Assessment of the St Jude Medical Portico Resheathable Aortic Valve System-Alternative Access
Phase: NA
Conditions: Aortic Valve Stenosis
Sponsor: Abbott Medical Devices

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 1 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
 
 
 
Portico Alternative Access 
 
“Assessment of the St Jude Medical Portico Resheathable Aortic Valve System-
Alternative Access” 
 
CRD_878 
Study Document No: SJM-CIP-10144 
Version D 
Date: 10-Oct-2017 
Clinical Investigation Plan (CIP) 
 
 
 
 
 
 
 
Sponsor  
 
 
 
Abbott 
5050 Nathan Lane 
Plymouth MN 55442 
USA 
 
 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 2 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
SITE PRINICPAL INVESTIGATOR SIGNATURE PAGE 
Portico Alternative Access 
 
Version D, 10-Oct-2017 
Reference #: SJM-CIP-10144 
 
I have read and agree to adhere to the clinical investigational plan and all regulatory requirements 
applicable in conducting this clinical study. 
 
 
Site Principal Investigator 
 
Printed name: 
____________________________________ 
Signature:_______________________________________ 
Date:  ____________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
October, 10th 2017 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 4 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
 
Table of Contents 
Page 
1.0 Synopsis ................................................................................................................................. 6 
2.0 Background and Justification for Clinical Study .............................................................. 11 
3.0 Device under Investigation .................................................................................................. 13 
3.1 Portico TF and ALT Delivery System .................................................................................. 13 
3.2 Device Handling and Storage .............................................................................................. 14 
3.3 Device Accountability .......................................................................................................... 14 
4.0 Study Design ........................................................................................................................ 15 
4.1 Purpose ............................................................................................................................... 15 
4.2 Study Design and Scope ..................................................................................................... 15 
4.3 End Points ........................................................................................................................... 15 
4.4 Study Population ................................................................................................................. 16 
5.0 Procedures ............................................................................................................................ 18 
5.1 Informed Consent Process .................................................................................................. 18 
5.2 Subject Screening ............................................................................................................... 19 
5.3 Point of Enrollment .............................................................................................................. 19 
5.4 Study Activities .................................................................................................................... 19 
5.5 Procedures .......................................................................................................................... 21 
5.6 Enrollment Visit ................................................................................................................... 24 
5.7 Implant/Procedure ............................................................................................................... 24 
5.8 Scheduled Follow-ups ......................................................................................................... 25 
5.9 Unscheduled Visit for Evaluation of Suspected Neurological Event ................................... 26 
5.10 Blood Work .......................................................................................................................... 26 
5.11 Imaging ................................................................................................................................ 27 
5.12 Medications ......................................................................................................................... 27 
5.13 Description of Activities Performed by Sponsor Representatives ....................................... 28 
5.14 Subject Study Completion ................................................................................................... 28 
5.15 Subject Withdrawal .............................................................................................................. 28 
6.0 Statistical Considerations ................................................................................................... 29 
6.1 General Statistical Methods ................................................................................................ 29 
6.2 Endpoints ............................................................................................................................ 29 
6.3 Sample Size ........................................................................................................................ 30 
6.4 Justification of Clinical Investigation Design ........................................................................ 31 
6.5 Timing of Analysis ............................................................................................................... 31 
6.6 Success Criteria .................................................................................................................. 31 
6.7 Interim Analysis ................................................................................................................... 31 
6.8 Statistical Criteria for Termination ....................................................................................... 31 
6.9 Deviations from Statistical Plan ........................................................................................... 31 
7.0 Study Committees ................................................................................................................ 31 
7.1 Clinical Event Committee (CEC) ......................................................................................... 31 
7.2 Subject Selection Committee .............................................................................................. 31 
8.0 Risks and Benefits of the Clinical Study ............................................................................ 32 
8.1 Anticipated Clinical Benefits ................................................................................................ 32 
8.2 Anticipated Adverse Events and Adverse Device Effects ................................................... 32 
8.3 Residual Risks Associated with the Device Under Investigation ......................................... 34 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 5 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
9.0 Requirements for Investigator Records and Reports ....................................................... 35 
9.1 Deviations from CIP ............................................................................................................ 35 
9.2 Safety Reporting .................................................................................................................. 35 
9.3 Records Retention ............................................................................................................... 37 
10.0 Clinical Data Handling ......................................................................................................... 37 
10.1 Data Management Plan ....................................................................................................... 37 
10.2 Document and Data Control ................................................................................................ 38 
11.0 Monitoring ............................................................................................................................. 38 
12.0 Compliance Statement ......................................................................................................... 39 
12.1 Statement of Compliance .................................................................................................... 39 
12.2 Regulatory Inspections ........................................................................................................ 39 
12.3 Repeated and Serious Non-Compliance ............................................................................. 39 
13.0 Core Lab ................................................................................................................................ 40 
14.0 Suspension or Premature Termination of the Clinical Investigation .............................. 40 
14.1 Study Conclusion ................................................................................................................ 41 
15.0 Publication Policy ................................................................................................................ 41 
Appendix A: Abbreviations .......................................................................................................... 42 
Appendix B: CIP Revision History ............................................................................................... 43 
Appendix C: Bibliography ............................................................................................................ 44 
Appendix D: Definitions ............................................................................................................... 46 
Appendix E: Risk Calculations .................................................................................................... 52 
Appendix F: Quality of Life-EQ-5D 3L ......................................................................................... 53 
Appendix G: Frality Assessment ................................................................................................. 54 
Appendix H: Scales ....................................................................................................................... 56 
Appendix I : NYHA Classification ................................................................................................ 63 
Appendix J: ATS Guidelines for the Six Minute Walk Test ....................................................... 64 
Appendix K : Sample Informed Consent .................................................................................... 68 
Appendix L : Case Report Forms ................................................................................................ 69 
Appendix M. German Handling of Serious Adverse Events ..................................................... 70 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 6 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
 Synopsis  
1.0
 
Title: 
Assessment of the St. Jude Medical PorticoTM Re-sheathable Aortic Valve 
System – Alternative Access 
Acronym: 
Portico Alternative Access 
Purpose: 
The purpose of this clinical investigation is to expand the indication of the 
Portico TF Delivery System and obtain approval of the Alternative Access 
Delivery System to place a Portico transcatheter aortic valve through an 
alternative access site, specifically subclavian/axillary or transaortic (TAo) 
in subjects with symptomatic severe native aortic stenosis who are 
considered high surgical risk.   
Endpoints: 
Primary Endpoint: 
The study will have a single primary safety endpoint of major vascular 
complications through 30 days, as defined by the Valve Academic 
Research Consortiumi (VARC-2) for each access arm of the study.   
Secondary Endpoints for each access arm of the study: 
1. The event rates at 30 days of the following: 
 
All-cause mortality  
 
Cardiovascular mortality 
 
Disabling stroke  
 
Non-disabling stroke 
 
Life-threatening bleeding requiring transfusion 
 
Acute kidney injury requiring dialysis 
 
Composite of 
o Periprocedural encephalopathy 
o all stroke 
o all TIA 
2. The event rates at 1 year of the following: 
 
All-cause mortality 
 
Cardiovascular mortality 
 
Disabling stroke  
 
Moderate and severe aortic regurgitation 
3. Improvement from baseline as compared to 30 days by: 
 
NYHA Functional Classification 
 
Six minute walk test 
 
Effective Orifice Area (EOA) 
4. Acute device success defined as: 
 
Absence of procedural mortality  
 
Correct positioning of a single prosthetic heart valve into the 
proper anatomical location  
 
Intended performance of the prosthetic heart valve 
o mean aortic valve gradient <20 mmHg 
o peak velocity <3 m/s 
o no moderate or severe prosthetic valve regurgitation 
In addition successful access, delivery and deployment of the valve and 
retrieval of the delivery system will be collected. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 7 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
Design: 
This is a multicenter prospective, non-randomized, 2-arm investigational 
study without concurrent or matched controls, designed to assess the use 
of the Portico TF or Alternative Access Delivery System to place a 
transcatheter aortic valve through an alternative access site, specifically 
subclavian/axillary and TAo. 
A minimum of 45 subjects will undergo transcatheter aortic valve 
replacement (independent of valve size) using the Portico TF or 
Alternative Access Delivery System in each study access arm 
(subclavian/axillary and TAo). A minimum of 45 implants will be accessed 
via the subclavian/axillary access site and a minimum of 45 implants will 
be accessed via the TAo access site. A maximum of 12 investigational 
sites with prior alternative access technique experience in Europe will be 
trained to participate in the study. Enrollment is anticipated to be 
completed approximately 8 months from the date of first enrollment. Data 
will be collected at pre-procedure, peri-procedure and at discharge as well 
as at 30 days, 6 months and 1 year post implantation. All active subjects 
will be followed for 1 year. 
 
Data from other prospective Portico clinical trials with ALT access in 
similar patient populations outside of Europe may be included in the 
analysis and support the submission for CE Mark. CE Mark will be 
submitted for each access route after implantation and 30 day follow up 
are completed. 
 
Although the study will not test a hypothesis, the primary endpoint event 
rate for each cohort will be presented within the context of the range of 
rates reported for alternative access delivery of transcatheter valves in the 
literature. 
Devices used: 
The devices to be used in this study are the Portico delivery systems 
which are available in two different lengths, 110 and 65cm. Both of these 
devices are considered investigational for alternative access use.  The 
110cm delivery system is already CE marked for Transfemoral access.  
This study will also use the CE marked Transfemoral/Alternative Access 
Loading systems (18 or 19F) and Portico valves available in 23, 25, 27 
and 29mm sizes. 
Study Population 
A patient becomes a subject once he/she has been fully informed about 
the study, has agreed to participate, signed & dated the consent. 
Inclusion/Exclusion 
Criteria  
Inclusion Criteria 
1. Subject has provided written informed consent prior to uploading 
CT scan to core lab. 
2. Subject is ≥ 18 years of age or legal age in host country.  
3. Subject’s aortic annulus diameter meets the range indicated in the 
Instructions for Use as measured by multislice CT conducted 
within 180 days prior to the index procedure. 
4. Subject has senile degenerative aortic stenosis seen by 
echocardiography within 90 days of index procedure as measured 
by one of the following: 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 8 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
 
Mean gradient ≥ 40 mmHg 
 
Peak velocity ≥ 4.0 m/s  
 
Doppler Velocity Index < 0.25   
 
Aortic valve area (AVA) of < 1.0 cm2 or indexed EOA < 0.6 
cm2/m2. 
5. Subject has symptomatic aortic stenosis as demonstrated by 
NYHA Functional Classification of Class II, or greater or other 
symptoms of aortic stenosis (e.g. syncope). 
6. Subject is deemed high operable risk and preferred TAVI delivery 
route is alternate access (subclavian/axillary or direct aortic) per 
the medical opinion of the center’s heart team and confirmed by 
SSC. 
 
High risk is defined as an STS mortality > 8% or documented heart 
team agreement ≥ high risk for SAVR due to frailty or co-morbidities 
Exclusion Criteria 
1. Subject is unwilling or unable to comply with all study-required 
follow-up evaluations. 
2. Subject has a documented history of a cerebral vascular accident 
(CVA) or transient ischemic attack (TIA) within 6 months (less than 
or equal to 180 days) prior to the index procedure. 
3. Subject has carotid artery disease requiring intervention. 
4. Subject has evidence of a myocardial infarction (MI) within 30 days 
prior to patient index procedure. 
5. Subject has a native aortic valve that is congenitally unicuspid, 
bicuspid, quadricuspid or non-calcified as seen by 
echocardiography. 
6. Subject has severe mitral valvular regurgitation. 
7. Subject has severe mitral stenosis. 
8. Subject has a pre-existing prosthetic cardiac device, valve, or 
prosthetic ring in any position. 
9. Subject refuses any blood product transfusion. 
10. Subject has resting left ventricular ejection fraction (LVEF) less 
than 20%. 
11. Subject has documented, untreated symptomatic coronary artery 
disease (CAD) requiring revascularization. 
12. Subject has had a percutaneous interventional or other invasive 
cardiovascular or peripheral vascular procedure less than or equal 
to 14 days prior to index procedure. 
13. Subject has severe basal septal hypertrophy that would interfere 
with transcatheter aortic valve placement. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 9 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
14. Subject has a history of, or is currently diagnosed with, 
endocarditis. 
15. There is imaging evidence of intracardiac mass, thrombus, or 
vegetation. 
16. Subject is considered hemodynamically unstable (requiring 
inotropic support or mechanical heart assistance). 
17. Subject is in acute pulmonary edema or requiring intravenous 
diuretic therapy to stabilize heart failure. 
18. Subject with severe pulmonary disease as determined by STS 
score. 
19. Subject is on chronic oral steroid therapy. 
20. Subject has a documented hypersensitivity or contraindication to 
anticoagulant or antiplatelet medication. 
21. Subject has renal insufficiency as evidenced by a serum creatinine 
greater than 3.0 mg/dL (265.5 µmol/L) or end-stage renal disease 
requiring chronic dialysis. 
22. Subject has morbid obesity defined as a BMI greater than or equal 
to 40. 
23. Subject has ongoing infection or sepsis. 
24. Subject has uncontrolled blood dyscrasias as defined: leukopenia 
(WBC<3000 mm3), acute anemia (Hb<9 g/dL), thrombocytopenia 
(platelet count <50,000 cells/mm3,). 
25. Anatomy falling outside the recommended values in the IFU, 
unless specifically approved by the Subject Selection Committee. 
26. Subject has an active peptic ulcer or has had gastrointestinal (GI) 
bleeding within 90 days prior to the index procedure. 
27. Subject is currently participating in another investigational drug or 
device study, unless approved by the Sponsor. 
28. Subject has/had emergency surgery for any reason within 30 days 
of the index procedure. 
29. Subject has a life expectancy less than 1 year. 
30. Subject has other medical, social or psychological conditions that, 
in the opinion of the site Heart Team or the Subject Selection 
Committee, preclude the subject from study participation. 
31. Subject is diagnosed with a state of dementia which would 
fundamentally complicate rehabilitation from the procedure or 
compliance with follow-up visits. 
32. Subject has a documented allergy to contrast media that cannot 
adequately be treated, nitinol alloys, porcine tissue, or bovine 
tissue. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 10 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or 
used without the express written consent of Abbott 
33. Significant aortic disease including abdominal aortic or thoracic 
aneurysm defined as maximal luminal diameter 5cm or greater  
34. Subjects with severe pulmonary hypertension and severe RV 
dysfunction 
35. Subjects with hypertrophic cardiomyopathy 
 
Transaortic Subject Cohort Specific Exclusion Criteria 
1. Subject has a chest condition (anatomical or otherwise) that 
prevents TAo access. 
2. Subject has pre-existing patent RIMA graft that would preclude 
access. 
3. Subject has a porcelain aorta, defined as an extensive 
circumferential calcification of the ascending aorta that would 
complicate TAo access. 
 
Subclavian/Axillary Subject Cohort Specific Exclusion Criteria 
1. Subject’s access vessel (subclavian/axillary) diameter will not allow 
for introduction of the 18/19 Fr delivery system. 
2. Subject’s subclavian/axillary arteries have severe calcification 
and/or tortuosity. 
3. Subject has a history of LIMA/RIMA graft that would preclude 
access 
 
Data Collection 
Data will be collected pre-procedure, peri-procedure, and discharge as 
well as 30 days, 6 months and 1 year post implantation. 
A Clinical Events Committee (CEC) will adjudicate the relatedness of 
endpoint events with respect to the procedure, delivery system, valve and 
by event type according to the VARC-2 endpoint definitions document. 
CEC adjudications will be used when assessing and reporting study 
results. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 11 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 Background and Justification for Clinical Study 
2.0
Aortic Stenosis (AS) is currently the most common valvular disease in the Western population1 
and its prevalence tends to increase with age, being present in 4.6% of adults ≥75 years.2 
Replacement of the aortic valve remains an effective treatment of severe AS. There was a near 
doubling of surgical aortic valve replacements (AVRs) over a 10-year period (1995-2004)3 and 
the need for AVR is projected to escalate as the population grows older due to the increase in 
life expectancy.4 
The average life expectancy of patients with severe, symptomatic AS is 2-3 years from the 
onset of symptoms with a significant risk of sudden death.5 Symptomatic aortic stenosis is an 
accepted indication for surgery, in which valve replacement can both reduce symptoms and 
extend life.6 Despite this, many patients with severe aortic stenosis do not undergo surgery 
because of excessive risk, advanced age, or preference. Prognosis with medical management 
is poor1 and prior to TAVR, percutaneous alternatives to surgery have been limited to balloon 
valvuloplasty with palliation that is modest and short-lived.7,8  
Many patients with severe AS are considered high surgical risk and do not undergo AVR due to 
severe comorbidities. Because of the limited therapeutic options in patients deemed at high 
surgical risk, there was interest in the development of a less invasive method to restore valve 
function.  
With technological advancements, an alternative to surgical AVR, known as TAVR 
(Transcatheter Aortic Valve Replacement) and TAVI (Transcatheter Aortic Valve Implantation) 
has been under active investigation and proven safe and effective by a number of groups.9-15 
This concept was first demonstrated by Andersen et al16 in 1992, who delivered a porcine 
bioprosthesis attached to a wire-based stent at various aortic sites with satisfactory 
hemodynamic results. In 2002, Cribier et al,17 reported the first successful human TAVI for the 
treatment of severe symptomatic aortic stenosis. Several single-center trials followed which 
demonstrated that this new approach was feasible for the treatment of severe aortic stenosis in 
patients who were inoperable or at a very high risk for standard surgical aortic valve 
replacement. 
The safety and effectiveness of TAVI is now confirmed with the recent published results of the 
randomized, controlled PARTNER trial18, CoreValve IDE29 which demonstrated the noninferiority 
of TAVI as compared to conventional AVR in high risk patients.  
The first two devices commercially available were the Medtronic CoreValve™ (Medtronic Inc., 
Minneapolis, Minnesota), and the Edwards Sapien™ valve (Edwards Lifesciences Corporation, 
Irvine, CA) which received CE Mark in 2007 for transarterial implantation. In addition, the 
Edwards Sapien prosthesis received CE Mark for transapical implantation in December 2007. 
The Edwards Sapien XT™ valve (Edwards Lifesciences Corporation, Irvine, CA) received CE 
Mark in 2010 for transarterial and transapical implantation. In October 2011, two additional 
valves received CE Mark: the JenaValve™ valve (JenaValve Technology München, Germany) 
and the Symetis Acurate TA™ system (Symetis, Ecublens, Switzerland). Both valves are 
designed for a percutaneous aortic valve implantation via a transapical route. 
Transcatheter aortic valve replacement was originally described through an antegrade 
transseptal route by Cribier and colleagues in 2002.19 Because of the complexity of the 
procedure and risks associated with crossing the mitral valve, this approach has been 
abandoned in favor of more reproducible alternatives, primarily the transfemoral (TF) route. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 12 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Typically, TF access is the initial default strategy unless the vascular anatomy conveys a 
prohibitive risk due to vessel tortuosity, small caliber, or heavy calcification. 
Although the TF route is the least invasive, it may not be feasible in every patient.20 General 
(absolute and relative) contraindications to the TF approach include severely calcified or 
tortuous iliac arteries; an iliac artery diameter of < 6 mm to < 9 mm (depending on the type of 
device used); previous aortofemoral bypass grafts; severely angulated aorta or atherosclerotic 
aortic arch; transverse ascending arch (for balloon-expandable devices); and aortic aneurysm 
with extensive mural thrombus and coarctation of the aorta. In a recent evaluation by Kurra et. 
al. of 100 patients undergoing TAVR screening, 35% of patients had at least one criterion of 
unsuitable iliofemoral anatomy, including 27 patients with small minimal luminal diameter (<8 
mm), 12 patients with severe circumferential calcification at the iliac bifurcation (>60%), and 4 
with severe angulation of the iliac arteries (<90°).21 
The decision of using one delivery approach versus another is typically based upon a 
multidisciplinary team’s consensus, comprising the expertise of interventional cardiologists, 
imaging cardiologists, cardiac surgeons, and cardiac anesthetists - following a careful 
evaluation of the patient. Even though the experience and skills of the operators have improved 
and new technologies have become available since the initial TAVI experiences, patient 
selection remains a key element in the TAVI outcome. Selection criteria have a crucial influence 
on complication rates and clinical outcomes after TAVI.22 
Subclavian/axillary and Transaortic (TAo) access have been introduced  as alternative routes in 
patients with difficult transfemoral access for implantation of a transcatheter heart valve23. 
Compared to the TF approach, subclavian/axillary and TAo access provides a less remote 
access point to the aortic valve. This shorter distance also reduces bending stress on the 
delivery system through multiple vasculature points potentially improving steerability and 
placement control of the transcatheter aortic valve. 
The subclavian/axillary approach is  preferably performed  via the left subclavian artery. Hence, 
a patent left internal mammary artery (LIMA) graft is a relative contraindication for TAVR from 
the left side. In these patients, the right subclavian artery can be used; however, it may be 
challenging to achieve the correct angulation of the transcatheter aortic valve during positioning. 
The presence of a permanent pacemaker in the left pectoral region is not an absolute 
contraindication.20 
Transaortic (TAo) approach, also known as “direct aortic” access, provides proximate, direct 
access to the aortic annulus allowing for precise manipulation of both the delivery system and 
transcatheter heart valve. This is important in cases where the implantation with other 
approaches (e.g., TF, TA) may be difficult such as cases with a vertical valve orientation, a 
horizontal ascending aorta, or where the native valve is at the upper limit of the size.20 
TAo approaches are either through a ministernotomy or through a mini-right thoracotomy. In a 
ministernotomy, a limited skin incision (5 cm) is made starting just below the sternal notch. A 
partial upper sternotomy (J-shape) is performed through the second or third right intercostal 
space. This exposes the upper portion of the ascending aorta for direct cannulation. A 
ministernotomy is preferred in obese patients, patients with an ascending aorta in the mid-line/to 
the left or a short ascending aorta, and in patients with poor respiratory reserve because the 
pleura remains intact, and it has less effect on the respiratory dynamics. This approach can also 
be used in patients with previous coronary artery bypass grafting and a patent LIMA graft 
provided that the LIMA graft is not in the mid-line and the innominate vein and aorta are not in 
close proximity to the sternum.20 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 13 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
The use of each of these alternate access approaches has been demonstrated to be a safe and 
effective means of delivering transcatheter aortic valves as evidenced by the approved products 
mentioned above and thus increases the number of patients who can be treated successfully 
and can ultimately benefit from transcatheter aortic valve replacement. 
 Device under Investigation 
3.0
 
3.1
Portico TF and ALT Delivery System 
The study will use the CE Marked PorticoTM transcatheter valves available in 23, 25, 27, and 
29mm sizes. The devices under investigation are the Portico TF (110cm) Delivery System and 
the Alternative Access (65cm) Delivery System which both come in 18 Fr or 19 Fr diameter. 
Both delivery systems are over-the-wire, (0.035”-compatible). The outer diameter of the delivery 
systems is 18 Fr and 19 Fr at the distal end and 13 Fr at the proximal end. 
The delivery system design facilitates gradual, controlled deployment of the valve. If needed, 
the valve may be re-sheathed and repositioned up to 2 times, provided the valve has not been 
>80% deployed. 
The valve is deployed annulus end first, from the distal end of the delivery system. The distal 
end of the delivery system includes an atraumatic radiopaque tip to guide the delivery system 
and facilitate visualization. The protective sheath covers and maintains the valve in the 
collapsed position. The protective sheath features a marker band that provides a reference point 
used to determine the extent of the valve deployment. The protective sheath may be advanced 
or retracted to facilitate valve loading and deployment. When the protective sheath is retracted, 
the inner shaft is exposed. The valve is loaded onto the inner shaft. Retainer tabs on the valve 
lock into a retainer receptacle that is mounted on the inner shaft. The inner shaft also features a 
radiopaque inner shaft marker band that provides a reference point used to align the valve in 
the native annulus. 
.  
 
Figure 1: Portico Delivery System 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 14 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Table 1:  Regulatory Status of Devices 
Device 
Component 
Model/Type 
Investigational or 
Market Released 
110cm Delivery 
System 
18F TF Delivery System 
Market Released* 
110cm Delivery 
System 
19F TF Delivery System 
Market Released* 
65cm Delivery 
System 
18F ALT Delivery System 
Investigational 
65cm Delivery 
System 
19F ALT Delivery System 
Investigational 
Loading System 
18F Transfemoral/Alternative Access Loading System 
Market Released 
Loading System 
19F Transfemoral/Alternative Access Loading System 
Market Released 
Valve 
PRT-23 
Market Released 
Valve 
PRT-25 
Market Released 
Valve 
PRT-27 
Market Released 
Valve 
PRT-29 
Market Released 
*Will be investigational when used for alternative access delivery 
 
3.2
Device Handling and Storage 
Abbott requires all investigational products be stored, according to the labeling, in a secure area 
to prevent unauthorized access or use.  This will prevent non-investigational use of products 
that are provided only for use in this study. 
 
3.3
Device Accountability 
An Abbott representative will notify the sites of activation. Investigational product shall be 
shipped after the site is activated and shipping authorization is complete.   
The Principal Investigator or an authorized designee must maintain a device accountability log 
documenting the date of receipt, the identification of each investigational device (batch number, 
lot number or unique code), the subject identification, the date of use, the expiration date and 
final disposition.  
Storage locations for the investigational use only labeled devices will be locked with access 
restricted only to Investigators and authorized research personnel. 
St. Jude Medical must also maintain device accountability documenting all shipments and 
returns of investigational labeled devices. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 15 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 Study Design 
4.0
 
4.1
Purpose 
The purpose of this clinical investigation is to expand the indication of the Portico TF Delivery 
System and obtain approval of the Alternative Access Delivery System to place a transcatheter 
aortic valve through an alternative access site, specifically subclavian/axillary or TAo in subjects 
with symptomatic severe native aortic stenosis who are considered high surgical risk.  
 
4.2
Study Design and Scope 
This is a multicenter prospective, non-randomized, 2-arm investigational study without 
concurrent or matched controls, designed to assess the use of the Portico TF or Alternative 
Access Delivery System to place a Portico transcatheter aortic valve through an alternative 
access site, specifically subclavian/axillary or TAo. 
A minimum of 45 subjects will undergo transcatheter aortic valve replacement (independent of 
valve size) via the Portico TF or Alternative Access Delivery System in each arm. A minimum of 
45 implants will be accessed via the subclavian/axillary access site arm of the study and a 
minimum of 45 implants will be accessed via the TAo access site arm of the study. A maximum 
of 12 investigational sites with prior alternative access technique experience in Europe and will 
be trained to participate in the study. Enrollment is anticipated to be completed approximately 8 
months from the date of first enrollment. Data will be collected at pre-procedure, peri-procedure 
and at discharge as well as at 30 days, 6 months and 1 year post implantation. All active 
subjects will be followed for 1 year. 
 
Data from other prospective clinical trials of ALT access in similar patient populations outside of 
Europe may be included in the analysis and support the submission for CE Mark. CE Mark will 
be submitted for each access route after implantation and 30 day follow up are completed. 
 
Although the study will not test a hypothesis, the primary endpoint event rate for each cohort will 
be presented within the context of the range of rates reported for alternative access delivery of 
transcatheter valves in the literature. 
 
4.3
End Points 
 
4.3.1 Primary Endpoint for Each Access Arm of the Study: 
The study will have a primary safety endpoint for each arm of the study which is the rate of 
major vascular complications through 30 days, as defined by the Valve Academic Research 
Consortiumii (VARC-2).   
 
4.3.2 Secondary Endpoints: 
The following secondary endpoints will be evaluated for each arm of the study. 
1. The event rates at 30 days of the following: 
 
All-cause mortality  
 
Cardiovascular mortality 
 
Disabling stroke  
 
Non-disabling stroke 
 
Life-threatening bleeding requiring transfusion 
 
Acute kidney injury requiring dialysis 
 
Composite of 
o periprocedural encephalopathy 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 16 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
o all stroke 
o all TIA 
2. The event rates at 1 year of the following: 
 
All-cause mortality 
 
Cardiovascular mortality 
 
Disabling stroke  
 
Moderate and severe aortic regurgitation 
3. Improvement from baseline as compared to 30 days by: 
 
NYHA functional classification 
 
Six minute walk test 
 
Effective orifice area 
4. Acute device success defined as: 
 
Absence of procedural mortality 
 
Correct positioning of a single prosthetic heart valve into the proper anatomical location  
 
Intended performance of the prosthetic heart valve 
o mean aortic valve gradient <20 mmHg  
o peak velocity < 3 m/s  
o no moderate or severe prosthetic regurgitation 
 
In addition successful access, delivery and deployment of the valve and retrieval of the delivery 
system will be collected. 
 
4.4
Study Population 
The subjects targeted for this study have symptomatic severe native aortic stenosis and are 
deemed high operable risk in the medical opinion of the center’s heart team and subsequently 
the Subject Selection Committee (see section 7.2 for details).  In the opinion of the implant 
team, the preferred access route for the patients enrolled in the trial should be alternate access 
(subclavian/axillary or direct aortic).  The determination of the preferred route may take into 
account patient specific anatomical considerations and other risk factors as well as implanter 
and patient preference.  To participate in this study, patients must meet all inclusion and none of 
the exclusion criteria for the study. 
 
4.4.1 Inclusion Criteria 
To participate in this clinical study, the subject must meet all of the following inclusion criteria: 
1. Subject has provided written informed consent prior to uploading CT scan to core lab. 
2. Subject is ≥ 18 years of age or legal age in host country.  
3. Subject’s aortic annulus diameter meets the range indicated in the Instructions for Use 
as measured by multislice CT conducted within 180 days prior to the index procedure. 
4. Subject has senile degenerative aortic stenosis seen by echocardiography within 90 
days of index procedure as measured by one of the following: 
a. Mean gradient ≥ 40 mmHg 
b. Peak velocity ≥ 4.0 m/s   
c. Doppler Velocity Index < 0.25 
d. Aortic valve area (AVA) of < 1.0 cm2 or indexed EOA < 0.6 cm2/m2 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 17 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
5. Subject has symptomatic aortic stenosis as demonstrated by NYHA Functional 
Classification of Class II or greater or other symptoms of aortic stenosis (e.g. syncope) 
6. Subject is deemed high operable risk and preferred TAVI delivery route is alternative 
access (subclavian/axillary or direct aortic) per the medical opinion of the center’s heart 
team and confirmed by SSC 
a. High risk is defined as STS mortality ≥8% or documented heart team agreement 
≥ high risk for SAVR due to frailty or co-morbidities 
 
4.4.2 Exclusion Criteria 
Subjects are not eligible for clinical study participation if they meet any of the following exclusion 
criteria: 
1. Subject is unwilling or unable to comply with all study-required follow-up evaluations. 
2. Subject has a documented history of a cerebral vascular accident (CVA) or transient 
ischemic attack (TIA) within 6 months (less than or equal to 180 days) prior to the index 
procedure. 
3. Subject has carotid artery disease requiring intervention. 
4. Subject has evidence of a myocardial infarction (MI) within 30 days prior to patient index 
procedure. 
5. Subject has a native aortic valve that is congenitally unicuspid, bicuspid, quadricuspid or 
non-calcified as seen by echocardiography. 
6. Subject has severe mitral valvular regurgitation. 
7. Subject has severe mitral stenosis. 
8. Subject has a pre-existing prosthetic cardiac device, valve, or prosthetic ring in any 
position. 
9. Subject refuses any blood product transfusion. 
10. Subject has resting left ventricular ejection fraction (LVEF) less than 20%. 
11. Subject has documented, untreated symptomatic coronary artery disease (CAD) 
requiring revascularization. 
12. Subject has had a percutaneous interventional or other invasive cardiovascular or 
peripheral vascular procedure less than or equal to 14 days prior to index procedure. 
13. Subject has severe basal septal hypertrophy that would interfere with transcatheter 
aortic valve placement. 
14. Subject has a history of, or is currently diagnosed with endocarditis. 
15. There is imaging evidence of intracardiac mass, thrombus, or vegetation. 
16. Subject is considered hemodynamically unstable (requiring inotropic support or 
mechanical heart assistance). 
17. Subject is in acute pulmonary edema or requiring intravenous diuretic therapy to 
stabilize heart failure. 
18. Subject with severe pulmonary disease as determined by STS score. 
19. Subject is on chronic oral steroid therapy. 
20. Subject has a documented hypersensitivity or contraindication to anticoagulant or 
antiplatelet medication. 
21. Subject has renal insufficiency as evidenced by a serum creatinine greater than 3.0 
mg/dL (265.5 µmol/L) or end-stage renal disease requiring chronic dialysis. 
22. Subject has morbid obesity defined as a BMI greater than or equal to 40. 
23. Subject has ongoing infection or sepsis. 
24. Subject has uncontrolled blood dyscrasias as defined:  leukopenia (WBC<3000 mm3, 
acute anemia (Hb<9g/dL), thrombocytopenia (platelet count <50,000 cells/mm3). 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 18 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
25. Anatomy falling outside the recommended values in the IFU, unless specifically 
approved by the Subject Selection Committee. 
26. Subject has an active peptic ulcer or has had gastrointestinal (GI) bleeding within 90 
days prior to the index procedure. 
27. Subject is currently participating in another investigational drug or device study, unless 
approved by the Sponsor. 
28. Subject has/had emergency surgery for any reason within 30 days of the index 
procedure. 
29. Subject has a life expectancy less than 1 year. 
30. Subject has other medical, social or psychological conditions that, in the opinion of the 
site Heart Team or the Subject Selection Committee, preclude the subject from study 
participation. 
31. Subject is diagnosed with a state of dementia which would fundamentally complicate 
rehabilitation from the procedure or compliance with follow-up visits. 
32. Subject has a documented allergy to contrast media that cannot adequately be treated, 
nitinol alloys, porcine tissue, or bovine tissue. 
33. Significant aortic disease including abdominal aortic or thoracic aneurysm defined as 
maximal luminal diameter 5cm or greater  
34. Subjects with severe pulmonary hypertension and severe RV dysfunction 
35. Subjects with hypertrophic cardiomyopathy 
 
4.4.3 Transaortic Subject Cohort Specific Exclusion Criteria 
Subjects are not eligible for participation in the TAo access arm if they meet any of the 
following exclusion criteria: 
1. Subject has a chest condition (anatomical or otherwise) that prevents TAo access. 
2. Subject has pre-existing patent RIMA graft that would preclude access. 
3. Subject has a porcelain aorta, defined as an extensive circumferential calcification of 
the ascending aorta that would complicate TAo access. 
 
4.4.4 Subclavian/Axillary Subject Cohort Specific Exclusion Criteria 
Subjects are not eligible for participation in the subclavian/axillary access arm if they meet 
any of the following exclusion criteria: 
1. Subject’s access vessel (subclavian/axillary) diameter will not allow for introduction of 
the 18/19 Fr delivery system. 
2. Subject’s subclavian/axillary arteries have severe calcification and/or tortuosity. 
3. Subject has a history of LIMA/RIMA graft that would preclude access 
 
 Procedures 
5.0
 
5.1
Informed Consent Process 
Prior to enrolling in the clinical study and conducting study-specific procedures, all subjects will 
be consented, as required by applicable regulations and the center’s EC.  Informed consent 
must be obtained from each subject, signed and dated by the subject and by the person 
obtaining the consent. 
The Principal Investigator or his/her authorized designee will conduct the Informed Consent 
Process. This process will include a verbal discussion with the subject on all aspects of the 
clinical study that are relevant to the subject’s decision to participate in the clinical study. The 
subject will be given enough time to review the consent and ask any questions regarding the 
study. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 19 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
The subject shall be provided with the informed consent form that is written in a language that is 
understandable to the subject and has been approved by the center’s EC.  Failure to obtain 
informed consent from a subject prior to study enrollment should be reported to Abbott within 5 
working days and to the reviewing center’s EC consistent with the center’s EC reporting 
requirements.  
 
5.2
Subject Screening 
Potential study subjects should be evaluated for study participation by site staff. This site staff 
evaluating the potential subject should be trained on the CIP and delegated to do so. 
Subjects meeting the inclusion/exclusion criteria will be fully informed about the study and asked 
to participate. If the subject agrees, a duly signed and dated Patient Informed Consent will be 
obtained. Patients who do not meet the inclusion/exclusion criteria will not be eligible to 
participate in this study. 
 
5.3
Point of Enrollment 
Subjects are considered enrolled in the study from the moment the subject has provided written 
Patient Informed Consent.  
 
5.4
Study Activities 
Table 2.Study Activity Definitions 
 Study Activity Definitions 
Study Activity 
Definition 
Adverse Event 
Assessment 
Adverse events will be documented according to definitions in 
Appendix D. 
Barthel Index 
A scale used to measure performance in activities of daily living (ADL). 
Each performance item is rated on this scale with a given number of 
points assigned to each level or ranking. It uses ten variables 
describing ADL and mobility where a higher number is associated with 
a greater likelihood of being able to live at home with a degree of 
independence following discharge from the hospital. 
Blood Work 
 
Blood lab tests will be collected at each required interval.  The specific 
lab tests are indicted in Table 4 
Cardiac Rhythm 
Monitoring 
 
Assessment of heart rate, QRS and dominant rhythm preprocedure 
and during the procedure. 
Chest X-Ray 
Imaging conducted at Baseline per institutional guidelines. 
Coronary and Aortic 
Angiogram with 
Runoff 
Angiographic imaging off aortic arch the coronary, subclavian and 
axillary arteries. Assessment to be conducted per institutional 
guidelines. 
CT Scan 
Assessment to be conducted per institutional guidelines.  
Echocardiography 
 
Each site is responsible for performing the echocardiogram (echo) 
according to the Echocardiographic protocol. Echocardiogram will be 
copied to CD/DVD (or other large media storage device) and provided 
to an Echocardiographic Core Lab for evaluation.  
Electrocardiogram 
(ECG) 
Assessment of dominant rhythm, heart rate, and QRS interval via 12-
lead.  

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 20 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Frailty Index 
 
Used to assess if frailty is a high risk factor for subjects. Frailty index 
assessment is defined in APPENDIX G: FRALITY ASSESSMENT 
Informed Consent 
An Ethics Committee and Sponsor-approved Informed Consent must 
be obtained. 
Medical History 
General medical history of the patient: 
 
Previous cardiovascular operations  
 
Coexisting cardiovascular diseases 
 
Clinically significant peripheral vascular disease 
 
Previous peripheral vascular operations 
 
Other coexisting medical conditions (eg, diabetes, 
hypertension, kidney and lung disease, endocarditis) 
Medication 
Assessment 
Only the following medication will be collected at each specified 
interval: 
 
Beta Blockers 
 
Calcium Channel Blockers 
 
Anticoagulants  
 
Antiplatelet agents including Aspirin  
 
Diuretics 
 
ACE-Inhibitors 
 
Angiotensin Receptor Blocker (ARBs) 
Modified Rankin 
Stroke Scale 
This assessment must be completed by a rater who has a current 
certificate that demonstrates completion of an accredited training 
program for this stroke scale, using the structured interview found in 
(APPENDIX H: SCALES). 
 
The modified Rankin Scale (mRS) is functional measurement to 
assess the degree of disability or dependence in the daily activities of 
people who have suffered a stroke. 
NIH Stroke Scale 
This assessment must be completed by a rater who has a current 
certificate that demonstrates completion of an accredited training 
program for this stroke scale. 
 
The NIHSS is an 11-item neurologic examination stroke scale used to 
evaluate the effect of acute cerebral infarction on the levels of 
consciousness, language, neglect, visual-field loss, extraocular 
movement, motor strength, ataxia, dysarthria, and sensory loss. 
Certified personnel rate the patient’s ability to answer questions and 
perform activities. Ratings for each item are scored with 3 to 5 grades 
with 0 as normal, and there is an allowance for untestable items.  
NYHA Classification 
The New York Heart Association (NYHA) Functional Classification 
provides a simple way of classifying the extent of heart failure and 
defined in APPENDIX I : NYHA CLASSIFICATION. 
Physical 
Assessment 
At the baseline visit the following measurement must be assessed: 
 
Age on consent date 
 
Gender 
 
Height 
The following measurements must be assessed at all visits: 
 
Weight 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 21 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
Heart rate  
 
Heart rhythm  
 
Physical Assessment   
Procedure 
Information 
Procedure information must be collected including: 
 
Pre-procedure Information 
 
Procedure Information 
 
Procedure Evaluation 
 
Post-procedure Information 
Procedural imaging  
All imaging collected during the procedure (intra-procedure) such as 
the cineangiogram and/or echocardiography should be collected and 
provided to the Sponsor. 
QoL Questionnaire 
EQ-5D 3L is a standardized instrument for use as a measure of health 
outcomes. The process to complete this questionnaire is indicated in 
APPENDIX F: QUALITY OF LIFE-EQ-5D 3L. 
Surgical Risk 
Assessment 
Surgical Risk Assessment tools Consists of the 3 assessments as 
defined in Appendix E: Risk Calculations: 
 
Logistic EuroSCORE 
 
EuroSCORE II 
 
STS Risk Score 
Six Minute Walk 
Test 
Used to quantitatively assess submaximal exercise tolerance as 
defined in APPENDIX J: ATS GUIDELINES FOR THE SIX MINUTE 
WALK TEST. 
 
 
5.5
Procedures 
The clinical study will be conducted in accordance with the CIP.  All parties participating in the 
conduct of the clinical study will be qualified by education, training, or experience to perform 
their tasks and this training will be documented appropriately. The data collection elements 
required for each follow-up are summarized in Table 3 below. 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 22 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express written consent of 
Abbott 
 
Table 3: List of all study specific activities/procedures 
 
Follow-up procedure scheme 
Study Activity 
Visit window [days] 
Baseline 
(within 30 days) 
Procedure 
 
Discharge 
[+0 to 7 days] 
30-Day 
[-7/+14 days] 
6-Month 
[±30 days] 
1-Year 
[±30 days] 
90 day visit after 
neuro event 
[±14 days] 
Informed Consent 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Surgical Risk Assessment 
X 
 
 
 
 
 
 
Coronary and Aortic Angiogram with runoff 
X 
‡ 
 
 
 
 
 
 
Physical Assessment 
X 
 
X 
X 
X 
X 
 
Barthel Index 
X 
 
X 
X 
 
X 
X 
Modified Rankin Stroke Scale  (mRS) 
X 
 
 
X 
 
X 
X 
NIH Stroke Scale (NIHSS) 
X 
 
X 
X 
 
X 
X 
Echocardiogram 
X 
X
§ 
X 
X 
X 
X 
 
CT Scan 
X * 
 
 
 
 
 
 
Cine angiogram 
 
X
§ 
 
 
 
 
 
Electrocardiogram (ECG) 
X 
 
X 
X 
X 
X 
 
Chest x-ray 
X 
 
 
 
 
 
 
Cardiac Rhythm Monitoring  
X 
 
 
 
 
 
Blood Work 
X 
X
¤ 
X 
X 
X 
 
NYHA Classification 
X 
X 
X 
X 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 23 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express written consent of 
Abbott 
Study Activity 
Visit window [days] 
Baseline 
(within 30 days) 
Procedure 
 
Discharge 
[+0 to 7 days] 
30-Day 
[-7/+14 days] 
6-Month 
[±30 days] 
1-Year 
[±30 days] 
90 day visit after 
neuro event 
[±14 days] 
Frailty Index 
X 
 
 
X 
 
X 
 
QoL Questionnaire 
X 
 
 
X 
 
X 
 
Six Minute Walk Test 
X 
 
 
X 
 
X 
 
Medication Assessment 
X 
 
X 
X 
X 
X 
 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
 
‡ Coronary and aortic angio may be completed up to 120 days prior to index procedure 
* CT scan may be completed up to 180 days prior to index procedure 
§ All index procedure imaging must be sent to Abbott  
¤ Index procedure bloodwork is tested twice (See Table 4): 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 24 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
5.6
Enrollment Visit  
The baseline visit procedures must take place within 30 days of the index procedure. It is not 
necessary to repeat the coronary and aortic angiogram, if completed within 120 days of the 
planned index procedure. It is not necessary to repeat the CT scan (#12) if it will be completed 
within 180 days of the planned index procedure. The baseline visit consists of the following 
activities: 
1. Obtain Informed Consent and Data Protection Form 
2. Medical History including current diagnosis and Demographics 
3. Initial Screening: Perform an initial screening to determine study eligibility 
4. Chest X-Ray (CXR)  
5. Surgical Risk Assessment 
6. Coronary and Aortic Angiogram with runoff 
7. Physical Assessment  
8. Barthel Index 
9. Modified Rankin Stroke Scale 
10. NIH Stroke Scale 
11. Echocardiogram 
12. Computed Tomography (CT) Scan (required for sizing) 
13. Electrocardiogram (ECG) 
14. Blood work 
15. New York Heart Association (NYHA) Functional Classification 
16. Frailty Index Assessment 
17. Quality of Life Questionnaire (QoL) 
18. Six Minute Walk Test 
19. Medication Assessment 
 
 
5.7
Implant/Procedure 
The medical team performing the study procedure will typically consist of: 
 
the primary cardiac surgeon at the site who will perform the TAo procedure 
 
the primary interventional cardiologist at the site who will perform the subclavian/axillary 
procedure 
 
second operator (cardiac surgeon or interventional cardiologist) who is recommended to 
be present during the procedure  
 
perfusionist 
 
anesthesiologist 
At least one transcatheter aortic valve may be deployed via the physician determined alternative 
access pathway in every subject who has signed the Informed Consent Form, and Data 
Protection Form. Although not recommended, if a physician determines it is in the best interest 
of the subject to have a second transcatheter aortic valve placed, a subject may receive an 
additional transcatheter aortic valve. 
The procedure visit will consist of the following activities: 
 
5.7.1 Pre procedure Activities  
1. Blood work (within 72 hours prior to index procedure, refer to Table 4) 
 
Urea 
 
Creatinine 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 25 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
2. ECG 
 
5.7.2 Procedure Activities 
1. Assess for adverse events 
2. Document transcatheter aortic valve deployment information 
3. Cardiac Rhythm Monitoring 
 
Rhythm changes will be monitored and recorded at the following time points: 
a. Immediately post valvuloplasty (if applicable) 
b. After valve deployment and system retrieval 
4. Procedural imaging (angiogram, intra-procedure echocardiography) 
 
5.7.3 Post Procedure Activities 
1. Blood work (within 48 hours post implant, refer to Table 4) 
 
Creatinine 
 
Urea 
 
5.7.4 Procedural Exclusion 
During the procedure, the implanting investigator may determine transcatheter aortic valve 
implantation using the Portico TF or ALT Delivery System is neither feasible nor in the best 
interest of the subject. Any subject that does not have a delivery system enter his or her body 
will be withdrawn from the study. Data collected on these subjects, at baseline, will consist of 
reason(s) for exclusion and possible adverse events. Subjects that have a Delivery System 
enter his or her body but no valve will be followed for 30 days to collect adverse events. 
Following the procedure, the delivery and loading systems should be securely disposed of per 
hospital requirements for hazardous materials. If there are any concerns noted with the delivery 
system, loading system, or valve during the procedure, they should be reported and returned to 
Abbott. 
 
5.8
Scheduled Follow-ups 
 
5.8.1 Discharge Visit 
The discharge visit will take place at the time of hospital discharge or 7 days post implant, 
whichever occurs first. Discharge testing maybe completed the day after procedure up until 
discharge or within 7 days if the subject has yet to be discharged. The discharge assessment 
will include: 
1. Physical assessment 
2. Barthel Index 
3. NIH Stroke Scale 
4. Echocardiography (to be performed between 24 hours and 7 days post implant) 
5. ECG 
6. Blood work 
7. Medication assessment 
8. Adverse events assessment 
 
5.8.2 30-Day Visit 
The 30-Day visit window is 30-7/+14 days after the index procedure, and will include: 
1. Physical assessment 
2. Barthel Index 
3. Modified Rankin Stroke Scale 
4. NIH Stroke Scale 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 26 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
5. Echocardiography  
6. ECG 
7. Blood work 
8. NYHA Functional Classification  
9. Frailty Index assessment 
10. Quality of Life Questionnaire (QOL) 
11. Six Minute Walk Test 
12. Medication assessment 
13. Adverse events assessment 
 
5.8.3 6-Month Visit 
The 6-Month (180 days) visit window is 180±30 days after the index procedure and will include:  
1. Physical assessment 
2. Echocardiography  
3. ECG 
4. NYHA Functional Classification 
5. Medication assessment 
6. Adverse events assessment 
 
5.8.4 1 Year Visit 
The 1 year (360 days) visit window is 360±30 days after the index procedure and will include: 
1. Physical assessment 
2. Modified Rankin Stroke Scale 
3. NIH Stroke Scale 
4. Echocardiography  
5. ECG 
6. Barthel Index 
7. Blood work 
8. NYHA Functional Classification  
9. Frailty Index assessment 
10. Quality of Life Questionnaire (QoL) 
11. Six Minute Walk Test 
12. Medication assessment 
13. Adverse events assessment 
 
5.9
Unscheduled Visit for Evaluation of Suspected Neurological Event 
If the subject experiences a neurological event (TIA, stroke, or encephalopathy), the event 
should be documented on an adverse event form and further evaluation should be performed at 
an unscheduled visit 90 days (±14 days)1 from the date of the neurological event. The 
unscheduled visit will include the following assessments: 
1. Barthel Index 
2. NIH Stroke Scale 
3. Modified Rankin Stroke Scale 
 
5.10 Blood Work 
Subject’s blood samples will be collected at the intervals indicated in Table 4 
                                                          
1 FDA’s Current Thinking Regarding Neurological Assessments for Transcatheter Valve Trials (Revised: August 25, 2011) 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 27 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Table 4. Laboratory Scheme 
Lab Test 
Baseline 
Procedure 
Discharge 
30 days,  & 1 Year 
Pre 
Post 
Complete Blood Count  
 
White Blood Cell 
Count 
 
Red Blood Cell 
Count 
 
Hemoglobin 
 
Hematocrit 
X 
 
 
X 
 
Platelet count 
X 
 
 
X 
 
Urea and Creatinine 
X 
X* 
X** 
X 
X 
BNP  
or  
ProBNP 
X 
 
 
X 
X 
INR (if subject is on 
Coumadin/Warfarin) 
X 
 
 
 
 
Troponin 
or 
CK, CK-MB 
X 
 
 
 
 
Albumin 
X 
 
X 
* Within 72 hours before index procedure 
**Within 48 hours after index procedure 
 
5.11 Imaging 
Echocardiographic examinations will be conducted at the intervals indicated in Table 3 of this 
Clinical Investigation Plan. Each site is responsible for performing the echocardiogram 
according to the Echocardiographic Protocol. 
Echocardiographic examinations will be forwarded to the Echocardiographic Core Laboratory for 
interpretation. It is the responsibility of each site to perform the local interpretation of the 
echocardiogram for clinical assessment. 
The Echocardiographic Core Laboratory will not be responsible to notify the site of any 
abnormal findings that are identified in the echo study. The responsibility of the 
Echocardiographic Core Laboratory is to complete the echocardiography data collection forms 
and submit these to the Sponsor. 
The Echocardiographic Core Laboratory will provide the study required interpretation and 
documentation of each echocardiogram submitted. Data obtained from the core laboratory 
readings will be used for study purposes only and not for clinical treatment of the subject. Abbott 
will use only the measurements from the Echocardiographic Core Laboratory for analysis. If the 
Core Laboratory determines the echocardiogram is unreadable, the site will be responsible for 
having the subject return for another echocardiogram. 
 
5.12 Medications 
The subject’s use of the following medications will be collected at each visit: 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 28 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
Beta Blockers 
 
Calcium Channel Blockers 
 
Anticoagulants 
 
Antiplatelet agents including Aspirin  
 
Diuretics  
 
ACE Inhibitors 
 
Angiotensin Receptor Blockers (ARBs) 
 
5.13 Description of Activities Performed by Sponsor Representatives 
Trained Sponsor personnel may perform certain activities to ensure compliance to the clinical 
investigational plan and may provide technical expertise during the implant procedure. 
 
5.14 Subject Study Completion 
When the subject’s participation in the clinical study has been completed the subject will return 
to the medical care as per physician’s recommendation. 
 
5.15  Subject Withdrawal 
Subjects must be informed about their right to withdraw from the study at any time and for any 
reason without sanction, penalty or loss of benefits to which the subject is otherwise entitled and 
withdrawal from the study will not jeopardize their future medical care or relationship with the 
Investigator. Subjects will be asked to specify the reason for the termination, but have the right 
not to answer. 
The Investigator may decide to withdraw a subject from the study at any time with reasonable 
rationale. The subject’s future care will not be influenced by a decision, voluntary or otherwise, 
to withdraw from the study. All reasonable efforts should be made to retain the subject in the 
clinical study until completion of the study. 
 
Reasons for subject’s withdrawal include, but are not limited to: 
1. Subject refuses to continue participating in the study 
2. Subject does not have a delivery system enter his or her body 
3. Subject does not meet the inclusion/exclusion criteria and does not require additional 
follow-up for safety reasons. 
4. Subject is deceased (cause must be documented) 
5. Subject’s non-compliance 
6. Subject’s participation is terminated by the PI or Investigator, although the subject 
consented, since participation is no longer medically appropriate 
 
Every effort will be made to obtain follow-up data. Potential methods of subject tracking should 
be documented and may include:  
 
Attempting to contact the subject by multiple phone calls and letters documented at the 
site  
 
Mailing a registered letter to the subject’s last known address requesting that the subject 
contact the site  
If a subject cannot be located after at least two documented contact attempts, the patient’s 
general practitioner shall quickly be contacted to investigate about the subjects whereabouts 
and its health status. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 29 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Note: If a subject misses one or more of the scheduled follow up visits (inclusive of the assigned 
visit windows), this will be considered as a missed visit. The subject may therefore still return for 
subsequent visits and will not be excluded from the study. 
If a subject withdraws from the clinical study, the site will record the subject’s reasons for 
withdrawal, on a Withdrawal CRF. 
When subject withdrawal from the clinical study is due to an adverse event the subject will be 
followed 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.   
 Statistical Considerations 
6.0
The following section describes the statistical methods for the clinical investigation and 
justification of the design. 
 
6.1
General Statistical Methods 
Baseline and procedural data will be presented using appropriate descriptive statistics. 
Continuous data will be summarized using descriptive statistics including mean, standard 
deviation, median and range. Categorical data will be summarized by the frequencies and 
percentages in the corresponding categories. 
 
6.2
Endpoints 
 
6.2.1 Primary Endpoint 
The primary safety endpoint is major vascular complications through 30 days, as defined by the 
Valve Academic Research Consortiumiii (VARC-2) for each access arm of the study.  
 
6.2.1.1 Analysis Methodology 
The proportion of subjects experiencing a primary safety endpoint through 30 days (less than or 
equal to 30 days) post implant will be estimated as the number of subjects who experience the 
safety endpoint divided by the total number of subjects in the analysis population (see Section 
6.2.1.2). The 95% upper confidence limit for the proportion of subjects experiencing a primary 
safety endpoint will be calculated using the exact binomial method. 
 
6.2.1.2 Analysis Population 
All subjects who have received a Patient Information Sheet, and signed an Informed Consent 
Form and Data Protection Form will be considered enrolled in the study. However, the analysis 
population will be based on subjects who have provided signed Informed Consent Form and 
Data Protection Form and had the SJM TAVI delivery system enter his/her body. The 
anticipated dropout rate for this study population is expected to be low, as part of the selection 
criteria is subject compliance with all follow-up visits. Subjects that withdraw from the 
investigation or are lost to follow-up will not be replaced in the analysis dataset. 
It is anticipated that there may be subjects who are enrolled in the study but are not included in 
the analysis population. There may be subjects who gave consent to participate in the study but 
did not satisfy the baseline inclusion exclusion criteria, these are considered screen failures. 
There may also be subjects who have enrolled in the study and started the procedure, but do 
not have the SJM TAVI delivery system enter his/her body and are procedural exclusions due to 
their anatomy, circumstances related to the procedure, or physician judgment; these are 
considered to be procedural exclusion subjects. Screen failure subjects and procedurally 
excluded subjects will not be part of the analysis population. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 30 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
In general, data analysis will be performed based on the analysis population on a per subject 
basis. If more than 1 device has entered the subject’s body, the data analysis may be 
summarized on a per device basis, as appropriate. 
 
6.2.2 Secondary Endpoints 
The following endpoints will be summarized using descriptive statistics for each access arm of 
the study. 
Event rates at 30 days for all-cause mortality, cardiovascular mortality, disabling stroke, non-
disabling stroke, life threatening bleeding requiring transfusion, and acute kidney injury requiring 
dialysis and composite of periprocedural encephalopathy/all stroke/and all TIA: 
The count and proportion of subjects who experience each of above endpoints as adjudicated 
by the CEC through 30 days post implant will be summarized. Subjects in the analysis 
population defined in section 6.2.1.2 will be included in the analysis. 
Event rates at one year for all-cause mortality, cardiovascular mortality and disabling stroke: 
Kaplan-Meier survival analysis will be used to estimate the event rates of all cause mortality, 
cardiovascular mortality and disabling stroke at one year post implant. Subjects in the analysis 
population defined in section 6.2.1.2 will be included in the analysis. The index procedure 
(TAVI) day is considered Day 0. The time-to-event will be determined from the date of index 
procedure to the first occurrence of the event for subjects experiencing the event, or, for those 
subjects not experiencing the event, to the last date they are known to be free of the event (this 
usually will be the last follow-up, contact date, or death date). 
Rate of moderate or severe aortic regurgitation at one year: 
The count and proportion of subjects with moderate or severe aortic regurgitation at one year 
will be summarized.  
Functional improvements in NYHA classification, 6 minute walk test and EOA will be compared 
at 30 days: 
Changes of NYHA classification, 6 minute walk and EOA at 30 days from baseline will be 
summarized using descriptive statistics.  
Acute device success: 
The count and proportion of subjects with acute device success (see Section 4.3.2) will be 
summarized.  
 
6.3
Sample Size 
The sample size of 45 subjects for each access route is based on the desire to estimate the rate 
of 30-day vascular complication with a sufficient degree of precision. The rate of major vascular 
complications at 30 days in Portico TF EU study was 5.9%.  The rate of major vascular 
complications reported for other TAVI valves at 30 days in a weighted meta-analysis of 3,519 
patients from 16 studies ranged from 5.0% to 23.3%24. The same meta-analysis calculated a 
major vascular complication pooled estimate 30-day rate of 11.9% (95% CI 8.6%-16.4%24). 
Assuming an event rate of 5.9%, with 45 subjects, the exact 90% CI is (1.45%, 15.32%). 
Therefore, a sample size of 45 will result in the 90% confidence interval half-width of 9.42% and 
the 95% upper confidence limit is within the range reported in the literature 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 31 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
To ensure enrollment balance, each investigational center cannot enroll more than 50% of 
sample size (23) of each access arm without the prior written approval of the Sponsor.  
 
6.4
Justification of Clinical Investigation Design 
The Portico valve has demonstrated safety and favorable clinical results via TF access in the TF 
EU Portico Trial (n=222). The study will evaluate the safety of alternative access for the 
approved Portico transcatheter aortic and includes a primary safety endpoint of major vascular 
complications at 30 days. This endpoint is appropriate because vascular access is the only new 
aspect being investigated in this study and 30-days has been established by VARC2 as the 
appropriate time period to assess early safety events such as major vascular complications25. 
Numerous studies have demonstrated that vascular complication rates at 30 days with ALT 
access are similar to that of the TF approach26-27 and that survival at 1 and 2 years is similar 
between the subclavian and the TF approach28. The sample size of 45 subjects is adequate to 
ensure that the rate of the primary endpoint, major vascular complications at 30 days, is 
consistent with the rate for Portico valves delivered by TF access as well as with rates reported 
in the literature.  
 
6.5
Timing of Analysis 
CE Mark will be submitted for each access route. The analyses for CE Mark report will be 
conducted separately for each access route on datasets locked after 45 subjects in each access 
route have had the 30-day study visit (excepting deaths, withdrawals and loss-to-follow-up 
before 30 days) or crossed the 30-day visit window without a visit (missed visit).   
 
6.6
Success Criteria 
The study has one primary endpoint without formal hypothesis. The primary endpoint result will 
be compared with data reported in the literature and is expected to fall within the range of 5-
23.324% (pooled estimate 11.9% and CI 8.6%-16.4%). 
 
6.7
Interim Analysis 
No interim analyses are planned for this study. 
 
6.8
Statistical Criteria for Termination 
There are no statistical criteria for termination of this study. 
 
6.9
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. 
 
Study Committees  
7.0
 
7.1
Clinical Event Committee (CEC)  
An independent CEC will be established for the trial. The primary function, responsibilities and 
membership will be described in detail in a CEC charter.  
 
 
7.2
 Subject Selection Committee 
The Subject Selection Committee will consist of cardiac surgeons and interventionalists who will 
be responsible for ensuring subject eligibility for implant according to the protocol. After study 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 32 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Informed Consent Form and Data Protection Form are obtained and study eligibility is 
confirmed, subject data will be reviewed by the Subject Selection Committee prior to the implant 
procedure to confirm, risk assessment, echo and CT measurements. CT Imaging, will be 
reviewed to ensure acceptable annular measurements for the Portico Transcatheter Heart 
Valve. 
The Subject Selection Committee’s decision on whether to include the subject in the study must 
be documented and communicated to the enrolling site by the Sponsor. If the Subject Selection 
Committee considers the subject ineligible for implant, the subject will be withdrawn from the 
study and the reason for exclusion documented. 
The membership and process is further defined in the Subject Selection Committee Charter. 
 Risks and Benefits of the Clinical Study  
8.0
 
8.1
Anticipated Clinical Benefits 
There are no guaranteed benefits from participation in this study. Implantation of the 
transcatheter heart valve in the annular position may result in one or more of the following: 
improved valvular function, acute alleviation of symptoms related to aortic stenosis, improved 
morbidity and mortality. In addition, these or additional benefits may occur to future subjects 
through experience gained in this clinical study. 
 
8.2
Anticipated Adverse Events and Adverse Device Effects 
Anticipated adverse events associated with any transcatheter aortic valve placement may 
include, but are not limited to: 
1. Access site complications (e.g., pain, bleeding, infection, hematoma, pseudoaneurysm, 
etc.) 
2. Acute coronary obstruction 
3. Acute myocardial infarction 
4. Access site injury 
5. Allergic reaction to antiplatelet agents, contrast medium, anesthesia, or valve components 
6. Anaphylactic shock/toxic reaction 
7. Annulus rupture 
8. Aortic rupture 
9. Ascending aorta trauma 
10. Atrio-ventricular node block 
11. AV fistula 
12. Bleeding  
13. Cardiac arrhythmias 
14. Cardiovascular or vascular injury, such as perforation or damage (dissection) of vessels, 
ventricle, myocardium or valvular structures that may require intervention 
15. Conduction system injury 
16. Death 
17. Endocarditis 
18. Embolism: air, calcification or thrombus 
19. Exercise intolerance (weakness) 
20. Fever 
21. Heart failure 
22. Hematoma 
23. Hemodynamic compromise 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 33 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
24. Hemolysis 
25. Hemolytic anemia 
26. Hemorrhage 
27. Hypotension or hypertension 
28. Immunological reaction 
29. Infection 
30. Leakage, regurgitation 
31. Left ventricular failure/rupture 
32. Left ventricular impairment (due to apical scar) 
33. Myocardial ischemia 
34. Mitral valve insufficiency 
35. Multi-organ failure 
36. Neurological changes including stroke/transient ischemic attack; 
37. Non-structural dysfunction (i.e., entrapment by pannus, paravalvular leak, inappropriate 
sizing or positioning) 
38. Pannus 
39. Paravalvular leak 
40. Pericardial effusion 
41. Perforation of the myocardium or a blood vessel 
42. Potential coronary obstruction 
43. Renal failure 
44. Renal insufficiency 
45. Respiratory failure (shortness of breath) 
46. Sepsis 
47. Septal rupture 
48. Stenosis (high gradient) 
49. Stroke 
50. Structural valve deterioration (i.e., calcification, leaflet tear) 
51. Systemic peripheral ischemia 
52. Tamponade 
53. Valve explant 
54. Valve embolization 
55. Valve migration or malposition 
56. Valve stenosis 
57. Valve thrombosis 
58. Ventricular failure (acute) 
59. Ventricular rupture 
60. Vessel dissection or spasm 
 
It is possible these complications could lead to: 
 
Transfusion 
 
Conversion to open surgical procedure 
 
Reoperation or re-intervention 
 
Emergent balloon valvuloplasty 
 
Emergent percutaneous coronary intervention (PCI) 
 
Emergent surgery (i.e., coronary artery bypass, heart valve replacement) 
 
Explantation of the valve 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 34 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
Permanent Disability 
 
Death 
 
Permanent Pacemaker implantation 
 
Valve in valve implantation 
There are no known interactions of the Portico TF or ALT Delivery System with concomitant 
medical treatment.  
Subjects experiencing an adverse event shall be treated per the standard of care at the 
investigation site. 
There may be additional risks that are unknown at this time and risks that are unanticipated. 
Further study related tests which are not standard of care for a TAVI procedure have added 
risks which may include:  
 
Six minute walk test:  the possible risks from this test are that the subject may experience 
fatigue, shortness of breath, chest pain and/or leg cramps.  This test is done under the 
supervision of a trained professional in a testing area where medical care is immediately 
available. The test will be immediately stopped if the subject experiences chest pain, intolerable 
shortness of breath, leg cramps or pale appearance. 
 
Blood work:  the risk of inserting a needle into a vein in the subjects arm may include temporary 
discomfort from the needle stick.  There is also a small risk of infection, bruising, swelling, 
bleeding or fainting.  These risks are minimized by cleansing the site carefully prior to obtaining 
the blood sample and applying pressure to the site after the blood sample is obtained. 
 
Echocardiogram:  a lubricant (gel) is used on the skin to improve picture quality and this may 
feel cold.  There are no known risks associated with receiving an echocardiogram there may be 
discomfort from the pressure of the transducer as the images are taken. 
 
8.3
Residual Risks Associated with the Device Under Investigation  
An analysis of the risks associated with the design of the TF and ALT Delivery systems have 
been performed. 
The benefit of using a transcatheter aortic valve via alternative access in high-risk and/or 
inoperable patients outweighs the residual risks associated with TAVI treatment. The inoperable 
patient population is at an increased risk of death despite maximal medical therapy. In clinical 
practice, at least 30% of the high-risk patient population with severe aortic stenosis does not 
undergo surgery,1-3 so TAVI provides a less invasive treatment option, with similar outcomes to 
surgery.4 
The unique features of the TF and ALT Delivery systems include the ability to resheath, 
reposition, and redeploy to allow for optimal placement at the implant location prior to full 
deployment. These design features may reduce the risk of adverse events related to 
misplacement and adjustments made post implant. 
Abbott’s final opinion is that the residual risks associated with the TF and ALT Delivery systems 
are outweighed by the potential benefit for use in patients with an increased risk of death 
despite maximal medical therapy. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 35 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 Requirements for Investigator Records and Reports 
9.0
 
9.1
Deviations from CIP 
A deviation is defined as an event where the clinical investigator, site personnel, Sponsor or 
Sponsor representative did not conduct the clinical study according to the Clinical 
Investigational Plan, EC requirements or the Investigator Agreement.   
Deviations from the CIP should be avoided, except in cases where the investigator determines 
that adhering to the CIP might expose the subject to unreasonable risks.  
Regulations require that the PI maintain accurate, complete, and current records, including 
documents showing the date of and reason for every deviation from the Clinical Investigational 
Plan.  Relevant information for each deviation will be documented on a Deviation Case Report 
Form. The site will submit the CRF to Abbott. 
Regulations require Investigators obtain approval from Abbott and the EC [as required] before 
initiating changes in or deviations from the protocol, except when necessary to protect the life or 
physical well-being of a subject in an emergency.  Under emergency circumstances, deviations 
from the CIP to protect the rights, safety and well-being of human subjects may proceed without 
prior approval of the Sponsor and the EC. Such deviations shall be documented and reported to 
the Sponsor and the EC as soon as possible, but no later than 5 working days. 
Prior approval must be requested when the PI anticipates, contemplates, or makes a conscious 
decision to depart from the CIP, except when unforeseen circumstances are beyond the 
Investigator’s control (e.g. a subject who fails to attend a scheduled follow-up visit, a subject is 
too ill to perform a CIP-required test, etc.).  All deviations, including those beyond the 
Investigator’s control, must be reported on a CRF. 
To obtain approval, the Principal Investigator may call or email and discuss the potential 
deviation with Abbott or designee prior to initiating any changes.   
All deviations must be reported to appropriate regulatory authorities in specified timelines (if 
appropriate). 
 
9.2
Safety Reporting 
Safety surveillance and safety reporting for this study are both performed by the Investigator 
(per the local country requirements) and starts as soon as the subject is enrolled in this study 
(date of signature of the informed consent). German requirements are outlined in Appendix M. 
Safety surveillance and safety reporting will continue until the last investigational visit has been 
performed, the subject is deceased, the subject/investigator concludes his participation into the 
study or the subject/investigator withdraws the subject from the study, except as otherwise 
specified in the CIP. 
All reportable adverse event data including deaths and device deficiency data will be collected 
throughout the clinical study and will be reported to the Sponsor through the EDC system. The 
Investigator will record all reportable adverse events and device deficiencies on the appropriate 
case report forms.  
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 subject is withdrawn, or completes the 
study.  The status of the subject’s condition should be documented at each visit.   

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 36 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
The Investigator will report the event to the EC per their reporting requirements.  
Reportable events to Sponsor are:  
1. Endpoint VARC-2 events 
 
Death 
 
Vascular complications 
 
Stroke/TIA 
 
Life threatening bleeding requiring transfusion 
 
Acute kidney injury requiring dialysis 
2. All Adverse Device Effects 
3. All Serious Adverse Events (whether or not the event is considered device or procedure 
related) 
4. Device deficiencies, that could have led to a serious adverse device effect 
 
if either suitable action had not been taken  
 
if intervention had not been made or 
 
if circumstances had been less fortunate 
Non-serious adverse events documentation and reporting are limited to cardiovascular and 
neurovascular events; they all have to be reported regardless of their relationship with the 
device or the procedure. All above events will be reported to the Sponsor, as soon as possible, 
but no later than 72 hours of first learning of the event. 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant 
authorities as per regulations.  
The following information should be collected for each event: 
1. Date AE occurred 
2. Date the center, Investigator, became aware of the event 
3. Main symptoms of the event 
4. Treatment 
5. Seriousness 
6. Relationship to device and/or procedure 
7. Status 
Additional information may be requested, when required, by the Sponsor in order to support the 
reporting of AEs to regulatory authorities. 
If required by national and local laws or regulations, the Investigator must notify the EC of the 
AEs reported to the Sponsor. 
All adverse events will be reported as per applicable regulatory requirements.  
 
9.2.1 Subject Death 
All subject deaths are to be documented and reported to the Sponsor within 72 hours after 
becoming aware of the event. 
The subject death CRF should always be accompanied with the relevant adverse event CRF 
and relevant source documentation. In the event of a subject death, an autopsy should be 
performed whenever possible and the Portico valve explanted and returned to Abbott for 
evaluation. Death summaries and autopsy reports should be provided to Abbott. 
 
9.2.2 Device Deficiency (DD)  
During the trial, the Investigator will be responsible for reporting all device deficiencies. A device 
deficiency is defined as an inadequacy of a medical device with respect to its identity, quality, 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 37 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
durability, reliability, safety or performance and includes malfunctions, user errors and 
inadequate labeling. 
If the device deficiency involves an adverse event, the Principal Investigator must complete an  
adverse event form including information on the device deficiency and report to the Sponsor 
within 5 days after becoming aware of the event. If the device deficiency does not involve an 
adverse event, then the Investigator must complete the device deficiency form within 5 days 
after becoming aware of the event 
 
9.3
Records Retention 
The Principal Investigator will maintain all clinical study documents from prior, during and (as 
specified) after the clinical study on file at the site for a minimum of 15 years after the 
termination of this study, or longer as per local laws, or when it is no longer needed to support a 
marketing application, whichever is later.   
The PI must contact the Sponsor prior to destroying or archiving off-site any records and reports 
pertaining to this study to ensure that they no longer need to be retained on-site. 
All original subject files must be stored for the longest possible time permitted by the regulations 
at the hospital, research institute, or practice in question. If archiving can no longer be 
maintained at the site, the Investigator will notify the Sponsor.  
All data and documents will be made available on request of the relevant authorities in case of 
an audit. 
The Sponsor will archive and retain all essential clinical study documents from prior, during and 
(as specified) after the clinical study as per requirements.  
 Clinical Data Handling 
10.0
Overall, 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 and may be transferred to the Sponsor’s locations outside 
of Europe and/or any other worldwide regulatory authority in support of a market-approval 
application. 
Abbott respects and protects personally identifiable information that we collect or maintain. As 
part of our commitment, Abbott is certified to the U.S. - European Union Framework Agreement 
regarding human resources and subject clinical trial personal information. 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 study.  All data will be secured against unauthorized access. 
The Principal Investigator or institution will provide direct access to source data during and after 
the clinical study for monitoring, audits, EC 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 study. 
 
10.1 Data Management Plan 
A detailed Data Management Plan will be established, prior to study initiation, to ensure 
consistency of the data. This document will include procedures used for data review, database 
cleaning, issuing and resolving data queries, study/database closeout, and data export for 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 38 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
statistical analysis. If appropriate, the DMP may be updated throughout the study duration. All 
revisions will be tracked and document controlled. 
CRF data will be captured in a validated electronic database management system hosted by 
Abbott.  
Only authorized site personnel will be permitted to enter the CRF data through the electronic 
data capture (EDC) system deployed by Abbott. An electronic audit trail will be used to track any 
subsequent changes of the entered data. 
 
10.2 Document and Data Control 
 
10.2.1
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.  
 
10.2.2
Recording data 
Source documents will be created and maintained by the investigational site team throughout 
the clinical study. 
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. 
Required CRFs will be signed by authorized site personnel.  
 Monitoring  
11.0
Monitoring will be conducted by trained and experienced clinical representatives according to 
the Abbott Clinical Monitoring standard operating procedure.  
Prior to beginning the study, Abbott will contact the investigator or designee to discuss the study 
and data requirements during a site initiation visit.  
After enrollment begins, a Abbott monitor will periodically review the subject records and 
associated source documents.  Each actively enrolling site will be visited at least annually. 
During these routine visits, the investigator shall make subject and study records available to 
the clinical monitor for monitoring. There will be 100% source verification on all available source 
documentation. In case of a subject not being able to be located, the monitor will verify that 
adequate measures have been undertaken to contact the subject’s  treating General 
Practitioner and exchange data about the whereabouts and health status of the subject. 
Monitoring reports will be created for each visit. 
Once all subjects have completed the study a close out visit will be completed.  
It is the responsibility of Abbott as the Sponsor of the study to ensure the study is conducted, 
recorded, and reported according to the approved protocol, subsequent amendment(s), 
applicable regulations, and guidance documents and to secure compliance from each 
investigative site as necessary. 
Investigators are required to adhere to the protocol, signed investigator agreement and any 
conditions required by the EC. If a site has long-standing, open monitoring findings or 
challenges with compliance, the monitor or study management shall consider developing a 
corrective and preventative action plan. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 39 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 Compliance Statement 
12.0
 
12.1 Statement of Compliance 
The study will be performed in accordance with the most current versions of the World Medical 
Association (WMA) Declaration of Helsinki, ISO 14155 and any regional and/or national 
regulations and will be compliant to this International Standard and any regional and national 
regulations, as appropriate. 
The investigator will not start enrolling subjects or requesting informed consent from any subject 
prior to obtaining EC approval and Competent Authority approval, if applicable, and 
authorization from the sponsor in writing for the study. 
In case additional requirements are imposed by the EC or Competent Authority, those 
requirements will be followed, if appropriate. If any action is taken by an EC, and regulatory 
requirements with respect to the study, that information will be forwarded to Abbott. 
As Sponsor, Abbott has taken up general liability insurance in accordance with the requirements 
of the applicable local laws. Appropriate country representative will be utilized to understand the 
requirements for the type of insurance that will be provided for subjects, such information will be 
incorporated into the informed consent, as applicable. 
 
12.2 Regulatory Inspections 
The investigator and/or delegate should contact Abbott immediately upon notification of a 
governmental agency inspection at the site. A clinical monitor or designee will assist the 
investigator and/or delegate in preparing for the audit. 
An investigator who has authority to grant access will permit authorized governmental agency 
employees, at reasonable times and in reasonable manner, to enter and inspect any 
establishment where devices are held (including any establishment where devices are used or 
where records or results are kept). 
An investigator, or any person acting on behalf of such a person with respect to the study, will 
permit authorized governmental agency employees, at reasonable times and in reasonable 
manner, to inspect and copy all records relating to the study. 
An investigator will permit authorized governmental agency employees to inspect and copy 
records that identify subjects, upon notice that governmental agency has reason to suspect that 
adequate informed consent was not obtained, or that reports required to be submitted by the 
investigator, to the Sponsor or EC have not been submitted or are incomplete, inaccurate, false 
or misleading. 
 
12.3 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 Clinical Research Associate or clinical representative 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 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 40 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
If an investigator is found to be repeatedly non-compliant with the signed agreement, the CIP or 
any other conditions of the clinical study, the Sponsor will either secure compliance or, at its 
sole discretion, terminate the Investigator’s participation in the clinical study. 
 
 Core Lab 
13.0
Echocardiographic examinations will be forwarded to an echocardiographic core laboratory for 
interpretation. It is the responsibility of each site to perform the local interpretation of the 
echocardiogram for clinical assessment. The echocardiographic core laboratory will not be 
responsible to notify the site of any abnormal finding that are identified in the echo study. 
The echocardiographic core laboratory will provide the study required interpretation and 
documentation of each echocardiogram submitted to the Sponsor. Data obtained from the core 
laboratory readings will be used for study purposes only and not for clinical treatment of the 
subject. 
 
Suspension or Premature Termination of the Clinical Investigation 
14.0
The Sponsor reserves the right to terminate the clinical investigation at any stage, with 
appropriate written notice to the investigators, ECs and relevant Regulatory authorities, if 
required.  
 
A Principal Investigator, EC 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 in either 
arm of the study or when so instructed by the EC or regulatory authority, the Sponsor may 
suspend the clinical investigation while the risk is assessed.  
 
Termination criteria are set based on a maximum allowable number of major vascular 
complications through 30 days across the two study arms. The study will continue in the arm of 
the study not under suspension. The Sponsor will terminate the clinical investigation if an 
unacceptable risk for major vascular complications through 30 days is confirmed with 
accumulating data as noted in the table below.  The termination criterion is selected to be x 
events such that the probability of observing x or more events is < 0.05 assuming that the 
number of events follows a binomial distribution with event probability 0.119. This event 
probability is based on the 30-day rate of major vascular complications reported in the literature 
(see Section 6.3). 
 
If the Sponsor completes an analysis of the reasons for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, the Sponsor will 
inform the Principal Investigators, EC, or regulatory authority, where appropriate, of the 
rationale, providing them with the relevant data supporting this decision. Approval from the EC 
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. 
 
Number 
enrolled (n) 
Number of events (major vascular 
complications through 30 days) to 
Probability of observing ≥ x 
events 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 41 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
meet termination criteria (x) 
20 
6 
0.0251 
30 
8 
0.0211 
40 
9 
0.0423 
 
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.  
 
 
 
14.1 Study Conclusion 
The study will be concluded when: 
1. All sites are closed AND 
2. The final report generated by Abbott has been provided to sites or Abbott has provided 
formal documentation of study closure 
 
Publication Policy 
15.0
The results of the clinical study will be submitted, whether positive or negative for publication.  
A ‘Publication Agreement’ will be signed between the Principal Investigator and the Sponsor 
either as a separate Publication Agreement or within the Clinical Trial Agreement. 
For more information on publication guidelines, please refer to the International Committee of 
Medical Journal Editors (ICMJE) on www.icmje.org. 
This study will be posted on ClinicalTrials.gov and results will be posted on ClinicalTrials.gov as 
required.  
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 42 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix A: Abbreviations 
 
Select or add abbreviations used 
Abbreviation 
Term 
ADE 
AE 
ASADE 
CA 
CEC 
CIP 
CRF 
DD 
DMP 
EC 
ECG 
eCRF 
EDC 
EMEA 
IB 
ICMJE 
ISO 
MP 
NA 
PI 
RDC 
SADE 
SAE 
SJM 
USADE 
WMA 
Adverse Device Effect 
Adverse Event 
Anticipated Serious Adverse Device Effect 
Competent Authority 
Clinical Events Committee 
Clinical Investigational Plan 
Case Report Form 
Device Deficiency 
Data Management Plan 
Ethics Committee 
Electrocardiogram 
Electronic Case Report Form 
Electronic Data Capture 
Europe, Middle East, Africa 
Investigator Brochure 
International Committee of Medical Journal Editors 
International Organization for Standardization 
Monitoring Plan 
Not Applicable 
Principal Investigator 
Remote Data Capture 
Serious Adverse Device Effect 
Serious Adverse Event 
St. Jude Medical 
Unanticipated Serious Adverse Device Effect 
World Medical Association 
 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 43 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix B: CIP Revision History 
Procedure for CIP Amendments 
 
This CIP may be amended as appropriate by the Sponsor. Rationale will be included with each 
amended version in the revision history table below. The version number and date of 
amendments will be documented. 
 
The acknowledgement of the amended CIP by the Steering Committee Co-chairs and the 
Principal Investigators will be collected on the signature pages. 
 
EC and relevant Regulatory Authorities, if applicable, will approve all amendments to the CIP. 
 
Revision History 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Not 
Applicable 
VA 
22 Sep 2016 
First release of CIP 
NA 
 
VB 
2 Feb 2017 
Requested updates from 
Competent Authority 
 
 
VB 
3 Mar 2017 
Requested updates from 
Competent Authority 
 
 
VC (Switzerland 
only) 
31 May 2017 
Requested updates from 
Competent Authority 
 
 
VC (Switzerland 
only) 
22 Jun 2017 
Requested updates from 
Competent Authority 
 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 44 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix C: Bibliography 
1. Lung B, Baron G, Butchart EG, Delahaye F, Gohlke-Barwolf C, Levang OW, Tornos P, 
Vanoverschelde JL, Vermeer F, Boersma E, Ravaud P, Vahanian A. A prospective 
survey of patients with valvular heart disease in Europe: The Euro Heart Survey on 
Valvular Heart Disease. Eur Heart J 2003; 24:1231—43. 
2. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a 
population-based study. Lancet 2006;368:1005-11. 
3. http://www.sts.org/sites/default/files/documents/20112ndHarvestExecutiveSummary.pdf 
Last accessed August 17, 2011. 
4. US Census Bureau. United States Census 2000. Washington, DC: US Census Bureau; 
2001. 
5. Bonow RO, Carabello BA, Kanu C, de Leon Jr AC, Faxon DP, Freed MD, Gaasch WH, 
Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS, 
Smith Jr SC, Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, 
Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B. 
ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: 
a report of the American College of Cardiology/American Heart Association Task Force 
on Practice Guidelines (writing committee to revise the 1998 Guidelines for the 
Management of Patients With Valvular Heart Disease): developed in collaboration with 
the Society of Cardiovascular Anesthesiologists: endorsed by the Society for 
Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. 
Circulation 2006; 114: e84—231. 
6. Task Force. Guidelines for the management of patients with valvular heart disease: 
executive summary. Circulation. 1998;98:1949 –1984. 
7. Otto CM, Mickel MC, Kennedy JW, Alderman EL, Bashore TM, Block PC, Brinker JA, 
Diver D, Ferguson J, Holmes DR Jr. Three-year outcome after balloon aortic 
valvuloplasty: insights into prognosis of valvular aortic stenosis. Circulation. 
1994;89:642– 650. 
8. Lieberman EB, Bashore TM, Hermiller JB, Wilson JS, Pieper KS, Keeler GP, Pierce 
CH, Kisslo KB, Harrison JK, Davidson CJ. Balloon aortic valvuloplasty in adults: failure 
of procedure to improve long-term survival. J Am Coll Cardiol. 1995;26:1522–1528. 
9. Grube E, Laborde JC, Gerckens U, et al. Percutaneous implantation of the CoreValve 
self-expanding valve prosthesis in high-risk patients with aortic valve disease: the 
Siegburg first-in-man study. Circulation 2006;114:1616-24. 
10. Grube E, Laborde JC, Zickmann B, et al. First report on a human percutaneous 
transluminal implantation of a self-expanding valve prosthesis for interventional 
treatment of aortic valve stenosis. Catheter Cardiovasc Interv 2005;66:465-9. 
11. Hanzel GS, Harrity PJ, Schreiber TL, et al. Retrograde percutaneous aortic valve 
implantation for critical aortic stenosis. Catheter Cardiovasc Interv 2005;64:322-6. 
12. Webb JG, Chandavimol M, Thompson CR, et al. Percutaneous aortic valve 
implantation retrograde from the femoral artery. Circulation 2006;113:842-50. 
13. Grube E, Schuler G, Buellesfeld L, et al. Percutaneous aortic valve replacement for 
severe aortic stenosis in high-risk patients using the second- and current third 
generation self-expanding CoreValve prosthesis: device success and 30-day clinical 
outcome. J Am Coll Cardiol 2007;50:69-76. 
14. Webb JG, Pasupati S, Humphries K, et al. Percutaneous transarterial aortic valve 
replacement in selected high-risk patients with aortic stenosis. Circulation 
2007;116:755-63. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 45 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
15. Cribier A, Eltchaninoff H, Tron C, et al. Treatment of calcific aortic stenosis with the 
percutaneous heart valve: mid-term follow-up from the initial feasibility studies: the 
French experience. J Am Coll Cardiol 2006;47:1214-23. 
16. Andersen HR, Knudsen LL, Hasenkam JM. Transluminal implantation of artificial heart 
valves: description of a new expandable aortic valve and initial results with implantation 
by catheter technique in closed chest pigs. Eur Heart J. 1992;13:704-708 
17. Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Sebagh L, Bash A, Nusimovici 
D, Litzler PY, Bessou JP, Leon MR. Early experience with percutaneous transcatheter 
implantation of heart valve prosthesis for the treatment of end-stage inoperable patients 
with calcific aortic stenosis. J Am Coll Cardiol. 2004;43:698 –703. 
18. Malaisrie SC, Tuday E, Lapin B, et al. Transcatheter aortic valve implantation decreases 
the rate of unoperated aortic stenosis. Eur J Cardiothorac Surg. 2011;40:43-48. 
19. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an 
aortic valve prosthesis for calcific aortic stenosis: first human case description. 
Circulation 2002; 106: 3006-8. 
20. Vohra H, Attia R, Bapat V. Alternative Access Routes For TAVR - The Feasibility, 
Safety, and Efficacy of Transcatheter Aortic Valve Replacement from the Several 
Possible Access Sites Available. Cardiac Interventions Today. 2012 Sep/Oct:46-52 
21. Kurra V, Schoenhagen P, Roselli EE, Kapadia SR, Tuzcu EM, Greenberg R, Akhtar M, 
Desai MY, Flamm SD, Halliburton SS, Svensson LG, Sola S. Prevalence of significant 
peripheral artery disease in patients evaluated for percutaneous aortic valve insertion: 
Preprocedural assessment with multidetector computed tomography. J Thorac 
Cardiovasc Surg. 2009 May;137(5):1258-64 
22. Al-Lamee R, Godino C, Colombo A. Transcatheter aortic valve implantation, current 
principles of patient and technique selection and future perspectives. Circulation: 
Cardiovasc Interv. 2011;4:387-395. 
23. Bruschi G, et al. Direct aortic access for transcatheter self-expanding aortic bioprosthesis 
valves implantation. Ann Thorac Surg. 2012;94:497-503 
24. Genereux P, Head S, Van Mieghem N, et al. Clinical Outcomes After Transcatheter 
Aortic Valve Replacement Using Valve Academic Research Consortium Definitions: A 
Weighted Meta-Analysis of 3,519 Patients from 16 Studies. J Am Coll Cardiol 
2012;59:2317-2326 
25. Kappetein AP, Head SJ, Genereux P, et al. Updated Standardized Endpoint Definitions 
for Transcatheter Aortic Valve Implantation: The Valve Academic Research Consortium-
2 Consensus Document. J Am Coll Cardiol 2012;60:1438-1454 
26. Frohlich G, Baxter P, Malkin C, et al. Comparative Survival After Transapical, Direct 
Aortic and Subclavian Transcateter Aortic Valve Implantation (Data from the UK TAVI 
Registry). J Am Coll Cardiol 2015;1555-1559 
27. Muensterer A, Mazzitelli D, Ruge H, et al. Safety and efficacy of the subclavian access 
route for TAVI in cases of missing transfemoral access. Clin Res Cardiol 2013;102:627-
636 
28. Petronio AS, De Carlo M, Bedogni F, et al. 2-Year Results of CoreValve Implantation 
Through the Subclavian Access: A Propensity-Matched Comparison with Femoral 
Access. J Am Coll Cardiol 2012;60:502-507 
29. Adams DH, Popma J., Reardon M., et.al Transcatheter Aortic-Valve Replacement with a 
Self-Expanding Prosthesis. N Engl J Med 2014; 370:1790-1798. 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 46 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix D: Definitions 
Cardiovascular 
Mortality 
 
(VARC2) 
Any 1 of the following criteria: 
 
Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac 
tamponade, worsening heart failure) 
 
Death caused by non-coronary vascular conditions such as neurological 
events, pulmonary  embolism, ruptured aortic aneurysm, dissecting aneurysm, 
or other vascular disease 
 
All procedure-related deaths, including those related to a complication of the 
procedure or treatment for a complication of the procedure 
 
All valve-related deaths including structural or nonstructural valve dysfunction 
or other valve-related adverse events 
 
Sudden or unwitnessed death 
 
Death of unknown cause 
Myocardial  
Infarction 
 
(VARC2) 
POST_TAVI Definition (VARC2) 
Periprocedural MI (less than or equal to (≤) 72 h after the index procedure) 
New ischemic symptoms (eg, chest pain or shortness of breath), or new ischemic 
signs (eg, ventricular arrhythmias, new or worsening heart failure, new ST-
segment changes, hemodynamic instability, or imaging evidence of new loss of 
viable myocardium or new wall motion abnormality),  
AND  
Elevated cardiac biomarkers within 72 h after the index procedure consisting of at 
least 1 sample postprocedure with a peak value exceeding 15x upper reference 
limit (troponin) or 5x for CK-MB. If cardiac biomarkers are increased at baseline 
(>99th percentile), a further increase of at least 50% postprocedure is required AND 
the peak value must exceed the previously stated limit. 
 
Spontaneous MI (greater than 72 h after the index procedure) 
Any 1 of the following criteria: 
 
Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with 
at least 1 value above the 99th percentile URL, together with evidence of 
myocardial ischemia with at  least 1 of the following: 
o Symptoms of ischaemia 
o ECG changes indicative of new ischemia [new ST-T changes or new 
Left Bundle Branch Block] 
o New pathological Q waves in at least 2 contiguous leads 
o Imaging evidence of new loss of viable myocardium or new wall 
motion abnormality 
 
Sudden, unexpected cardiac death, involving cardiac arrest, often with 
symptoms suggestive of myocardial ischemia, and accompanied by 
presumably new ST-segment elevation, or new LBBB, and/or evidence of 
fresh thrombus by coronary angiography and/ or at autopsy, but death 
occurring before blood samples could be obtained, or at a time before the 
appearance of cardiac biomarkers in the blood. 
 
Pathological findings of an acute myocardial infarction. 
Stroke 
 
(FDA/VARC2) 
This study is following the FDA’s definition of Stroke per FDA’s Current Thinking 
Regarding Neurological Assessments for Transcatheter aortic valve Trials 
(Revised: 25 Aug 2011). 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 47 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
1. Definitions:  
a. Stroke: Stroke is an acute symptomatic episode of neurological dysfunction 
attributed to a vascular cause.  
Subclassifications of stroke:  
Ischemic Stroke is defined as an acute symptomatic episode of focal 
cerebral, spinal, or retinal dysfunction caused by an infarction of central 
nervous system tissue.  
Hemorrhagic Stroke is defined as an acute symptomatic episode of focal or 
global cerebral or spinal dysfunction caused by a nontraumatic 
intraparenchymal, intraventricular, or subarachnoid hemorrhage.  
Stroke Disability (consistent with VARC2 Definitions):  
 
Severity 
i. Disabling (Major):  an mRS score of 2 or more at 90 days and an increase 
of at least 1 mRS category from an individual’s prestroke baseline 
ii. Non-disabling (Minor):  an mRS score of <2 at 90 days or 1 that does not 
result in an increase of at least 1 mRS category from an individual’s prestroke 
baseline 
b. Cerebral Infarction: Evidence of brain cell death from imaging studies or 
pathological examination. If there are clinical symptoms, then it is a stroke; 
otherwise, it is an asymptomatic cerebral infarction.  
c. Transient Ischemic Attack (TIA): A transient (less than 24 hrs) episode of 
neurological dysfunction caused by focal brain, spinal cord, or retinal 
ischemia, without acute infarction. No evidence of infarction if imaging 
performed.  
d. Encephalopathy: Altered mental state (e.g., seizures, delirium, confusion, 
hallucinations, dementia, coma, psychiatric episode).  
e. Intracranial Hemorrhage: Collection of blood between the brain and skull. 
Subcategorized as epidural, subdural, and subarachnoid bleeds.  
Bleeding 
 
(VARC2) 
 
Life-threatening or disabling bleeding 
 
Fatal bleeding (BARC type 5) OR 
 
Bleeding in a critical  organ, such as intracranial, intraspinal, intraocular, or 
pericardial necessitating pericardiocentesis, or intramuscular with compartment 
syndrome (BARC type 3b and 3c) OR 
 
Bleeding causing hypovolemic shock or severe hypotension requiring 
vasopressors or surgery (BARC type 3b) OR 
 
Overt source of bleeding with drop in hemoglobin of greater than or equal to 5 
g/dl or whole blood or packed red blood cells (RBCs) transfusion greater than 
or equal to 4 U (BARC type 3b). Given 1 U of packed RBC typically will raise 
blood hemoglobin concentration by 1 g/dL, an estimated decrease in 
hemoglobin will be calculated. 
 
Major bleeding (BARC type 3a) 
 
Overt bleeding either associated with a drop in the hemoglobin level of at least 
3.0 g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC, or causing 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 48 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
hospitalization or permanent injury, or requiring surgery AND 
 
Does not meet criteria of life-threatening or disabling bleeding  
 
Minor bleeding (BARC type 2 or 3a, depending on the severity) 
 
Any bleeding worthy of clinical mention (eg, access site hematoma) that does 
not qualify as life-threatening, disabling, or major 
Acute Kidney 
Injury (AKIN 
Classification) 
 
(VARC2) 
Change in serum creatinine (up to 48 h) compared with baseline 
 
Stage 1  
Increase in serum creatinine to 150% to 199% (1.5 to 1.99 X increase compared 
with baseline) or increase of greater than or equal to 0.3 mg/dL (26.4 mmol/L) or 
Urine output <0.5 mL/kg per hour for >6 but <12 hours 
 
Stage 2  
Increase in serum creatinine to 200% to 299% (2.0 to 2.99 X increase compared 
with baseline) or  
Urine output <0.5 mL/kg per hour for >12 but <24 hours 
 
Stage 3  
Increase in serum creatinine to greater than or equal to 300% (3 X increase 
compared with baseline) or serum creatinine of ≥ 4.0 mg/dL (354 mmol/L) with an 
acute increase of at least 0.5 mg/dL (44 mmol/L)or Urine output <0.3 mL/kg per 
hour for ≥24 hours or anuria for ≥12 hours. Patients receiving renal replacement 
therapy are considered to meet Stage 3 criteria irrespective of other criteria. 
Vascular 
Access Site 
and Access-
Related 
Complications 
(VARC2) 
Major vascular complications 
 
Any aortic dissection, aortic rupture, annulus rupture, left ventricle perforation, 
or new apical aneurysm/pseudo-aneurysm or 
 
Access site or access-related vascular injury (dissection, stenosis, perforation, 
rupture, arteriovenous fistula, pseudoaneurysm, hematoma, irreversible nerve 
injury, compartment syndrome, percutaneous closure device failure) leading to 
death, life-threatening or major bleeding*, visceral ischaemia or neurological 
impairment or 
 
Distal embolization (non-cerebral) from a vascular source requiring surgery or 
resulting in amputation or irreversible end-organ damage or 
 
The use of unplanned endovascular or surgical intervention associated with 
death, major bleeding, visceral ischaemia or neurological impairment or 
 
Any new ipsilateral lower extremity ischemia documented by patient symptoms, 
physical exam, and/or decreased or absent blood flow on lower extremity 
angiogram or 
 
Surgery for access site-related nerve injury or 
 
Permanent access site-related nerve injury 
 
Minor vascular complications 
 
Access site or access-related vascular injury (dissection, stenosis, perforation, 
rupture, arteriovenous fistula, pseudoaneuysms, hematomas, percutaneous 
closure device failure) not leading to death, life-threatening or major 
bleeding*, visceral ischaemia or neurological impairment or 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 49 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
Distal embolization treated with embolectomy and/or thrombectomy and not 
resulting in amputation or irreversible end-organ damage or 
 
Any unplanned endovascular stenting or unplanned surgical intervention not 
meeting the criteria for a major vascular complication or 
 
Vascular repair or the need for vascular repair (via surgery, ultrasound-guided 
compression, transcatheter embolization, or stent-graft) or 
 
Percutaneous closure device failure 
Failure of a closure device to achieve haemostasis at the arteriotomy site leading 
to alternative treatment (other than manual compression or adjunctive 
endovascular ballooning) 
Acute Device 
Success 
(VARC) 
Acute device success is defined as a subject who achieves a) successful vascular 
access, delivery and deployment of the device and successful retrieval of the 
delivery system, b) correct position of the device in the proper anatomical location, 
c) intended performance of the prosthetic heart valve, and d) only 1 valve 
implanted in the proper anatomical location. 
 
Device success is a ‘technical’ composite endpoint meant to characterize the acute 
device and procedural factors which underlie vascular access, delivery, and 
performance of the TAVI system. Echocardiography should be routinely utilized as 
the standard for measuring prosthetic valve stenosis and regurgitation immediately 
after TAVI, and should always be performed in a resting state, either within 24–48 
h after the index procedure or before hospital discharge. 
 
 
 
 
 
Prosthetic 
Valve Stenosis 
Criteria 
In conditions 
of normal or 
near normal 
stroke volume 
(50–70 ml). 
 
(VARC2) 
 
Parameter 
Normal 
Mild Stenosis 
Moderate/severe 
Stenosis 
Peak velocity 
(m/s) 
less than 3 
3–4 
greater than 4 
Mean gradient 
(mm Hg) 
less than 20 
20–40 
greater than 40 
Doppler velocity 
index 
greater than or equal 
to 0.35 
0.35–0.25 
less than 0.25 
Effective orifice 
area (cm2) 
greater than 1.1 
1.1–0.8 
less than 0.80 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prosthetic 
Valve 
Regurgitation 
Criteria 
(Central and 
Paravalvular) 
Parameter 
Mild 
Moderate 
Severe 
Valve structure 
and motion 
Usually normal 
Usually abnormal 
Usually abnormal 
Left ventricular 
size 
Normal 
Normal/mildly dilated 
Dilated 
Doppler parameters (qualitative or semiquantitative) 
                                                          
 Effective orifice area (EOA) used in this protocol is 1.0 cm2 for Portico valve of 23 mm diameter. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 50 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
(VARC2) 
Jet width in 
central jets (% 
LVO 
diameter): 
color 
Narrow 
(less than or equal to 
25%) 
Intermediate 
(26%–64%) 
Large 
(greater than or 
equal to 65%) 
Jet density: 
CW Doppler 
Incomplete or faint 
Dense 
Dense 
Jet 
deceleration 
rate (PHT, 
ms): CW 
Doppler 
Slow  
(greater than 500) 
Variable (200–500) Steep (less than 200)
LV outflow vs. 
pulmonary 
flow: PW 
Doppler 
Slightly increased 
Intermediate 
Greatly increased 
Diastolic flow reversal in the descending aorta (semi-quantitative 
parameters) 
PW Doppler 
Absent or brief early 
diastolic 
Intermediate 
Prominent, 
holodiastolic 
Circumferential 
extent of 
paraprosthetic 
AR 
less than 10% 
10–29% 
greater than or equal 
30% 
Doppler parameters (quantitative) 
Regurgitant 
volume 
(ml/beat) 
less than 30% 
30–59% 
greater than or equal 
60% 
Regurgitant 
fraction 
less than 30% 
30–49% 
greater than or equal 
50% 
 
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 study. 
This definition includes events related to the investigational medical device or the comparator. 
This definition includes events related to the procedures involved. 
 
Serious Adverse Event (SAE) 
An adverse event that led to: 
1. Death 
2. A serious deterioration in the health of the subject, that either resulted in: 
 
A life-threatening illness or injury OR 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 51 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
A permanent impairment to a body structure or a body function OR 
 
An in-patient or prolonged hospitalization OR 
 
A medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function OR 
 
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, 
without serious deterioration in health, 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 Serious Adverse Device Effect (USADE) 
A serious adverse device effect which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report. 
 
Device Deficiency (DD) 
A Device Deficiency is defined as an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety or performance. Device deficiencies include malfunctions, 
use errors and inadequate labeling 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 52 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix E: Risk Calculations 
This clinical study requires the use of 3 surgical risk assessment tools: 
1. Logistic EuroSCORE (www.euroscore.org/calcold/html) 
2. Euro SCORE II (http://euroscore.org/calc.html), and 
3. The Society of Thoracic Surgeons’ (STS) risk calculation tools, Version 2.73 
(http://riskcalc.sts.org/STSWebRiskCalc273/de.aspx) 
 
 
 
 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 53 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
Appendix F: Quality of Life-EQ-5D 3L 
By placing a checkmark in one box in each group below, please indicate which statements best 
describe your own health state today. 
Mobility 
I have no problems in walking about 
  
I have some problems in walking about 
  
I am confined to bed 
  
Self-Care 
I have no problems with self-care 
  
I have some problems washing or dressing myself 
  
I am unable to wash or dress myself 
  
Usual Activities (eg, work, study, housework, family or leisure activities) 
I have no problems with performing my usual activities 
  
I have some problems with performing my usual activities 
  
I am unable to perform my usual activities 
  
Pain/Discomfort 
I have no pain or discomfort 
  
I have moderate pain or discomfort 
  
I have extreme pain or discomfort 
  
Anxiety/Depression 
I am not anxious or depressed 
  
I am moderately anxious or depressed 
  
I am extremely anxious or depressed 
  
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 54 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix G: Frality Assessment 
 
The Frailty Index Data Collection Form will be used as an assessment tool to determine if frailty 
is a high risk factor for subjects prior to enrollment. This assessment will be performed after the 
Informed Consent has been obtained and prior to procedure. The assessment can be 
administered by either an Investigator or research coordinator. 
The frailty assessment consists of 3 evaluations: 
1. Katz Index of Independence in Activities of Daily Living  
2. Grip Strength 
3. 15 Foot walk test 
 
Katz Index of Independence in Activities of Daily Living Activities  
Points (1 or 0)  
Independence 
(1 Point) 
NO supervision, direction or personal 
assistance 
Dependence 
(0 Points) 
WITH supervision, direction, 
personal assistance or total care
BATHING  
Points: 
________  
(1 POINT) Bathes self completely or 
needs help in bathing only a single part 
of the body such as the back, genital 
area or disabled extremity  
(0 POINTS) Need help with 
bathing more than one part of the 
body, getting in or out of the tub 
or shower. Requires total bathing 
DRESSING  
Points: 
________  
(1 POINT) Get clothes from closets 
and drawers and puts on clothes and 
outer garments complete with 
fasteners. May have help tying shoes. 
(0 POINTS) Needs help with 
dressing self or needs to be 
completely dressed.  
TOILETING  
Points: 
________  
(1 POINT) Goes to toilet, gets on and 
off, arranges clothes, cleans genital 
area without help. 
(0 POINTS) Needs help 
transferring to the toilet, cleaning 
self or uses bedpan or commode.
TRANSFERR
ING  
Points: 
________  
(1 POINT) Moves in and out of bed or 
chair unassisted. Mechanical transfer 
aids are acceptable. 
(0 POINTS)Needs help in moving 
from bed to chair or requires a 
complete transfer. 
CONTINENC
E  
Points: 
________  
(1 POINT) Exercises complete self 
control over urination and defecation.  
(0 POINTS) Is partially or totally 
incontinent of bowel or bladder.  
FEEDING  
Points: 
________  
(1 POINT) Gets food from plate into 
mouth without help. Preparation of food 
may be done by another person.  
(0 POINTS) Needs partial or total 
help with feeding or requires 
parenteral feeding.  
 
TOTAL Points:______________ 
 
 
Grip strength   Subjects elbow should be at a 90 degree angle without arm supported or 
resting on table or against chest wall. Each grasp should be completed with the dynamometer in 
the dominant hand. 
Grasp 1____________ Grasp 2___________ Grasp3____________    

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 55 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
Average Grip Strength_____________ 
 
 
 
15 Foot/4.9m Walk    
This examination should be performed indoors, along a long, flat, straight, enclosed corridor with 
a hard surface that is seldom traveled.  The walking course must be 15 Feet/4.9m in length.  The 
time to walk this distance is to be recorded.  
 
 _______________seconds 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 56 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix H: Scales 
 
These assessments must be completed by a rater who has a current certificate that 
demonstrates completion of an accredited training program for this stroke scale. Certifications 
can be completed using the following link: http://StJudeMedical.trainingcampus.net 
Modified Rankin Scale (mRS) 
The determination of the scale should be made from 5 to 0. 
The purpose of the mRS is to record whether the patient is severely, moderately, or slightly 
disabled and whether the patient is performing all usual activities without symptoms or not. 
Because subjects and family members may understate the severity of disability, it is important 
for the rating clinician to understand that the mRS is a clinical scale and not a patient-reported 
outcome. The rater may ask questions but must assess the disability whether or not in 
agreement with the subject or family. 
“Improving the assessment of outcomes in stroke: use of a structured interview to assign grades 
on the Modified Rankin Scale” Stroke; 33:2243-2246) 
 
Score Description 
5 
 
Severe disability 
 
Someone needs to be available at all times;  
 
Care may be provided by either a trained or an untrained caregiver 
Question: Does the person require constant care?  
4 
 
Moderately severe disability 
 
Need for assistance with some basic activities of daily living, but does not 
require constant care 
Question: Is assistance essential for eating, using the toilet, daily hygiene, or 
walking?  
3 
 
Moderate disability 
 
Need for assistance with some instrumental activities of daily living but not 
basic activities of daily living.  
Question: Is assistance essential for preparing a simple meal, doing household 
chores, looking after money, shopping, or traveling locally?  
2 
 
Slight disability;  
 
Limitations in participation in usual social roles 
 
Independent for activities of daily living.  
Questions: Has there been a change in the person’s ability to work or look after 
others if these were roles before stroke? Has there been a change in the person’s 
ability to participate in previous social and leisure activities? Has the person had 
problems with relationships or become isolated?  
1 
 
No significant disability 
 
Symptoms present but no other limitations.  
Question: Does the person have difficulty reading or writing, difficulty speaking or 
finding the right word, problems with balance or coordination, visual problems, 
numbness (face, arms, legs, hands, feet), loss of movement (face, arms, legs, 
hands, feet), difficulty with swallowing, or other symptom resulting from stroke?  
0 
 
No symptoms at all 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 57 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
No limitations and no symptoms 
 
National Institute of Health Stroke Scale (NIHSS) 
 
The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that 
provides a quantitative measure of stroke-related neurologic deficit. The NIHSS was developed 
in 1983 by NIH-sponsored stroke research neurologists. 
 
NIHSS Administration Process 
The NIHSS items are to be administered in the designated order.  This helps to maintain the 
tool’s reliability or reproducibility and validity. Performance in each category is to be recorded 
after each subscale exam. Examiners should not go back and change any scores and the 
examiner must always score the patient’s first attempt. Some patients may later correct an error, 
but scores should not be changed. Examiners are to follow the directions provided for each 
exam technique. Scores recorded should reflect what the patient does, not what the clinician 
thinks the patient can do. The clinician should record answers while administering the exam and 
work quickly. Except where indicated, the patient should not be coached (ie, repeated requests 
to patient to make a special effort). 
 
NIHSS Item Instructions & Scale Definitions 
The first group of items on the NIHSS is intended to assess wakefulness or level of 
consciousness (LOC). A decrease in a patient’s LOC can indicate deterioration in clinical status. 
The pathophysiology for this decline can be metabolic (hypoxia, systemic organ failure, toxins, 
infections or ischemia), structural (injury or compression of the brainstem, as a result of direct 
mass lesions, such as intracranial hematomas or secondary mass volume such as cerebral 
edema), or a combination of the two. 
 
1a. Level of Consciousness 
This is an evaluation of the overall impression of alertness. The examiner assesses the patient’s 
response to random verbal stimuli. The Investigator must chose a response if a full evaluation is 
prevented by such obstacles as an endotracheal tube, language barrier, orotracheal 
trauma/bandages. A 3 is scored only if the patient makes no movement (other than reflexive 
posturing) in response to noxious stimulation. 
Scale Definition: 
0 = Alert; keenly responsive. 
1 = Not alert; but arousable by minor stimulation to obey, answer, or respond. 
2 = Not alert; requires repeated stimulation to attend, or is obtunded and requires strong 
or painful stimulation to make movements (not stereotyped.) 
3 = Responds only with reflex motor or autonomic effects or totally unresponsive, flaccid 
and areflexic. 
 
1b. LOC Questions 
The patient is asked the month and his/her age. The answer must be correct — there is no 
partial credit for being close. Aphasic and stuporous patients who do not comprehend the 
questions will score 2. Patients unable to speak because of endotracheal intubation, orotracheal 
trauma, severe dysarthria from any cause, language barrier, or any other problem not 
secondary to aphasia are given a 1. It is important that only the initial answer be graded and 
that the examiner not “help” the patient with verbal or non-verbal cues. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 58 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Scale Definition 
0 = Answers both questions correctly. 
1 = Answers one question correctly. 
2 = Answers neither question correctly. 
 
1c. LOC Commands 
This evaluates the patient’s ability to follow one-step commands. The patients is asked to open 
and close his or her eyes and then to grip and release the non-paretic hand.  The examiner may 
substitute another simple one-step command if the hands cannot be used. Credit is given if an 
unequivocal attempt is made but not completed due to weakness. If the patient does not 
respond to the command, the task should be demonstrated to the patient and the result scored. 
Patients with trauma, amputation, or other physical impediments should be given suitable one-
step commands and only the first attempt is scored. 
Scale Definition 
0 = Performs both tasks correctly. 
1 = Performs one task correctly. 
2 = Performs neither task correctly. 
 
The second and third items of the NIHSS are intended to evaluate a stroke patient’s vision. 
Visual field cues and impaired eye movements are frequently demonstrated by patients with 
acute stroke. 
 
2. Best Gaze 
This item evaluates extraocular movements. Abnormal findings can indicate pathophysiology 
involving the frontal lobe, brainstem, cerebellar or vestibular dysfunction or generalized 
dysfunction of the cerebral cortex. 
 
Only horizontal eye movements are tested, however these can be voluntary or reflexive. If the 
patient is alert and able to follow commands, the evaluator will ask the patient to follow his or 
her fingers with his or her eyes from left of midline to right of midline while keeping the head still. 
A patient with pre-existing blindness can be asked verbally to move the eyes to the right, left, up 
and down. If the patient does not understand or attend to command, gaze can be assessed by 
establishing eye contact and then moving one’s face to the right and left of midline. If the patient 
is unresponsive, this item can be scored using the oculocephalic reflex (dolls eyes maneuver.) 
This technique requires the rapid rotation of the patient’s head side to side with the eyelids held 
open and observing for movement in the direction opposite to the head turn. 
Scale Definition 
0 = Normal. Able to move both eyes left to right across midline. 
1 = Partial gaze palsy. Gaze is abnormal in one or both eyes, but forced deviation, or 
total gaze paresis is not present. Able to move one or both eyes, but may not be able to 
cross midline. 
2 = Forced deviation. Total gaze paresis is not overcome by the oculocephalic 
maneuver.  
 
3.  Best Visual. 
This item is a visual field assessment. Abnormalities here usually arise from damage of the optic 
radiations or occipital lobes. This item tests the upper and lower quadrants of vision by 
confrontation exam. The examiner positions himself or herself opposite the patient’s face. The 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 59 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
patient is then asked (while looking at the examiners nose) to count the fingers of the examiner 
as they are introduced in the patient’s visual field quadrants. Patients can be encouraged as 
appropriate. Stroke patients who are unable to understand these instructions can be evaluated 
by response to moving fingers displayed by confrontation. These patients will often look in the 
direction of moving fingers displayed by the assessor in the four quadrants without 
comprehension of the examination. Such patients can also be tested by visual threat. This is 
done by introducing a striking hand threat into the patient’s visual fields. A blink response 
implies that vision is intact. If there is unilateral blindness or enucleation, the test is completed 
for the functioning eye. 
Scale Definition 
0 = No visual loss. 
1 = Partial hemianopia. Includes loss in only one quadrant. 
2 = Complete hemianopia. Loss of vision in both top and bottom quadrants on the right 
or left side of a patient’s visual field. 
3 = Bilateral hemianopia. Blindness of any cause, including cortical blindness, or if visual 
loss is noted on both right and left sides of the visual fields. 
The next several items of the NIHSS are intended to assess voluntary movement of the 
stroke patient. 
 
4.  Facial Palsy. 
This item evaluates symmetry or equality of facial movement. Facial asymmetry is often seen 
even in minor strokes and can be the first clue to the presence of swallowing difficulties or 
dysphasia. The examiner asks the patient or gestures for the patient to show his or her teeth, 
raise eyebrows and squeeze eyes closed. In poorly responsive patients or patients who are 
unable to follow commands or gestures, painful stimuli can be introduced by a sterna rub and a 
grimace can be evaluated. If facial trauma/bandages orotracheal tape, or other physical barriers 
obscure the face, these should be removed to the extent possible. Pathologic findings on this 
item indicate a lower motor neuron lesion of ipsilateral cranial nerve VII. Bilateral findings can 
indicate brainstem lesions. 
Scale Definition 
0 = Normal. Symmetrical movements. 
1 = Minor paralysis. Flattened nasolabial fold, asymmetry on smiling. 
2 = Partial paralysis. Total or near-total paralysis of lower face. 
3 = Complete paralysis of one or both sides of face. Absence of movement in the upper 
and lower face.  
 
5. Motor Arm. (a. Left Arm, b. Right Arm) 
This item evaluates symmetry of voluntary movement in both upper extremities. The arms are 
evaluated one at a time by instructing or demonstrating to the patient to lift his or her arm up 
(palm up) to a 90 degree angle (45 degrees if lying down.) and holding it up for a count of 10. 
Gestures or pantomime may be used to gain cooperation of the aphasic or confused stroke 
patient but noxious stimuli should not be used. The score is determined by the patient’s ability to 
resist gravity. After one extremity is scored, the process is repeated and scored for the opposite 
extremity. The non-paretic arm is tested first. Only in cases of amputation or joint fusion at the 
shoulder should an examiner record a score of untestable (UN) and clearly write the reason for 
this choice. 
Scale Definition 
0 = No drift. Limb holds 90 (or 45) degrees for a full 10 seconds. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 60 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
1 = Drift. Limb holds 90 (or 45) degrees, but then drifts down before full 10 seconds; 
does not hit bed or other support. 
2 = Some effort against gravity. Limb cannot get to or maintain 90 (or 45) degrees, drifts 
down to bed, but has some effort against gravity. 
3 = No effort against gravity. Limb falls. 
4 = No movements. Flaccid extremities with no effort noted. 
 
6. Motor Leg. ( a. Left Leg, b. Right Leg) 
This item is evaluated similarly to item 5. Each lower extremity is evaluated separately, 
beginning with the non-paretic leg. Patients should always be in supine position. The leg is lifted 
or elevated to 30 degrees off the bed and held for a count of five seconds. The aphasic patient 
can be encouraged using urgency in the voice or pantomime, but again, no noxious stimuli 
should be used for this item. Only in the case of amputation or joint fusion at the hip should the 
examiner record a score of untestable and clearly write the reason for this choice. 
Scale Definition 
0 = No drift. Leg holds 30 degree position for full five seconds. 
1 = Drift. Leg falls by the end of the five second period, but does not hit bed. 
2 = Some effort against gravity. Leg falls to bed by five seconds, but has some effort 
against gravity. 
3 = No effort against gravity. Leg falls to bed immediately. 
4 = No movement. Flaccid extremities with no effort noted. 
 
7. Limb Ataxia. 
This is used to evaluate the stroke patient’s coordination of movements which may indicate a 
unilateral cerebellar lesion. A weakened extremity can appear poorly coordinated when 
evaluating ataxia, but item 7 is scored as present only if the ataxia or poorly controlled 
movements are out of proportion to the extremity weakness noted in items 5 or 6. Each limb is 
evaluated and scored separately with the patient’s eyes open. The exam technique is finger to 
nose or heel to shin testing. The examiner instructs the patient to touch his or her finger to touch 
the examiner’s finger, then to repeatedly touch their nose and retouch the examiner’s finger. 
This is done for each upper extremity and scored. If the patient cannot understand the 
command or is unable to move his arm, ataxia is scored as absent. Lower extremity ataxia is 
evaluated by instructing the patient  to lift his or her leg and slide the heel of his or her foot down 
the opposite shin, and repeat the motion at least twice. Only in the case of amputation or joint 
fusion should the examiner record a score as untestable and the reason should be noted. In 
case of blindness, test by having the patient touch own nose from extended arm position. 
Scale Definition 
0 = Absent. 
1 = Present in one limb. 
2 = Present in two limbs. 
 
8. Sensory. 
Sensory and perceptual deficits are common in stroke patients and need to be carefully 
evaluated to ensure patient safety. Abnormal findings or sensory loss usually indicate lesions or 
dysfunction involving the contralateral thalamus or parietal lobe cortex. Tactile sensation is 
tested by sensation or grimace to pin prick or withdrawal to noxious stimulus for the obtunded or 
aphasic patient. The body areas that should be tested include at least the face, arms (not 
hands) legs (not feet) and trunk. The ability to sense pin prick from the left to right side is tested 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 61 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
for normal or abnormal feelings, whether it “feels different” from the opposite side. The patient is 
asked, “Do you feel the pin?” and “Does it feel the same on both sides?” A score of two should 
only be given when a severe or total loss of sensation can be clearly demonstrated. Stuperous 
or aphasic patients will therefore probably score 1 or 0. The patient with brainstem stroke with 
bilateral sensory loss will score 2. If the patient does not respond and is quadriplegic, score 2. 
Patients in a coma (item 1a = 3) automatically score 2 on this item 
Scale Definition 
0 = Normal. No sensory loss. 
1 = Mild to moderate sensory loss. Patient feels pin prick is less sharp or is dull on the 
affected side or there is a loss of superficial pain with pin prick, but patient is aware of 
being touched. 
2 = Severe to total sensory loss. Patient is not aware of being touched on the face, arm 
and leg. 
 
9. Best Language. 
Language deficits are known to be common in stroke patients. Disturbances in speech and 
communication most commonly indicate lesions involving the Brocha’s Area, Wernicke’s Area or 
the frontal, parietal, or parieto-occipital areas of the left hemisphere. The primary language 
center is located in the left cerebral hemisphere in most people. A small number of people will 
have language function centered in the right hemisphere. A great deal of information about 
comprehension will be obtained in the preceding sections of the examination. The NIHSS uses 
a standardized set of visual stimuli (pictures, sentences, word list, appendix A) that are shown to 
the patient, and the patient is instructed to describe the picture, name the objects, read the 
sentences or say the words. Accommodations for patients with limited vision or education can 
be made my eliciting enough verbal feedback to introduce stimuli to determine the scoring 
described below. The examiner may ask the patient to identify common objects placed in the 
hand or repeat and produce speech. The intubated patient should be asked to write. The patient 
in a coma (item 1a = 3) will score 3 on this item. The examiner must chose a score for the 
patient with stupor or limited cooperation, but a score of 3 should only be used if the patient is 
mute and follows no one-step commands. 
Scale Definition 
0 = No aphasia. Normal fluent speech. 
1 = Mild to moderate aphasia. Some obvious loss of fluency or facility of comprehension 
without significant limitation on ideas expressed or form of expression. Reduction of 
speech and/or comprehension however, makes conversation about provided materials 
difficult or impossible. For example, in conversation about provided materials, examiner 
can identify picture or naming card content from patient’s response.  
2 = Severe aphasia. All communication is through fragmentary expression; great need 
for inference, questioning and guessing by the listener. Often limited to one-word 
answers. Range of information that can be exchanged is limited; listener carries burden 
of communication. Examiner cannot identify materials provided from patient response.  
3 = Mute. Global aphasia. No usable speech or auditory comprehension. 
 
10. Dysarthria. 
This item assesses the quality of the stroke patient’s speech. This exam is done by having the 
patient read a list of words (Appendix A) or having the patient repeat single words.  If the patient 
has severe aphasia, the clarity of articulation of spontaneous speech can be rated. The 
examiner should record this item as untestable only if the patient in intubated or has other 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 62 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
physical barriers to producing speech and the reason should be clearly recorded. The NIH 
recommends that the examiner not tell the patient why he or she is being tested.  
Scale Definition 
0 = Normal 
1= Mild to moderate dysarthria. Patient slurs at least some words and at worst, can be 
understood with some difficulty. 
2 = Severe dysarthria. Patient’s speech is so slurred as to be unintelligible in the 
absence of or out of proportion to any dysphasia or is mute. 
 
11. Extinction and Inattention (formerly neglect). 
This item primarily evaluates the contralateral parietal lobe cortex. A stroke patient’s ability to 
perceive needs to be evaluated, documented and incorporated into the plan of care as early as 
possible. The recognition of visual, tactile, special or personal inattention deficits can help 
prevent patient falls, one of the most common complications after stroke. This item is last on the 
stroke scale because it requires the examiner to consider information obtained during prior 
sections of the scale. Sensory information may be sufficient to score a patient, but in situations 
where abnormalities are not clear, double simultaneous stimulation (DSS) is recommended. To 
perform tactile DSS testing the patient is first asked to close his or her eyes. The examiner then 
introduces touch stimuli alternatively from the left to right side. The patient is asked to 
discriminate which arm or leg is being touched. After a consistent response is produced, the 
examiner introduces tactile stimulation to both sides at once. The normal individual can identify 
sensation on both sides. A stroke patient without sensory impairment on individual limb testing 
may have difficulty with DSS and extinguish or neglect the weaker sensory information on the 
affected side. Thus, he or she will only feel simultaneous information on the “good” side. If a 
patient is aphasic but appears to attend to both sides, the score is normal. The concept of DSS 
is also applicable to visual fields testing and, in cooperative patients, testing of hearing. 
Scale Definition 
0 = Normal 
1 = Visual, tactile, auditory, special or personal inattention or extinction to bilateral 
simultaneous stimulation in one of the sensory modalities. 
2 = Profound hemi-inattention or extinction to more than one modality. Patient does not 
recognize own hand or orients to only one side of space.  
 
Scoring and Outcomes 
Upon completion of all items, the examiner compiles the patient’s score. Total scores on the 
NIHSS range from 0 to 42, with higher values reflecting more severe cerebral infarcts. The level 
of stroke severity as measured by the NIH stroke scale scoring system is further stratified as 
follows: 
 
0= no stroke  
 
1-4= minor stroke  
 
5-15= moderate stroke  
 
15-20= moderate/severe stroke  
 
21-42= severe stroke 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 63 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix I : NYHA Classification 
Class I 
Patient has cardiac disease but without resulting limitations of 
ordinary physical activity. Ordinary physical activity (eg, walking 
several blocks or climbing stairs) does not cause undue fatigue, 
palpitation, dyspnea, or anginal pain. Limiting symptoms may occur 
with marked exertion. 
 
Class II 
 
 Patient has cardiac disease resulting in slight limitation of ordinary 
physical activity. Patient is comfortable at rest. Ordinary physical 
activity such as walking more than 2 blocks or climbing more than 1 
flight of stairs results in limiting symptoms (eg, fatigue, palpitation, 
dyspnea, or anginal pain). 
 
Class III 
 
 Patient has cardiac disease resulting in marked limitation of physical 
activity. Patient is comfortable at rest. Less than ordinary physical 
activity (eg, walking 1 to 2 level blocks or climbing 1 flight of stairs) 
causes fatigue, palpitation, dyspnea, or anginal pain. 
 
Class IV 
Patient has dyspnea at rest that increases with any physical activity. 
Patient has cardiac disease resulting in inability to perform any 
physical activity without discomfort. Symptoms may be present even 
at rest. If any physical activity is undertaken, discomfort is increased. 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 64 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix J: ATS Guidelines for the Six Minute Walk Test 
This Six Minute Walk (6MWT) Test measures the distance that a patient can quickly walk on a 
flat, hard surface in a period of 6 minutes. It evaluates the global and integrated responses of all 
the systems involved during exercise, including the pulmonary and cardiovascular systems, 
systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. 
It does not provide specific information on the function of each of the different organs and 
systems involved in exercise or the mechanism of exercise limitation, as is possible with 
maximal cardiopulmonary exercise testing. 
 
SAFETY ISSUES 
1. Testing should be performed in a location where a rapid, appropriate response to an 
emergency is possible. The appropriate location of a crash cart should be determined by 
the physician supervising the facility.  
2. Supplies that must be available include oxygen, sublingual nitroglycerine, aspirin, and 
albuterol (metered dose inhaler or nebulizer). A telephone or other means should be in 
place to enable a call for help.  
3. The technician should be certified in cardiopulmonary resuscitation with a minimum of Basic 
Life Support by an American Health Association–approved cardiopulmonary resuscitation 
course. Advanced cardiac life support certification is desirable. Training, experience, and 
certification in related health care fields (registered nurse, registered respiratory therapist, 
certified pulmonary function technician, etc.) are also desirable. A certified individual should 
be readily available to respond if needed.  
4. Physicians are not required to be present during all tests. The physician ordering the test or 
a supervising laboratory physician may decide whether physician attendance at a specific 
test is required.  
5. If a patient is on chronic oxygen therapy, oxygen should be given at their standard rate or 
as directed by a physician or a protocol. 
  
Reasons for immediately stopping a 6MWT include the following: (1) chest pain, (2) intolerable 
dyspnea, (3) leg cramps, (4) staggering, (5) diaphoresis, and (6) pale or ashen appearance.  
 
Technicians must be trained to recognize these problems and the appropriate responses. If a 
test is stopped for any of these reasons, the patient should sit or lie supine as appropriate 
depending on the severity or the event and the technician's assessment of the severity of the 
event and the risk of syncope. The following should be obtained based on the judgment of the 
technician: blood pressure, pulse rate, oxygen saturation, and a physician evaluation. Oxygen 
should be administered as appropriate.  
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 65 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
CONTRAINDICATIONS  
Absolute contraindications for the 6MWT include the following: unstable angina during the 
previous month and myocardial infarction during the previous month. Relative contraindications 
include a resting heart rate of more than 120, a systolic blood pressure of more than 180 mm 
Hg, and a diastolic blood pressure of more than 100 mm Hg.  
 
Patients with any of these findings should be referred to the physician ordering or supervising 
the test for individual clinical assessment and a decision about the conduct of the test. The 
results from a resting electrocardiogram done during the previous 6 months should also be 
reviewed before testing. Stable exertional angina is not an absolute contraindication for a 
6MWT, but patients with these symptoms should perform the test after using their antiangina 
medication, and rescue nitrate medication should be readily available. A deviation from the 
Clinical Investigation Plan will need to be collected if the subject is unable to complete this test. 
 
LOCATION 
The 6MWT should be performed indoors, along a long, flat, straight, enclosed corridor with a 
hard surface that is seldom traveled. If the weather is comfortable, the test may be performed 
outdoors. The walking course must be 30 m in length. A 100-ft hallway is, therefore, required. 
The length of the corridor should be marked every 3 m. The turnaround points should be marked 
with a cone (such as an orange traffic cone). A starting line, which marks the beginning and end 
of each 60-m lap, should be marked on the floor using brightly colored tape.  
 
PROCEDURE 
 
REQUIRED EQUIPMENT 
 
Countdown timer (or stopwatch) 
 
Mechanical lap counter 
 
Two small cones to mark the turnaround points 
 
A chair that can be easily moved along the walking course 
 
Worksheets on a clipboard 
 
A source of oxygen 
 
Sphygmomanometer 
 
Telephone 
 
Automated electronic defibrillator 
 
PATIENT PREPARATION  
 
Comfortable clothing should be worn. 
 
Appropriate shoes for walking should be worn. 
 
Patients should use their usual walking aids during the test (cane, walker, etc.). 
 
The patient's usual medical regimen should be continued. 
 
A light meal is acceptable before early morning or early afternoon tests. 
 
Patients should not have exercised vigorously within 2 hours of beginning the test. 
 
This test should be performed about the same time of day for each interval to minimize 
intraday variability. 
 
A "warm-up" period before the test should not be performed. 
 
The patient should sit at rest in a chair, located near the starting position, for at least 10 
minutes before the test starts. During this time, check for contraindications, measure pulse 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 66 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
and blood pressure, and make sure that clothing and shoes are appropriate. Complete the 
first portion of the worksheet. 
 
Baseline Measurements 
1. Have the patient stand and rate their baseline dyspnea and overall fatigue using the Borg 
scale. 
2. Set the lap counter to zero and the timer to 6 minutes. Assemble all necessary equipment 
(lap counter, timer, clipboard, Borg Scale, worksheet) and move to the starting point. 
 
Instruct the patient as follows:  
“The object of this test is to walk as far as possible for 6 minutes. You 
will walk back and forth in this hallway. Six minutes is a long time to 
walk, so you will be exerting yourself. You will probably get out of 
breath or become exhausted. You are permitted to slow down, to stop, 
and to rest as necessary. You may lean against the wall while resting, 
but resume walking as soon as you are able.  
 
You will be walking back and forth around the cones. You should pivot 
briskly around the cones and continue back the other way without 
hesitation. Now I'm going to show you. Please watch the way I turn 
without hesitation." 
 
Demonstrate by walking one lap yourself. Walk and pivot around a cone briskly.  
 
"Are you ready to do that? I am going to use this counter to keep track 
of the number of laps you complete. I will click it each time you turn 
around at this starting line. Remember that the object is to walk AS 
FAR AS POSSIBLE for 6 minutes, but don't run or jog.  
 
Start now, or whenever you are ready." 
 
Position the patient at the starting line. You should also stand near the starting line during the 
test. Do not walk with the patient. As soon as the patient starts to walk, start the timer. 
 
Do not talk to anyone during the walk. Use an even tone of voice when using the standard 
phrases of encouragement. Watch the patient. Do not get distracted and lose count of the laps. 
Each time the participant returns to the starting line, click the lap counter once (or mark the lap 
on the worksheet). Let the participant see you do it. Exaggerate the click using body language, 
like using a stopwatch at a race. 
 
After the first minute, tell the patient the following (in even tones): 
"You are doing well. You have 5 minutes to go."  
 
When the timer shows 4 minutes remaining, tell the patient the following: 
"Keep up the good work. You have 4 minutes to go." 
 
When the timer shows 3 minutes remaining, tell the patient the following: 
"You are doing well. You are halfway done." 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 67 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
When the timer shows 2 minutes remaining, tell the patient the following: 
"Keep up the good work. You have only 2 minutes left." 
 
When the timer shows only 1 minute remaining, tell the patient: 
"You are doing well. You have only 1 minute to go." 
 
Do not use other words of encouragement (or body language to speed up). 
 
If the patient stops walking during the test and needs a rest, say this: 
"You can lean against the wall if you would like; then continue walking 
whenever you feel able." 
 
Do not stop the timer. If the patient stops before the 6 minutes are up and refuses to continue (or 
you decide that they should not continue), wheel the chair over for the patient to sit on, 
discontinue the walk, and note on the worksheet the distance, the time stopped, and the reason 
for stopping prematurely. 
 
When the timer is 15 seconds from completion, say this:  
"In a moment I'm going to tell you to stop. When I do, just stop right 
where you are and I will come to you." 
 
When the timer rings (or buzzes), say this: "Stop!" 
 
Walk over to the patient. Consider taking the chair if they look exhausted. Mark the spot where 
they stopped. 
 
Post-test 
Record the postwalk Borg dyspnea and fatigue levels and ask this: 
"What, if anything, kept you from walking farther?" 
 
1. Record the number of laps from the counter (or tick marks on the worksheet).  
2. Record the additional distance covered (the number of meters in the final partial lap) using 
the markers on the wall as distance guides. Calculate the total distance walked, rounding to 
the nearest meter, and record it on the worksheet.  
Congratulate the patient on good effort and offer a drink of water. 
 
 
 
 
 
 
 
 
 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 68 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix K : Sample Informed Consent 
The consent template will be kept under a separate cover and is available upon request. 
 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 69 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix L : Case Report Forms 
The case report forms will be kept under a separate cover and are available upon request. 
 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 70 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Appendix M. German Handling of Serious Adverse Events 
 
The scope of this section is to implement the reporting obligation in accordance with §3, section 
5 of the German MPSV (Medical Products Safety Ordinance), taking into consideration that 
notification must be done immediately in accordance § 5, section 2 of the MPSV.  
 
1.  
Definition of SAE according to §2, Section 5 MPSV:  
Serious Adverse Event: any untoward event occurring within a clinical investigation 
requiring authorization, which directly or indirectly led to, or which might have led or 
could lead to death or a serious deterioration in the health of the patient, a user or 
other person, without taking into account whether the event was caused by the 
medical device.  
2.  
Notification of SAEs:  
 
 
As soon as the investigator becomes aware of an SAE during the course of a 
study, the sponsor (SJM) must be informed immediately, and in no case later than 
72 hours after becoming aware.  
 
The sponsor (SJM) also has the obligation to inform the BfArM of all SAEs 
according to following table.  
Condition for reporting to 
BfArM 
Country of 
occurence
Timeline for 
reporting to 
BfArM 
Form 
a causal relationship 
between the SAE and the 
investigational medical 
device, a comparator 
device, diagnostic or 
therapeutic procedures 
performed as part of the 
clinical trial or other 
conditions of the trial 
conduct cannot be 
excluded 
Germany 
immediately 
Single report 
German SAE Report Form 
Please send to MPSAE@bfarm.de 
all other 
countries 
where the 
clinical trial 
is 
performed 
immediately 
Summary table 
MEDDEV 2.7/3 SAE report table 
 
All SAEs shall be documented using 
the same Excel file, in a cumulative 
manner, using the same Excel sheet. 
 
Please send to MPSAE@bfarm.de 
a causal relationship 
between the SAE and the 
investigational medical 
device, a comparator 
device, diagnostic or 
therapeutic procedures 
performed as part of the 
clinical trial or other 
conditions of the trial 
conduct can be excluded 
All 
quarterly 
Summary table 
MEDDEV 2.7/3 SAE report table 
 
Please complete the MEDDEV Excel 
sheet as outlined above. 
 
Please send to MPSAE@bfarm.de 
quarterly 
All SAEs 
All 
Quarterly 
SAE summary evaluation 
 
Evaluation 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 71 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
Annex 3.1 complication rate 
 
Please send to MPSAE@bfarm.de 
 
Please observe our notes on 
completing the SAE summary 
evaluation 
 
o The German SAE Report Form is available on the BfArM homepage: 
http://www.bfarm.de/SharedDocs/Formulare/EN/MedicalDevices/report_form_clinica
l_trials_SAE.html 
 
 
Please note that the SAE gets a unique ID which consists of 4 Parts: 
- 
The Study Code (CRD_XXX for the SJM Study Code of this study) 
- 
The Center ID (ORACLEID = CenterName) 
- 
The Patient No 
- 
The Date of SAE in the format (Year(2-digits)MonthDay) 
Example: CRD_878_EU0284_01_160203 for an event which occurred on 3 
February for Patient 1 in center EU0284 within the Study CRD_878. 
 
The German Quarterly Report Template is available on the BfArM Homepage: 
http://www.bfarm.de/SharedDocs/Formulare/EN/MedicalDevices/sae_template.html 
Table Complication Rates 
http://www.bfarm.de/SharedDocs/Formulare/EN/MedicalDevices/sae_complication_r
ates.html 
Instructions for completing the quarterly assessment form for serious adverse events 
http://www.bfarm.de/SharedDocs/Formulare/EN/MedicalDevices/sae_template_note
s.html 
 
 
The investigator will be instructed on this obligation during the initiation visit. 
 
Information about the obligation must be documented in the "training log".  
 
Written confirmation that this working procedure has been passed on to the trial 
center is sent to the investigator and then attached to the study file.  
 
 
3. Responsibility of the investigators: 
 
1. The investigator has to notify the SAE to the sponsor without undue delay. 
2. SAEs should be reported either by  
1. EDC (primary reporting tool) 
i. E-Mail: AdverseEvent@sjm.com 
 
The investigator or main investigator is obliged to respect the deadline for 
notification of SAEs. 
 
A person within the study center will be designated to collect the necessary 
information. 
 
A person within the study center will be designated to pass on this information to 
the sponsor. A list of people (including a representative) will be prepared for this 
purpose. 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 72 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
 
4. Responsibilities of the monitor (Abbott): 
 
 
The monitor will be instructed of his/her responsibilities with regard to SAEs. 
 
If the monitor discovers an SAE during the course of the study that was not notified 
or not notified within the notification deadline, the sponsor's action plan will take 
effect. The BfArM is then notified of the SAE without undue delay and the 
investigator is informed of it straight away.  
 
5. Responsibilities of the sponsor 
 
 
The sponsor (Abbott) shall notify any SAEs without undue delay (at the latest 
however within 72 hours) after awareness. 
 
A person will be designated to verify SAEs that occur during the clinical study. 
 
A list of SJM people who shall be informed about SAEs is to be drawn up. 
 
A person will be designated who is responsible for the assessment of any SAEs. 
 
A person or team will be designated who is responsible for initiating corrective 
actions if necessary. 
 
 
6. Responsibilities of the sponsor in Germany 
 
 
All people within Abbott who are involved in this clinical study be will instructed of the 
notification deadlines and are obliged to respect them. 
 
SAEs/PERs (Product Event Reports) are coordinated by the German project 
manager (CPL) or by Jörg Scheiner (Manager Clinical Safety/Compliance, 
Germany). 
 
SAE notifications to the BfArM and the Ethics Committee are to be made by the CPL 
or by Clinical Safety. 
 
The Field Clinical Manager or the study office will take care of SAE/PER notifications 
should both of the above people be unable to do so. 
 
Vigilanz-Responsible for this study: Jörg Scheiner (Manager Clinical Study Logistics, 
Abbott, Germany) 
Phone: +49-6196-7711-241, E-Mail: AdverseEvents-Germany@sjm.com 
 
7. Notification of SAEs in other countries 
 
SAEs are also reported to following countries 
 
Denmark 
 
Italy 
 
Netherlands 
 
Sweden 
 
Ukraine 
 
United Kingdom 
 

 
SJM-CIP-10144 Ver.D 
Study Name: Portico Alternative Access 
Clinical Investigational Plan  
 
Template: 86357  Rev. C                                                                                                                      Page 73 of 73 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed 
or used without the express written consent of Abbott 
 
                                                          
i Kappetein AP, Head SJ, Genereux P, et al.  Updated Standardized Endpoint Definitions for Transcatheter Aortic 
Valve Implantation: The Valve Academic Research Consortium-2 Consensus Document. J Am Coll Cardiol 
2012;60:1438-1454. 
ii Kappetein AP, Head SJ, Genereux P, et al.  Updated Standardized Endpoint Definitions for Transcatheter Aortic 
Valve Implantation: The Valve Academic Research Consortium-2 Consensus Document. J Am Coll Cardiol 
2012;60:1438-1454. 
iii Kappetein AP, Head SJ, Genereux P, et al.  Updated Standardized Endpoint Definitions for Transcatheter Aortic 
Valve Implantation: The Valve Academic Research Consortium-2 Consensus Document. J Am Coll Cardiol 
2012;60:1438-1454.