and are to be conducted under the discretion of the surgeon in accordance 
to the hospital’s standard of care. 
Transesophageal Echocardiography (TEE) with Doppler 
Transesophageal echocardiography (TEE) with Doppler must be performed prior to any epicardial surgical 
intervention. The purpose of the TEE with Doppler is to assess for presence of thrombus.  If a thrombus is 
present in the left atrium or LAA, the subject will not be enrolled or randomized into the study and no 
AtriClip will be placed.   
 
The AtriClip LAA Exclusion System must be used only by properly trained and qualified medical personnel 
in accordance with the Instructions for Use (IFU).  Failure to properly follow instructions may result in 
improper functioning of the device. 


 
 
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If the subject continues to meet all study eligibility criteria (including intra-operative exclusion criteria), 
they will be enrolled and randomized.  If the subject is randomized to the group to receive the AtriClip 
LAA Exclusion System placement, the following steps are performed: 
 
Note: A recommended surgical technique is presented below. It is recognized that individual patient 
anatomic variation, surgical conditions, or surgeon preference may necessitate modifications to the 
outlined procedures.  Regardless, surgeons must adhere to the AtriClip LAA Exclusion System sizing 
criteria, device selection, and device use instructions as outlined in the IFU. 
5.2 
Left Atrial Appendage (LAA) Exclusion (Index Procedure) 
5.2.1 
No AtriClip arm 
If the subject is randomized to the no AtriClip arm, the left atrial appendage should be left intact with no 
management. 
5.2.2 
AtriClip arm 
If the subject is randomized to the AtriClip arm, the left atrial appendage should be managed using the 
AtriClip LAA Exclusion System.  The left atrial appendage is typically accessible and exclusion of the Left 
Appendage by the AtriClip is believed to introduce little time or risk to the primary operation.   In the event 
that, the surgeon deems that the AtriClip device is not able to be utilized for left atrial appendage after 
randomization, because of anatomical limitations or that it is not feasible or safe to address the LAA, the 
appendage may be left intact.  In the event that a subject is randomized but must early terminate before or 
after the index procedure; the subject will be followed for 30 days for safety purposes.   
General Placement of the AtriClip: 
Refer to the IFU for proper AtriClip size selection as well as AtriClip positioning and deployment 
instructions.  Using a Kitner or forceps, the open AtriClip® device is passed over the tip of the left atrial 
appendage.  The tip of the appendage is gently teased into the AtriClip.  The device is then lowered into the 
base of the appendage.  Awareness of the proximity of the circumflex artery and its relationship to the 
targeted location at the base of the left atrial appendage is critical. The AtriClip is applied on the left atrial 
appendage ensuring the alignment and complete closure of the LAA.   
 
 
  
 
 
   
Post Index Procedure - Subject Assessment  
To assess the subject status with regard to potential bleeding, assessments of hemoglobin and hematocrit 
shall be performed post index procedure per the hospital’s standard of care. 
 
 


 
 
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5.3 
Post-Surgical Follow-up Anticoagulation Therapy 
Subjects who are diagnosed with POAF during their postoperative course should be treated per the 
institution’s standard of care and may include anticoagulation therapy.  
The decision to administer anticoagulation therapy in the post-operative/follow-up setting is at the 
discretion of the Investigator/Institution taking into consideration, the subject’s ability to safely initiate and 
sustain anticoagulation therapy.   
The anticoagulants that may be used in medical management may include: 
 
Acenocoumarol 
 
Acetylsalicylic acid 
 
Apixaban 
 
Dabigatran 
 
Edoxaban 
 
Heparin 
 
Nadroparin 
 
Rivaroxiban 
 
Warfarin 
 
Other (to be specified)  
These are the anticoagulants that may be utilized in medical management.  The decision of which 
anticoagulant to use (if any) is left to the discretion of the Investigator. 
6.0 IDENTITY OF STUDY DEVICES 
The devices utilized for the study include: 
AtriClip Gillinov-Cosgrove LAA Exclusion Systems which are indicated for the occlusion of the left atrial 
appendage, under direct visualization, in conjunction with other open cardiac surgical procedures.  Direct 
visualization, in this context, requires that the surgeon is able to see the heart directly, without assistance 
from a camera, endoscope, etc., or any other viewing technology. This includes procedures performed by 
sternotomy (full or partial) as well as thoracotomy (single or multiple). 
 
All medical devices used during this study are cleared for commercial distribution and are to be used in 
accordance with approved product labeling. 
 
Device Description 
When closed, the AtriClip applies uniform pressure over the length of the AtriClip to ensure consistent, 
reproducible, and secure exclusion of the LAA.  The AtriClip is available in the following lengths to 
accommodate different sizes of LAA: 35 mm, 40 mm, 45 mm, and 50 mm. 
The AtriClip was cleared under K093679.  The frame assembly of the implantable AtriClip consists of two 
Nitinol (nickel titanium) springs connecting two opposing titanium tubes (core), which are covered with a 
Polyurethane elastomer.  This assembly is covered with a knit braided polyester fabric, composed entirely 
of Polyethylene terephthalate (PET).  The Nitinol springs are biased toward the closed position allowing 
the device to close in the absence of opposing forces (Figure 1).  When closed, the AtriClip applies uniform 
pressure over the length of the AtriClip to ensure consistent, reproducible, and secure exclusion of the LAA. 


 
 
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Figure 1 
 
6.1 
Product Accountability 
The investigator will maintain control over and keep a complete device inventory record for all study 
devices received from AtriCure.  All shipping record receipts received with the study devices will be 
maintained.  All study devices that are used during each procedure will be documented. 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


 
 
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8.0 
DATA MANAGEMENT AND INTEGRITY 
8.1 
Data Completion and Record Keeping 
8.1.1 
Source Documents 
Source documents are documents on which information regarding subjects are first recorded. PI subject 
files or hospital records generally are the basis of source document information. This may include but is 
not limited to, original subject files, hospital/clinic records, original recordings/tracing, and digital images 
from automated instruments, X-ray films, and laboratory results. 
 
Source documents must be retained by the PI as part of the subject’s permanent medical record. The 
information in the source documents is used to complete the eCRFs. All information captured on the eCRFs 
should be completely and accurately supported in source documentation.  Study Monitors will verify data 
reported on eCRFs with site source documents.  Any additional information relevant to the study should be 
included in the source documents. In particular, any deviations from the study protocol or procedures should 
be recorded in the source documents. The PI will retain originals of all source documents, subject consent 
forms, and study data. 
 
 


 
 
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8.1.2 
Data Collection 
An EDC system will be utilized by study site personnel to transfer study data from source records (medical 
records and/or source document worksheets) onto common eCRFs. This system is a web-based, secure 
electronic software application This system is designed, developed, and maintained in a manner that is 
compliant with national and international GCP data protection/data privacy and electronic record/electronic 
signature (e.g., 21 CFR Part 11) regulatory requirements.  The platform software has been validated in 
accordance with 21 CFR Part 11, European Commission’s Directive on Data Protection and US Safe Harbor 
Certification.  Prior to being released for data entry, validation of the study level components (i.e. data entry 
screens, associated edit checks and work flow) will be conducted in accordance with approved user 
acceptance testing procedures. Access to this system will be controlled so that only authorized users will 
have the ability to enter into the system.  The system is considered a closed system according to 21 CFR 
Part 11 Electronic Records; Electronic Signatures. 
The EDC system will be used to facilitate the collection of all study data at the site. Designated site 
personnel will be responsible for entering subject data into the EDC system. All external and Sponsor 
internal users will be trained on the EDC application at a level dependent on their planned function.  
An EDC digital User Manual will be available under the help menu within the EDC website to assist in the 
collection and entry of source data into the electronic casebook. 
Investigative study sites will be asked to enter subject data into the eCRFs no later than 2 weeks from the 
time the subject was seen for their scheduled study visit. 
Detailed description of the eCRF components are included in the eCRF Completion Instructions. These 
will be provided to the Investigators prior to initiating subject enrollment.  The respective eCRFs must be 
fully completed for each subject and signed electronically. 
Data collected during the clinical investigation for each subject will be maintained as accurately and 
completely as possible with entries into an electronic data capture system provided by AtriCure.  The 
personal data recorded on all documents, including copy documents, and within the system will be regarded 
as confidential.  The Investigator will be responsible for the timing, completeness and accuracy of the 
details entered within the electronic data capture system.  All data entered in the database must have source 
documents in the subject’s medical records. 
Data will be entered into the electronic data capture system by members of the Investigational team who 
have received training in the use of the system.  The system will generate data queries at the point of data 
entry based on validation checks defined by AtriCure. Such validation checks will primarily be focused on 
validation of key variables including selected subject demographics, appropriate value ranges and date 
checks. Resolution of the queries will be the responsibility of the Clinical Investigator and investigation 
team members.  Following completion of all data queries on each eCRF, the Clinical Investigator will be 
responsible for reviewing and confirming agreement to the data within the system. 
The Investigator must record the subject’s participation in this clinical investigation in the subject’s hospital 
notes.  In addition, the Investigator must keep a separate list of all subjects entered into this clinical 
investigation showing each subject’s name, date of birth and assigned subject number (for identification 
purposes).  A subject Identification Log will be provided in the Investigator’s File for this purpose. 
 
 


 
 
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8.1.3 
Data Correction 
Corrections to eCRFs will be prompted via automated electronic edit checks and queries manually created 
by reviewers.  The corrections and the individual making the correction(s) to the eCRF will be within EDC. 
8.1.4 
Investigator Regulatory Binder 
Each Investigator must maintain an accurate, complete, and current copy of the Investigator Regulatory 
Binder.  Upon receipt of copies of changes or revision updates to the Binder from the Sponsor, the 
Investigator will add the updated document to the Regulatory Binder.  If an Investigator holds multiple 
copies of the Regulatory Binder, then all copies must be updated with the current revisions. 
8.1.5 
Study Correspondence 
Each Investigator and all personnel from the investigational site will maintain records of all correspondence, 
electronic, written, and verbal, relating to any aspect of the clinical investigation.  The records are 
maintained in the Investigator Regulatory Binder consisting of, but not limited to correspondence with other 
participating clinical investigators, the reviewing IRB, and the Sponsor.  The CRA will examine the 
contents of the correspondence. 
8.1.6 
Data Privacy 
Subjects will be made aware that their personal data will be collected and processed in accordance with 
data protection legislation including the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Subjects will be asked to sign an Authorization for Release of Personal Health Information (PHI) 
for the purpose of this investigation. This authorization may be combined with the ICF depending on local 
IRB preference.  Results from the Clinical Investigation may be published. However, subject confidentiality 
will be maintained at all times and it will not be possible to identify individual subjects from any data 
presented.  
8.1.7 
Record Retention, Inspection, and Custody 
The PI must maintain all documentation related to the study until notified by the Sponsor. The PI will allow 
representatives of the Sponsor, IRB, the FDA, or other government regulatory agencies to inspect all study 
records, eCRFs, and corresponding portions of the subject’s office and/or hospital medical records at 
regular intervals during the study. These inspections are to verify adherence to the protocol, integrity of the 
data being captured on the eCRFs, and compliance with applicable regulations. 
Subject medical records will be kept confidential.  Study reports will not identify subjects by name.  These 
reports may be submitted to the FDA and/or regulatory authorities.  
If custody of the records is transferred, notice of such a transfer should be given to the Sponsor no later 
than ten (10) working days after the transfer occurs. 
The Investigator should retain copies of all documents pertaining to this clinical investigation (including 
source documentation, the informed consent document and any other documents to identify the subjects) 
for at least 2 years after this clinical investigation is completed.  In addition, if the Clinical Investigator 
moves/retires, etc., he/she should provide AtriCure Inc. the name and address of the person who will look 


 
 
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after and be responsible for the subjects’ clinical investigation related records. 
8.1.8 
Medical Dictionary Coding 
Medical dictionary coding will be performed using a coding thesaurus algorithm.  The MedDRA will be 
used upon data entry and query resolution for AEs, SAEs, via automated and manual coding processes. 
8.1.9 
Data Quality Assurance 
Quality control and quality assurance processes implemented during this study to ensure subject safety 
rights, and welfare are protected and to foster data integrity are characterized below. 
8.1.10 Investigator Training - Protocol Specific Training 
Protocol training will be scheduled once IRB approval is obtained and the Clinical Study Agreement is 
executed.  AtriCure, Inc. will train the study site on the protocol and that training will be documented.  It is 
ultimately the responsibility of the Investigator to ensure all clinical site personnel participating in this study 
are trained. 
The index procedure may only be performed by qualified investigators, familiar with the study procedures 
and techniques.   
8.1.11 Monitoring 
This study will be monitored by the sponsor to ensure: 
 
The rights, safety and well-being of the subjects are protected; 
 
The reported study data is accurate, complete, and verifiable from source documents; and 
 
The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), applicable GCPs, and with applicable local/regional regulatory 
requirements. 
 
 
 
 
 
 
 
 
 
  
 
 
In order to perform the monitoring role effectively, the CRA must verify eCRF entries with source 
documents.  The CRA must be given access to primary subject data which supports the information 
recorded on the eCRF, i.e. hospital notes, appointment books, original laboratory records, etc.  Access to 


 
 
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these documents must also be given should the regulatory authority in the instance of an external inspection.  
Since a subject has the right to refuse access to these documents on the grounds of confidentiality, consent 
to access is included in the informed consent document, which the subject signs. 
The Principal Investigator will receive reasonable notification prior to each monitoring visit during the 
course of this clinical investigation.  At each visit, the Principal Investigator will be expected to co-operate 
with the CRA for the review and verification of eCRFs and any additional records that may have been 
previously arranged between the Principal Investigator and the CRA. 
8.2 
Changes to Protocol, Protocol Deviations and Protocol Amendments 
8.2.1 
Changes to Protocol 
The Investigator should not implement any deviation from, or changes to the protocol without agreement 
by the sponsor and prior review and documented approval/favorable opinion from the IRB of an 
amendment, except where necessary to eliminate an immediate hazard(s) to study subjects, or when the 
change(s) involves only logistical or administrative aspects of the study (e.g., change in CRA(s), change of 
telephone number(s)). In the event of an emergency situation, the Investigator must notify the CRA or 
AtriCure immediately.  A full written report of the situation must be forwarded to the IRB who approved 
the original protocol and AtriCure within 10 working days of the event. 
8.2.2 
Protocol Deviations 
The Investigator agrees to conduct the study in accordance with this protocol; however, protocol deviations 
may occur during the course of the study.  Protocol deviations are events occurring during the conduct of 
the study which are not in compliance with the protocol and for which an amendment has not been granted. 
Protocol deviations can be committed by the Sponsor, the PI, or study subject. A deviation can be identified 
from a number of sources. Potential sources include, but are not limited to: a member of the PI’s staff, the 
CRA during monitoring visits, or a member of the data management or statistical groups when entering or 
analyzing data.  The PI or PI’s representative are encouraged to contact the CRA or AtriCure as soon as 
possible upon observing a protocol deviation.  Regardless of the source, it is crucial to document the 
deviation and record all corrective actions. Protocol deviations will be reported in the final report. 
The process for capturing deviations will be detailed in the monitoring plan.  The process will require that 
documentation describe the deviation, appropriate actions taken, and will be included in the study file for 
the respective PI and subject.  The study site representative will be advised to record the deviation and 
relevant discussion with the Sponsor about the deviation in subject source documents. 
Protocol deviations affecting the scientific soundness of the study or the rights, safety, or welfare of the 
subjects, will be reported by the PI, as required by the IRB. 
Protocol deviations will be summarized and grouped into relevant categories for analysis and may include, 
but not be limited to, subjects who: 
 
Entered the study although they did not satisfy the eligibility criteria; or 
 
Developed withdrawal criteria during the study, but not removed. 
 
 


 
 
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8.2.3 
Protocol Amendments 
If it becomes necessary to amend the protocol, then the nature of the amendment will be agreed between 
the Sponsor and the Principal Investigator(s) and this will be recorded with a justification for the 
amendment. The appropriate IRBs will be informed of amendments prior to implementation of the change. 
9.0 
STATISTICAL METHODS 
9.1 
Clinical Study Objective 
The objectives of this study are to: 
1. Compare impact of POAF among two randomized treatment arms; patients with POAF and 
surgical LAA closure (using AtriClip Gillinov-Cosgrove LAA Exclusion Systems) versus 
patients with POAF and no surgical LAA closure. 
2. Evaluate Healthcare resource utilization [i.e. Hospital length of stay (LOS), emergency room 
and/or hospital re-admissions, and costs associated with specific adverse events that may be 
related to atrial fibrillation]. 
3. Evaluate long-term outcomes of LAA closure with AtriClip in patients at risk of developing 
POAF. 
These patients will be enrolled prior to a scheduled existing cardiac procedure and randomized prior to the 
study index procedure (AtriClip placement). Perioperative event rates and postoperative outcomes 
including reoperation for bleeding, hospital length of stay, neurologic consults for stroke/TIAs, ED visits, 
and hospital readmissions through interval follow ups 
 will be determined.   
9.2 
Study Endpoints 
The following endpoints will be collected for this hypothesis generating pilot study: 
1. Perioperative complications associated with AtriClip placement. [Defined as: stroke, major 
bleeding that requires re-operation and/or transfusion of > 2 U packed red blood cells (PRBC) 
within any 24-hour period during the first 2 days’ post-index procedure, myocardial infarction 
(MI), or death.] 
2. Intraoperative successful exclusion of LAA. [Defined as no (0 mm) flow between LAA and 
LA and < 5 mm LAA remnant by intraoperative TEE with Doppler.] 
3. Composite event rates between the group of subjects diagnosed with POAF (AtriClip vs no 
AtriClip) through 365 days’ post index procedure and between the group of subjects not 
diagnosed with POAF (AtriClip vs no AtriClip) through 30 days’ post index procedure.  Events 
to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular 
accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, 
neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.   
4. Composite event (listed above) rates through 365-days post index procedure for all AtriClip 
patients, regardless of whether the patient develops POAF. 
5. Healthcare resource utilization variance between groups as related to the composite events 
above.  [Specifically hospital length-of-stay (LOS), reoperation for bleeding, neurologic 
consults for stroke or TIA, emergency department (ED) visits, and hospital readmissions.] 
 
 


 
 
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9.3 
Healthcare resource utilization 
Healthcare resource utilization will be compared between groups.  Major resource use collected at various 
study visits/follow-up calls will include hospital resources (OR time, LOS, etc.), cardiac related medication 
use, readmissions, including 30 days readmit, neurological consults, additional procedures during follow-
up related to index procedures, and rehabilitation associated with post index procedure strokes.  Costs from 
standard sources (DRGs, CPT codes, RedBook, published studies for SAE and Rehab, etc.) may be assigned 
to assess economic impact and summed over the 365-day treatment period to obtain total treatment costs.   
9.4 
Sample Size and Power 
This is a prospective, multicenter, randomized (2:1), unblinded study conducted in up to 2000 patients at 
risk of POAF based on the CHA2DS2-VASc and HASBLED scoring at up to 20 USA sites.  All patients 
who undergo a valve or CABG (structural heart) procedure with direct visual access to the LAA will be 
eligible to participate based upon the inclusion and exclusion criteria defined in this protocol.   
 
 
   
 
 
 
 
   
 
 
 
 
 
 
 
  
 
   
 
 
 
 
  
 
 
   
 
 
   
 
  
A total of up to 2000 patients (approx. 1333 in AtriClip group, approx. 667 in SOC group) at risk of POAF 
will be enrolled in this study. It is assumed that 40% of the patients will be diagnosed with POAF. A two 
treatment group one-sided Z-test with continuity correction and an  = 0.05 will have 80% power to detect 
the difference between a medical management (SOC) safety rate of PS = 12.5% and a mechanical exclusion 


 
 
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(AtriClip) safety rate of PC = 6.25% at 30-days post-op when the sample size (for completers) for patients 
diagnosed with POAF is 485 in the AtriClip group and 243 in the SOC group (a total sample size of 728). 
Adjusting for loss to follow-up, 533 patients in the AtriClip group and 267 in the SOC group (a total sample 
size of 800) are expected to be diagnosed with POAF. 
9.5 
Randomization 
Upon enrollment, subjects will be assigned a sequential identification number at each site and a 
corresponding sealed envelope which will be opened prior to the index procedure to reveal the treatment 
group. Subjects will be randomized 2:1 (2 with AtriClip to 1 anticoagulation therapy and without AtriClip).  
Randomization sequences will be generated by AtriCure Statistician using SAS version 9.4 (SAS Institute 
Inc., Cary, North Carolina) and will be stratified by site.   
9.6 
Analysis Populations 
Intent-To-Treat (ITT) Population: The effectiveness, safety, health economic and Qualify of life analyses 
will be based on the ITT population. The ITT Population is defined as all subjects randomized to either the 
AtriClip LAA Closure or anticoagulation therapy and without AtriClip LAA Closure group and on whom 
the surgical index procedure is attempted (even if the index procedure is aborted). 
POAF Diagnosis (POAF) Population: This population will include all ITT subjects diagnosed with POAF. 
This will be the primary analysis population for effectiveness and health economic endpoints. 
Per-Protocol (PP) Population: A PP population may be defined for effectiveness, health economic and 
Quality of Life analyses. This population is defined by POAF population but without any major protocol 
violations, that is, those that could potentially bias the results.  
9.7 
Analysis of Study Endpoints 
Study endpoints will be summarized by treatment group and overall as appropriate.  Continuous variables 
will be summarized by presenting the number of subjects, mean, standard deviation, median, minimum, 
maximum by procedure group (AtriClip LAA Closure or anticoagulation therapy and without AtriClip LAA 
Closure). Tabulation of categorical variables by group will include counts and percentages. 95% confidence 
intervals will be provided as appropriate.  
Since this is an exploratory study, additional analyses, additional analysis populations, covariates and 
summary tables and/or graphs will be generated as needed. 
In all analyses described below, the null hypothesis will be a two-sided test of no treatment group difference. 
All statistical tests will use a two-sided significance level of =0.05.  
9.7.1 
Effectiveness and Health Economic Analysis 
A Pearson’s Chi-Squared test will be used to compare the incidence of successful LAA exclusion between 
the two procedure groups. Alternatively, a Fisher’s Exact test will be used if justified by small cell counts 
(less than 5) and Clopper-Pearson (Exact) 95% CI will also be reported.  
In addition, LAA exclusion might also be analyzed using multiple logistic regression model with the 
proportion of the event of successful LAA exclusion as the dependent variable and the following 
independent variables: sites (or clusters of sites), surgical approach (sternotomy, right mini-thoracotomy or 
other), age, gender, CHA2DS2- VASc score, HASBLED score and relevant interaction terms. 


 
 
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Healthcare resource use will be assessed by examining either total resource use, treatment costs or formal 
cost effectiveness/cost utility analysis.  Resource use such as hospital length of stay, OR time, and total 
treatment costs will be compared between the treatment groups using a two-way analysis of variance 
(ANOVA) model with procedure group (AtriClip LAA Closure or anticoagulation therapy and without 
AtriClip LAA Closure) and site as fixed effects in the model.  
These endpoints will also be compared using the two-sided t-test. A Shapiro-Wilk test of normality will be 
performed and if the normality assumption is not met, an approximate non-parametric model (e.g. Wilcoxon 
rank-sum test) may be performed.  
A Pearson’s Chi-Squared test will be used to compare difference in 30 day readmits, number of neurological 
consults, additional procedures, and patient medication use between the two procedure groups.   
Formal economic models utilizing treatment effectiveness (Quality adjusted life years, costs to reduce 
stroke, etc.) may be built with collected data and other secondary sources accounting for specific country 
perspective and discounted appropriately.   
9.7.2 
Safety Analysis 
A Pearson’s Chi-Squared test will be used to compare the incidence of complications associates with LAA 
exclusion between the two procedure groups. Alternatively, a Fisher’s Exact test will be used if justified by 
small cell counts (less than 5) and Clopper-Pearson (Exact) 95% CI will also be reported. Thromboembolic 
and hemorrhagic events will be similarly analyzed.  
In addition, complications associated with LAA exclusion and thromboembolic/hemorrhagic might also be 
analyzed using multiple logistic regression model similar to the effectiveness endpoint (successful LAA 
exclusion) described above.  
9.8 
Detailed Analysis Plan 
Prior to looking at the data and database closure, if needed, a detailed statistical analysis  
plan will be prepared and finalized to completely specify the statistical procedures to be applied to the data 
by the statistician who will conduct the analysis. The plan will amplify on the methods discussed in this 
protocol, will address any protocol changes that would affect the analysis, and will provide a rationale for 
any changes to the analysis. 
10.0 
Safety Monitoring 
Subject safety will be monitored throughout the course of this study by monitoring for Adverse Events and 
Product Complaints related to the AtriClip device.  The AtriClip device used during the index procedure 
for the clinical study has been cleared for marketing by the FDA and is being used within the current 
labeling and indications for use.  Any event that occurs that may have caused or contributed to a death or 
serious injury or that indicates the AtriClip device has malfunctioned and would be likely to cause or 
contribute to a death or serious injury if the malfunction were to recur will be reported in compliance with 
21 CRF Part 803. 
In addition to general surgical risks, additional risks specifically associated with the AtriClip implant are 
as follows: 
 
Incomplete exclusion of left atrial appendage (LAA) 
 
Additional surgery if the device is not placed in the correct position. 
 
Allergic reaction to the implant materials 


 
 
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 
Device misplacement or embolization 
 
Device breakage  
 
Inability to move or retrieve device 
There may also be other risks that are unforeseen at this time. 
10.1 
Adverse Events 
10.1.1 Definition of an Adverse Event 
Adverse Event (AE): any undesirable clinical occurrence or change from a patient’s baseline (pre-index 
procedure) condition, whether it is device related or not. 
 
Adverse Event Identification: a condition that is one of the following: 
a. A unique symptom or event that is a change from the subject’s baseline status 
b. A series of symptoms or events that can be categorized as a single entity based on definitions 
found herein 
c. A specific diagnosis responsible for a clinical change 
d. A worsening or exacerbation of a pre-existing condition 
10.2 
Serious Adverse Events 
10.2.1 Definition of a Serious Adverse Event 
Serious Adverse Event (SAE): any adverse event is considered serious if it results in death, is life 
threatening, requires hospitalization (initial or prolonged), results in disability or permanent damage, causes 
congenital anomaly/birth defect, requires intervention to prevent impairment or damage, or other serious 
(important medical events) which may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the above outcomes. 
Note: “Death” should not be reported as an adverse event.  The cause of death should be reported as an 
adverse event.  The only exception is “Sudden Death” when the cause is unknown. 
10.2.2 Subject Death 
Subject death during the investigation must be reported by the Investigator (or designee) by completing the 
Study Exit eCRF in the database along with the cause of death.  The electronic Adverse Event Form is 
necessary if the event was related to the AtriClip device or placement of the device.  In addition, subject 
death must be reported to the IRB in accordance with IRB requirements.  
10.2.3 Adverse Event Classification 
The investigator is required to provide: 
 
Time interval of the event – The time interval of the occurrence of the adverse event should be 
assessed in relationship to timing of the index procedure (AtriClip placement) 
 
Date of event onset and outcome of the event, or date of death 
 
Severity of the event – (Mild, Moderate, Severe) 
 
Action taken for medical management of the event 
 
Relationship of the event – it is the PIs responsibility to assess the relationship of an AE and provide 
primary cause.  Events will be categorized by relationship to the AtriClip device, the applier, ancillary 
device, and the index procedure or other.   


 
 
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 
Adverse events will be assessed to determine if the event meets the definition of a serious adverse 
event.   
10.2.4 Reporting Adverse and Serious Adverse Events 
The investigator (or designee) will record all AEs (both serious and non-serious and regardless of 
relationship) in the source documents.  The Investigator at each site participating site is responsible for 
reporting AEs and SAEs to AtriCure only when they are related to the LAA exclusion index procedure or 
device.  AEs related to the LAA exclusion procedure or device will be reported on the eCRF.  The CRFs 
allow the investigator to indicate whether or not the adverse events are related to the AtriClip device or 
AtriClip placement (index procedure). 
 
Use a separate Adverse Event Form to document each event 
 
The Adverse Event Form must be electronically signed by the Investigator 
Note: It is the responsibility of the Investigator to inform their IRB of SAEs as required by their 
IRB procedures and in conformance with FDA requirements. 
All Serious Adverse Events that are related to the LAA exclusion index procedure or device must be 
reported by the Investigator by submitting the AE eCRF to AtriCure within 10 days of becoming aware of 
the AE and recorded on the Serious Adverse Event Source Document Collection Form  An event determined 
by the Investigator to be life threatening or to have led to death should be reported within 24 hours. 
The Investigator shall send a written report including a narrative description of the SAE to AtriCure within 
three (3) working days of the initial report.  The Investigator should follow all unresolved SAEs until the 
events are resolved, or the subject has exited the study or the AE is otherwise explained. 
11.0 
PRODUCT COMPLAINTS 
11.1 
Medical Device Reporting and Product Complaints 
All reported device observations, malfunctions or failures for AtriClip LAA products will be reported on 
the Device Complaint Form within 10 days of observation of the Product Complaint via email to 
.  In the event of a suspected observation or device problem, the device shall be 
returned to the sponsor for analysis.  In addition, the Investigational Device Observation eCRF should be 
completed within 10 days of a suspected observation or device problem.   
Whenever an event involving an AtriCure device is subject to reporting under that Medical Device 
Reporting (MDR) regulation, AtriCure shall submit to the FDA the appropriate reports required by MDR 
within the time frames as identified in 21 CFR Part 803.  Criteria for reporting malfunctions and potentially 
serious injuries is based on interpretations of medical intervention, potential for serious injury, and impact 
of a malfunction to a device’s essential functionality.  AtriCure will follow - reference documents 
 
 medical device in compliance 
with reporting, 21 CFR Part 803 and 21 CFR Part 820: Code of Federal Regulations, Quality system 
Regulations. 


 
 
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11.2 
Source of Product Complaint Data 
Means of obtaining product complaint data include review of the subject’s medical records or observation 
by the PI and/or study staff or the CRA. 
12.0 
STUDY OVERSIGHT 
12.1 
Independent Oversight 
No independent oversight is anticipated for this study. 


 
 
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Works Cited 
Azoulay. (2014, July 21). Initiation of warfarin in patients with atrial fibrillation: early effects on ischaemic strokes. 
Eur Heart J., 1881-7. 
Blackshear. (1996, Feb). Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. 
Ann Thorac Surg., 755-9. 
Chua. (2013). Clinical utility of CHADS2 and CHA2DS2-VASc scoring systems for predicting postoperative atrial 
fibrillation after cardiac surgery. Journal of Thoracic and Cariovascular Surgery, 919. 
Cox, D. J. (1993). Hazards of postoperative atrial arrhythmias. Ann Thoracic Surg, 539-549. 
Creswell. (1993). Hazards of postoperative atrial arrhythmias. Ann Thorac Surg, 539-549. 
Gallego. (2012). Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and 
mortatlity in anticoagulated patients with atrial fibrillation. Circ arrhythm Electrophysiol, 312-8. 
Gallego. (2012). Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and 
mortatlity in anticoagulated patients with atrial fibrillation. Circ Arrhythm Electrophysiology, 312-8. 
Gomes. (2013). Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ, 121-7. 
Joung. (2014). New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary 
artery by-pass graft. American Heart Journal. 
Kasirajan. (2009). Additive costs of postoperative complications for isolated coronary artery bypass grafting patients 
in Virginia. Ann Thorac Surg., 40-46. 
Kim. (2013). Routine left atrail appendage ligation during cardiac surgery may prevent postoperative atrail 
fibrillation-related cerebrovascular accident. J Thoracic Cardiovasc Surg, 582-9. 
LaPar. (2014). Postoperative atrial fibrillation significantly increases mortality, hospital readmission, and hospital 
costs. Ann Thorac Surg, 527-33. 
Lee. (2014). New-onset atrial fibrillation predicts long-term newly developed atrial fibrillation after coronary artery 
bypass graft. Am Heart J, 593-600. 
Lip. (2010). Underuse of Oral Anticoagulation in AF, A systematic review. American Journal of Medicine, 638-645. 
Maessen. (n.d.). Heart Rythm Paper. 
Rolden. (2013). The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or 
CHA2DS2-VASc scores in anticoaulated patients with atrial fibrillation. J Am Coll Cardiol, 2199-204. 
Ruiz-Nodar. (2012). Should we recommend oral anticoagulation therapy in patients with atrial fibrillation 
undergoing coronary artery stenting with a high HAS-BLED bleeding risk score? Circ Cardiovasc Interv., 
459-66. 
Tung. (2015). Rates of ischemic stroke during warfarin treatment for atrial fibrillation. Stroke, 1120-2. 
Viles-Gonzalez. (2012). The Clinical Impact of Incomplete Left Atrial Appendage Closure With the Watchman 
Device in Patients With Atrial Fibrillation. Journal of the American College of Cardiology. 
Whitlock. (2014). Predictors of early and late stroke following cardiac surgery. CMAJ. 
Yusuf. (2014). (Predictors of early and late stroke following cardiac surgery. Canadian Medical Association 
Journal. 
 
 
 
 


 
 
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13.0 
Appendices 
APPENDIX 1 - EQ-5D-5L Questionnaire 
 
 
 


 
 
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VAS 
 
 
 
 
 


 
 
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Health Questionnaire / English version for the USA SCRIPT FOR TELEPHONE INTERVIEW 
 
 
GENERAL INTRODUCTION 
It is suggested that the telephone interviewer follows the script of the EQ-5D. Although allowance should 
be made for the interviewer’s particular style of speaking, the wording of the questionnaire instructions 
should be followed as closely as possible. In the case of the EQ-5D descriptive system on pages 2 and 3, the 
exact wording must be followed. 
 
It is recommended that the interviewer has a copy of the EQ-5D in front of him or her as it is administered 
over the telephone. This enables the respondent’s answers to be entered directly on the EQ-5D by the 
interviewer on behalf of the respondent (i.e. the appropriate boxes on pages 2 and 3 are marked and the scale 
on page 4 is marked at the point indicating the respondent’s ‘health today’). If the respondent asks for 
clarification, the interviewer can help by re-reading the question verbatim. The interviewer should not try 
to offer his or her own explanation but suggest that the respondent uses his or her own interpretation. 
 
If the respondent has difficulty regarding which box to mark, the interviewer should repeat the 
question verbatim and ask the respondent to answer in a way that most closely resembles his or her 
thoughts about his or her health today. 
 
INTRODUCTION TO EQ-5D 
(Note to interviewer: please read the following) 
We are trying to find out what you think about your health. I will first ask you some simple questions about 
your health TODAY. I will then ask you to rate your health on a measuring scale. I will explain what to do 
as I go along but please interrupt me if you do not understand something or if things are not clear to you. 
Please also remember that there are no right or wrong answers. We are interested here only in your personal 
view. 
 
 
 


 
 
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EQ-5D DESCRIPTIVE SYSTEM: INTRODUCTION 
First I am going to read out some questions. Each question has a choice of five 
answers. Please tell me which answer best describes your health TODAY. Do not 
choose more than one answer in each group of questions. 
(Note to interviewer: it may be necessary to remind the respondent regularly that the 
timeframe is TODAY. It may also be necessary to repeat the questions verbatim) 
 
EQ-5D DESCRIPTIVE 
SYSTEM MOBILITY 
First I'd like to ask you about mobility. Would you say that: 
1. You have no problems walking? 
2. You have slight problems walking? 
3. You have moderate problems walking? 
4. You have severe problems walking? 
5. You are unable to walk? 
(Note to interviewer: mark the appropriate box on the EQ-5D questionnaire) 
 
SELF-CARE 
Next I'd like to ask you about self-care. Would you say that: 
1. You have no problems washing or dressing yourself? 
2. You have slight problems washing or dressing yourself? 
3. You have moderate problems washing or dressing yourself? 
4. You have severe problems washing or dressing yourself? 
5. You are unable to wash or dress yourself? 
(Note to interviewer: mark the appropriate box on the EQ-5D questionnaire) 
 
USUAL ACTIVITIES 
Next I'd like to ask you about your usual activities, for example work, study, 
housework, family or leisure activities. Would you say that: 
1. You have no problems doing your usual activities? 
2. You have slight problems doing your usual activities? 
3. You have moderate problems doing your usual activities? 
4. You have severe problems doing your usual activities? 
5. You are unable to do your usual activities? 
(Note to interviewer: mark the appropriate box on the EQ-5D questionnaire) 
 
 
 


 
 
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PAIN / DISCOMFORT 
Next I'd like to ask you about pain or discomfort. Would you say that: 
1. You have no pain or discomfort? 
2. You have slight pain or discomfort? 
3. You have moderate pain or discomfort? 
4. You have severe pain or discomfort? 
5. You have extreme pain or discomfort? 
(Note to interviewer: mark the appropriate box on the EQ-5D questionnaire) 
 
ANXIETY / DEPRESSION 
Finally, I'd like to ask you about anxiety or depression. Would you say that: 
1. You are not anxious or depressed? 
2. You are slightly anxious or depressed? 
3. You are moderately anxious or depressed? 
4. You are severely anxious or depressed? 
5. You are extremely anxious or depressed? 
(Note to interviewer: mark the appropriate box on the EQ-5D questionnaire) 
 
EQ VAS: INTRODUCTION 
(Note for administrator: If possible, it might be useful to send a visual aid (i.e. the EQ VAS) before the 
telephone call so that the respondent can have this in front of him or her when completing the task) 
Now, I would like to ask you to say how good or bad your health is TODAY. 
I'd like you to try to picture in your mind a scale that looks a bit like a thermometer. Can you do 
that? The best health you can imagine is marked 100 (one hundred) at the top of the scale and the 
worst health you can imagine is marked 0 (zero) at the bottom. 
 
EQ VAS: TASK 
I would now like you to tell me the point on this scale where you would put your health today. 
(Note to interviewer: mark the point on the scale at the point indicating the respondent’s ‘health today’) 
Thank you for taking the time to answer these questions. 
 
 
 


 
 
Study Number: CP2015-2 
CONFIDENTIAL 
Page 47 of 48 
Record: Clinical Study Protocol 
 
 
Version date: 15Feb2017/ Rev: H 
 
APPENDIX 2 - Risk/Benefit Assessment 
 
Risk Category: Minimal. 
Summary:  The AtriClip device is commonly used for the exclusion of the left atrial appendage (LAA). 
The risks to subjects undergoing surgery to place the AtriClip device are listed below. 
 
1.0 
POSSIBLE RISKS AND DISCOMFORTS: 
Risks associated with having the AtriClip placed (does not address the risks and discomforts associated 
with cardiac surgery). 
 
Possible risks and discomforts that may be associated with the use of the AtriClip during procedure are 
identified below.  
 
Incomplete exclusion of left atrial appendage (LAA) 
 
Additional surgery if the device is not placed in the correct position. 
 
Allergic reaction to the implant materials 
 
Device misplacement or embolization 
 
Device breakage 
 
Inability to move or retrieve device 
 
Injury, perforation or tear of the LAA which may lead to blood loss 
 
POTENTIAL RISKS 
Complications may occur at any time during the procedure, post procedure or follow-up period that could 
specifically occur with the AtriClip® or the placement of the AtriClip® include the following: 
 
Myocardial infarction 
 
Blood loss requiring transfusion 
 
Cerebrovascular accident (CVA) 
 
Circumflex artery impingement  
 
Death 
 
Stroke 
 
Pericarditis 
 
Peripheral ischemia 
 
Transient ischemic attack (TIA) 
 
2.0 
POSSIBLE BENEFITS 
Benefits may include but are not limited to, the following: 
 
Prevention of thromboembolic events (blood clots). 
 
Prevention of ischemic stroke and systemic (non-CNS) embolism. 


 
 
Study Number: CP2015-2 
CONFIDENTIAL 
Page 48 of 48 
Record: Clinical Study Protocol 
 
 
Version date: 15Feb2017/ Rev: H 
 
 
Elimination of oral blood thinners resulting in a reduction of bleeding complications associated 
with long-term anticoagulation. 
 
Eliminating the need for life-long compliance to oral anticoagulant therapy and the frequent blood 
tests (depending on oral anticoagulant agent), and lifestyle changes associated with blood thinning 
medications. 
 
Advancing the medical and scientific knowledge that may benefit future patients with similar 
conditions may be gained through this clinical study. 
 
There may also be other benefits that are unforeseen at this time. 
 
3.0 
ALTERNATIVE PROCEDURES/TREATMENTS 
There are some alternative ways for closing your left atrial appendage that does not involve using the 
AtriClip: 
 
Sewing or closing appendage with sutures or ligatures 
 
Stapling the appendage closed with a medical stapling device 
 
MINIMIZATION OF RISKS 
Measures which will be taken to minimize risks related to the study include: 
 
The investigators in this study will be selected based on their experience in treating patients with 
atrial fibrillation and performing surgical procedures 
 
Investigators will be chosen that are qualified to complete study index procedures and are 
experienced in the placement of the AtriCure AtriClip device. 
 
Well defined clinical study protocol, including specific inclusion/ exclusion criteria to enroll 
appropriate subjects in the trial. 
 
Close patient monitoring during the surgical procedure and follow-up period. 
 
Alternative to Participation:  Patients may decline and would be treated with the same standard of care.   
CONCLUSION:  This clinical study is justified because the study sponsor and clinical investigators 
believe the potential benefits outweigh the potential risks.