AMPLATZER Duct Occluder II Additional Sizes Clinical Study
Phase: NA
Conditions: Patent Ductus Arteriosus
Sponsor: Abbott Medical Devices

Clinical Investigation Plan Cover Page 
NCT Number: 03055858 
ADO II AS 
AMPLATZER Duct Occluder II Additional Sizes (ADO II AS) Clinical Study 
Study Document No: SJM-CIP-10171 
Version D 
Date: 02-AUG-2018 
Sponsor 
St. Jude Medical, Inc. 
Global Clinical Affairs 
5050 Nathan Lane North 
Plymouth, MN 55442 USA 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 1 of 51 
 
ADO II AS 
AMPLATZER Duct Occluder II Additional Sizes (ADO II AS) Clinical Study 
CRD_805 
Study Document No: SJM-CIP-10171 
Version D 
Date:  2 August 2018 
Clinical Investigation Plan (CIP) 
 
 
 
Sponsor  
St. Jude Medical, Inc. 
 
Global Clinical Affairs 
 
5050 Nathan Lane North 
 
Plymouth, MN 55442 USA 
 
National 
Evan M Zahn, MD 
Coordinating 
Cedars-Sinai Health System  
Investigator 
Co-Director, Congenital Heart Program 
 
Director, Division of Pediatric Cardiology 
 
Advanced Health Sciences Pavilion, Suite A3600 
 
127 S. San Vicente Blvd. 
 
Los Angeles, CA 90048 
 
 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 2 of 51 
Table of Contents 
 
1 
Introduction ............................................................................................................................................... 5 
1.1 
Continued Access Protocol (CAP) Enrollment ................................................................................. 5 
1.2 
Scope and Description of CAP Enrollments ..................................................................................... 5 
2 
Background and justification for clinical investigation ............................................................................... 5 
2.1 
Disease to be treated ....................................................................................................................... 5 
2.2 
Current Treatment Options ............................................................................................................... 6 
2.3 
AMPLATZER PDA Occluder ............................................................................................................ 7 
2.4 
Study Rationale (IDE and CAP) ....................................................................................................... 8 
2.4.1 
Pivotal IDE Rationale.................................................................................................................... 8 
2.4.2 
CAP Rationale .............................................................................................................................. 8 
3 
Device(s) under investigation .................................................................................................................... 9 
3.1 
Identification and description of the devices under investigation ..................................................... 9 
3.1.1 
Identification ................................................................................................................................. 9 
3.1.2 
Device Description and Intended Indications for Use ................................................................ 10 
3.1.3 
Device handling and storage ...................................................................................................... 10 
3.2 
Devices accountability .................................................................................................................... 10 
4 
Clinical Investigation Design ................................................................................................................... 11 
4.1 
Clinical Investigation Design for Pivotal IDE Subjects ................................................................... 11 
4.2 
Clinical Investigation Design for CAP Subjects .............................................................................. 11 
4.3 
Objective ......................................................................................................................................... 11 
4.4 
Endpoints ........................................................................................................................................ 11 
4.4.1 
Primary Endpoints (IDE and CAP) ............................................................................................. 11 
4.4.2 
Secondary Endpoint (IDE and CAP) .......................................................................................... 12 
4.4.3 
Descriptive Endpoints and Additional Data for Pivotal IDE Subjects ......................................... 12 
4.4.4 
Descriptive Endpoints and Additional Data for CAP Subjects ................................................... 12 
4.5 
Study Population ............................................................................................................................ 13 
4.5.1 
Inclusion Criteria ......................................................................................................................... 13 
4.5.2 
Exclusion Criteria ........................................................................................................................ 13 
5 
Procedures .............................................................................................................................................. 13 
5.1 
Informed Consent Process ............................................................................................................. 14 
5.1.1 
Special circumstances for informed consent .............................................................................. 14 
5.2 
Point of Enrollment ......................................................................................................................... 14 
5.3 
Scheduled Procedures ................................................................................................................... 15 
5.3.1 
Screening and Baseline for Pivotal IDE subjects ....................................................................... 15 
5.3.2 
Screening and Baseline for CAP subjects.................................................................................. 15 
5.3.3 
Implant/Procedure ...................................................................................................................... 16 
5.3.4 
Post-Procedure ........................................................................................................................... 17 
5.3.5 
Scheduled Follow-ups for Pivotal IDE Subjects ......................................................................... 17 
5.3.6 
Scheduled Follow-ups for CAP Subjects.................................................................................... 18 
5.4 
Study Flow Chart ............................................................................................................................ 18 
5.5 
Description of activities performed by Sponsor Representatives ................................................... 22 
5.6 
Subject Study Completion .............................................................................................................. 22 
5.7 
Subject Withdrawal ......................................................................................................................... 22 
5.8 
Requirements for Clinical Laboratories .......................................................................................... 23 
5.9 
Study Committees .......................................................................................................................... 23 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 3 of 51 
5.9.1 
Publication Committee................................................................................................................ 23 
5.9.2 
Clinical Events Committee (CEC) .............................................................................................. 23 
6 
Statistical Considerations ........................................................................................................................ 24 
6.1 
Endpoints ........................................................................................................................................ 24 
6.1.1 
Primary Safety Endpoint (IDE and CAP) .................................................................................... 24 
6.1.2 
Primary Effectiveness Endpoint (IDE and CAP) ........................................................................ 24 
6.1.3 
Secondary Endpoint (IDE and CAP) .......................................................................................... 25 
6.1.4 
Descriptive Endpoints and Additional Data for Pivotal IDE Subjects ......................................... 25 
6.1.5 
Descriptive Endpoints and Additional Data for CAP Subjects ................................................... 26 
6.2 
Justification of Clinical Investigation Design .................................................................................. 26 
6.3 
Overall Sample Size for Pivotal IDE Subjects ................................................................................ 26 
6.4 
Overall Sample Size for CAP Subjects .......................................................................................... 26 
6.5 
Timing of Analysis for Pivotal IDE Subjects ................................................................................... 27 
6.6 
Success Criteria for Pivotal IDE Subjects ...................................................................................... 27 
6.7 
Deviations from Statistical Plan ...................................................................................................... 27 
7 
Risks and Benefits .................................................................................................................................. 27 
7.1 
Risks associated with the Device under Investigation ................................................................... 27 
7.1.1 
Anticipated Adverse Device Effects ........................................................................................... 27 
7.1.1 
Risks associated with Clinical Investigation Assessments ......................................................... 29 
7.2 
Possible interactions with concomitant treatments ........................................................................ 30 
7.3 
Risk Control Measures ................................................................................................................... 30 
7.4 
Anticipated Benefits ........................................................................................................................ 31 
7.5 
Risk-to-Benefit Rationale ................................................................................................................ 31 
7.6 
History of device modifications or recall ......................................................................................... 31 
8 
Requirements for Investigator records and reports ................................................................................ 31 
8.1 
Deviations from CIP ........................................................................................................................ 31 
8.2 
Safety reporting .............................................................................................................................. 32 
8.2.1 
Subject Death ............................................................................................................................. 33 
8.2.2 
Unanticipated Adverse Device Effect ......................................................................................... 33 
8.2.3 
Complaints .................................................................................................................................. 33 
8.3 
Source records ............................................................................................................................... 33 
8.4 
Records retention ........................................................................................................................... 33 
9 
Clinical Data Handling ............................................................................................................................. 33 
9.1 
Protection of Personally Identifiable Information ............................................................................ 34 
9.2 
Data Management Plan .................................................................................................................. 34 
9.3 
Document and Data Control ........................................................................................................... 34 
9.3.1 
Traceability of Documents and Data .......................................................................................... 34 
9.3.2 
Recording Data ........................................................................................................................... 34 
10 
Monitoring ........................................................................................................................................... 34 
11 
Compliance Statement ....................................................................................................................... 34 
11.1 
Statement of Compliance ............................................................................................................... 34 
11.2 
Quality Assurance audits and Regulatory Inspections ................................................................... 35 
11.3 
Repeated and Serious Non-Compliance ........................................................................................ 35 
12 
Suspension or premature termination of the clinical investigation ..................................................... 35 
13 
Clinical Investigation Conclusion ........................................................................................................ 36 
14 
Publication Policy ............................................................................................................................... 36 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 4 of 51 
15 
Reporting Results on ClincalTrials.gov Website ................................................................................ 36 
Appendix A: CIP Revisions ............................................................................................................................ 37 
Appendix B: Definitions .................................................................................................................................. 39 
Non-study Specific Definitions .................................................................................................................... 39 
Study Specific Definitions ........................................................................................................................... 40 
Appendix C: Labels ........................................................................................................................................ 42 
Appendix D: Bibliography ............................................................................................................................... 43 
Appendix E: American Heart Association Recommendations for Prophylaxis .............................................. 45 
Appendix F: Transthoracic Echocardiography (TTE) Protocol ....................................................................... 47 
Appendix G: Case Report Forms ................................................................................................................... 50 
Appendix H: Template Informed Consent Form ............................................................................................. 51 
 
 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 5 of 51 
1 
Introduction 
This document is a clinical investigation plan (CIP) for the AMPLATZER Duct Occluder II® Additional Sizes 
(ADO II AS) clinical investigation. This clinical investigation is intended to demonstrate the safety and 
effectiveness of St. Jude Medical’s ADO II AS in subjects with a patent ductus arteriosus (PDA). This clinical 
investigation will be conducted under an investigational device exemption (IDE) and is intended to support 
market approval of the ADO II AS device in the United States and other countries. This clinical investigation 
is sponsored by St. Jude Medical (SJM). 
 
This clinical investigation will be conducted in accordance with this CIP. All parties involved in the conduct 
of the clinical investigation will be qualified by education, training, or experience to perform their tasks and 
this training will be documented appropriately. 
 
1.1 
Continued Access Protocol (CAP) Enrollment 
Protocol revision C allows for additional subject enrollment in the ADO II AS study, with additional 
prospective collection of safety and effectiveness data on the ADO II AS device upon completion of 
enrollment of the pivotal cohort and while the pre-market approval (PMA) application is being prepared and 
under FDA review.  
1.2 
Scope and Description of CAP Enrollments 
This revision to the protocol provides additional language within Sections 4, 5, and 6, which describe 
procedural details applicable to CAP subjects enrolled under the revised protocol. Sections pertaining only 
to CAP subjects are organized as sub-sections of their corresponding protocol section. These sub-sections 
are labeled ‘for CAP Subjects’ and are underlined for identification. For these subjects, the content of these 
sub-sections replaces the corresponding content of the associated protocol section. If sections of this 
protocol are not accompanied by a section specified for CAP subjects, then the original IDE section will be 
followed for all subjects. 
 
Subjects previously enrolled in the IDE will not be affected by the protocol revision as they will continue to 
follow the pivotal IDE requirements. 
2 
Background and justification for clinical investigation 
2.1 
Disease to be treated 
In the fetus, 85% of the blood bypasses the unexpanded lungs. The blood flows from the right ventricular 
outflow tract through the ductus arteriosus to the aorta. At birth, the increase in oxygen tension leads to 
inhibition of local prostaglandins and causes functional closure of the ductus, followed by anatomic closure. 
A patent ductus arteriosus (PDA) is a persistence of the fetal connection (ductus arteriosus) between the 
aorta and pulmonary artery after birth, resulting in a persistent left-to-right shunt. PDA is the most common 
congenital heart lesion in newborns and accounts for approximately 5 to 10% of all congenital heart defects. 
The incidence of a PDA is approximately 1 in 2,000 term newborns and this incidence increases to >50% in 
premature babies, and >80% in severely premature low birth weight infants (<1200 gm) [1]. PDA is more 
commonly seen in female infants, with a female-to-male ratio of 2:1 for PDA [2]. 
 
Typically the PDA will close in the first 10-18 hours of life, and anatomically, it is generally closed within six 
weeks [3]. PDA anatomy varies considerably both in diameter, length and configuration. Krichenko et al 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 6 of 51 
provided angiographic classification of the different PDA configurations labeled as A-type through E-type, 
which recently has been expanded by Philip et al [4] to also include the tubular and longer F-type 
configuration commonly seen in premature born infants [5]. The PDA diameter refers to its narrowest 
segment, which is smaller than 4 mm in 78% of cases [6]. 
 
While this lesion may spontaneously resolve in some neonates, persistence, particularly in premature 
infants is a major health concern. The presence of a hemodynamically significant PDA in premature infants 
has been associated with an increased risk of developing necrotizing enterocolitis, chronic respiratory 
disease, pulmonary hemorrhage, intraventricular hemorrhage, and death [1, 7]. Should a baby survive the 
neonatal period with a significant PDA, this lesion can result in continued morbidity during infancy, which 
includes failure to thrive, chronic respiratory infections, and repeated hospital admissions. 
 
Closure of PDA is indicated to restore hemodynamic status and to prevent congestive heart failure, 
pulmonary vascular disease, and, in the long-term, bacterial endocarditis [8]. The risk of endocarditis with 
small residual shunts remains unknown, although continued bacterial endocarditis prophylaxis is generally 
advocated as long as flow persists or a murmur can be auscultated [9]. 
2.2 
Current Treatment Options 
The current standard of care for a persistent patent ductus arteriosus (PDA) includes the following two 
treatment options: surgical ligation or closure with alternative devices. 
Surgical Ligation 
PDA was the first congenital cardiac heart disease to be conquered by surgeons. The first surgical ligation 
of a PDA was performed by Gross and Hubbard in 1939 [10]. Surgical ligation or ligation and division were 
the standard of care for persistent PDA until the advent of transcatheter closure. Today surgery remains the 
standard of care for PDA closure in preemies and infants with large hemodynamically significant PDAs. 
Although the standard of care, surgical ligation has been associated with the potential risk for significant 
procedural complications (pneumothorax, hypothermia, bleeding, phrenic nerve palsy, chylothorax, wound 
infection, vocal cord paralysis, and thoracic scoliosis [1, 7, 11, 12]), significant post-procedural clinical 
decline known as post-ligation syndrome [13], and poor long-term outcomes including neuro-developmental 
delay, retinopathy of prematurity and chronic lung disease (bronchopulmonary dysplasia) [11, 12]. Because 
a growing body of literature has suggested that surgical ligation of PDA in premature neonates may actually 
result in worse outcomes than no treatment at all a trend of permissive conservative observation of this 
lesion has developed, reserving surgery for only the most severe cases. Unfortunately, recent data 
suggests that this approach is associated with an increased risk for the development of chronic lung 
disease and death [15]. 
Transcatheter device closure 
The first interventional closure of a PDA was performed by Portsmann in 1967 [14] and has emerged as the 
gold standard for treatment of this lesion in larger infants, children and adults [7]. Historically, transcatheter 
closure of a PDA has not been performed in infants and premature neonates for a variety of reasons 
including: fear of patient fragility; concerns regarding vascular access and arterial injury; unknown effects of 
intravenous contrast media; concerns regarding catheter manipulation; and most importantly, absence of a 
suitable PDA closure device. Recently, a growing body of clinical evidence has emerged suggesting that 
transcatheter closure of PDA can be performed safely and effectively in selected infants and premature 
newborns. The ADO II AS device has the ideal characteristics (size, shape, delivery system) for this unique 
population but its lack of availability in the USA has limited wide spread adaptation of this procedure.  

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 7 of 51 
2.3 
AMPLATZER PDA Occluder 
The AMPLATZER Duct Occluder II received PMA approval on August 15, 2013. A multi-center US study of 
the AMPLATZER Duct Occluder II, included 192 subjects who were greater than six months in age and 
greater than six kilograms in weight [16]. A total of 178/192 (92.7%) subjects were successfully implanted 
with the AMPLATZER Duct Occluder II. There were 3 reports of device or procedure-related Serious 
Adverse Events (SAEs) within 180 days of implant (3/192; 1.56%). Of the successful implants, complete 
closure of the ductus was reported in 98.19% of subjects at the six-month follow-up interval. The 
AMPLATZER Duct Occluder II Additional Sizes device was designed as a line extension to ADO II to allow 
closure of smaller sizes of a PDA. 
Key differences between the ADO II and ADO II AS device are the size and shape. The ADO II device has 
a narrow waist with larger retention discs, while the ADO II AS device has a cylindrical waist with lower 
profile retention discs that are minimally larger than the waist and resulting in a nearly isodiametric device. 
The ADO II device is larger and designed to treat a PDA with a diameter ranging between 2.5 and 5.5 mm 
and a length between 5 and 12 mm. The ADO II AS is designed to treat a PDA with a diameter ≤ 4.0 mm 
and a length ≥ 3.0 mm. 
The ADO II AS is a self-expanding nitinol mesh occlusion device with a central waist and retention discs 
deployed on both ends. The central waist of the device ranges in diameter from 3 to 5 mm in 1 mm 
increments. The retention discs have a diameter 1, 1.25, or 1.5 mm larger than the waist diameter for the 3, 
4, and 5 mm waist diameters, respectively.  Each device size is available in 2, 4, or 6 mm length. The 
device can be delivered forward from a 4 French (4F) delivery catheter either by the aortic or venous route. 
The central waist is designed to fill the ductal lumen, and the retention discs are designed to deploy in the 
pulmonary and the aortic end of the ductus arteriosus. The ADO II AS comes pre-attached to a delivery 
cable. The delivery cable’s distal tip is extremely flexible and has angiographically visible properties, which 
helps to achieve precise placement of the proximal disc during device placement and unscrewing. 
TorqueVue Low Profile Delivery Catheter has 4F outer diameter compatible with all 9 ADO II AS occluders. 
The ADO II AS device has a design well suited to the anatomy of the infant and neonatal PDA which tends 
to be more tubular (so-called F-type) than the PDA of older children and adults which tends to be conical in 
shape [17]. Importantly, the short lengths (2 and 4 mm) of the ADO II AS may greatly reduce the risk of 
descending aortic or left pulmonary arterial stenosis that can be caused by device protrusion from either 
end of the PDA in these small patients. The ADO II AS device has a tubular shape with low profile discs, 
which makes it suitable for insertion into a tubular PDA from either an anterograde or a retrograde 
approach, facilitating successful implant and making it possible to avoid access via the femoral artery 
(important in premature infants). Finally, the softer delivery wire and low profile system (4F) used for the 
ADO II AS device are ideal for the small delicate vasculature of small infants. Procedural related 
complications associated with implanting the device in small infants may be minimized by utilizing an 
echocardiographic anterograde approach and avoiding invasive hemodynamic measurement and 
angiographic image acquisition. 
 
Although the device is recommended for ductal diameters up to 4 mm, the largest waist diameter available 
is 5 mm with the retention discs only 1.5 mm larger. This leaves very little extra anchoring with this device 
compared to either the ADO or the ADO II, and therefore, the maximum diameter for deployment should be 
less than or equal to 4 mm. Tubular PDA’s in young infants may stretch more easily. The small, flexible 
retention discs provide minimal anchoring support, meaning that the device relies heavily on constraint of 
the central portion for stable positioning. Careful device diameter sizing is required in larger ductal 
diameters to avoid embolization. The device may be implanted in ducts that are longer in length than the 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 8 of 51 
length of the device, as long as the selected device diameter satisfies the specified diameter within the 
sizing chart. 
2.4 
Study Rationale (IDE and CAP) 
2.4.1 
Pivotal IDE Rationale 
The rationale for this investigation is to offer patients a safe and effective device for closure of a small PDA 
(≤ 4 mm diameter) with an FDA approved device. Current treatment for smaller PDAs includes off label use 
of devices. Major drawbacks of current devices in terms of this unique population include: device length (too 
long, placing the left pulmonary artery and descending aorta at risk for obstruction), device shape (large 
retention disks placing the left pulmonary artery and descending aorta at risk for obstruction), and stiffness 
of delivery systems. Currently there is no FDA approved device for PDA closure in patients <5 kg or <6 
months of age, which encompasses virtually all infants, neonates and premature neonates. 
 
2.4.2 
CAP Rationale 
The rationale for the CAP is to allow current IDE study implanters to maintain their technical proficiency in 
ADO II AS device implantation and to allow additional implanters to gain experience with the device after 
enrollment completion in the pivotal cohort and while the pre-market approval (PMA) application for the 
ADO II AS device is being prepared and is under FDA review. Data from the CAP may be used to support 
post approval requirements for the ADO II AS occluder.  
 
 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 9 of 51 
3 
Device(s) under investigation 
3.1 
Identification and description of the devices under investigation 
3.1.1 
Identification 
Figure 1: ADO II AS Device 
 
Table 1: Identification of Devices under Investigation 
Device Name 
Model/Type 
A 
mm (in) 
B 
mm (in) 
C 
mm (in) 
Investigational 
or Market 
Released 
ADO II AS Occluder 
9- PDA2ASIDE-03-02 
4.00 (0.157) 
3.00 (0.118) 
2.00 (0.079) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-03-04 
4.00 (0.157) 
3.00 (0.118) 
4.00 (0.157) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-03-06 
4.00 (0.157) 
3.00 (0.118) 
6.00 (0.236) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-04-02 
5.25 (0.207) 
4.00 (0.157) 
2.00 (0.079) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-04-04 
5.25 (0.207) 
4.00 (0.157) 
4.00 (0.157) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-04-06 
5.25 (0.207) 
4.00 (0.157) 
6.00 (0.236) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-05-02 
6.50 (0.256) 
5.00 (0.197) 
2.00 (0.079) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-05-04 
6.50 (0.256) 
5.00 (0.197) 
4.00 (0.157) 
Investigational 
ADO II AS Occluder 
9- PDA2ASIDE-05-06 
6.50 (0.256) 
5.00 (0.197) 
6.00 (0.236) 
Investigational 
AMPLATZER™ 
TorqVue™ LP 
Catheter 
9-TVLPC4F90/080 
Not  
Applicable 
Not 
Applicable 
Not  
Applicable 
Market Released 
 
Table 2: Device Sizing Chart for subjects >2 Kg 
Measured Ductus 
Diameter mm (in) 
Minimal Measured Ductus Length mm (in) 
3–4 (0.118–0.157) 
4.1–6 (0.161–0.236) 
6.1–8 (0.240–0.315) 
≤2 (≤0.079) 
9-PDA2ASIDE-03-02 
9- PDA2ASIDE-03-04 
9- PDA2ASIDE-03-06 
2.1–3 (0.083–0.118) 
9- PDA2ASIDE-04-02 
9- PDA2ASIDE-04-04 
9- PDA2ASIDE-04-06 
3.1–4 (0.122–0.157) 
9- PDA2ASIDE-05-02 
9- PDA2ASIDE-05-04 
9- PDA2ASIDE-05-06 
 
 

 
Study Document No: SJM-CIP-10171  
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Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 10 of 51 
Table 3: Device Sizing Chart for subjects ≤2 Kg 
Measured Ductus 
Diameter mm (in) 
Minimal Measured Ductus Length mm (in) 
3–6 (0.118–0.236) 
≥6.1 (≥0.240) 
≤1.5 (<0.059) 
9-PDA2ASIDE-03-02 
9- PDA2ASIDE-03-04 
1.6–2.5 (0.063–0.098) 
9- PDA2ASIDE-04-02 
9- PDA2ASIDE-04-04 
2.6–4 (0.102–0.157) 
9- PDA2ASIDE-05-02 
9- PDA2ASIDE-05-04 
3.1.2 
Device Description and Intended Indications for Use 
The AMPLATZER Duct Occluder II Additional Sizes (ADO II AS) is a percutaneous transcatheter occlusion 
device intended for the non-surgical closure of PDAs. The AMPLATZER TorqVue LP Delivery System is 
intended to facilitate the attachment, loading, delivery and deployment of the ADO II AS. 
The ADO II AS is a self-expandable Nitinol mesh occlusion device for the occlusion of patent ductus 
arteriosus (PDA). The device configuration is a central waist with two retention disks. The central waist is 
designed to fill the defect and the two retention disks are designed to be deployed on the arterial and 
venous sides of the defect. Because of the isodiametric design of the device it may be implanted in ducts 
longer than the device as long as the diameter of the device is sufficiently large to constrain the device 
within the PDA. Devices are available in three lengths to accommodate various lengths of PDA. The ADO II 
AS has a screw attachment for a delivery wire and radiopaque marker bands at both ends. 
The AMPLATZER TorqVue LP Catheter consists of a delivery catheter, Touhy-Borst hemostasis valve, 
loading device, and a self-sealing hemostasis valve. The delivery catheter was designed to facilitate 
attachment, loading, delivery and deployment of AMPLATZER devices pre-loaded onto a delivery wire. The 
TorqVue LP Catheter is not investigational. 
3.1.3 
Device handling and storage 
Sponsor requires all investigational products be stored, according to the labeling and instructions for use, in 
a secure area to prevent unauthorized access or use. 
3.2 
Device accountability 
Investigational product shall be shipped to sites or approved SJM personnel after sites receive 
documentation of site activation and shipping authorization is complete.  
 
The Principal Investigator or an authorized designee must maintain records of the date of receipt, the 
identification of each investigational device (batch number, serial number or unique code), the subject 
identification, the date of use, the expiration date and final disposition.  
 
Storage locations for the devices at investigational sites will be locked with access restricted only to 
investigators and authorized personnel. 
 
Sponsor must also maintain device accountability documenting all shipments and returns of investigational 
devices. 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 11 of 51 
4 
Clinical Investigation Design 
4.1 
Clinical Investigation Design for Pivotal IDE Subjects 
The ADO II AS IDE study is a single arm, prospective, multicenter, non-randomized clinical investigation 
designed to characterize the safety and effectiveness of the ADO II AS device in patients with a patent 
ductus arteriosus (PDA). The study will be conducted at up to 10 centers within the United States. 
 
Subjects will be implanted with the ADO II AS device using a transcatheter femoral vessel approach under 
fluoroscopic and echocardiographic guidance. Clinical follow-up will be performed at 1 month, 6 months, 12 
months, 24 months, and 36 months following the implant procedure. A pre-market approval (PMA) 
application will be submitted after 40 subjects have reached 6 months of follow-up post implant attempt. A 
minimum of 15 subjects will be enrolled with a weight ≤ 2 kg. In the event there is difficulty in enrolling 15 
subjects with a weight of < 2 kg, a PMA application will be submitted after 25 subjects with weight > 2 kg 
have reached 6 months of follow-up. An additional submission will be done when 15 subjects with a weight 
of < 2 kg reach 6 months of follow-up. Follow-up after 6 months will be used to satisfy the post-approval 
requirements. Enrollment and follow-up occurring after the PMA is submitted will be used to satisfy post-
approval requirements. 
 
The clinical investigation will be conducted at approximately 10 centers in the United States.  
Up to fifty (50) subjects will be enrolled in the clinical investigation. No site may enroll more than 30% of 
total subjects. 
 
The expected duration of enrollment is approximately 18 months. The total duration of the clinical 
investigation is expected to be 4.5 years. 
4.2 
Clinical Investigation Design for CAP Subjects 
A maximum of 150 subjects may be enrolled under Revision C of this protocol. A maximum of 10 centers in 
the United States may participate in this study. There will be no limit on the number of subjects enrolled at 
each site. 
4.3 
Objective 
The objective of this clinical investigation is to characterize the safety and effectiveness of the ADO II AS 
device to close the ductus arteriosus in subjects with a patent ductus arteriosus (PDA). 
4.4 
Endpoints 
The safety and effectiveness endpoints of the clinical investigation are as follows:  
4.4.1 
Primary Endpoints (IDE and CAP) 
Primary Safety Endpoint: 
The primary safety endpoint is the rate of major complications through 180 days after an attempted ADO II 
AS device implant (refer to Appendix B for definitions). 
 
 
 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 12 of 51 
Primary Effectiveness Endpoint: 
The primary effectiveness endpoint is the rate of effective closure of the ductus arteriosus among patients 
with a successful ADO II AS implant as assessed by the presence of either a Grade 0 or Grade 1 shunt, as 
defined below, at the six-month follow-up by transthoracic echocardiography (TTE). 
 
PDA shunt definition: 
• 
Grade 0—none; 
• 
Grade 1—trivial (narrow jet adjacent to the device via the PDA). Note: the presence of flow via 
existing or newly formed aortopulmonary collaterals should not be considered as representing a 
shunt via the PDA. (see references in Appendix F by Skinner and Acherman) 
• 
Grade 2—mild (broader jet filling proximal left pulmonary artery branch and extending to main 
pulmonary artery); 
• 
Grade 3/4—moderate to severe (wide jet filling the main pulmonary artery and extending to 
pulmonary valve or distal pulmonary artery branches, which also may be accompanied with the 
presence of flow reversal in the abdominal aortic Doppler pattern during diastole) 
4.4.2 
Secondary Endpoint (IDE and CAP) 
The secondary endpoint is the rate of significant obstruction of the pulmonary artery or aorta through the 6-
month follow-up visit per the following definitions: 
1. Significant obstruction of the left pulmonary artery is defined as less than 30% flow to the left lung 
by lung perfusion scan or a peak instantaneous gradient in left pulmonary artery ≥35 mmHg by 
echocardiogram if lung perfusion scan is not available. OR 
2. Significant obstruction of the aorta is defined as a gradient of ≥20 mmHg in the aortic isthmus by 
invasive aortic catheterization or a mean gradient ≥20 mmHg in the aortic isthmus by 
echocardiogram if invasive aortic catheterization is not available. 
4.4.3 
Descriptive Endpoints and Additional Data for Pivotal IDE Subjects 
Descriptive endpoints will be reported using summary statistics.   
• 
Implant success  
• 
PDA shunt grade status at each follow-up visit 
• 
Gradient measurements of the pulmonary artery and aorta at each follow-up visit 
• 
Major and Minor Complications 
• 
Death 
• 
Additional data: demographics and baseline characteristics, procedure information, and left 
ventricular function and dimensions, pulmonic and tricuspid regurgitation, adverse events, 
withdrawal and protocol deviations will also be summarized at each follow-up visit.   
4.4.4 
Descriptive Endpoints and Additional Data for CAP Subjects 
Descriptive endpoints will be reported using summary statistics.   
• 
Implant success  
• 
Major and Minor Complications 
• 
Death 
• 
Additional data:  
Demographics and baseline characteristics, procedure information, left ventricular function and 
dimensions and pulmonic and tricuspid regurgitation at 6 months, and adverse events, withdrawal 
and protocol deviations will also be summarized at each follow-up visit.   

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
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Page 13 of 51 
4.5 
Study Population 
The intended population for this clinical investigation is patients greater than 3 days of age with a PDA 
requiring closure.  
4.5.1 
Inclusion Criteria 
To participate in this clinical investigation, the subject must meet all of the following inclusion criteria: 
• 
Diagnosis of a PDA 
• 
PDA ≤ 4mm in diameter 
• 
PDA ≥ 3mm in length 
• 
Subject (or legally authorized representative) is willing to comply with all pre-procedure, post-
procedure, and follow-up testing requirements and provides consent to participate in the clinical 
study * 
 
* This study is enrolling children and all local laws and governing IRB requirements will be followed for 
obtaining informed consent. 
4.5.2 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria must be excluded from the clinical investigation: 
• 
Weight < 700 grams at time of the procedure 
• 
Age < 3 days at time of procedure 
• 
Coarctation of the aorta 
• 
Left pulmonary artery stenosis 
• 
Cardiac output that is dependent on right to left shunt through the PDA due to pulmonary 
hypertension 
• 
Intracardiac thrombus 
• 
Active infection requiring treatment at the time of implant 
• 
Female subjects of child bearing potential are either pregnant or desire to become pregnant within 
six months post implant  
• 
Other disease process likely to limit survival to less than six (6) months 
• 
Participating in another study for an investigational drug and/or device that may clinically interfere 
with this study's endpoints 
5 
Procedures 
Approval from the Sponsor must be received prior to initiating study procedures. 
 
Enrolled subjects (as defined in section 5.2) will undergo a PDA closure procedure with the ADO II AS 
device. Post-procedure, the subject will have follow-up visits at 30 days, 6 months, 12 months, 24 months, 
and 36 months. Subjects who do not have a successful implant will be withdrawn upon completion of the 
30-day follow-up visit. Upon completion of the 36-month follow-up visit, the subject will be considered to 
have completed the follow-up requirements of this clinical investigation. The Principal Investigator should 
arrange for appropriate care of subjects following study completion.  
 
The following sections provide a detailed description of procedures required by this CIP. 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 14 of 51 
5.1 
Informed Consent Process 
The Principal Investigator or his/her authorized designee will conduct the Informed Consent Process, as 
required by applicable regulations and the center’s IRB. This process will include a verbal discussion with 
the patient and/or patient’s legally authorized representative on all aspects of the clinical investigation that 
are relevant to the patient’s decision to participate, such as details of clinical investigation procedures, 
anticipated benefits, and potential risks of clinical investigation participation. During the discussion, the 
Principal Investigator or his/her authorized designee will avoid any improper influence on the patient’s 
legally authorized representative and will respect patient’s legal rights. The patient’s legally authorized 
representative shall be provided with the informed consent form written in a language that is 
understandable to the subject’s legally authorized representative and has been approved by the center’s 
IRB. The patient’s legally authorized representative shall have adequate time to review, ask questions and 
consider participation. 
 
If the patient’s legally authorized representative agrees to participate, the Informed Consent form must be 
signed and dated by the patient’s legally authorized representative and by the person obtaining the consent. 
The signed original Informed Consent will be filed in the subject’s hospital or research charts, and a copy 
will be provided to the subject. 
 
The Principal Investigator or his/her authorized designee will document the informed consent process in the 
subject’s hospital and/or research charts. The date of signature will be entered on an appropriate Case 
Report Form (CRF). 
 
Failure to obtain informed consent from a subject prior to clinical investigation enrollment should be 
reported to Sponsor within 5 working days and to the reviewing center’s IRB according to the IRB’s/ EC’s 
reporting requirements. 
 
The Principal Investigator or his/her authorized designee will inform the subject of any important new 
information about the clinical investigation. 
5.1.1 
Special circumstances for informed consent 
Patients under the age of 18 will be enrolled in this clinical investigation. Informed consent must be obtained 
using the IRB approved informed consent in accordance with IRB requirements. 
 
If the patient is under the age of 18, the legally authorized representative will represent the patient during 
the informed consent process, which will be performed according to the requirements in section 5.1. The 
patient under the age of 18 will also be informed about the clinical investigation within his/her ability to 
understand. Per state, local, and/or IRB requirements, processes will be followed and documented to collect 
assent for minor children. 
5.2 
Point of Enrollment 
A patient is considered enrolled in the clinical investigation from the moment the patient’s legally authorized 
representative has provided a written Patient Informed Consent, has been confirmed to meet all inclusion 
criteria, meets none of the exclusion criteria, and the TorqVue™ LP Catheter (9-TVLPC4F90/080) is 
inserted into the vasculature of the subject. An intra-procedural echocardiogram or angiogram must be 
performed to confirm the sizing inclusion criteria of the PDA length (≥ 3 mm) and PDA diameter (≤ 4 mm) 
prior to inserting the delivery catheter into the vasculature. 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 15 of 51 
The Principal Investigator or delegated study personnel will record enrollment information (name of the 
clinical investigation, date of consent and Inclusion/exclusion information) in the hospital records and 
complete and submit an Enrollment CRF in a timely manner. 
 
Notification of enrollment to the Sponsor is considered to have occurred when the Procedure CRF has been 
received by the Sponsor. 
5.3 
Scheduled Procedures  
The Principal Investigator is responsible for ensuring all clinical investigation data is collected as required 
per CIP scheduled procedures. 
 
Trained Sponsor personnel may provide technical expertise and technical guidance on the use of the ADO 
II AS device, including training and proctored case coverage. Refer to section 5.6 for specifics. 
5.3.1 
Screening and Baseline for Pivotal IDE subjects 
Potential subjects presenting at the investigational sites will be fully informed about the clinical investigation, 
following the established Informed Consent process described in section 5.1. Once a duly dated and signed 
Informed Consent Form is obtained, the study-specific screening procedures and assessments may begin.  
 
The following assessments are performed as part of the screening process through medical record review 
or prospective tests and evaluations: 
• 
Demographics- including subject’s age and gender 
• 
Physical examination-  
o 
include subject’s weight, upper and lower extremity blood pressure measurements taken 
during visit, heart murmur evaluation, and assessment of femoral pulses. 
• 
Medical History-  
o 
indicate subject’s risk factors, relevant co-morbidities, neonatal ICU status, previous cardiac 
procedures 
• 
Cardiovascular History (most recent information closest to baseline visit)  
• 
Pregnancy test (required only for females of child bearing potential) 
• 
Transthoracic echo (TTE) - within 14 days prior to the device implant procedure 
o 
PDA measurements, left ventricular function and dimensions (area and length), pulmonary 
and aortic flow and dimensions, and pulmonic and tricuspid valve regurgitation 
• 
Electrocardiogram (ECG) 
• 
Chest X-ray (CXR) – Anteroposterior view 
 
Baseline assessments must be collected within 30-days prior to the procedure, unless noted differently 
above. Records of patients who are screened must be maintained. 
 
In case the subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject is 
considered a screening failure. The Principal Investigator or the delegated study personnel will record the 
screening failure in the hospital records and on a screening log as required. 
5.3.2 
Screening and Baseline for CAP subjects 
Potential subjects presenting at the investigational sites will be fully informed about the clinical investigation, 
following the established Informed Consent process described in section 5.1. Once a duly dated and signed 
Informed Consent Form is obtained, the study-specific screening procedures and assessments may begin.  

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 16 of 51 
 
The following assessments are performed as part of the screening process through medical record review 
or prospective tests and evaluations: 
• 
Demographics- including subject’s age and gender 
• 
Physical examination-  
o 
include subject’s weight, heart murmur evaluation, and assessment of femoral pulses. 
• 
Medical History-  
o 
indicate subject’s risk factors, relevant co-morbidities, neonatal ICU status, previous cardiac 
procedures 
• 
Cardiovascular History (most recent information closest to baseline visit)  
• 
Pregnancy test (required only for females of child bearing potential) 
• 
Transthoracic echo (TTE) - within 14 days prior to the device implant procedure 
o 
PDA measurements, left ventricular function and dimensions (area and length), pulmonary 
and aortic flow and dimensions, and pulmonic and tricuspid valve regurgitation 
• 
Electrocardiogram (ECG) 
• 
Chest X-ray (CXR) – Anteroposterior view 
 
 
Baseline assessments must be collected within 30-days prior to the procedure, unless noted differently 
above. Records of patients who are screened must be maintained. 
 
In case the subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject is 
considered a screening failure. The Principal Investigator or the delegated study personnel will record the 
screening failure in the hospital records and on a screening log as required. 
 
5.3.3 
Implant/Procedure 
The ADO II AS device is implanted either transvenously or transarterially via the femoral vessels. To 
minimize complications in small infants (≤ 2 kg) it is recommended to utilize the anterograde transvenous 
approach via the femoral vein as the preferred approach. The use of invasive hemodynamic measurements 
and angiograms are not required in this study to minimize complications, and instead whenever possible 
hemodynamic assessments and visualization of the anatomy may be performed using intra-operative 
echocardiography. The operator must complete an intra-procedural echocardiogram or angiogram to 
confirm the sizing inclusion criteria of the PDA length (≥ 3 mm) and PDA diameter (≤ 4 mm) prior to 
inserting the TorqVue™ LP Catheter into vasculature. 
 
Proper sizing of the ADO II AS device is important in all subjects to reduce risk of complications. Refer to 
the Instructions for Use (IFU) in Appendix C: Product Labeling for important instructions regarding device 
sizing.  
 
The recommended use of Heparin is considered optional, and not required if the subject is at high risk for 
bleeding complications. 
 
Record the required information on the appropriate CRF. 
• 
Transthoracic Echocardiogram (TTE) or angiogram – Intra-procedural 
o 
PDA measurements to confirm eligibility 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
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Page 17 of 51 
• 
Procedural data (including access site, medications (heparin dose), hemodynamics (gradients 
derived from echocardiography), contrast usage (use of contrast is optional) & fluoroscopy, device 
deployment) 
• 
Evaluation and data collection of any reportable adverse events 
 
Subjects that are enrolled (i.e. have a TorqVue™ LP Catheter inserted), but do not have an ADO II AS 
study device implanted will be followed through the 30 day follow-up visit.  Adverse events will be collected 
either in-person or via telephone as documented in section 8.2. Sponsor Representatives may be involved 
in providing support during the implant/procedure. 
5.3.4 
Post-Procedure 
Perform the following assessments within 48 hours after the procedure and prior to discharge: 
• 
Physical exam (PE) – including murmur evaluation 
• 
Chest X-ray (CXR) – Anteroposterior view 
• 
Electrocardiogram (ECG) 
• 
Transthoracic echo (TTE) 
• 
Evaluation and data collection of any reportable adverse events 
 
At the post-procedure visit, the following additional procedures may be required (refer to Table 6 for 
criteria): 
• 
Lung Perfusion scan 
• 
Aortic Catheterization (or other confirmatory testing such as cardiac CT/MRI) 
 
Table 4: Post-Procedure Visit Window 
Visit 
Window 
Post-procedure 
Within 48 hours after procedure and prior to discharge 
 
Subjects should be on appropriate endocarditis prophylaxis according to the American Heart Association 
recommendations for prophylaxis (Appendix E).  
 
5.3.5 
Scheduled Follow-ups for Pivotal IDE Subjects 
Follow-up visits are scheduled at 1 month, 6 months, 12 months, 24 months, and 36 months after the 
device implant/procedure. The scheduled visit windows are calculated from the enrollment date (procedure 
date). 
 
Table 5: Follow-up Windows 
Visit 
Window 
1 month 
30 days +/- 7 days 
6 months 
180 days +/- 20 days 
12 month 
+/- 30 days 
24 month 
+/- 60 days 
36 month 
+/- 60 days 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 18 of 51 
 
At each follow-up visit, the following procedures must be completed: 
• 
Physical exam (PE) – including weight, murmur, femoral pulse, and upper/lower extremity blood 
pressure evaluation 
• 
Transthoracic echo (TTE) 
• 
Evaluation and data collection of any reportable adverse events 
 
At each follow-up visit, the following additional procedures may be required (refer to Table 6 for criteria): 
• 
Electrocardiogram (ECG) 
• 
Lung Perfusion scan 
• 
Aortic Catheterization (or other confirmatory testing such as cardiac CT/MRI) 
 
Sponsor Representatives may be involved in providing support during the Follow-up procedures. 
5.3.6 
Scheduled Follow-ups for CAP Subjects 
After implant, the subject will return to the clinic at 1 and 6 months. The following procedures must be 
completed: 
 
• 
Physical exam (PE) – including weight, murmur, and femoral pulse 
• 
Evaluation and data collection of any reportable adverse events 
• 
TTE (TTE is not required at the 1 month visit for subjects weighing > 2kg at time of enrollment) 
 
The following additional procedures may be required (refer to Table 7 for criteria): 
• 
Lung Perfusion scan 
• 
Aortic Catheterization (or other confirmatory testing such as cardiac CT/MRI) 
 
If the ductus arteriosus is not effectively closed (Grade 0 or Grade1 shunt) at 6 months, as assessed by the 
Echo Core Lab, the site will be notified of the finding and the TTE must be repeated at the 12 month visit. 
 
Subjects will have a 12 month follow-up and annually thereafter through the 36 month follow-up via 
telephone. Assessments completed at these follow-ups include: 
• 
Adverse Event Assessment – sites should follow patients per their standard of care for any 
reported adverse events. 
 
5.4 
Study Flow Chart 
The Study Flow Chart (Figure 1) and Table 6, Pivotal IDE subjects or Table 7, CAP subjects, below 
summarize subject flow and requirements of this clinical investigation. 
 
 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 19 of 51 
Figure 2: Study Flow Chart 
 
U.S. Non-Randomized 
Trial
Subject Assessed for 
Inclusion / Exclusion Criteria
Informed Consent 
Process
Implant procedure
Subject in Follow-Up
NO
 TorqVue™ LP 
Catheter enters body?
NO
Screen Failure – 
Complete 
Screening Log
Screen Failure?
YES
Screen Failure – 
Complete 
Screening Log
YES
ADO II AS device 
successfully placed?
NO
Subject followed 
for 30 days
YES
 
 
 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 20 of 51 
Table 6:  Schedule of Assessments for Pivotal IDE Subjects 
 
 
 
 
Visit 
 
 
 
 
 
Study Activity 
Baseline 
Procedure 
Post-Procedure 5 
1 month 
(30 days +/- 7 
days)
6 Month 
(180 days +/- 20 
days)
12 Month 
(+/- 30 days) 
24 Month 
(+/- 60 days) 
36 Month 
(+/- 60 days) 
Office Visit 
X 
 
X 
X 
X 
X 
X 
X 
Informed Consent Process 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Physical Examination  
(murmur evaluation) 
X 
 
X 
X 
X 
X 
X 
X 
Chest X-Ray (AP) 
X 
 
X 
 
 
 
 
 
Electrocardiogram (ECG) 
X 
 
X 
X 
 
 
 
 
Echocardiogram (TTE)  
X 
X6 
X4 
X4 
X4 
X 
X 
X 
Angiogram 
 
X6 
 
 
 
 
 
 
Lung Perfusion Scan 2 
 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Aortic catheterization; or other confirmatory testing 3 
 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Adverse Event 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) if applicable 
1 Required only for females of child bearing potential and must be completed prior to the implant procedure. 
 
2 Perform a lung perfusion scan if peak instantaneous gradient in left pulmonary artery is ≥ 35mmHg by 
echocardiogram. 
 
3 Perform aortic catheterization to obtain invasive measurement of the gradient if the mean gradient by 
echocardiogram in the aortic isthmus is ≥ 20mmHg. If aortic catheterization is contraindicated, then an 
alternative imaging study, such as computed tomography (CT) aortic angiography imaging or magnetic 
resonance (MR) aortic angiography imaging may be utilized. Rationale for not performing aortic 
catheterization shall be specified on the case report form. CT aortic angiography or MR aortic angiography 
may be used to confirm a significant aortic obstruction whenever there is ≥ 50% diameter narrowing at the 
aortic isthmus. 
 
NOTE - Alternatively, a clinical exam may be used to confirm aortic obstruction. Rationale for not 
performing a confirmatory imaging study (aortic catheterization, MR imaging, or CT imaging) shall 
be specified on the case report form. 
 
Exam criteria = 1) Diminished lower extremity pulses or a blood pressure discrepancy of ≥ 20mmHg 
between the upper and lower extremities AND 2) an abnormal abdominal aortic Doppler pattern 
(blunted profile with diminished upstroke, holo-diastolic antegrade flow, or flow reversal during 
diastole). 
 
4 If the Echo Core Lab identifies a new significant gradient in the pulmonary artery or the aorta as defined in 
(2) or (3) during the review of the follow-up echocardiograms through six months, a lung perfusion scan or 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 21 of 51 
aortic catheterization will be required to determine if the result meets the secondary endpoint. If obstruction 
is detected and confirmed via a lung perfusion scan or aortic catheterization (or other confirmatory testing) 
only an echocardiogram will be required at subsequent follow-up visits. 
 
5 Post-procedure visit must be within 48 hours after the procedure and prior to discharge. 
 
6 Either an intra-procedure echocardiogram (TTE) or angiogram will be allowed to confirm the sizing 
inclusion criteria of the PDA length (≥ 3 mm) and PDA diameter (≤ 4 mm) prior to inserting the TorqVue™ 
LP Catheter into vasculature. 
 
Table 7: Schedule of Assessments for CAP Subjects 
 
 
 
 
Visit 
 
 
 
 
 
Study Activity 
Baseline 
Procedure 
Post-Procedure 5 
1 month 
(30 days +/- 7 
days)
6 Month 
(180 days +/- 20 
days)
12 Month 
(+/- 30 days) 
24 Month 
(+/- 60 days) 
36 Month 
(+/- 60 days) 
Office Visit 
X 
 
X 
X 
X 
 
 
 
Telephone Visit 
 
 
 
 
 
X8 
X 
X 
Informed Consent Process 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Physical Examination  
(murmur evaluation) 
X 
 
X 
X 
X 
 
 
 
Chest X-Ray (AP) 
X 
 
X 
 
 
 
 
 
Electrocardiogram (ECG) 
X 
 
X 
 
 
 
 
 
Echocardiogram (TTE)  
X 
X6 
X4 
X4, 7 
X4 
(X)8 
 
 
Angiogram 
 
X6 
 
 
 
 
 
 
Lung Perfusion Scan 2 
 
 
(X) 
(X) 
(X) 
 
 
 
Aortic catheterization; or other confirmatory testing 3 
 
 
(X) 
(X) 
(X) 
 
 
 
Adverse Event 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) if applicable 
1 Required only for females of child bearing potential and must be completed prior to the implant procedure. 
 
2 Perform a lung perfusion scan if peak instantaneous gradient in left pulmonary artery is ≥ 35mmHg by 
echocardiogram. 
 
3 Perform aortic catheterization to obtain invasive measurement of the gradient if the mean gradient by 
echocardiogram in the aortic isthmus is ≥ 20mmHg. If aortic catheterization is contraindicated, then an 
alternative imaging study, such as computed tomography (CT) aortic angiography imaging or magnetic 
resonance (MR) aortic angiography imaging may be utilized. Rationale for not performing aortic 
catheterization shall be specified on the case report form. CT aortic angiography or MR aortic angiography 
may be used to confirm a significant aortic obstruction whenever there is ≥ 50% diameter narrowing at the 
aortic isthmus. 
 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 22 of 51 
NOTE - Alternatively, a clinical exam may be used to confirm aortic obstruction. Rationale for not 
performing a confirmatory imaging study (aortic catheterization, MR imaging, or CT imaging) shall 
be specified on the case report form. 
 
Exam criteria = 1) Diminished lower extremity pulses or a blood pressure discrepancy of ≥ 20mmHg 
between the upper and lower extremities AND 2) an abnormal abdominal aortic Doppler pattern 
(blunted profile with diminished upstroke, holo-diastolic antegrade flow, or flow reversal during 
diastole). 
 
4 If the Echo Core Lab identifies a new significant gradient in the pulmonary artery or the aorta as defined in 
(2) or (3) during the review of the follow-up echocardiograms through six months, a lung perfusion scan or 
aortic catheterization will be required to determine if the result meets the secondary endpoint. If obstruction 
is detected and confirmed via a lung perfusion scan or aortic catheterization (or other confirmatory testing) 
only an echocardiogram will be required at subsequent follow-up visits. 
 
5 Post-procedure visit must be within 48 hours after the procedure and prior to discharge. 
 
6 Either an intra-procedure echocardiogram (TTE) or angiogram will be allowed to confirm the sizing 
inclusion criteria of the PDA length (≥ 3 mm) and PDA diameter (≤ 4 mm) prior to inserting the TorqVue™ 
LP Catheter into vasculature. 
 
7 If the subject weighed > 2kg at the time of enrollment, the 1 month TTE is not required. 
 
8 If the Echo Core lab determines that the ductus arteriosus is not effectively closed (Grade 0 or Grade1 
shunt) at the 6 month visit, the TTE must be repeated at the 12 month visit. 
5.5 
Description of activities performed by Sponsor Representatives 
Trained Sponsor personnel will provide technical expertise and technical guidance on the use of the ADO II 
AS device, including training and proctored case coverage. 
 
While Sponsor representatives may perform these activities, the Principal Investigator remains responsible 
for ensuring all clinical investigation data is collected as required per CIP. 
5.6 
Subject Study Completion  
Subject participation in the clinical investigation will conclude upon completion of the 36-month visit. Upon 
completion of subject participation in the clinical investigation, the subject will return to standard of care. 
 
5.7 
Subject Withdrawal 
Subjects must be informed about their right to withdraw from the clinical investigation 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 investigation will not jeopardize their future medical care or relationship with the 
investigator. Subjects will be requested to specify the reason for the request to withdraw. The investigator 
must make all reasonable efforts to retain the subject in the clinical investigation until completion of the 
clinical investigation. 
 
If a subject misses one or more of the scheduled follow-up visits (i.e., does not have a scheduled follow-up 
within the assigned visit windows) without being lost to follow-up, the subject will be considered as having 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 23 of 51 
missed the visit (which will be deemed to be a deviation from the CIP and the applicable form should be 
completed). If the subject has missed a visit, the subject shall return for subsequent follow-up visits. 
 
A subject will be considered ‘Lost to Follow-up’ after two missed visits, a minimum of two unsuccessful 
phone calls from investigational site personnel to the subject or contact to schedule the next follow-up visit. 
These two phone calls must be documented in the subject’s hospital records. If the subject is deemed lost 
to follow-up, a letter should be sent to the subject’s last known address or to the subject’s general 
practitioner (GP). A copy of the letter must be maintained in the subject’s hospital records. 
 
When subject withdrawal from the clinical investigation is due to an adverse event the subject will be 
followed outside of the clinical investigation until resolution of that adverse event or determination that the 
subject’s condition is stable. The status of the subject’s condition should be documented at the time of 
withdrawal. 
 
In case of subject withdrawal, the site should make attempts to schedule the subject for a final study visit. At 
this final study visit, the subject will undergo the following assessments: 
• 
Physical exam (PE) 
• 
Evaluation and data collection of any reportable adverse events 
5.8 
Requirements for Clinical Laboratories 
An independent Core Lab will be used to review and adjudicate the transthoracic echocardiography (TTE). 
Service details will be outlined in the applicable Service Agreement. 
5.9 
Study Committees 
5.9.1 
Publication Committee 
A Publication Committee may be established to oversee study publications. Publication Committee 
membership may include the national coordinating investigator, Principal Investigators, a representative of 
St. Jude Medical, and a statistician. The Publication Committee will be responsible for identifying, selecting 
and approving publication proposals and determining authorship according to a Publication Plan. A 
Publication Committee charter will define membership of the committee and outline the roles and 
responsibilities of the committee, as well as rules to define authorship. 
5.9.2 
Clinical Events Committee (CEC) 
An independent CEC will be responsible for providing review and adjudication of pre-defined clinical events, 
including major and minor complications, deaths, or other events or endpoints as outlined in the CEC 
Charter. The CEC is responsible for reviewing all reportable Adverse Events as defined in section 8.2. 
 
The CEC will also advise the Sponsor regarding the continuing safety of subjects and those yet to be 
recruited, as well as the continuing validity and scientific merit of the clinical investigation. CEC members 
will not be investigators in the clinical investigation. At any time during the investigation, the CEC may offer 
opinions or provide formal recommendations concerning aspects of the study that impact subject safety 
(e.g. safety-related protocol changes or input regarding study-related adverse event rates). 
 
The primary function, responsibilities and membership of the CEC will be described in detail in a CEC 
charter. 
 

 
Study Document No: SJM-CIP-10171  
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Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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6 
Statistical Considerations 
The following section describes the statistical methods for the clinical investigation and justification of the 
design. For the Primary and Secondary Endpoints, pivotal IDE subjects will be analyzed separately from 
CAP subjects.  
6.1 
Endpoints  
6.1.1 
Primary Safety Endpoint (IDE and CAP) 
The primary safety endpoint is the rate of major complications through 180 days after an attempted ADO II 
AS device implant (refer to Appendix B for definition).  
6.1.1.1 Analysis Methodology 
The proportion of subjects experiencing a primary safety endpoint through 180 days will be estimated. The 
95% confidence interval for the proportion of subjects experiencing a primary safety endpoint will be 
calculated using the exact binomial method. The numerator for the event rate is the number of subjects who 
experienced an event through 180 days. The denominator is the number of subjects in the analysis 
population (see Section 6.1.1.2). The primary safety endpoint rate will be descriptively compared with the 
rate reported in the literature for the ADO II AS device. The overall estimated rate for major complications 
based on published literature for the ADO II AS device [17-21] is approximately 10.0%. 
6.1.1.2 Analysis Population 
The primary analysis of the safety endpoint will include enrolled subjects as defined in section 5.2 excluding 
the following subjects:  
• 
Subjects with a successful implant who withdraw (e.g., due to death, subject preference or loss-to-
follow-up) before 180 days without an event 
• 
Subjects who have an unsuccessful implant who withdraw before 30 days without an event 
6.1.2 
Primary Effectiveness Endpoint (IDE and CAP) 
The primary effectiveness endpoint is the rate of effective closure of the ductus arteriosus among subjects 
with a successful ADO II AS implant as assessed by the presence of either a Grade 0 or Grade 1 shunt 
(see Section 4.4.1) at the six-month follow-up by transthoracic echocardiography. 
6.1.2.1 Analysis Methodology  
The proportions of subjects who have effective closure of the ductus arteriosus at the 6-month follow-up will 
be estimated. The 95% confidence interval for the rate of effective closure of the ductus arteriosus will be 
calculated using the exact binomial method. The numerator for the event rate is the number of subjects who 
have effective closure of the ductus arteriosus at 6-month follow-up. The denominator is the number of 
subjects in the analysis population (see Section 6.1.2.2). The primary effectiveness endpoint will be 
descriptively compared with the rate reported in the published literature [19,20,22] for the ADO II AS device. 
Among subjects successfully implanted with the device the PDA occlusion rate is estimated to be 
approximately 99%. 
6.1.2.2 Analysis Population 
The primary analysis of the effectiveness endpoint will include enrolled subjects who achieve a successful 
implant, defined as leaving the catheterization lab with an ADO II AS implanted in the PDA. If a subject has 
more than one device attempted during the same procedure, but leaves the procedure with an ADO II AS 
device within the ductus arteriosus the procedure is considered successful. Subjects without an implanted 

 
Study Document No: SJM-CIP-10171  
Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 25 of 51 
ADO II AS device in the ductus arteriosus will be excluded. Additionally, subjects withdrawn before 6-month 
follow-up, or with no data for residual flow by transthoracic echocardiography assessed by the Echo Core 
Lab at the 6-month follow-up visit will be excluded. 
6.1.3 
Secondary Endpoint (IDE and CAP)  
The secondary endpoint is the rate of significant obstruction of the pulmonary artery or aorta through the 6-
month follow-up visit per the following definitions: 
1. Significant obstruction of the left pulmonary artery is defined as less than 30% flow to the left lung 
by lung perfusion scan or a peak instantaneous gradient in left pulmonary artery ≥35 mmHg by 
echocardiogram if lung perfusion scan is not available. OR 
2. Significant obstruction of the aorta is defined as a gradient of ≥20 mmHg in the aortic isthmus by 
invasive aortic catheterization or a mean gradient ≥20 mmHg in the aortic isthmus by 
echocardiogram if invasive aortic catheterization is not available. 
6.1.3.1 Analysis Methodology 
The proportions of subjects experiencing a secondary endpoint through the 6-month follow-up visit will be 
estimated. The 95% confidence interval for the proportion of subjects experiencing a secondary endpoint 
will be calculated using the exact binomial method. The numerator for the event rate is the number of 
subjects who experience an event by the 6-month follow-up visit. The denominator is the number of 
subjects in the analysis population (see Section 6.1.3.2).  
6.1.3.2 Analysis Population 
The analysis of the secondary endpoint will include all enrolled subjects who achieve a successful implant, 
which is defined as leaving the catheterization lab with an ADO II AS implanted in the PDA. If a subject has 
multiple devices attempted during the same procedure, but leaves procedure with an ADO II AS device 
within the ductus arteriosus the procedure is considered successful. Subjects without an implanted ADO II 
AS device in the ductus arteriosus will be excluded.  Additionally, subjects withdrawn before 6-month follow-
up without an event will be excluded. Subjects who do not have the 6-month follow-up endpoint data and do 
not experience an event (aortic or pulmonary obstruction) before 6-month follow-up will also be excluded. 
6.1.4 
Descriptive Endpoints and Additional Data for Pivotal IDE Subjects 
The following endpoints will be summarized using descriptive statistics.  
• 
Implant success: 
The frequency and percentage of implant success (defined in Section 6.1.3.2) will be reported. This 
analysis will include enrolled subjects.  
• 
PDA shunt status at each follow-up visit: 
The frequency and percentage of PDA shunt status at each follow-up visit, as assessed by the Echo 
Core Lab, will be reported. Shunt sizes categories are: Grade 0/1, 2, and Grade 3/4. This analysis will 
include subjects who achieve a successful implant. 
• 
Obstruction measurements at each follow-up visit: 
The frequency and percentage of significant obstruction of the left pulmonary artery and the frequency 
and percentage of significant aortic obstruction (defined in Section 6.1.3) at each follow-up visit will be 
reported. Both analyses will include subjects who achieve a successful implant.  
• 
Major and Minor Complications: 
The frequency and percentage of major and minor complications (refer to Appendix B for definition) 
from the time of the implant procedure will be reported.  
• 
Death: 
The frequency and percentage of death will be reported. 

 
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Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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• 
Additional data:  
Demographics and baseline characteristics, procedure information, left ventricular function and 
dimensions, pulmonic and tricuspid regurgitation, adverse events, withdrawal and protocol deviations 
will also be summarized.   
6.1.5 
Descriptive Endpoints and Additional Data for CAP Subjects 
The following endpoints will be summarized using descriptive statistics.  
• 
Implant success: 
The frequency and percentage of implant success (defined in Section 6.1.3.2) will be reported. This 
analysis will include enrolled subjects.  
• 
Major and Minor Complications: 
The frequency and percentage of major and minor complications (refer to Appendix B for definition) 
from the time of the implant procedure will be reported.  
• 
Death: 
The frequency and percentage of death will be reported. 
• 
Additional data:  
Demographics and baseline characteristics, procedure information, left ventricular function and dimensions 
and pulmonic and tricuspid regurgitation at 6 months, and adverse events, withdrawal and protocol 
deviations will also be summarized at each follow-up visit.  
6.2 
Justification of Clinical Investigation Design 
Based on the clinical observations and safety profile established through over 5400 ADO II AS devices 
shipped internationally, published literature with the ADO II AS device outside the United States, and 
previous internally run clinical studies examining ADO II AS, a single arm, prospective, multicenter, non-
randomized clinical investigation is designed to characterize the safety and effectiveness of the ADO II AS 
device in small infants with a patent ductus arteriosus (PDA). Additionally, the device characteristics are 
very similar to the FDA-approved ADO II and AMPLATZER Vascular Plug II (AVP II) devices. 
6.3 
Overall Sample Size for Pivotal IDE Subjects 
The ADO II AS is a modified version of a previously FDA approved device (ADO II) for the same lesion, but 
in smaller sizes and lower profile retention discs. The ADO II AS represents a line-extension to ADO II. 
Furthermore, the ADO II AS device has been commercially available in Europe since 2011 with more than 
5000 devices sold to date. Favorable clinical results with the ADO II AS device from centers outside of the 
US have been published and provide confidence that the device is safe and effective. Therefore, a 
minimum sample size of 40 subjects (minimum of 15 subjects ≤2 kg) at up to 10 investigational sites is 
proposed for this study. To account for subject dropout the study will enroll up to 50 subjects. 
6.4 
Overall Sample Size for CAP Subjects 
A maximum of 150 subjects may be enrolled under Revision C of this protocol.  A maximum of 10 
investigational sites in the United States may participate in this study.  Protocol revision C allows for 
additional subject enrollment in the ADO II AS study, with additional prospective collection of safety and 
effectiveness data on the ADO II AS device upon enrollment completion in the pivotal cohort and while the 
PMA application for the ADO II AS device is being prepared and is under FDA review.  
 

 
Study Document No: SJM-CIP-10171  
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Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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6.5 
Timing of Analysis for Pivotal IDE Subjects  
A pre-market approval (PMA) application will be submitted after 40 subjects have reached 6 months of 
follow-up post implant attempt. A minimum of 15 subjects will be enrolled with a weight ≤ 2 kg. In the event 
there is difficulty in enrolling 15 subjects with a weight of < 2 kg, a PMA application will be submitted after 
25 subjects with weight > 2 kg have reached 6 months of follow-up. An additional submission will be done 
when 15 subjects with a weight of < 2 kg reach 6 months of follow-up. Follow-up after 6 months will be used 
satisfy post-approval requirements. Enrollment and follow-up occurring after the pivotal cohort is enrolled 
will be used to satisfy post-approval requirements. 
6.6 
Success Criteria for Pivotal IDE Subjects 
The trial has two primary endpoints for safety and effectiveness without formal hypothesis. The safety and 
effectiveness results will be compared with data reported in the literature.  
6.7 
Deviations from Statistical Plan 
If any deviations from the original statistical plan occur, such deviations will be documented in the clinical 
study report or statistical report containing the analysis results. 
7 
Risks and Benefits 
Risks associated with the device are managed in accordance with ISO 14971. The risk analysis included an 
objective review of published and available unpublished medical and scientific data. The sections below 
provide an overview of residual risks identified in the risk management report and anticipated benefits of the 
medical device. The additional tests and assessments required by the clinical investigation were analyzed 
for additional risks to subjects of this clinical investigation, and are incorporated in the sections below. 
7.1 
Risks associated with the Device under Investigation 
7.1.1 
Anticipated Adverse Device Effects 
The risks associated with the implant procedure are similar to those of other cardiac catheterization 
procedures in infants and children and are documented below. Radiation risks associated with the 
procedure are comparable to a diagnostic catheterization procedure. 
 
• 
Air embolism 
• 
Allergic reaction 
• 
Arrhythmia 
• 
Arteriovenous fistulae 
• 
Bleeding at the access site 
• 
Brachial plexus injury 
• 
Bruising 
• 
Cardiac tamponade 
• 
Death 
• 
Deep venous thrombosis 
• 
Dissection 
• 
Embolism 
• 
Endocarditis 
• 
Hematoma 
• 
Hemodynamic compromise 
• 
Infection 
• 
Myocardial infarction 
• 
Perforation 
• 
Peripheral pulse loss 
• 
Pseudoaneurysm 
• 
Respiratory distress 
• 
Stroke/transient ischemic attack 
• 
Thrombosis 
• 
Valve damage 
• 
Vascular access site injury 
• 
Vascular occlusion 
• 
Vessel damage 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 28 of 51 
 
The following is a list of the anticipated adverse device effects associated with the ADO II AS device under 
investigation: 
 
• 
Air embolism 
• 
Allergic dye reaction 
• 
Allergic drug reaction 
• 
Anesthesia reactions 
• 
Apnea 
• 
Arrhythmia 
• 
Bacterial endocarditis 
• 
Bleeding 
• 
Cardiac perforation 
• 
Cardiac tamponade 
• 
Chest pain 
• 
Device embolization 
• 
Device erosion 
• 
Death 
• 
Fever 
• 
Hemolysis 
• 
Headache/migraine 
• 
Hypertension 
• 
Hypotension 
• 
Myocardial infarction 
• 
Nickel sensitization  
• 
Nickel toxicity 
• 
Palpitations 
• 
Partial obstruction of the Aorta 
• 
Partial obstruction of the Pulmonary Artery 
• 
Pericardial effusion 
• 
Pericarditis 
• 
Peripheral embolism 
• 
Pleural effusion 
• 
Pulmonary embolism 
• 
Reintervention for device removal 
• 
Stroke 
• 
Transient ischemic attack 
• 
Thrombus 
• 
Valvular regurgitation 
• 
Vascular access site injury 
• 
Vessel perforation 
• 
Carcinogenicity 
 
Potential carcinogenicity risk. The ADO II AS device consists of a nickel-titanium alloy. In vitro testing has 
demonstrated that that nickel is released from this device for a minimum of 60 days. Some forms of nickel 
have also been associated with carcinogenicity (ability to cause cancer) in animal models. In humans, 
carcinogenicity has been demonstrated only through an inhalation route (breathing nickel in), which will not 
occur with this procedure. 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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7.1.1 
Risks associated with Clinical Investigation Assessments 
The risks associated with the ADO II AS device implant procedure are similar to those of other cardiac 
catheterization procedures. Radiation risks associated with the procedure are comparable to a diagnostic 
catheterization procedure. 
 
The risks associated with the ADO II AS device are similar to other implantable cardiac occlusion devices.  
 
Additional study required procedures are listed below with the associated risks/discomforts. 
 
Blood Draw 
There may be some minor discomfort and/or anxiety associated with drawing blood including pain or bruising 
associated with the needle from the blood draw. Fainting and local infection can also occur. 
 
Aortic Catheterization 
Aortic catheterizations have a risk for injury to the vessel, allergic reaction to dye, anesthesia reaction 
irregular heartbeat, infection, poisonous products in the bloodstream, loss of blood flow to the extremities 
from the catheter placement, damage or injury to the heart, lungs, valves or vessels from the catheter or wire 
advancement, air or blood clot formation in a vessel or heart which may cause temporary or complete 
blockage of blood flow to the heart, brain, or extremities, irregular blood pressure, fever, injury to the nerves 
that control the arm or shoulder, kidney dysfunction due to exposure to contrast media (liquid used for 
imaging) and death.  
 
Lung Perfusion Scan 
Lung perfusion scans expose the patient to a small dose of radiation (about as much radiation as natural 
exposure over a year). There is always a slight risk from being exposed to radiation.  
 
Computed Tomography (CT) Aortic Angiography  
There may be risks due to the radiation used during the CT imaging. There is also a risk for an allergic 
response to the contrast media/dye used during the CT imaging procedure. 
 
Magnetic Resonance (MR) Aortic Angiography 
MR imaging use magnetic and radio waves to generate images of the vasculature. The risk from these waves 
is no greater than experienced in daily life. There is also a risk for an allergic response to the contrast 
media/dye used during the MRI procedure. 
 
Echocardiogram  
The electrodes placed on subject’s chest may cause discomfort such as redness or itching. The subject may 
feel slight pressure from the transducer or probe that the technician utilizes to take measurements.  
 
Chest X-ray 
The risks of chest x-rays include exposure to small doses of radiation (about as much radiation as natural 
exposure over 10 days). There is always a slight risk from being exposed to any radiation. 
 
Electrocardiogram 
The electrodes placed on subject’s chest can sometimes cause discomfort such as redness or itching.  

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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7.2 
Possible interactions with concomitant treatments 
The risks from intra-procedural medications administration upon undergoing ADO II AS implant are no 
different from the risks associated with medications prescribed during a cardiac catheterization procedure or 
implant of commercially available transcatheter PDA occluder device. 
7.3 
Risk Control Measures 
Every possible effort will be taken to minimize the risks, including: 
• 
Careful selection of experienced Investigators for the clinical investigation  
o 
Cardiologists with training and education in pediatric cardiology and experience using 
transcatheter techniques to close PDAs 
o 
Prior experience with transcatheter closure procedures using devices such as ADO, ADO II 
or other similar devices with a minimum of 60 cases  
o 
Institutions will have the necessary infrastructure to support trial procedures: 
▪ 
Cardiac catheterization lab or NICU bedside capability to perform intra-procedural 
echocardiography and fluoroscopy 
▪ 
Anesthesiology support, as needed 
▪ 
Catheterization laboratory, operating room, post anesthesia recovery, intensive care 
and step down unit spaces to accommodate cases with and without complications 
▪ 
On-site emergency cardiac surgery services 
• 
Adequate monitoring for each clinical investigation site 
• 
Conducting the clinical investigation in accordance with the CIP, all applicable laws and regulations 
and any conditions of approval imposed by the appropriate IRB or applicable regulatory authorities 
where the clinical investigation is performed 
• 
Preparation of the ADO II AS device and implant procedure in accordance with the device IFUs 
• 
Training of Investigators both on the CIP and ADO II AS implant procedure 
o 
All site staff will participate and complete a training module on the CIP 
o 
All implanting physicians must complete an implanter training module 
o 
Implanting physicians with no prior successful transcatheter PDA closure experience with 
ADO II AS in small infants (≤2 kg) will receive proctoring for a minimum on one case. 
• 
Assessment of continuing safety of subjects in the clinical investigation by an independent CEC 
 
The following measures have also been taken to reduce the risks of specific study device related adverse 
events: 
• 
Subject eligibility criteria include maximum diameter and minimum lengths of the PDA to be treated 
with the ADO II AS which should reduce the likelihood of partial obstruction of the pulmonary artery 
or aorta. 
• 
Whenever possible, subjects will be given a loading dose of Heparin at the beginning of the 
procedure to reduce the risk of thrombus formation on the devices. The use of heparin in patients 
with a risk of bleeding is considered optional. 
• 
The physicians will be trained on the procedure, specifically device size selection and placement, to 
reduce the risk of device embolization, partial obstruction of the aorta or pulmonary artery and 
hemolysis which could be potentially caused by the ADO II AS. 
• 
The physicians will be instructed to use their clinical judgement to monitor subjects for potential 
adverse events related to nickel and to report such events with the goal of protecting the welfare of 
the subject if the root cause of the adverse event is determined to be nickel related, paying special 
attention to subjects weighing less than 6kg at baseline 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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• 
The physicians will be encouraged to utilize an anterograde implant approach, while avoiding the 
need for arterial access. Additionally, the protocol will not require the acquisition of invasive 
hemodynamic measurements to minimize complication and shorten procedure time. Device implant 
is recommended to be performed based on echocardiographic and fluoroscopic guidance without 
needing to utilize intravenous contrast agents and angiograms. 
• 
Physicians are required to follow The American Heart Association Recommendations for 
endocarditis prophylaxis during the clinical study.  
7.4 
Anticipated Benefits 
The ADO II AS will be implanted via transcatheter approach, therefore avoiding open heart surgery. The 
device has been designed to be delivered through a 4F catheter delivery system which may decrease the risk 
of vascular access site injuries and temporary loss of peripheral pulse compared to a 5F or larger catheter 
delivery system. The device has also been designed to conform to different defect lengths allowing this 
device to be placed in short PDAs. 
7.5 
Risk-to-Benefit Rationale 
Risks associated with participating in this clinical study are not anticipated to be any different from risks 
associated with undergoing implant with commercially available transcatheter devices such as ADO II or 
coils. The potential benefit of participating in this clinical study is close follow-up of the subject by their 
treating physicians. Potential benefits of the ADO II AS device compared to currently available options are 
minimally invasive PDA closure with a smaller device suitable for a smaller sized PDA, and a lower rate of 
complications. Future neonatal patients with PDA may benefit from the results of this clinical trial. 
7.6 
History of device modifications or recall 
There have been no recalls or field actions during the global marketing and sale of the ADO II AS device. 
8 
Requirements for Investigator records and reports 
8.1 
Deviations from CIP 
A deviation is defined as an instance(s) of failure to follow, intentionally or unintentionally, the requirements of 
the CIP. The investigator should not deviate from the CIP. 
 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety and well-
being of subjects; such non-compliance exposes subjects to unreasonable risks. Examples: failure to adhere 
to the inclusion/exclusion criteria, failure to perform safety assessments intended to detect adverse events. 
Investigators should seek to minimize such risks by adhering to the CIP. 
 
The PI must maintain accurate, complete, and current records, including documents showing the date of and 
reason for each deviation from the CIP. Relevant information for each deviation will be documented as soon 
as possible on the applicable CRF. The site will submit the CRF to the Sponsor. 
 
The PI is required to adhere to local regulatory requirements for reporting deviations to IRB. 
 
An investigator shall notify the Sponsor and the reviewing IRB of any deviation from the investigational plan 
to protect the life or physical well-being of a subject in an emergency. Such notice shall be given as soon as 
possible, but in no event later than 5 working days after the emergency occurred. Except in such an 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 32 of 51 
emergency, prior approval by the Sponsor is required for changes in or deviations from a plan, and if these 
changes or deviations may affect the scientific soundness of the plan or the rights, safety, or welfare of 
human subjects, FDA and IRB is also required. 
8.2 
Adverse Event Reporting 
Safety surveillance within this trial (and the safety reporting performed by the investigator), starts as soon as 
the subject is enrolled. The safety surveillance and the safety reporting will continue until the last 
investigational visit has been performed, the subject is deceased, the subject/investigator concludes his/her 
participation into the clinical investigation or the subject withdrawal from the clinical investigation. 
 
All adverse event data required to be reported will be collected throughout the clinical investigation and will 
be reported to the Sponsor on a CRF. 
 
Adverse events will be monitored until they are adequately resolved or the subject has ended his/her 
participation in the trial, whichever comes first. The status of the subject’s condition should be documented at 
each visit. 
 
For the purposes of this clinical investigation the following events will be reported (see Appendix B for 
definitions): 
• 
Unanticipated adverse device effects 
• 
All adverse events viewed/interpreted by investigator to be potentially related to either a) the implant 
procedure or b) the study device (ADO II AS) regardless of seriousness 
 
Note – If relatedness is unknown or cannot be determined, then the event must be reported. 
 
Note – if a procedure is abandoned and a non-study device is used to close the PDA, adverse events 
associated with the non-study device will not be reported. 
 
Records relating to the subject’s subsequent medical course must be maintained and submitted (as 
applicable) to the Sponsor until the event has subsided or, in case of permanent impairment, until the event 
stabilizes and the overall clinical outcome has been ascertained. Adverse events will be monitored until they 
are adequately resolved. The status of the subject’s condition should be documented at each visit.  
 
SAE Reporting 
Reportable adverse events that are deemed by the investigator to be serious should be reported 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 above. 
 
The date the site staff became aware the event met the criteria of an SAE must be recorded in the source 
document.  The Investigator will further report the SAE to the local IRB/EC according to the institution’s 
IRB/EC reporting requirements. 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
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8.2.1 
Subject Death 
Subject deaths will be documented and reported to the Sponsor as soon as possible (but no later than 3 
calendar days) after becoming aware of the event via the applicable CRF. 
8.2.2 
Unanticipated Adverse Device Effect 
If an unanticipated adverse device effect occurs, the investigator must notify the Sponsor and the IRB 
immediately, but no later than 3 calendar  days of the investigator’s knowledge of the event, as required by 
21 CFR §812.150. St. Jude Medical will take any steps necessary to investigate the event, and, as 
appropriate, will be responsible for notifying FDA and all other participating IRBs and investigators. 
8.2.3 
Complaints 
During the study, the investigator will be responsible for reporting all complaints. If the complaint does not 
involve an AE, the investigator must notify the St. Jude Medical (SJM) Postmarket Surveillance Department 
by emailing the information on the device to complaints_amplatzer@sjm.com or calling 651-756-5400 as 
soon as possible after becoming aware of the complaint. 
 
If the complaint involves an AE, the investigator must complete an AE Case Report Form (CRF) including the 
information on the complaint and report to St Jude Medical as soon as possible.  
 
Should a subject death be caused by the SJM device or the device contributed to the death, the investigator 
should complete a Form 3500A (MedWatch) and submit to SJM and the FDA within 10 days after becoming 
aware of the event. 
8.3 
Source records 
Source documents will be created and maintained by the investigational site team throughout the clinical 
investigation. The data reported on the CRFs will be derived from, and be consistent with, these source 
documents, and any discrepancies will be explained in writing. 
8.4 
Records retention 
The Sponsor and the Principal Investigators will maintain the clinical investigation documents as required. 
Measures will be taken to prevent accidental or premature destruction of these documents. The Principal 
Investigator or the Sponsor may transfer custody of records to another person/party and document the 
transfer at the investigational site or the Sponsor’s facility, as appropriate. 
 
These documents must be retained by the investigational site for a period of 2 years after the conclusion of 
the clinical investigation and made available for monitoring or auditing by the Sponsor’s representative or 
representatives of the applicable regulatory agencies. 
 
All original source documents must be stored for the maximum time required by the regulations at the 
hospital, research institute, or practice in question. If original source documents can no longer be maintained 
at the site, the investigator will notify the Sponsor.  
9 
Clinical Data Handling 
The Sponsor will be responsible for the data handling. The Sponsor and/or its affiliates will be responsible for 
compiling and submitting all required reports to governmental agencies. Data will be analyzed by the Sponsor 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 34 of 51 
and may be transferred to the Sponsor’s locations worldwide and/or any other worldwide regulatory authority 
in support of a market-approval application. 
9.1 
Protection of Personally Identifiable Information 
St. Jude Medical respects and protects personally identifiable information collected or maintained for this 
clinical investigation. The privacy of each subject and confidentiality of his/her information will be preserved in 
reports and when publishing any data. Confidentiality of data will be observed by all parties involved at all 
times throughout the clinical investigation. All data will be secured against unauthorized access. 
9.2 
Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, database cleaning, and 
issuing and resolving data queries. If appropriate, the DMP may be updated throughout the clinical 
investigation duration. All revisions will be tracked and document controlled. 
 
Subject data will be captured in a validated electronic data capture (EDC) system hosted by the Sponsor. 
 
Only authorized site personnel will be permitted to enter the CRF data through the EDC system deployed by 
St. Jude Medical. An electronic audit trail will be used to track any subsequent changes of the entered data. 
9.3 
Document and Data Control 
9.3.1 
Traceability of Documents and Data 
The investigator will ensure accuracy, completeness legibility and timeliness of the data reported to the 
Sponsor on the CRFs and in all required reports. 
9.3.2 
Recording Data 
The CRF will be reviewed by the authorized site personnel. An appropriate comment will be provided to 
explain changes to data reported on the CRF. 
10 Monitoring 
It is the responsibility of the Sponsor to ensure the clinical investigation is conducted, recorded and reported 
according to the approved CIP, subsequent amendment(s), applicable regulations and guidance documents. 
 
Monitoring will be conducted according to St. Jude Medical’s Clinical Monitoring work instruction. 
Prior to beginning the clinical investigation, the Sponsor will contact the investigator or designee to discuss 
the clinical investigation and data requirements. A designated monitor will periodically review the subject 
records and associated source documents. The investigator shall make subject and clinical investigation 
records available to the clinical monitor for monitoring. 
11 Compliance Statement 
11.1 Statement of Compliance 
In addition to applicable regional or local laws and regulations, this clinical investigation will be conducted in 
compliance with the most current version of the World Medical Association (WMA) Declaration of Helsinki 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 35 of 51 
and 21 CFR Parts 50, 54, 56 and 812. In the event of any conflicts, local laws and regulations will have 
precedence and in such cases, good faith efforts will be made to adhere to the intent of the other documents. 
 
The investigator will sign a Clinical Trial Agreement and agrees to be compliant with it. The investigator will 
not start enrolling subjects or requesting informed consent from any subject prior to obtaining IRB approval 
and relevant Regulatory Authority approval, if applicable, and authorization from the Sponsor in writing for the 
clinical investigation. If additional requirements are imposed by the IRB or relevant Regulatory Authority, 
those requirements will be followed. If any action is taken by an IRB or a relevant Regulatory Authority with 
respect to the clinical investigation, that information will be forwarded to the Sponsor. 
11.2 Quality Assurance audits and Regulatory Inspections 
The investigator and/or delegate should contact the Sponsor immediately upon notification of a regulatory 
authority inspection at the site. A monitor or designee will assist the investigator and/or delegate in preparing 
for the audit. The Sponsor may perform quality assurance audits, as required. 
 
The Principal Investigator or institution will provide direct access to source data during and after the clinical 
investigation for monitoring, audits, IRB review and regulatory authority inspections, as required. The 
Principal Investigator or institution will obtain permission for direct access to source documents from the 
subject, hospital administration and national regulatory authorities before starting the clinical investigation. 
11.3 Repeated and Serious Non-Compliance 
In the event of repeated non-compliance or a one-time serious non-compliance, as determined by the 
Sponsor, a monitor or designee will attempt to secure compliance by one or more of the following actions: 
• 
Visiting the investigator, 
• 
Contacting the investigator by telephone, 
• 
Contacting the investigator in writing, 
• 
Retraining of the investigator. 
 
If an investigator is found to be repeatedly non-compliant with the signed agreement, the CIP or any other 
conditions of the clinical investigation, the Sponsor will either secure compliance or, at its sole discretion, 
terminate the investigator’s participation in the clinical investigation. In case of termination, the Sponsor will 
inform the responsible regulatory authority, as required, and ensure that the IRB is notified, either by the 
Principal Investigator or by the Sponsor. 
12 Suspension or premature termination of the clinical investigation 
The Sponsor reserves the right to terminate the clinical investigation at any stage, with appropriate written 
notice to the investigators, IRB and relevant Regulatory authorities, if required.  
 
A Principal Investigator, IRB or regulatory authority may suspend or prematurely terminate participation in a 
clinical investigation at the investigational sites for which they are responsible. The investigators will follow 
the requirements specified in the Clinical Trial Agreement.  
 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation or when so instructed 
by the IRB or regulatory authority, the Sponsor may suspend the clinical investigation while the risk is 
assessed. The Sponsor will terminate the clinical investigation if an unacceptable risk is confirmed. If the 
Sponsor completes an analysis of the reasons for the suspension, implements the necessary corrective 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 36 of 51 
actions, and decides to lift the temporary suspension, the Sponsor will inform the Principal Investigators, IRB, 
or regulatory authority, where appropriate, of the rationale, providing them with the relevant data supporting 
this decision. Approval from the IRB or regulatory authority, where appropriate, will be obtained before the 
clinical investigation resumes. If subjects have been informed of the suspension, the Principal Investigator or 
authorized designee will inform them of the reasons for resumption. 
 
If the Sponsor suspends or prematurely terminates the clinical investigation at an individual investigational 
site in the interest of safety, the Sponsor will inform all other Principal Investigators. 
 
If suspension or premature termination occurs, the Sponsor will remain responsible for providing resources to 
fulfill the obligations from the CIP and existing agreements for following up the subjects enrolled in the clinical 
investigation, and the Principal Investigator or authorized designee will promptly inform the enrolled subjects 
at his/her investigational site, if appropriate. 
13 Clinical Investigation Conclusion 
The clinical investigation will be concluded when: 
• 
All sites are closed AND 
• 
The final report has been provided to investigators or the Sponsor has provided formal 
documentation of clinical investigation closure. 
14 Publication Policy 
Publications or presentations of clinical investigation methods or results will adhere to St. Jude Medical’s 
publication policy, which is based on Good Publication Practices and International Committee of Medical 
Journal Editors (ICMJE) guidelines. A copy of the policy will be provided upon request of the investigator. 
Publication planning and authorship determinations will be overseen by the Publications Committee (see 
section 5.10.1), and investigators will be notified via email about the dissemination of study data and 
opportunities for involvement as authors on publications/presentations. 
15 Reporting Results on ClincalTrials.gov Website 
Upon receiving IDE approval from the FDA, this clinical investigation will be registered on ClinicalTrials.gov. A 
full report of the pre-specified outcomes, regardless of the results, will be made public through the 
ClinicalTrials.gov website no later than 12 months after clinical investigation completion, as required by 
section 801 of the FDA Amendments Act. If this clinical investigation is terminated early, the Sponsor will 
make every effort to hasten the release of the pre-specified outcomes through the ClinicalTrials.gov website. 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 37 of 51 
Appendix A: CIP Revisions 
 
Procedure for CIP Amendments 
 
This clinical investigation plan will be amended as needed throughout the clinical investigation. Rationale 
will be included with each amended version in the Revision History table below. The version number and date 
of amendments will be documented. The amendment will identify if it is mandatory or optional to implement 
the amendment. 
 
Special considerations will be made when the changes affect the investigational device design and/or 
patients’ safety, rights and well-being. 
 
Amendments to the CIP will originate from the Sponsor. The approval of the Coordinating Investigator (if 
applicable) and the Principal Investigators will be collected on the signature pages.  
 
As appropriate, IRB and regulatory authorities will be notified of amendments to the CIP and subject Informed 
Consent. 
 
Administrative changes to or formal clarifications of the CIP are allowed. They will be documented in writing 
and provided to the investigators. This information will be incorporated when an amendment occurs. 
 
Revision History 
 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Not 
Applicable 
A 
07 Nov 2016 
First release of CIP 
NA 
1 
B 
06 Apr 2017 
1. Removed blood draw 
requirement for nickel serum 
analysis due to patient safety. 
1. Removed references 
throughout document and 
added additional 
language in risk section 
pertaining to nickel.  
2 
C 
13 Dec 2017 
1. Reflect acquisition of SJM by 
Abbott. Sponsor remains SJM. 
Additional changes have been 
made for clarity of procedures 
and/or analysis methods. 
2. Language in Section 5 
‘Procedure’ section aligns with 
language in 5.4.1 
Implant/Procedure section. 
3. Change was made to bring the 
protocol into alignment with 
the Instructions for Use. 
4. Removed exclusion criteria 
regarding gestational age < 24 
1. Replaced SJM logo with 
Abbott logo and clarified 
details throughout the 
CIP.  
2. Specified subjects that do 
not receive the device at 
time of implant will be 
followed for 30 days and 
withdrawn in Section 5 
‘Procedures’. 
3. Allow use of intra-
procedure angiogram to 
confirm the sizing 
inclusion criteria of the 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 38 of 51 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
weeks as other exclusion 
criteria requiring ‘weight 
greater than 700g at time of 
implant’ and ‘other disease 
process likely to limit survival 
to less than six (6) months’ 
ensure that appropriate 
patients are enrolled. This will 
permit enrollment, for 
example, of a 3-month old 
infant or a 5-year old child that 
was born at 23 weeks 
gestation who is clinically 
stable and has a high 
likelihood of survival beyond 
6-months post-implant.  
5. Added CAP to allow current 
IDE study implanters to 
maintain their technical 
proficiency in ADO II AS 
device implantation and to 
allow additional implanters 
within each of the clinical sites 
activated for the IDE study to 
gain experience with the 
device. Data from the CAP 
may be used to support the 
pre-market approval (PMA) 
application for the ADO II AS 
occluder. 
 
PDA length and diameter 
intra-procedure. 
4. Removed exclusion 
criterion regarding 
gestational age < 24 
weeks. 
5. Added 150 subjects in a 
continued access 
protocol (CAP). 
 
3 
D 
2 Aug 2018 
Added 3-day serious adverse 
event (SAE) reporting 
requirement to align with 
Sponsor procedures  
Updated section 8.2 to 
reflect 3-day SAE 
reporting requirement 
 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 39 of 51 
Appendix B: Definitions 
Non-study Specific Definitions 
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the investigational 
medical device under clinical investigation. 
 
This definition includes events related to the investigational medical device (ADO II AS) as well as events 
related to the procedures involved in the clinical protocol. 
 
Serious Adverse Event (SAE) 
An adverse event that led to: 
• 
Death 
• 
A serious deterioration in the health of the subject, that either resulted in: 
o 
A life-threatening illness or injury OR 
o 
A permanent impairment to a body structure or a body function OR 
o 
An in-patient or prolonged hospitalization OR 
o 
A medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function OR 
o 
A malignant tumor 
• 
Fetal distress, fetal death or a congenital abnormality or birth defect 
• 
A planned hospitalization for a pre-existing condition, or a procedure required by the CIP is not 
considered a serious adverse event. 
 
Adverse Device Effect (ADE) 
An adverse event related to the use of an investigational medical device. 
 
This definition includes adverse events resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the investigational medical device. 
 
This definition includes any event resulting from the use error or from intentional misuse of the investigational 
medical device. 
 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse event. 
 
Unanticipated Adverse Device Effect (UADE) 
As defined in 21 CFR §812.3, unanticipated adverse device effects (UADE) are defined as any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence 
in the CIP or application (including a supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects. 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 40 of 51 
Study Specific Definitions 
Related: 
The adverse event is related to the study device/procedure – i.e. an event that follows a reasonable temporal 
sequence from administration of the study intervention, follows a known or expected response pattern to the 
suspected intervention, that is confirmed by improvement on stopping and reappearance of the event on 
repeated exposure and that could not be reasonably explained by the known characteristics of the subject’s 
clinical state.  
 
In summary, the AE is related to the study device (ADO II AS) or procedure if the event satisfies all of 
following criteria: 
• 
Has a reasonable temporal relationship to intervention (e.g. device implant) 
• 
Could not readily have been produced or explained by the subject’s clinical state or have been due to 
environmental or other interventions 
• 
Follows a known pattern of response to intervention 
• 
Disappears or decreases with reduction in dose or cessation of intervention and recurs with re-
exposure 
 
Attempted ADO II AS Device Implant 
Insertion of the TorqVue™ LP Catheter (9-TVLPC4F90/080) into the vasculature of the subject. 
 
Major Complication 
Major complications are defined as device (ADO II AS) or procedure-related adverse events resulting in any 
of the following: 
• 
death,  
• 
life-threatening adverse event,  
• 
persistent or significant disability/incapacity, and/or  
• 
a major open surgical intervention which is performed by a surgeon under general anesthesia  
 
Examples of Major Complications: 
• 
Device or procedure related events leading to death 
• 
Cardiac perforation requiring percutaneous (e.g., pericardiocentesis) or open surgical intervention 
• 
Cardiac tamponade 
• 
Embolization requiring open surgical procedure (e.g., open heart surgery or femoral vessel cutdown 
procedure) to retrieve the device 
• 
Persistent hemodynamic instability requiring emergency cardioversion/defibrillation therapy or 
emergency blood transfusion and/or institution of inotropic therapy 
• 
Excessive blood loss or hemolysis requiring transfusion ≥ 20 cc/kg 
• 
Persistent or worsening respiratory instability 
• 
Cerebral or pulmonary embolism 
• 
Persistent cardiac arrhythmia requiring a pacemaker 
• 
Arteriovenous fistula requiring open surgical intervention 
• 
False aneurysm of the femoral artery requiring surgical intervention 
• 
Femoral vessel thrombophlebitis treated with intravenous antibiotics 
• 
Infection of the device (bacterial endocarditis) 
 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 41 of 51 
Minor Complication 
Minor complications are defined as device (ADO II AS) or procedure-related adverse events that do not fit the 
definition of a major complication. These will include adverse events which may require medical intervention 
but are not life threatening, are not likely to have long-term (> 6 months) sequelae, and do not require long 
term (> 6 months) therapy. The following are examples of adverse events considered to be minor 
complications: 
 
Examples of Minor Complications: 
• 
Embolization that occurs intra-operatively where the device is retrieved using a transcatheter 
approach (e.g., using a snare) without needing to perform an open surgical procedure, such as open 
heart surgery or an open femoral vessel cutdown procedure. 
• 
Reduced peripheral pulse (reversible) that can be managed with anti-thrombotic therapy (e.g., 
heparin, Aspirin) 
• 
Cardiac perforation not requiring percutaneous (e.g., pericardiocentesis) or open surgical intervention 
• 
Transient cardiac arrhythmia that is managed successfully with cardioversion or medication 
• 
Hematoma of the groin not requiring open surgical intervention 
 
 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 42 of 51 
Appendix C: Labels 
 
The approved product labeling will be kept under a separate cover and available upon request for FDA or IRB 
submissions. 
 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 43 of 51 
Appendix D: Bibliography 
1. Tashiro, Jun, Eduardo A. Perez, and Juan E. Sola. "Reduced Hospital Mortality with Surgical Ligation of 
Patent Ductus Arteriosus in Premature, Extremely Low Birth Weight Infants: A Propensity Score-matched 
Outcome Study."Annals of surgery (2015). 
2. Schneider, Douglas J. "The patent ductus arteriosus in term infants, children, and adults." In Seminars in 
perinatology, vol. 36, no. 2, pp. 146-153. WB Saunders, 2012. 
3. Mahoney LT, Coyell KG, Laurer RM: The Newborn Transitional Circulation: Two-dimensional Doppler 
Echocardiographic Study. J Am Coll Cardiol 1985;6:623. 
4. Philip, Ranjit, B. Rush Waller, Vijaykumar Agrawal, Dena Wright, Alejandro Arevalo, David Zurakowski, 
and Shyam Sathanandam. "Morphologic characterization of the patent ductus arteriosus in the premature 
infant and the choice of transcatheter occlusion device." Catheterization and Cardiovascular Interventions 
(2015). 
5. Krichenko A, Benson LN, Burrows P, et al: Angiographic classification of the isolated, persistently patent 
ductus arteriosus and implications for percutaneous catheter occlusion. Am J of Card 1989;63:877-80. 
6. Pass R: AMPLATZER Duct Occluder Device: A New Technology for the Closure of the Moderate-to-large-
sized Patent Ductus Arteriosus. Expert Rev Med Devices 2006;3:291-296. 
7. Schneider, Douglas J. "The patent ductus arteriosus in term infants, children, and adults." In Seminars in 
perinatology, vol. 36, no. 2, pp. 146-153. WB Saunders, 2012. 
8. Moore JW, Levi DS, Moore SD, Schneider DJ, Berdjis F. Interventional Treatment of Patent Ductus 
Arteriosus in 2004. Catheter Cardiovasc Interv 2005;64:91-101. 
9. Perloff, Joseph K.The Clinical Recognition of Congenital Heart Disease. Philadelphia: Saunders. Print. 
10. Gross RE, Hubbard JP. Surgical ligation of a patent ductus arteriosus: report of first successful case. 
Congenital Heart Disease, Hutchinson Ross Pub Co., 1982, p 253. 
11. Kabra, Nandkishor S., et al. "Neurosensory impairment after surgical closure of patent ductus arteriosus 
in extremely low birth weight infants: results from the Trial of Indomethacin Prophylaxis in Preterms." The 
Journal of pediatrics 150.3 (2007): 229-234. 
12. Chorne, Nancy, et al. "Patent ductus arteriosus and its treatment as risk factors for neonatal and 
neurodevelopmental morbidity." Pediatrics 119.6 (2007): 1165-1174. 
13. Teixeira, L. S., et al. "Postoperative cardiorespiratory instability following ligation of the preterm ductus 
arteriosus is related to early need for intervention." Journal of Perinatology 28.12 (2008): 803-810. 
14. Portsmann W, Wierny L, Warnke H, et al: Catheter closure of patent ductus arteriosus: 62 cases treated 
without thoracotomy. Radiol Clin North Am 1971;9:203-218. 
15. Weisz, Dany E., and Patrick J. McNamara. "Patent ductus arteriosus ligation and adverse outcomes: 
causality or bias?." Journal of clinical neonatology 3.2 (2014): 67. 
16. Philip, Ranjit, B. Rush Waller, Vijaykumar Agrawal, Dena Wright, Alejandro Arevalo, David Zurakowski, 
and Shyam Sathanandam. "Morphologic characterization of the patent ductus arteriosus in the premature 
infant and the choice of transcatheter occlusion device." Catheterization and Cardiovascular 
Interventions (2015). 
17. 17. Gruenstein, Daniel H., et al. "Transcatheter closure of patent ductus arteriosus using the 
AMPLATZER™ duct occluder II (ADO II)." Catheterization and Cardiovascular Interventions 89.6 (2017): 
1118-1128.Agnoletti, Gabriella, D. Marini, A. M. Villar, R. Bordese, and F. Gabbarini. "Closure of the 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
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Page 44 of 51 
patent ductus arteriosus with the new duct occluder II additional sizes device." Catheterization and 
Cardiovascular Interventions 79, no. 7 (2012): 1169-1174. 
18. Kenny, Damien, Gareth J. Morgan, James R. Bentham, Neil Wilson, Robin Martin, Andrew Tometzki, Paul 
Oslizlok, and Kevin P. Walsh. "Early clinical experience with a modified Amplatzer ductal occluder for 
transcatheter arterial duct occlusion in infants and small children." Catheterization and Cardiovascular 
Interventions 82, no. 4 (2013): 534-540. 
19. Sungur, Metin, Cemsit Karakurt, Nazan Ozbarlas, and Osman Baspinar. "Closure of patent ductus 
arteriosus in children, small infants, and premature babies with Amplatzer duct occluder II additional 
sizes: multicenter study."Catheterization and Cardiovascular Interventions 82, no. 2 (2013): 245-252. 
20. Bruckheimer, Elchanan, Max Godfrey, Tamir Dagan, Michael Levinzon, Gabriel Amir, and Einat Birk. "The 
Amplatzer duct occluder II additional sizes device for transcatheter PDA closure: Initial 
experience." Catheterization and Cardiovascular Interventions 83, no. 7 (2014): 1097-1101. 
21. Baspinar, Osman, Derya Aydin Sahin, Ayse Sulu, Ahmet Irdem, Gokhan Gokaslan, Ercan Sivasli, and 
Metin Kilinc. "Transcatheter Closure of Patent Ductus Arteriosus in Under 6 kg and Premature 
Infants." Journal of interventional cardiology 28, no. 2 (2015): 180-189. 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 45 of 51 
Appendix E: American Heart Association Recommendations for Prophylaxis 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
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Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
Clinical Investigation Plan 
 
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Page 47 of 51 
Appendix F: Transthoracic Echocardiography (TTE) Protocol 
The following guidelines should be followed when performing the baseline and follow-up trans-thoracic 
echocardiogram studies. The baseline echocardiogram is used to assess the status of PDA (dimensions and 
flow), along with left ventricular function and dimension measurements. The intra-procedural echocardiogram 
is used to confirm eligibility for the study and to guide the implant procedure. 
 
Machine settings:  Due to the several different types of equipment used for this test, gain setting must be 
adjusted to guarantee uniformity and quality imaging. The following guidelines should be followed for 
machine setup. 
 
• 
The echocardiographic machine digital acquisition protocol should be set at a minimum of 3 complete 
acquisition loops gated to the QRS complex (5 loops is the preferred setting). Please make sure these 
settings are changed in the echocardiogram machine “preferences” prior to starting the imaging protocol, 
and maintained throughout the study. In order for any ultrasound machine to perform these digital loops, 
ECG pads must be placed and hooked from the subject to the echo machine during the entire image 
acquisition session. 
• 
Please ensure that both the image frequency is optimized and that the 2-D and color Doppler gains are 
properly set so that image quality is maximized. 
• 
Color Doppler echocardiogram will be represented as “red towards and blue away” from the transducer. 
Variance or “turbulence” mapping will be used for color flow Doppler. 
• 
It is best practice to test the settings by increasing the color Doppler Gain control knob to increase color 
gain all the way until the image becomes “pixelated” (indicating excessive gain), then the knob should be 
dialed back until just below the point where the pixilation is eliminated and left at this level for the 
remainder of the imaging study. 
• 
Sensitivity to low velocity shunts will be maximized by decreasing Nyquist limit and limiting the size of the 
color window appropriately. This will be done in a stepwise technique while recording on videotape or CD 
in sequential fashion using digital clip storage media. Color flow gain will be adjusted at each step to 
maximize color saturation without overwriting tissue by the color flow signal. 
 
Imaging guidance:  The following guideline should be followed for assessing the PDA status, left ventricular 
function and dimensions, pulmonary and aortic flow and dimensions, and pulmonic and tricuspid valve 
regurgitation. 
 
• 
The Doppler Echocardiographic transducer orientation will align the ultrasound beam with the blood flow. 
• 
Doppler echocardiogram should be a complete assessment and reviewed closely in the parasternal short 
axis and parasternal long axis “ductus cut” and in the suprasternal views to interrogate the main 
pulmonary artery for flow through the PDA and also to the Doppler “pulsed, continuous wave and color” 
for any evidence of obstruction to the left pulmonary artery and descending aorta.  
• 
Evidence of any residual shunting will be quantified by measuring the width of the jet immediately as it 
exits from the ductus (device), along with an assessment of PDA shunt grade using the following 
definitions: 
o 
Grade 0—none; 
o 
Grade 1—trivial (narrow jet adjacent to the device via the PDA).  Note: the presence of flow via 
existing or newly formed aortopulmonary collaterals should not be considered as representing a 
shunt via the PDA [see references]. 
o 
Grade 2—mild (broader jet filling proximal left pulmonary artery branch and extending to main 
pulmonary artery); 

 
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Page 48 of 51 
o 
Grade 3/4—moderate to severe (wide jet filling the main pulmonary artery and extending to 
pulmonary valve or distal pulmonary artery branches, which also may be accompanied with the 
presence of flow reversal in the abdominal aortic Doppler pattern during diastole) 
 
Imaging measurements & assessments: 
Baseline: 
2D Imaging 
• 
Minimal ductal diameter (mm) 
• 
Maximal ductal diameter (mm) 
• 
Ductal length (mm) 
• 
Diameter of aortic isthmus (mm) 
• 
Diameter of aorta at diaphragm level (mm) 
• 
Diameter of proximal left pulmonary artery (mm) 
• 
LV end-diastolic area (parasternal short axis image) (mm2) 
• 
LV end-systolic area (parasternal short axis image) (mm2) 
• 
LV apical length in diastole (mm) 
• 
LV apical length in systole (mm) 
• 
Left ventricular ejection fraction (%) 
• 
Left ventricular shortening fraction (%) 
 
Spectral Doppler 
• 
Peak gradient in descending aorta at the isthmus (mmHg) 
• 
Mean gradient in descending aorta at the isthmus (mmHg) 
• 
Doppler pattern in abdominal  aorta 
o 
Blunted profile with diminished upstroke (Y/N) 
o 
Holodiastolic antegrade flow (Y/N) 
o 
Flow reversal during diastole (Y/N) 
• 
Peak gradient in PDA (mmHg) 
• 
Peak gradient in left pulmonary artery (mmHg) 
• 
Mean gradient in left pulmonary artery (mmHg) 
 
Color Doppler 
• 
Right-to-Left ductal shunting (Y/N) 
• 
Left-to-Right ductal shunting (Y/N) 
• 
Tricuspid regurgitation grade (None, Trace, Mild, Moderate, Severe) 
• 
Pulmonary regurgitation grade (None, Trace, Mild, Moderate, Severe) 
• 
Aortopulmonary collaterals (Y/N) 
 
Procedure: 
2D Imaging 
• 
Minimal ductal diameter (mm) 
• 
Maximal ductal diameter (mm) 
• 
Ductal length (mm) 
 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 49 of 51 
Post-Procedure and Follow-Up: 
2D Imaging 
• 
Device within PDA (Y/N) 
• 
Diameter of aortic isthmus (mm) 
• 
Diameter of aorta at diaphragm level (mm) 
• 
Diameter of proximal left pulmonary artery (mm) 
• 
LV end-diastolic area (parasternal short axis image) (mm2) 
• 
LV end-systolic area (parasternal short axis image) (mm2) 
• 
LV apical length in diastole (mm) 
• 
LV apical length in systole (mm) 
• 
Left ventricular ejection fraction (%) 
• 
Left ventricular shortening fraction (%) 
 
Spectral Doppler 
• 
Peak gradient in descending aorta at the isthmus (mmHg) 
• 
Mean gradient in descending aorta at the isthmus (mmHg) 
• 
Doppler pattern in abdominal  aorta 
o 
Blunted profile with diminished upstroke (Y/N) 
o 
Holodiastolic antegrade flow (Y/N) 
o 
Flow reversal during diastole (Y/N) 
• 
Peak gradient in left pulmonary artery (mmHg) 
• 
Mean gradient in left pulmonary artery (mmHg) 
 
Color Doppler 
• 
PDA residual shunt grade (None(0), Trivial(1), Mild(2), Moderate/Severe(3/4)) 
• 
Tricuspid regurgitation grade (None, Trivial, Mild, Moderate, Severe) 
• 
Pulmonary regurgitation grade (None, Trivial, Mild, Moderate, Severe) 
• 
Aortopulmonary collaterals (Y/N) 
 
Note:  peak gradient refers to “maximal instantaneous gradient” by echocardiography. 
References: 
1) Lopez, L., Colan, S. D., Frommelt, P. C., Ensing, G. J., Kendall, K., Younoszai, A. K., ... & Geva, T. 
(2010). Recommendations for quantification methods during the performance of a pediatric 
echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of 
Echocardiography Pediatric and Congenital Heart Disease Council. Journal of the American Society of 
Echocardiography, 23(5), 465-495. 
2) Skinner, J. R., & Silove, E. D. (1995). Aortopulmonary collateral arteries mimicking symptomatic ductal 
shunting in a preterm infant. British heart journal, 74(1), 93-94. 
3) Acherman, R. J., Siassi, B., Pratti-Madrid, G., Luna, C., Lewis, A. B., Ebrahimi, M., ... & Ramanathan, R. 
(2000). Systemic to pulmonary collaterals in very low birth weight infants: color doppler detection of 
systemic to pulmonary connections during neonatal and early infancy period. Pediatrics, 105(3), 528-532. 
 
 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 50 of 51 
Appendix G: Case Report Forms 
 
The approved CRFs will be kept under a separate cover and available upon request for Regulatory or IRB 
submissions. 
 
 

 
Study Document No: SJM-CIP-10171 Ver. D 
Study Name: ADO II AS 
 
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 
 
 
Page 51 of 51 
Appendix H: Template Informed Consent Form 
 
The approved Informed Consent Template will be kept under a separate cover and available upon request for 
Regulatory or IRB submissions.