Amplatzer™Trevisio™Delivery System Post-Approval Study
Conditions: PFO - Patent Foramen Ovale, ASD - Atrial Septal Defect, VSD - Muscular Ventricular Septal Defect, PIVSD - Post Infarct Muscular Ventricular Septal Defect
Sponsor: Abbott Medical Devices

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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Page 1 of 44 
  
 
 
NCT Number: NCT04433520 
Trevisio PAS 
Trevisio Post-Approval Study 
Study Document No: ABT-CIP-10319 
Version A 
Date: 03-JUN-2020 
 
 
Sponsor  
 
 
Abbott 
        
 
 
 
5050 Nathan Lane N 
      
  
 
 
Plymouth, MN 55442, USA 
        
 
 
 
USA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
Template: 86357 Rev. F 
 
Page 2 of 44 
 
 
Trevisio Post-Approval Study 
 
A single-arm, non-randomized, multi-center clinical study of the Amplatzer™ Trevisio™ 
Intravascular Delivery System for facilitating percutaneous, transcatheter implantation of the 
Amplatzer™ Occluder Devices  
 
 
 
Version Number 
Version A 
Date 
03 June 2020 
Planned Number of Sites and Region(s) 
Up to 30 sites in Europe  
Clinical Investigation Type 
Single arm, non-randomized, multi-center, post-approval study 
Abbott Medical Expert 
Dan Gutfinger, MD, PhD 
Medical Director, Medical Affairs 
Structural Heart Disease and Cardiac Surgery 
15900 Valley View Court 
Sylmar, CA 91342 
 
Sponsor 
 
Abbott 
5050 Nathan Lane N  
Plymouth, MN 55442, USA  
Electronic Data Capture Software 
Oracle 
 
CIP Author of Current Version  
 
 
 
Andrea Postier, Ph.D., M.P.H. 
Senior Clinical Research Scientist 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
 
Site Principal Investigator 
 
Printed name: 
Signature: 
Date: 
 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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express written consent of Abbott 
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TABLE OF CONTENTS 
 
1.0 
INTRODUCTION ......................................................................................................................... 10 
1.1 
Background ............................................................................................................................. 10 
1.2 
Rationale for Conducting this Clinical Study ............................................................................. 10 
2.0 
CLINICAL STUDY OVERVIEW ................................................................................................... 10 
2.1 
Clinical Study Objective ........................................................................................................... 10 
2.1.1 
Name of the Device(s) Being Studied ............................................................................... 10 
2.1.2 
Indication for Use .............................................................................................................. 11 
2.1.3 
Description of the Delivery System ................................................................................... 11 
2.1.4 
Device Handling................................................................................................................ 12 
3.0 
CLINICAL STUDY DESIGN ........................................................................................................ 12 
3.1 
Purpose ................................................................................................................................... 12 
3.2 
Design overview ...................................................................................................................... 12 
3.3 
Clinical Study Procedures and Follow-up Schedule ................................................................. 13 
3.4 
Measures Taken to Avoid and Minimize Bias ........................................................................... 13 
3.5 
Suspension or Early Termination of the Clinical Study ............................................................. 13 
4.0 
ENDPOINTS ............................................................................................................................... 14 
4.1 
Primary Endpoints ................................................................................................................... 14 
4.2 
Descriptive Endpoints .............................................................................................................. 14 
5.0 
SUBJECT SELECTION AND WITHDRAWAL ............................................................................. 14 
5.1 
Subject Population ................................................................................................................... 14 
5.2 
Subject Screening and Informed Consent ................................................................................ 15 
5.2.1 
Subject Screening ............................................................................................................. 15 
5.2.2 
Informed Consent ............................................................................................................. 15 
5.2.2.1 
Special Circumstances for Informed Consent ............................................................ 16 
5.3 
Eligibility Criteria ...................................................................................................................... 16 
5.3.1 
General Eligibility Criteria .................................................................................................. 16 
5.3.2 
Inclusion Criteria ............................................................................................................... 16 
5.3.2.1 
General Inclusion Criteria .......................................................................................... 16 
5.3.3 
Exclusion Criteria .............................................................................................................. 17 
5.3.3.1 
General Exclusion Criteria ......................................................................................... 17 
5.4 
Subject Enrollment ................................................................................................................... 17 
5.5 
Subject Withdrawal .................................................................................................................. 18 
5.6 
Number of Subjects ................................................................................................................. 18 

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5.6.1 
Subjects undergoing PFO or ASD closure ........................................................................ 18 
5.6.2 
Subjects undergoing muscular VSD or post-infarct muscular VSD closure ....................... 18 
5.7 
Total Expected Duration of the Clinical Study .......................................................................... 18 
6.0 
TREATMENT AND EVALUATION OF ENDPOINTS ................................................................... 18 
6.1 
Baseline ................................................................................................................................... 18 
6.1.1 
Baseline Clinical Assessments ......................................................................................... 18 
6.2 
Index Procedure ...................................................................................................................... 19 
6.2.1 
Assessments at the Time of Procedure ............................................................................ 19 
6.3 
Post–procedure (pre-hospital discharge or 7 days, whichever occurs first) .............................. 19 
6.3.1 
Subjects will undergo the following evaluations prior to hospital discharge: ...................... 19 
6.4 
Schedule of Events .................................................................................................................. 19 
7.0 
Adverse Events ........................................................................................................................... 20 
7.1 
Definitions ................................................................................................................................ 20 
7.1.1 
Adverse Event .................................................................................................................. 20 
7.1.2 
Serious Adverse Event ..................................................................................................... 20 
7.2 
Device Relationship ................................................................................................................. 21 
7.3 
Adverse Event and Complaint Reporting ................................................................................. 21 
7.3.1 
Adverse Event Reporting .................................................................................................. 21 
7.3.2 
Device Deficiency/Device Malfunction Reporting .............................................................. 21 
7.3.3 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor .................... 22 
7.3.4. 
Complaints ........................................................................................................................ 22 
8.0 
STATISTICAL CONSIDERATIONS ............................................................................................. 22 
8.1 
Analysis Populations ................................................................................................................ 22 
8.2 
Statistical Analyses .................................................................................................................. 23 
8.2.1 
Primary Effectiveness Endpoint Analysis .......................................................................... 23 
8.2.2 
Primary Safety Endpoint Analysis ..................................................................................... 24 
8.3 
Sample Size Calculation and Assumptions .............................................................................. 25 
8.3.1 PFO and ASD Closure Groups .............................................................................................. 25 
8.3.2 Muscular and Post-Infarct Muscular VSD Closure Groups ..................................................... 25 
8.4 
Timing of Analysis .................................................................................................................... 25 
8.5 
Subgroup Analysis ................................................................................................................... 25 
8.6 
Procedures for Accounting for Missing Data ............................................................................ 26 
8.7 
Statistical Criteria for Termination ............................................................................................ 26 
8.8 
Success Criteria ....................................................................................................................... 26 
8.9 
Deviations from Statistical Plan ................................................................................................ 26 
9.0 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ............................................................... 26 

ABT-CIP_10319 Ver. A
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10.0 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................................... 26 
10.1 
Selection of Clinical Sites and Investigators ............................................................................. 26 
10.2 
Clinical Study Finances and Agreements ................................................................................. 26 
10.3 
CIP Amendments ..................................................................................................................... 27 
10.4 
Training.................................................................................................................................... 27 
10.4.1 
Site Training ..................................................................................................................... 27 
10.5 
Monitoring ................................................................................................................................ 27 
10.6 
Deviations from CIP ................................................................................................................. 27 
10.7 
Quality Assurance Audit ........................................................................................................... 28 
10.8 
Sponsor Auditing ..................................................................................................................... 28 
11.0 
DATA HANDLING AND RECORD KEEPING .............................................................................. 28 
11.1 
Protection of Personally Identifiable Information ...................................................................... 29 
11.2 
Data Management Plan ........................................................................................................... 30 
11.3 
Source Documentation ............................................................................................................ 30 
11.4 
Case Report Form Completion ................................................................................................ 30 
11.5 
Record Retention ..................................................................................................................... 30 
12.0 
ETHICAL CONSIDERATION....................................................................................................... 31 
12.1 
Institutional Review Board/Medical Ethics Committee Review and Approval ........................... 31 
13.0 
CLINICAL STUDY CONCLUSION .............................................................................................. 31 
14.0 
PUBLICATION POLICY .............................................................................................................. 31 
15.0 
RISK ANALYSIS ......................................................................................................................... 32 
15.1 
Anticipated Clinical Benefits ..................................................................................................... 32 
15.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects .................................... 32 
15.3 
Residual Risks Associated with the Device Under Study, as Identified in the Risk Analysis 
Report ................................................................................................................................................ 32 
15.4 
Risks Associated with Participation in this Clinical Study ......................................................... 33 
15.5 
Steps Taken to Control or Mitigate Risks ................................................................................. 33 
15.6 
Risk to Benefit Rationale .......................................................................................................... 33 
APPENDIX I. RATES OF FORESEEABLE ADVERSE EVENTS ........................................................... 34 
APPENDIX II: ABBREVIATIONS AND ACRONYMS ............................................................................. 36 
APPENDIX III: SITE CONTACT INFORMATION ................................................................................... 37 
APPENDIX IV: LABELS ......................................................................................................................... 38 
APPENDIX V: CASE REPORT FORMS ................................................................................................ 39 
APPENDIX VI: INFORMED CONSENT FORM ...................................................................................... 40 
APPENDIX VII: MONITORING PLAN .................................................................................................... 41 
APPENDIX VIII: REVISION HISTORY ................................................................................................... 42 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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APPENDIX IX: CIP SUMMARY ............................................................................................................. 43 

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List of Tables 
 
Table 1. Device Name and Model Numbers ........................................................................................ 11 
Table 2. Schedule of Events ................................................................................................................ 20 
 
List of Figures 
 
Figure 1. Amplatzer Trevisio Intravascular Delivery System ............................................................ 12 
Figure 2. Clinical Study Flow Chart .................................................................................................... 13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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COMPLIANCE STATEMENT:  
 
This clinical study will be conducted in accordance with this Clinical Investigation Plan, the Declaration of 
Helsinki, ISO 14155:2011 standards and the appropriate local legislation(s). The most stringent 
requirements, guidelines or regulations must always be followed. The conduct of the clinical study will be 
approved by the appropriate Ethics Committee (EC) of the respective clinical site and as specified by 
local regulations. 
 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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express written consent of Abbott 
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1.0 
INTRODUCTION 
This document is a clinical investigational plan (CIP) for a prospective, multi-center, single-arm, post-
market study intended to support clinical follow-up of the CE-Marked Amplatzer Trevisio™ Intravascular 
Delivery System (Amplatzer Trevisio Delivery System). The device is intended for use with CE-Marked 
Amplatzer™ Occluder devices. This clinical study is sponsored by Abbott.     
This clinical study will be conducted in accordance with this CIP. All investigators involved in the conduct 
of the clinical study will be qualified by education, training, or experience to perform their tasks and this 
training will be documented appropriately. 
1.1 
Background 
The Amplatzer™ TorqVue™ Delivery System (ITV) has historically been used to facilitate the 
attachment, loading, delivery, and deployment of the Amplatzer Occluder devices. The Amplatzer 
Trevisio Delivery System is a new design iteration of the Amplatzer TorqVue delivery system with a 
redesigned delivery cable and a more flexible distal end, which is intended to impart less bias (i.e., tilt) on 
the occluder during the placement evaluation period before releasing the occluder from the delivery 
system. The delivery cable also has a proximal indicator to alert physicians when the occluder is 
approaching the end of the delivery sheath, which may reduce the use of fluoroscopy and patient 
exposure to radiation. All other components of the delivery system are identical to the currently marketed 
Amplatzer TorqVue Delivery System. 
1.2 
Rationale for Conducting this Clinical Study 
The purpose of this study is to evaluate the safety and effectiveness of the design iteration of the 
Amplatzer™ TorqVue™ Delivery System—the Amplatzer Trevisio Delivery System-- in a post-approval 
clinical setting. Data on the safety and effectiveness of the Amplatzer™ Trevisio Delivery System in 
patients undergoing closure of a patent foramen ovale (PFO), atrial septal defect (ASD), muscular 
ventricular septal defect (VSD), and post-infarct muscular VSD with Abbott’s Amplatzer™ PFO Occluder, 
Amplatzer™ Septal Occluder (ASO), Amplatzer™ Multi-fenestrated Septal Occluder – “Cribriform” (ASD-
MF), Amplatzer™ Muscular VSD Occluder, and Amplatzer™ Post-Infarct Muscular VSD Occluder will be 
collected. This study is intended to fulfill post-CE Mark requirements. 
2.0 
CLINICAL STUDY OVERVIEW 
2.1 
Clinical Study Objective  
The primary objective of this clinical study is to characterize the safety and effectiveness of the 
Amplatzer Trevisio Delivery System for facilitating percutaneous, transcatheter implantation of the 
Amplatzer PFO Occluder, Amplatzer ASO, Amplatzer ASD-MF Occluder, Amplatzer Muscular VSD 
Occluder, and Amplatzer Post-Infarct Muscular VSD Occluder. The Amplatzer Trevisio Delivery System 
is CE-Marked and commercially available.   
2.1.1 Name of the Device(s) Being Studied  
The device being studied is the Amplatzer Trevisio Delivery System, which is used to facilitate 
implantation of Abbott’s Amplatzer Occluder devices. Model numbers for the Amplatzer Trevisio Delivery 
System can be seen in Table 1. Refer to the Instructions for Use (IFU) for further detail about the delivery 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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Page 11 of 44 
system and occlusion devices (see Amplatzer Trevisio Intravascular Delivery System IFU; Amplatzer 
PFO Occluder IFU; Amplatzer Septal Occluder IFU; Amplatzer Multi-fenestrated Septal Occluder – 
“Cribriform” IFU; and the combined Amplatzer Muscular VSD Occluder and Post-Infarct Muscular VSD 
Occluder IFU).  
 
Table 1. Device Name and Model Numbers 
Device name (market-released)
Model/Type
Manufacturer
Amplatzer™ Trevisio™ Intravascular 
Delivery System 
 
9-ATV06F45/60
9-ATV07F45/60
9-ATV07F45/80 
9-ATV08F45/60
9-ATV08F45/80 
9-ATV09F45/80
9-ATV10F45/80
9-ATV12F45/80 
9-ATV13F45/80
 
 
 
 
Abbott Medical 
 
 
2.1.2  Indication for Use 
The Amplatzer Trevisio Intravascular Delivery System is intended to facilitate the attachment, loading, 
delivery and deployment of the Amplatzer Occluder devices.   
2.1.3 Description of the Delivery System  
The Amplatzer Trevisio Delivery System is designed to deliver Amplatzer Occluder devices. The delivery 
system is shipped separately from the occluders. The body of the delivery system sheath is radiopaque 
for visibility under fluoroscopy. The Amplatzer Trevisio Delivery System was sterilized with ethylene 
oxide and is for single use only. The more flexible delivery cable included in the Amplatzer Trevisio 
Delivery System will impart less bias (i.e., tilting) on the occluder during the placement evaluation period 
before releasing the occluder from the delivery system.  
 
The components of the Amplatzer Trevisio Delivery System are shown in Figure 1. The Trevisio cable is 
offered in both 60 cm and 80 cm sheath lengths with a 45° curve and has the same French sizes as the 
Amplatzer TorqVue™ 45° Delivery System. Please refer to the IFU for additional information regarding 
the delivery system used in this clinical study. 
 

ABT-CIP_10319 Ver. A
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Clinical Investigation Plan  
 
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Figure 1. Amplatzer Trevisio Intravascular Delivery System 
2.1.4 Device Handling  
Refer to the Amplatzer Trevisio Intravascular Delivery System IFU for more detail about proper handling, 
storage, and use requirements.   
3.0 
CLINICAL STUDY DESIGN 
3.1 
Purpose 
The purpose of this prospective, multi-center, single-arm, post-approval study (PAS) is to characterize 
the safety and effectiveness of the Amplatzer Trevisio Delivery System. 
3.2 
Design overview 
This PAS is a non-randomized, multi-center, single arm clinical study to evaluate the safety and 
effectiveness of the Amplatzer Trevisio Delivery System for facilitating percutaneous, transcatheter 
implantation of the Amplatzer PFO Occluder, Amplatzer ASO, Amplatzer ASD-MF Occluder, Amplatzer 
Muscular VSD Occluder, and Amplatzer Post-Infarct Muscular VSD Occluder.  
 
The majority of procedures that will utilize the Amplatzer Trevisio Delivery System will involve patients 
undergoing ASD and PFO closure, and it is anticipated that Trevisio usage in subjects with muscular 
VSD and post-infarct muscular VSD will be low. A minimum of 215 subjects undergoing PFO or ASD 
closure will be enrolled from up to thirty (30) centers in Europe (at least 100 of these subjects must be 
undergoing PFO closure). In addition to the 215 subjects undergoing PFO or ASD closure, a minimum of 

ABT-CIP_10319 Ver. A
Study Name: CRD_963 Trevisio PAS 
Clinical Investigation Plan  
 
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44 subjects undergoing muscular VSD or post-infarct muscular VSD closure will be enrolled. Subjects 
will be evaluated at baseline (pre-procedure), implant procedure, and prior to discharge or 7 days after 
the procedure, whichever occurs first. The total duration of the study is expected to be 12 months for the 
PFO and ASD closure groups. It is anticipated that it will take approximately five years to complete the 
study for the muscular VSD and post-infarct muscular VSD closure groups due to the low frequency of 
procedures in these patient populations.  
3.3 
Clinical Study Procedures and Follow-up Schedule 
Each subject will be assessed at baseline (pre-procedure), implant procedure, and prior to discharge or 
at 7 days, whichever occurs first. The study assessment flow chart is shown in Figure 2.  
  
 
Figure 2. Clinical Study Flow Chart 
3.4 
Measures Taken to Avoid and Minimize Bias 
This PAS is a non-randomized, multi-center, single arm clinical study. In order to minimize selection bias 
sites will make every effort to seek consent for participation from all eligible patients within their institution 
who are undergoing ASD, PFO, or VSD closure with the Amplatzer Trevisio Delivery System.  
3.5 
Suspension or Early Termination of the Clinical Study 
No formal statistical rule for early termination of the clinical study for insufficient effectiveness of the 
device being studied is defined. 
The Sponsor reserves the right to discontinue the clinical study at any stage with suitable written notice 
to the Principal Investigator. Possible reason(s) may include, but are not limited to: 
 
Sponsor oversight (e.g., Medical Director) decides to stop or terminate the clinical study 
due to a safety concern (such as higher frequency of anticipated adverse device effects) 
 
The study is no longer required by a regulatory authority, or the scope is reduced 
 
Should the clinical study be discontinued by the Sponsor, subjects will be followed per routine hospital 
practice with device-related AEs reported to the Sponsor as per vigilance/commercial reporting 
requirements. Should this occur, the Principal Investigator shall return all clinical study materials to the 
Sponsor and provide a written statement to the EC (if applicable). All applicable clinical study documents 
shall be subject to the same retention policy as detailed in Section 10.5 of the CIP.  

ABT-CIP_10319 Ver. A
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If the Sponsor suspends or prematurely terminates the clinical study at an individual site the Principal 
Investigator or authorized designee will promptly inform the enrolled subjects at his/her site, if 
appropriate.  
A Principal Investigator, EC or regulatory authority may suspend or prematurely terminate participation in 
the clinical study at the study site(s) for which they are responsible. The investigators will follow the 
requirements specified in the Clinical Trial Agreement.  
4.0 
ENDPOINTS 
The study has a primary effectiveness endpoint, a primary safety endpoint, and a number of descriptive 
endpoints.  
4.1 Primary Endpoints 
Primary Effectiveness Endpoint: Technical success – successful deployment and release 
of at least one device  
 
Primary Safety Endpoint: Device- or procedure-related serious adverse events through 
discharge or 7 days, whichever occurs first, including: 
 
 Cardiac perforation 
 Sustained atrial fibrillation requiring intervention 
 Device thrombus 
 Device erosion 
 Device embolization 
 Vascular complication requiring surgical intervention 
 Device- or procedure related serious adverse event leading to death 
4.2 
Descriptive Endpoints 
 The number of times the device is recaptured 
 The number of times the device is repositioned 
 Total fluoroscopy time 
 Ease of use – investigators will be asked survey questions about their first experience with 
the Amplatzer Trevisio Delivery System. 
5.0 
SUBJECT SELECTION AND WITHDRAWAL  
5.1 Subject Population 
This clinical study will enroll male and female adults and children with a PFO (adults only), ASD or VSD 
who are indicated for transcatheter closure. Patients must meet all general eligibility criteria and provide 
written informed consent prior to sites conducting any study-specific procedures not considered standard 
of care.  

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5.2 
Subject Screening and Informed Consent 
5.2.1 Subject Screening 
Potential subjects and/or legal guardians of potential pediatric (minor) subjects presenting at the clinical 
sites will be fully informed about the clinical study, following the established Informed Consent process 
(described in Section 5.2.2). Once a duly dated and signed Information and Consent Form is obtained, 
the clinical study-specific screening procedures may begin. For potential subjects who are considered 
minors, an informed assent or consent process will be followed in accordance with EC requirements 
(described in Section 5.2.2.1) prior to commencement of study-specific screening procedures. 
 
Subjects must be screened for clinical study eligibility by a member of the site’s clinical study team 
previously trained to the CIP. 
 
Patients being considered for PFO, ASD, or VSD closure with an Amplatzer occluder will be asked to 
sign an Informed Consent form if they wish to participate in the clinical study. Subject data will be 
collected following written, informed consent to participate in the clinical study. However, subjects will not 
be considered enrolled until they have met enrollment criteria as defined in Section 5.3.  
 
In case the subject does not meet all study eligibility criteria after provision of Informed Consent, the 
subject will not be included in the study. The Principal Investigator or the delegated clinical study 
personnel will record the screening failure in the hospital records and on a screening log as required. 
5.2.2 Informed Consent 
The Principal Investigator or his/her authorized designee (only if the patient is considered a minor) will 
conduct the informed consent process, as required by applicable regulations and the center’s EC. Adults 
above the legal age of consent who choose to participate in the study must be able to provide their own 
written, informed consent (i.e., no authorized designee may sign on their behalf). This process will 
include a verbal discussion with the patient or legally authorized representative (if the patient is a minor) 
on all aspects of the clinical study that are relevant to the patient’s decision to participate, such as details 
of clinical study procedures, anticipated benefits, and potential risks of clinical study participation. The 
patient and the legally authorized representative must be informed about their right to withdraw from the 
clinical study at any time and for any reason without sanction, penalty or loss of benefits to which the 
subject is otherwise entitled. Withdrawal from the clinical study will not jeopardize their future medical 
care or relationship with the Investigator.  
 
During the discussion, the Principal Investigator or his/her authorized designee will avoid any improper 
influence on the patient and will respect the patient’s legal rights. Financial incentives will not be given to 
the patient. The patient or patient’s legally authorized representative shall be provided with the Informed 
Consent form written in a language that is understandable to the patient and has been approved by the 
center’s EC. The patient or legally authorized representative shall have adequate time to review, ask 
questions, and consider participation. The Principal Investigator or his/her authorized designee will make 
efforts to ensure that the patient and/or subject’s legal guardian understands the information provided. If 
the patient and/or legally authorized representative agree(s) to participate, the Informed Consent form 
and appropriate assent form must be signed and dated by the patient and legally authorized 
representative and thereafter by the person obtaining the consent prior to any clinical study-specific 
procedures. The signed originals will be filed in the subject’s hospital or research charts, and a copy will 
be provided to the subject and his/her legally authorized representative. Failure to obtain informed 
consent from a subject prior to clinical study enrollment should be reported to Sponsor within 5 working 
days and to the reviewing center’s EC according to the EC’s reporting requirements. 

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If, during the clinical study, new information becomes available that can significantly affect a subject's 
future health and medical care, the Principal Investigator or his/her authorized designee (if applicable) 
will provide this information to the subject and/or legally authorized representative. If relevant, the subject 
and/or subject’s legally authorized representative will be asked to confirm their continuing informed 
consent in writing. 
5.2.2.1 Special Circumstances for Informed Consent  
Individuals who are considered minors may be enrolled in this clinical study. Written informed assent or 
consent must be obtained using the EC-approved informed assent or consent process in accordance 
with EC requirements. The legally authorized representative, which will in most cases be the minor’s 
parent(s), will represent the individual during the informed consent process, which will be performed 
according to the requirements in Section 5.2.2. The legally authorized representative(s) must sign an 
Informed Consent form in all cases. The minor will also be informed about the clinical study with respect 
to his/her ability to understand. The explicit wish of the minor who can form an opinion and assess 
information to decline participation or withdraw from the clinical study at any time will be respected.  
 
All other aspects of the informed consent process will be conducted in compliance with Section 5.2.2. 
5.3 
Eligibility Criteria 
5.3.1 General Eligibility Criteria 
Assessment for general eligibility criteria is based on medical records of the site and interview with a 
candidate patient. Patients must meet ALL of the inclusion criteria to be considered for the clinical study. 
If ANY of the exclusion criteria are met, the patient is excluded from the clinical study and cannot be 
enrolled. 
5.3.2 Inclusion Criteria 
5.3.2.1 General Inclusion Criteria 
 
1. Patient is indicated for implantation with the Amplatzer Septal Occluder for occlusion of 
a secundum atrial septal defect (Note: This does not include the indication for closure of 
a fenestration following a fenestrated Fontan procedure) OR subject is indicated for 
implantation with the Amplatzer PFO Occluder OR subject is indicated for implantation 
with the Amplatzer Muscular VSD Occluder OR subject is indicated for implantation with 
the Amplatzer Post-Infarct Muscular VSD Occluder 
 
2. Patient is of legal age and has provided his/her own written, informed consent 
 
 
OR 
 
Patient is a minor and has provided verbal and/or written informed consent or assent per 
local EC requirements, and his/her legally authorized representative, or representatives, 
have provided written informed consent on behalf of the minor according to local EC 
requirements 

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5.3.3 Exclusion Criteria 
5.3.3.1 General Exclusion Criteria 
1. Presence of anatomic or comorbid conditions, or other medical, social, or psychological 
conditions that, in the Principal Investigator’s opinion, could limit the subject’s ability to participate 
in the clinical study or to comply with follow-up requirements. 
2. Exclusion Criteria for Patients Undergoing ASD Closure with the Amplatzer ASO or Amplatzer 
ASD-MF Occluder 
 Patients known to have extensive congenital cardiac anomaly that can only be adequately 
repaired by cardiac surgery 
 Patients known to have sepsis within 1 month prior to implantation, or any systemic 
infection that cannot be successfully treated prior to device placement 
 Patients known to have demonstrated intracardiac thrombus on echocardiography 
(especially left atrial or left atrial appendage thrombi) 
 Patients whose size or condition (e.g., too small for transesophageal echocardiography 
[TEE] probe, catheter size, vasculature size, active infection) would cause the patient to 
be a poor candidate for cardiac catheterization 
 Patients with defect margins less than 5 mm to the coronary sinus, inferior vena cava rim, 
an atrioventricular valve, or the right upper lobe pulmonary vein 
3. Exclusion Criteria for Patients Undergoing PFO Closure 
 Presence of thrombus at the intended site of implant, or documented evidence of venous 
thrombus in the vessels through which access to the defect is gained. Thrombus must 
be ruled out prior to introducing the delivery system.  
 Active endocarditis or other infections producing bacteremia 
 Patients whose vasculature, through which access to the defect is gained, is inadequate 
to accommodate the appropriate sheath size 
 Anatomy in which the Amplatzer™ PFO device size required would interfere with other 
intra-cardiac or intravascular structures, such as valves or pulmonary veins 
 Patients with known hypercoagulable states 
 Patients with intra-cardiac mass or vegetation, thrombus, or tumor 
 
4. Exclusion Criteria for Patients Undergoing VSD Closure with the Amplatzer Muscular VSD 
Occluder or Amplatzer Post-Infarct Muscular VSD Occluder 
 Body weight <8 kg 
 Tetralogy of Fallot 
 Intracardiac thrombi on echocardiography 
5.4 Subject Enrollment 
A subject is considered enrolled in the clinical study when the subject and the subject’s legal 
representative (if applicable) provides written informed consent, has been confirmed to meet all inclusion 
criteria and none of the exclusion criteria, and implantation of an Amplatzer PFO Occluder, Amplatzer 
ASO, Amplatzer ASD-MF Occluder, Amplatzer Muscular VSD Occluder, or Amplatzer Post-Infarct 
Muscular VSD Occluder has been attempted with the Amplatzer Trevisio Delivery System, with implant 
attempt defined as the delivery system entering the subject’s anatomy. 

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5.5 Subject Withdrawal 
Each subject meeting all general screening and eligibility criteria shall remain in the clinical study until 
completion of the required follow-up period; however, a subject’s participation in any clinical study is 
voluntary and the subject has the right to withdraw at any time without penalty or loss of benefit. 
Conceivable reasons for discontinuation may include, but not be limited to, the following: 
 
Subject death 
 
Subject voluntary withdrawal  
 
No additional follow-up will be required and no data will be recorded from subjects once withdrawn from 
the clinical study, except for survival status (deceased/alive). 
 
However, if a subject withdraws from the study due to problems related to the safety or performance of 
the device under study, the Principal Investigator shall ask for the subject's permission to follow his/her 
status/condition outside of the clinical study. 
5.6 
Number of Subjects  
5.6.1 Subjects undergoing PFO or ASD closure 
A minimum of 215 subjects with PFO or ASD will be enrolled in the clinical study, with a predefined 
minimum of 100 subjects undergoing PFO closure. Enrollment will be closely monitored to ensure this 
minimum number of subjects is met early in the first half of the enrollment period. No site may enroll 
more than 20% of the maximum number of PFO and ASD subjects (n=43).  
5.6.2 Subjects undergoing muscular VSD or post-infarct muscular VSD closure  
A minimum of 44 subjects with muscular or post-infarct muscular VSD will be enrolled in the clinical 
study.  
5.7 
Total Expected Duration of the Clinical Study 
The total expected duration of the clinical study is approximately 12 months for the PFO and ASD 
closure groups, and it is anticipated to be approximately five years for the muscular VSD and post-infarct 
muscular VSD closure groups.  
6.0 
TREATMENT AND EVALUATION OF ENDPOINTS 
6.1 
Baseline 
The baseline visit will occur prior to the procedure.    
6.1.1 Baseline Clinical Assessments 
Data collected during prior examinations may be used for the study if the data were 
collected no more than 90 days prior to the baseline study assessment. The following 
assessments and information will be collected at the baseline visit:   
 
 Demographics- includes subject’s age and gender  

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 Physical examination- includes subject’s height, weight, blood pressure 
(measurements taken during visit)  
 Medical history- indicates subject’s risk factors, relevant co-morbidities, previous 
cardiac procedures, and medication use  
 Electrocardiogram (ECG), if performed 
 Previous echocardiography report indicating PFO, ASD or VSD morphology and 
pre-closure shunt status. If previous imaging reports are unavailable, 
intraprocedural echocardiography may be performed prior to the implant attempt 
(see section 6.2.1)  
6.2 
Index Procedure 
6.2.1 Assessments at the Time of Procedure  
The following assessments and information will be collected at the time of the procedure 
(PFO, ASD, or VSD closure) through prospective tests and evaluations per the local 
standard of care. If it is determined at the time of the procedure that the subject does not 
meet the definition of enrollment, the subject will not be considered enrolled. 
 Total fluoroscopy time 
 Time first catheter in, time last catheter out 
 PFO, ASD, or VSD morphology (if not obtained prior to the procedure) 
 Pre-closure shunt status as assessed by intraprocedural echocardiography (if not 
obtained prior to the procedure) 
 Procedure details (e.g., PFO, ASD, or VSD morphology; type of sedation; ancillary 
product use) 
 Procedure outcome (implant success or failure) 
 The number of times the device is recaptured 
 The number of times the device is repositioned 
 Post-closure (intra-procedural) shunt status as assessed by echocardiography  
 Adverse events, if applicable 
6.3 
Post–procedure (pre-hospital discharge or 7 days, whichever occurs first) 
6.3.1 Subjects will undergo the following evaluations prior to hospital discharge: 
o Physical exam 
o ECG  
o Adverse events, if applicable 
6.4 
Schedule of Events 
The following schedule applies to all subjects enrolled in the study. 
 
 
 
 

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Table 2. Schedule of Events 
Study Activity 
Enrollment 
& Baseline 
Procedure 
Discharge or 
7 days  
Informed Consent 
X 
 
 
Demographics, Clinical History 
X 
 
 
Physical Examination 
X 
 
X 
Electrocardiography 
(X) 
 
X 
Echocardiography 
(X) 
 X1 
 
Adverse Event Assessment 
 
X 
X 
1For subjects who do not have echocardiography images available prior to the procedure, 
two sets of imaging assessments will be performed during the procedure (i.e., pre-closure 
and post-closure).  
X = Required follow up; (X) = Optional measurement
 
7.0 
Adverse Events 
To comply with worldwide standards and guidelines on clinical study adverse event reporting, the 
Sponsor has adopted uniform and worldwide applicable standard definitions and reporting timelines to be 
used and adhered to by the investigators.  
7.1 
Definitions 
7.1.1 Adverse Event 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the medical device under study. 
 
Note 1: This definition includes events related to the medical device being studied. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to medical devices being 
studied. 
7.1.2 Serious Adverse Event 
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE).  
 
a) Led to a death, 
b) Led to a serious deterioration in health of the subject, that either resulted in  
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient hospitalization or prolongation of existing hospitalization, or 
4. medical or surgical intervention to prevent life threatening illness or injury or permanent 
impairment to a body structure or a body function, or 

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5. chronic disease. 
c) Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 
Note: A planned hospitalization for pre-existing condition, or a procedure required by the CIP, without a 
serious deterioration in health, is not considered to be an SAE. 
7.2 
Device Relationship 
Determination of whether there is a reasonable possibility that a product or device under study caused or 
contributed to an AE is to be determined by the Investigator and recorded on the appropriate case 
report form (CRF). Determination should be based on assessment of temporal relationships, evidence of 
alternative etiology, medical/biologic plausibility, and patient condition (e.g., pre-existing condition). 
7.3 
Adverse Event and Complaint Reporting 
7.3.1 Adverse Event Reporting 
Safety surveillance and reporting starts as soon as the patient has provided written, informed consent 
(per section 5.2) to participate in the clinical study. Safety surveillance and reporting will continue until 
the last follow-up visit has been performed, the subject is deceased, the subject concludes participation 
in the clinical study or the subject withdraws from the clinical study. All AE data, including deaths, will be 
collected throughout the time period defined above and will be reported to the Sponsor on a CRF. 
Additional information with regard to an adverse event should be updated within the appropriate CRF, 
including determination of whether COVID-19 (SARS-CoV-2 virus) caused or contributed to an 
AE. Unchanged, chronic, non-worsening or pre-existing conditions are not AEs and should not be 
reported.  
 
 
For the purposes of this clinical study, the following events will be reported: 
 Serious adverse events 
 Device- and/or procedure-related adverse events 
 
SAE Reporting 
The Principal Investigator should report all SAEs to the Sponsor as soon as possible but no later than 
outlined below.  
 
Clinical Site
Reporting timelines
All Sites 
SAEs must be reported to the Sponsor no later than 3 calendar days from the 
day the site personnel became aware of the event or as per the investigative 
site’s local requirements if the requirement is more stringent than those outlined. 
 
The date the site staff became aware the event met the criteria of an SAE must be recorded in the 
source document.  The Principal Investigator will further report the SAE to the local EC according to the 
institution’s EC reporting requirements. 
7.3.2 Device Deficiency/Device Malfunction Reporting 
A device malfunction is the failure of a device to meet its performance specifications or otherwise 
perform as intended, when used in accordance with the IFU or CIP. This includes any malfunction of the 

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Amplatzer Trevisio Delivery System. All device or delivery system deficiencies/malfunctions should be 
reported on the appropriate CRF (i.e., the Device Deficiency Form). Device deficiency is defined as an 
inadequacy of a medical device related to its identity, quality, durability, reliability, safety or performance, 
such as malfunction, misuse or use error and inadequate labeling. This includes the failure of the device 
or delivery system to meet its performance specifications or otherwise perform as intended. Note: 
Performance specifications include all claims made in the labeling of the device. 
 
The Principal Investigator should report all device or delivery system deficiencies to the Sponsor as soon 
as possible but no later than outlined below. 
 
Clinical Sites
Reporting timelines
All Sites
Device deficiencies must be reported to the Sponsor no later than 3 calendar days 
from the day the site personnel became aware of the event or as per the 
investigative site’s local requirements if the requirement is more stringent than 
those outlined above.
 
Device deficiencies/malfunctions should be reported to the EC per the investigative site’s local 
requirements. 
7.3.3 Adverse Event Reporting to Country Regulatory Authorities by the Sponsor  
The Sponsor will report SAEs and reportable device deficiencies/malfunctions to the country regulatory 
authority, per local requirements.  
7.3.4. Complaints 
The investigator is responsible for reporting all complaints to the Post Market Surveillance Department as 
they become aware of the complaint. A complaint is defined as any written, electronic or oral 
communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, 
effectiveness or performance of a device or delivery system after it is released for distribution. 
For events not reportable for this study (per section 7.3.1) and are considered as complaints, the 
investigator must notify Abbott’s Product Performance Group (PPG) by submitting the information on the 
device via email to complaints_amplatzer@abbott.com as soon as possible after becoming aware of the 
complaint. This information is not collected on a CRF for the study. 
8.0 
STATISTICAL CONSIDERATIONS 
8.1 
Analysis Populations 
The analysis population will include all subjects who have provided written informed consent, have been 
confirmed to meet all inclusion criteria and none of the exclusion criteria, and implantation of an 
Amplatzer PFO Occluder, Amplatzer ASO, Amplatzer ASD-MF Occluder, Amplatzer Muscular VSD 
Occluder, or Amplatzer Post-Infarct Muscular VSD Occluder has been attempted, with implant attempt 
defined as the delivery system entering the subject’s anatomy.  
 

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8.2 
Statistical Analyses  
8.2.1 Primary Effectiveness Endpoint Analysis  
The primary effectiveness endpoint is technical success – successful deployment and release of at least 
one device.  
 
8.2.1.1  PFO and ASD Closure Groups 
The performance goal for the primary effectiveness endpoint for the PFO and ASD closure groups is set 
at 95%, which is based on the technical success rates observed in the RESPECT trial and ASD PMS II 
study. The technical success rate for the Amplatzer Trevisio™ Intravascular Delivery System in the PFO 
and ASD closure groups is assumed to be 99%.  
 
Let π1 be the proportion of subjects who experience successful deployment and release of at least one 
device.  
 
The following hypothesis will be tested:  
 
H0:  π1 ≤ 95% 
Ha:  π1 > 95% 
 
π1 will be estimated as a binomial proportion. 
 
The hypothesis will be tested at a one-sided significance level of 2.5% using the exact binomial test. The 
null hypothesis will be rejected if the one-sided 97.5% lower confidence bound (LCB) for the proportion, 
π1, is greater than the performance goal of 95%. The one-sided 97.5% lower confidence bound for π1 will 
be estimated using the Clopper-Pearson method.  
 
8.2.1.2  Muscular and Post-Infarct Muscular VSD Closure Groups 
The performance goal for the primary effectiveness endpoint for the muscular VSD and post-infarct 
muscular VSD closure groups is set at 80% which is based on the observed interim technical success 
rate (77%) in the post-infarct VSD Occluder humanitarian device exemption study. The technical success 
rate for Amplatzer Trevisio™ Intravascular Delivery System in the muscular and post-infarct muscular 
VSD closure groups is assumed to be 93%, which is the observed technical success rate in the ongoing 
muscular VSD Occluder US post approval study.  
 
Let π2 be the proportion of subjects who experience successful deployment and release of at least one 
device.  
 
The following hypothesis will be tested:  
 
H0:  π2 ≤ 80% 
Ha:  π2 > 80% 
 
π2 will be estimated as a binomial proportion. 
 
The hypothesis will be tested at a one-sided significance level of 5% using the exact binomial test. The 
null hypothesis will be rejected if the one-sided 95% lower confidence bound (LCB) for the proportion, π2, 

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is greater than the performance goal of 80%. The one-sided 95% lower confidence bound for π2 will be 
estimated using the Clopper-Pearson method.  
8.2.2 Primary Safety Endpoint Analysis  
The primary safety endpoint is device- or procedure-related serious adverse events through discharge or 
7 days, whichever is earlier, including: 
 
 Cardiac perforation 
 Sustained atrial fibrillation requiring intervention 
 Device thrombus 
 Device erosion 
 Device embolization 
 Vascular complication requiring surgical intervention 
 Device- or procedure-related serious adverse event leading to death 
 
8.2.2.1 PFO and ASD Closure Groups 
A performance goal of 6% was chosen based on a conservative assumption of device- or procedure-
related serious adverse event rate of 2% prior to hospital discharge. This conservative estimate is based 
on serious adverse event rates from the RESPECT IDE trial (clinicaltrials.gov NCT00465270) and ASD 
PMS II study which reported rates of device- or procedure-related serious adverse events prior to 
hospital discharge were 2.7% and 1.2%, respectively. 
  
Let π3 be the proportion of subjects who experience device- or procedure-related serious adverse events 
through discharge or 7 days.  
 
The following hypothesis will be tested:  
 
H0:  π3 ≥ 6% 
Ha:  π3 < 6% 
 
π3 will be estimated as a binomial proportion.   
 
The hypothesis will be tested at a one-sided significance level of 2.5% using exact binomial test. The null 
hypothesis will be rejected if the one-sided 97.5% upper confidence bound (UCB) for the proportion, π3, 
is less than the performance goal of 6%. The one-sided 97.5% upper confidence bound for π3 will be 
estimated using the Clopper-Pearson method.  
 
8.2.2.2 Muscular and Post-Infarct Muscular VSD Closure Groups 
There is no formal statistical hypothesis for the primary safety endpoint for the VSD closure groups. The 
primary safety endpoint will be reported descriptively in the VSD closure groups.     
8.2.3 Descriptive Endpoint Analyses 
Descriptive endpoints include: 
 The number of times the device is recaptured 
 The number of times the device is repositioned 
 Ease of use – physicians will be asked survey questions about their experience with the 
Amplatzer Trevisio Delivery System compared to other device delivery systems 

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 Total fluoroscopy time 
 
For each descriptive endpoint, data will be presented using appropriate summary statistics. Continuous 
data will be summarized using descriptive statistics including mean, standard deviation, median and 
range. Categorical data will be summarized by the frequencies and percentages. Percentages will be 
based on the number of subjects in the analysis population as described in Section 8.1.  
8.3 
Sample Size Calculation and Assumptions 
The muscular and post-infarct muscular VSD closure groups are a clinically unique group of patients as 
compared to the PFO and ASD closure groups, and the frequency of presentation for VSD closure is 
anticipated to be lower.  
 
8.3.1 PFO and ASD Closure Groups 
 
Assuming a technical success rate of 99%, a performance goal of 95%, a one-sided significance level of 
2.5%, a sample size of 164 subjects will have 80% power to reject the primary effectiveness null 
hypothesis using the exact binomial methods. 
 
Assuming a device- or procedure-related serious adverse events rate of 2% prior to hospital discharge, a 
performance goal of 6%, a one-sided significance level of 2.5%, a sample size of 215 subjects will have 
>80% power to reject the primary safety null hypothesis using the exact binomial methods. 
 
The sample size of 215 PFO and ASD closure subjects is therefore based on the primary safety 
endpoint.  
8.3.2 Muscular and Post-Infarct Muscular VSD Closure Groups 
 
Assuming a technical success rate of 93% (based on the technical success rate in the muscular VSD US 
post approval study), a performance goal of 80%, and a one-sided significance level of 5%, a sample 
size of 44 VSD subjects will have 80% power to reject the primary effectiveness null hypothesis using the 
exact binomial methods. 
 
The sample size of 44 VSD closure subjects is based on the technical success endpoint.  
 
8.4 
Timing of Analysis 
The primary endpoints will be analyzed for the PFO and ASD closure groups when all PFO and ASD 
closure subjects have completed the study. It is anticipated that it will take longer to enroll patients with 
VSD and the primary endpoint will be analyzed for the VSD closure groups when all VSD closure 
subjects have completed the study.  The analyses will be completed for each cohort as the data for each 
cohort become available.  
8.5 
Subgroup Analysis 
Sub-group analyses (e.g.,sex) are planned for the study. Details about subgroup analysis will be 
described in the Statistical Analysis Plan.  

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Baseline characteristics, demographics, primary endpoints and clinical outcomes will be analyzed 
separately for each of the defect closure groups (i.e., PFO and ASD closure; muscular VSD and post-
infarct muscular VSD closure).   
8.6 
Procedures for Accounting for Missing Data 
All analyses will be based on available data with missing data excluded. Any unused or spurious data will 
be noted as appropriate. Since the primary effectiveness endpoint is evaluated during the procedure, 
and the primary safety endpoint is an acute outcome evaluated prior to discharge or 7 days after the 
procedure, whichever occurs first (i.e., while the subject is still at the medical facility), missing data for the 
primary endpoints is anticipated to be minimal.   
8.7 
Statistical Criteria for Termination 
There are no statistical criteria for termination of this clinical study. 
8.8 
Success Criteria 
In order to claim study success for the PFO and ASD closure groups, the null hypotheses for the primary 
effectiveness endpoint and primary safety endpoint must be rejected. In order to claim study success for 
the VSD closure groups, the null hypothesis for the primary effectiveness endpoint must be rejected. 
8.9 
Deviations from Statistical Plan 
Any major changes to the statistical plan will be documented in an amendment to the statistical plan. 
Less significant changes to the planned analyses will be documented in the final report.   
9.0 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The Principal Investigator/institution will permit direct access to source data/documents for the purpose 
of performing audits, EC review and regulatory inspections. 
 
Subjects providing informed consent are agreeing to allow clinical study monitors or regulatory 
authorities including foreign countries to review, in confidence, any records identifying the subjects in this 
clinical study. This information may be shared with regulatory agencies; however, Sponsor undertakes 
not to otherwise release the subject's personal and private information. 
10.0 QUALITY CONTROL AND QUALITY ASSURANCE 
10.1 Selection of Clinical Sites and Investigators 
The Sponsor will select investigators qualified by training and experience to participate in the clinical 
study. Sites will be selected based upon review of a recent site assessment, if applicable, and the 
qualifications of the investigators who will participate in the clinical study. 
10.2 Clinical Study Finances and Agreements 
The clinical study will be financed by Abbott.  Investigational sites will be compensated by Abbott for 
participation in the clinical study per the conditions of agreement between the Sponsor and the 
investigational site. 

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10.3 CIP Amendments  
Approved CIP amendments will be provided to the Principal Investigators by the Sponsor prior to 
implementing the amendment. The Principal Investigator is responsible for notifying the EC or equivalent 
committee of the CIP amendment (administrative changes) or obtaining EC’s approval of the CIP 
amendment (changes in subject care or safety), according to the instructions provided by the Sponsor 
with the CIP amendment.   
 
Acknowledgement/approval by the EC of the CIP amendment must be documented in writing prior to 
implementation of the CIP amendment. Copies of this documentation must also be provided to the 
Sponsor. 
10.4 Training 
10.4.1 Site Training 
All Investigators and clinical study personnel are required to attend Sponsor training sessions, which may 
be conducted at an Investigator's meeting, a site initiation visit, or other appropriate training sessions. 
Over-the-phone or self-training may take place as required. Training of Investigators and clinical study 
personnel will include, but is not limited to, the CIP requirements, study device usage, electronic case 
report form completion and clinical study personnel responsibilities. All Investigators and clinical study 
personnel that are trained must sign a training log (or an equivalent) upon completion of the training. 
Prior to signing the training log, Investigators and clinical study personnel must not perform any CIP-
related activities that are not considered standard of care at the site.  
10.5 Monitoring  
Sponsor and/or designee will monitor the clinical study over its duration according to the CIP-specific 
monitoring plan which will include the planned extent of source data verification. Prior to initiating any 
procedure, the Sponsor monitor (or delegate) will ensure that the following criteria are met:  
 
 
The Investigator understands and accepts the obligation to conduct the clinical study according to 
the CIP and applicable regulations and has signed the Clinical Trial Agreement. 
 
The Investigator and his/her staff should have sufficient time and facilities to conduct the clinical 
study and should have access to an adequate number of appropriate subjects to conduct the 
clinical study.  
 
Source documentation (including original medical records) must be available to substantiate 
proper informed consent procedures, adherence to CIP procedures, adequate reporting and 
follow-up of adverse events, accuracy of data collected on case report forms, and device 
information.  
10.6 Deviations from CIP 
The Principal Investigator should not deviate from the CIP for any reason except in cases of medical 
emergencies when the deviation is necessary to protect the rights, safety and well-being of the subject or 
eliminate an apparent immediate hazard to the subject. In that event, the Principal Investigator will notify 
Sponsor immediately by phone or in writing.  
 

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No waivers for CIP deviations will be granted by the Sponsor.  All deviations must be reported to the 
Sponsor using the Deviation CRF. The occurrence of CIP deviations will be monitored by the Sponsor for 
evaluation of Investigator compliance to the CIP and regulatory requirements and dealt with according to 
written procedures. Investigators will inform their EC or equivalent committee of all CIP deviations in 
accordance with their specific EC or equivalent committee reporting policies and procedures.  
 
In the event of repeated non-compliance, as determined by the Sponsor, a Sponsor’s monitor or 
company representative will attempt to secure compliance by one or more of the following (and not 
limited to):  
 Visiting the Principal Investigator and/or delegate 
 Telephoning the Principal Investigator and/or delegate 
 Corresponding with the Principal Investigator and/or delegate 
 
Repeated non-compliance with the signed agreement, the CIP or any other conditions of the clinical 
study may result in further escalation in accordance with the Sponsor’s written procedures, including 
securing compliance or, at its sole discretion, Sponsor may terminate the Principal Investigator's 
participation in the clinical study.  
10.7 Quality Assurance Audit 
A Sponsor representative or designee may request access to all clinical study records, including source 
documentation, for inspection during a Quality Assurance audit.  
 
In the event that an Investigator is contacted by a Regulatory Agency in relation to this clinical study, the 
Principal Investigator will notify Sponsor immediately. The Principal Investigator and Research 
Coordinator must be available to respond to reasonable requests and audit queries made during the 
audit process. The Principal Investigator must provide Sponsor with copies of all correspondence that 
may affect the review of the current clinical study (e.g., Inspectional Observations, Warning Letters, 
Inspection Reports, etc.). Sponsor may provide any needed assistance in responding to regulatory 
audits. 
10.8 Sponsor Auditing 
The following auditing requirements must be met:    
 
1. The Sponsor shall prepare an audit plan as well as the operating procedures for the related 
duties and conduct audits in accordance with the audit plan and the operating procedures. 
2. Individuals engaged in auditing (hereinafter referred to as "auditor") shall be different than those 
in charge of medical device development or monitoring. 
3. The auditor shall prepare an audit report documenting the matters confirmed in the audit to certify 
and verify that the audit has been conducted and submit them to the Sponsor.  
11.0 DATA HANDLING AND RECORD KEEPING  
Sponsor and/or its affiliates will maintain documentation of the systems and procedures used in data 
collection for the duration of the clinical study.  
 

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CRF data collection will be performed through a secure web portal and only authorized personnel will 
access the Electronic Data Capture (EDC) system using a unique username and password to enter, 
review or correct data. Passwords and electronic signatures will be strictly confidential.   
 
The data will be subjected to consistency and validation checks within the EDC system and 
supplemental review by the Sponsor.    
 
At the conclusion of the clinical study, completed CRF images with the date-and-time stamped electronic 
audit trail indicating the user, the data entered, and any reason for change (if applicable) will be provided 
to the study sites.  
 
For the duration of the clinical study, the Principal Investigator will maintain complete and accurate 
documentation including, but not limited to, medical records, clinical study progress records, laboratory 
reports, CRFs, signed ICFs, device accountability records (if applicable), correspondence with the EC 
and clinical study monitor/Sponsor, adverse event reports, and information regarding subject 
discontinuation or completion of the clinical study. 
11.1 Protection of Personally Identifiable Information 
The Sponsor respects and protects personally identifiable information collected or maintained for this 
clinical study.  
 
The Sponsor implements technical and physical access controls to ensure that Personal Information is 
accessible only to and processed only on a ‘need to know’ basis, including periodic review of access 
rights, and revocation of access when an individual’s employment is terminated or the individual 
transitions to a role that does not require access to Personal Information, and appropriate restrictions on 
physical access to premises, facilities, equipment, and records containing Personal Information. 
 
The Sponsor requires the study sites to transfer into Sponsor’s data management systems only 
pseudonymous Personal Information (key-coded) necessary to conduct the Clinical study, such as the 
patient’s medical condition, treatment, dates of treatment, etc. The Sponsor discloses as part of the 
clinical study informed consent process that some Sponsor representatives still may see Personal 
Information at the participating sites for technical support of the participating physicians on the device 
implant or procedures, monitoring and quality control purposes. Confidentiality of Personal Information 
will be observed by all parties involved at all times throughout the clinical study. The privacy of each 
subject and confidentiality of his/her information will be preserved in reports and when publishing any 
data. 
 
The Sponsor data management systems and processes were designed, developed, and tested 
according to industry standards to appropriately safeguard Confidential Information (including any 
Personal Information) against unauthorized access and/or interference by third parties, intrusion, theft, 
destruction, loss or alteration. Clinical study data are encrypted in transit and at rest.  
 
The Sponsor maintains a Privacy Incident procedure that complies in all respects with Applicable Law 
and industry best practices. 

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11.2 Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, data cleaning, and 
issuing and resolving data discrepancies. If appropriate, the DMP may be updated throughout the 
duration of the clinical study. All revisions will be tracked and document-controlled. 
11.3 Source Documentation  
Regulations and GCP require the Principal Investigator to maintain information in the subject’s original 
medical records that corroborates data collected on the CRFs. In order to comply with these regulatory 
requirements/GCP, the following information should be included in the subject record at a minimum and 
if applicable to the clinical study: 
 
Medical history/physical condition of the subject before involvement in the clinical study 
sufficient to verify CIP entry criteria 
 
Dated and signed notes on the day of entry into the clinical study referencing the Sponsor, 
CIP number, subject ID number and a statement that informed consent was obtained 
 
Dated and signed notes from each subject visit (for specific results of procedures and 
exams) 
 
Adverse events reported and their resolution, including supporting documents, such as 
discharge summaries, catheterization laboratory reports, ECGs, and lab results including 
documentation of site awareness of SAEs and of Investigator assessment of device 
relationship for SAEs. 
 
CIP-required laboratory reports and 12-lead ECGs, reviewed and annotated for clinical 
significance of out of range results (if applicable).  
 
Notes regarding CIP-required and prescription medications taken during the clinical study 
(including start and stop dates) 
 
Subject’s condition upon completion of or withdrawal from the clinical study 
 
Any other data required to substantiate data entered into the CRF 
 
Patient reported outcome measures may be completed using CRF worksheets. These 
serve as the source documentation. 
11.4 Case Report Form Completion  
Primary data collection based on source-documented hospital and/or clinic chart reviews will be 
performed clearly and accurately by site personnel trained on the CIP and CRF completion. The Principal 
Investigator will ensure accuracy, completeness, legibility and timeliness of the data reported to the 
Sponsor on the CRFs and in all required reports. Data on CRFs will be collected for all subjects that are 
enrolled into the clinical study. Only authorized site personnel will be permitted to enter the CRF data 
through the EDC system deployed by the Sponsor. An electronic audit trail will be used to track any 
subsequent changes of the entered data. 
11.5 Record Retention 
The Sponsor and Principal Investigator/Site will archive and retain all documents pertaining to the clinical 
study as per the applicable regulatory record retention requirements. The Principal Investigator must 

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obtain permission from Sponsor in writing before destroying or transferring control of any clinical study 
records. 
12.0 ETHICAL CONSIDERATION 
 
12.1 Institutional Review Board/Medical Ethics Committee Review and Approval 
Ethics Committee approval for the CIP and ICF/other written information provided to the patient will be 
obtained by the Principal Investigator at each study site prior to consenting and enrolling patients in this 
clinical study. The approval letter must be received prior to the start of this clinical study and a copy must 
be provided to the Sponsor.  
 
Any amendments to the CIP as well as associated ICF changes will be submitted to the EC and written 
approval obtained prior to implementation, according to each institution’s EC requirements.  
 
No changes will be made to the CIP or ICF or other written information provided to the patient without 
appropriate approvals, including the EC, the Sponsor, and the regulatory agencies (if applicable).  
 
Until the clinical study is completed, the Principal Investigator will advise his/her EC of the progress of 
this clinical study, per EC requirements. Written approval must be obtained from the EC yearly to 
continue the clinical study, or according to each institution’s EC requirements.  
 
No investigative procedures other than those defined in this CIP will be undertaken on the enrolled 
subjects without the written agreement of the EC and the Sponsor. 
13.0 CLINICAL STUDY CONCLUSION 
The end of the clinical study will coincide with the last subject’s pre-discharge assessment, or 
assessment at 7 days following the procedure, whichever occurs first. The clinical study report will be 
submitted within one year of the end of the study. 
 
The clinical study will be concluded when: 
 
All sites are closed AND 
 
The final report has been provided to Principal Investigators or the Sponsor has provided formal 
documentation of clinical study closure.  
14.0 PUBLICATION POLICY 
The data and results from the clinical study are the sole property of the Sponsor. The Sponsor shall have 
the right to access and use all data and results generated during the clinical study. The Investigators will 
not use this clinical study-related data without the written consent of the Sponsor for any purpose other 
than for clinical study completion or for generation of publication materials, as referenced in the Clinical 
Trial Agreement. Single-center results are not allowed to be published or presented before the multi-
center results. Any proposals for publications or presentations by the Investigators must be reviewed and 
approved by the Sponsor in a timely manner to enable Sponsor review in compliance with the Sponsor’s 
publication policy set forth in the Clinical Trial Agreement. 
 

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The Sponsor will be responsible for determining whether to register the clinical study on 
www.clinicaltrials.gov or any other clinical trials, in accordance with the International Committee of 
Medical Journal Editors guidelines, or any other applicable guidelines. In the event Sponsor determines 
that the clinical study should be registered, Sponsor shall be responsible for any such registration and 
results posting as required by the ClinicalTrials.gov website. Institution and/or Principal Investigator(s) 
shall not take any action to register the clinical study. 
15.0 RISK ANALYSIS 
 
The risks associated with the Amplatzer Trevisio Delivery System can be found in the IFU. The study 
does not require any additional procedures or assessments over standard of care. There are no 
additional risks introduced to study subjects. 
15.1 Anticipated Clinical Benefits 
The Amplatzer PFO Occluder is indicated for percutaneous, transcatheter closure of a PFO to reduce the 
risk of recurrent ischemic stroke in patients who have had a cryptogenic stroke due to presumed 
paradoxical embolism. The Amplatzer Septal Occluder is a percutaneous, transcatheter, atrial septal 
defect closure device intended for the occlusion of ASDs in secundum position or patients who have 
undergone a fenestrated Fontan procedure and who now require closure of the fenestration. The 
Amplatzer Cribriform Occluder is a percutaneous, transcatheter, ASD closure device intended for the 
closure of multi-fenestrated (cribriform) atrial septal defects. Patients indicated for ASD closure have 
echocardiographic evidence of fenestrated ostium secundum atrial septal defect and clinical evidence of 
right ventricular volume overload. The Amplatzer Muscular VSD Occluder is a percutaneous, 
transcatheter, VSD closure device indicated for use in patients with complex ventricular septal defects 
(VSD) of significant size to warrant closure (large volume left to right shunt, pulmonary hypertension, or 
clinical symptoms of congestive heart failure who are considered to be at high risk for standard transatrial 
or transarterial surgical closure based on anatomical conditions and/or based on overall medical 
condition. The Amplatzer Post-Infarct Muscular VSD Occluder is a minimally invasive alternative to 
achieving post-infarct muscular VSD closure in patients who are not satisfactory candidates for open 
surgical repair. The Amplatzer Trevisio Delivery System is an important accessory for delivery of 
Amplatzer occlusion devices and therefore shares the life-saving benefits of these occlusion devices. 
There are no additional benefits of being in the PAS beyond standard of care.  
15.2 Foreseeable Adverse Events and Anticipated Adverse Device Effects 
Risks associated with the specified device and procedure, together with their likely incidence, are 
described Appendix I. There may be risks related to the device under study that are unknown at present. 
Likewise, the exact frequency of those risks may be unknown. 
15.3 Residual Risks Associated with the Device Under Study, as Identified in the 
Risk Analysis Report 
Risk analysis of the Amplatzer Trevisio Delivery System has been performed in accordance with the Risk 
Analysis Plan and Use Failure Mode Effect Analysis (UFMECA) to systemically identify potential hazards 
associated with the design and use of this device. Based upon bench testing, published literature and 
post market data from previous device, all risks have been identified and determined to be within 
acceptable levels (see Appendix I). Information of residual risks and safety is disclosed in the IFU in the 
form of clear instructions of what actions to take or to avoid in order to avoid a hazardous situation of 
harm from occurring (contra-indications, warnings, and precautions).The anticipated AEs disclosed in the 

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IFU provide further information to enable the user, and potentially the patient, to make an informed 
decision that weights the residual risk against the benefit of using the device. 
15.4 Risks Associated with Participation in this Clinical Study 
Use of the Amplatzer Trevisio Delivery System in this study is identical to the use outside of this study. 
Thus, the possible risks and discomforts are similar to any routine commercial use of the Amplatzer 
Trevisio Delivery System.  These risks have been identified in the IFU. All pre-protocol required 
procedures are considered standard of care and do not constitute as additional risk for the clinical study 
participants.  
15.5 Steps Taken to Control or Mitigate Risks 
In-depth recommendations, special precautions and instructions regarding device handling and 
placement are included in the IFU. It is also stated in the IFU that the devices can only be used by 
physicians who are trained in standard transcatheter techniques. This statement is interpreted to mean 
that the physician users are expected to be aware of the known and foreseeable safety risks associated 
with the use of the devices including the surgical and/or non-surgical treatment of these conditions. 
 
All Investigators involved in the conduct of the clinical study will be qualified by education, training, or 
experience to perform their tasks. All adverse events and device deficiencies will be reported to the 
Sponsor and will be monitored internally for safety surveillance purposes. 
15.6 Risk to Benefit Rationale 
The benefit of using the Amplatzer PFO, ASD, and VSD devices is stated in section 15.1. The Amplatzer 
Trevisio Delivery System allows use of these devices as intended and thus shares the life-saving 
benefits of these occlusion devices. The residual risk evaluated in the risk analysis/evaluation documents 
has been judged to be acceptable based on the criteria defined in the risk management report. Based on 
this analysis and the benefit that these devices provide, it has been determined that the benefits of the 
devices outweigh the risks associated with use, design, and process. 
  

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APPENDIX I. RATES OF FORESEEABLE ADVERSE EVENTS 
Clinical data used to determine foreseeable adverse event rates were compiled from clinical evaluation 
reports, published literature, and data collected within seven (7) days post-implant procedure during the 
RESPECT trial and ASD PMS II trial (Abbott data on file). Clinical data from the VSD closure groups are 
not included due to the low frequency of VSD closure procedures.   
 
Adverse Event Terms 
Proposed Frequencies for Trevisio Intravascular Delivery System 
Very 
common 
(≥10%) 
Common or 
frequent 
(≥1.0% to 
<10%) 
Uncommon or 
infrequent 
(≥0.1% to 
<1.0%) 
Rare 
(≥0.01% to 
<0.1%) 
Very rare 
(<0.01%) 
Air embolism 
 
 
X 
 
 
Arrhythmia 
 
X 
 
 
 
Arteriovenous fistulae 
 
 
 
 
X 
Bleeding 
 
X 
 
 
 
Brachial plexus injury 
 
 
X 
 
 
Cardiac tamponade 
 
 
X 
 
 
Death 
 
 
 
 
X 
Dissection 
 
 
 
 
X 
Endocarditis 
 
 
X 
 
 
Fever 
 
 
X 
 
 
Hematoma 
 
X 
 
 
 
Infection 
 
 
X 
 
 
Myocardial infarction 
 
 
 
 
X 
Perforation 
 
 
X 
 
 
Peripheral embolism 
 
 
 
 
X 
Peripheral pulse loss 
 
 
 
 
X 
Stroke 
 
 
X 
 
 
Thrombosis 
 
 
X 
 
 
Tissue trauma/damage 
 
 
 
 
X 

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Adverse Event Terms 
Proposed Frequencies for Trevisio Intravascular Delivery System 
Very 
common 
(≥10%) 
Common or 
frequent 
(≥1.0% to 
<10%) 
Uncommon or 
infrequent 
(≥0.1% to 
<1.0%) 
Rare 
(≥0.01% to 
<0.1%) 
Very rare 
(<0.01%) 
Valve damage 
 
 
 
 
X 
Vascular access site 
complications 
 
X 
 
 
 
Vessel trauma/damage 
 
 
 
 
X 
 
 
 
 
 

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APPENDIX II: ABBREVIATIONS AND ACRONYMS 
AE = adverse event 
ASD = atrial septal defect 
ASD PMS II = Atrial Septal Defect Post-Market Surveillance Study II 
ASO = Amplatzer Septal Occluder 
CIP = clinical investigation plan  
CRF = case report form 
DMP = data management plan  
EC = ethics committee 
ECG/EKG = electrocardiogram  
EDC = electronic data capture 
FDA = Food and Drug Administration 
ICE = intracardiac echocardiogram  
IFU = instructions for use 
ITV = TorqVue Intravascular Delivery System  
M-F ASD = multi-fenestrated atrial septal defect 
PFO = patent foramen ovale 
RESPECT = Randomized Evaluation of Recurrent Stroke comparing PFO Closure to  
          Established Current Standard of Care Treatment (a randomized trial to assess   
          safety and effectiveness of PFO closure with the Amplatzer PFO Occluder in    
          cryptogenic stroke patients) 
SAE = serious adverse event 
TEE = transesophageal electrocardiogram 
UCB = upper confidence bound  
UFMECA = Use Failure Mode Effect Analysis 
VSD = ventricular septal defect 
 

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APPENDIX III: SITE CONTACT INFORMATION 
Contact information for each participating clinical site is available under separate cover.  

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APPENDIX IV: LABELS 
Product labels will be provided under a separate cover. A copy of the Labels can be obtained upon 
request from the Sponsor Clinical Project Manager. 

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APPENDIX V: CASE REPORT FORMS 
Case Report Forms will be provided under a separate cover. A copy of the Case Report Forms can be 
obtained upon request from the Sponsor Clinical Project Manager. 

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APPENDIX VI: INFORMED CONSENT FORM 
Informed Consent Forms will be provided under a separate cover. A copy of the Informed Consent 
Forms can be obtained upon request from the Sponsor Clinical Project Manager. 
 
 

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APPENDIX VII: MONITORING PLAN 
A copy of the Monitoring Plan can be obtained upon request from the Sponsor Clinical Project Manager 
for the clinical study. 

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APPENDIX VIII: REVISION HISTORY 
This CIP may be amended as appropriate by the Sponsor. Rationale will be included with each amended 
version in the revision history table below. The version number and date of amendments will be 
documented. 
 
EC and relevant Regulatory Authorities, if applicable, will be notified of amendments to the CIP. 
 
Amendment 
Number 
Version
Date
Details
Rationale
Not Applicable
A
03 June 2020
First release of CIP
NA
 

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APPENDIX IX: CIP SUMMARY 
Clinical Study Name 
and Number
ABT-CIP_10319 Ver. A / CRD 963 Trevisio PAS 
Title 
A single-arm, non-randomized, multi-center clinical study of the 
Amplatzer™ Trevisio™ Intravascular Delivery System for facilitating 
percutaneous, transcatheter implantation of the Amplatzer™ 
Occluder Devices 
Objective(s) 
The primary objective of this clinical study is to characterize the safety and 
effectiveness of the Amplatzer Trevisio Delivery System for facilitating 
percutaneous, transcatheter implantation of the Amplatzer PFO Occluder, 
Amplatzer ASO, Amplatzer Cribriform Occluder, Amplatzer Muscular VSD 
Occluder IFU, and Amplatzer Post-Infarct Muscular VSD Occluder IFU). 
Device Under 
Investigation
Amplatzer™ Trevisio™ Intravascular Delivery System 
Number of Subjects 
Required for Inclusion 
in Clinical Study
A minimum of 215 subjects with a PFO or ASD, and a minimum of 44 
subjects with a VSD, will be enrolled in the clinical study.  
Clinical Study Design 
Prospective, multi-center, single-arm, post-approval study  
Primary Endpoint(s) 
Primary Effectiveness Endpoint: Technical success – successful 
deployment and release of at least one device  
 
Primary Safety Endpoint: Device- or procedure-related serious adverse 
events through discharge or 7 days, whichever occurs first
Subject Follow-up 
Subjects will be followed through hospital discharge or 7 days, whichever 
occurs first. Post-implant follow-up data will include: shunt closure status 
(TEE/TTE imaging), adverse events, EKG results, and physical exam 
results.  
Inclusion Criteria 
Subject is indicated for implantation with the Amplatzer Septal Occluder, 
Amplatzer Multi-fenestrated Septal Occluder (“Cribriform”), Amplatzer PFO 
Occluder, Amplatzer Muscular VSD Occluder, or Amplatzer Post-Infarct 
Muscular VSD Occluder. For further detail see CIP section 5.3.2, p. 15.
Exclusion Criteria 
Exclusion criteria for subjects undergoing ASD closure include:  
 
Patients known to have extensive congenital cardiac anomaly that 
can only be adequately repaired by cardiac surgery 
 
Patients known to have sepsis within 1 month prior to implantation, 
or any systemic infection that cannot be successfully treated prior 
to device placement 

Patients known to have demonstrated intracardiac thrombus on 

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echocardiography (especially left atrial or left atrial appendage 
thrombi) 
 
Patients whose size or condition (e.g., too small for 
transesophageal echocardiography [TEE] probe, catheter size, 
vasculature size, active infection) would cause the patient to be a 
poor candidate for cardiac catheterization 
 
Patients with defect margins less than 5 mm to the coronary sinus, 
inferior vena cava rim, an atrioventricular valve, or the right upper 
lobe pulmonary vein 
Exclusion Criteria for Subjects Undergoing PFO Closure 
 Presence of thrombus at the intended site of implant, or 
documented evidence of venous thrombus in the vessels through 
which access to the defect is gained 
 Active endocarditis or other infections producing bacteremia 
 Patients whose vasculature, through which access to the defect is 
gained, is inadequate to accommodate the appropriate sheath size 
 Anatomy in which the AMPLATZER™ PFO device size required 
would interfere with other intra-cardiac or intravascular structures, 
such as valves or pulmonary veins 
 Patients with known hypercoagulable states 
 Patient with intra-cardiac mass or vegetation, thrombus, or tumor 
 
Exclusion Criteria for Patients Undergoing VSD Closure with the 
Amplatzer Muscular VSD Occluder or Amplatzer Post-Infarct Muscular 
VSD Occluder 
 Body weight <8 kg 
 Tetralogy of Fallot 
 Intracardiac thrombi on echocardiography 
 
For further detail see CIP section 5.3.3, p. 16.