Practical Evaluation of Fractional Flow Reserve (FFR) and Its Associated Alternate Indices During Routine Clinical Procedures
Conditions: Coronary Artery Disease, Acute Coronary Syndrome
Sponsor: Abbott Medical Devices

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 1 of 35 
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or used without the express written consent of St. Jude Medical 
Reference:  
SJM-CIP-10136 
PRESSUREwire; ClinicalTrials.gov identifier: NCT02935088 
PRESSUREwire 
“Practical Evaluation of Fractional Flow Reserve (FFR) and its Associated Alternate 
Indices During Routine Clinical Procedures” 
Clinical Investigation Plan (CIP) 
 
Sponsor                                  St. Jude Medical, Inc. 
5050 Nathan Lane North 
Plymouth, MN 55442 
United States 
Tel: +1 651-756-5400 
 
Clinical Coordinating               Professor Colin Berry 
Investigator                             Chair of Cardiology and Imaging 
University of Glasgow 
BHF Glasgow Cardiovascular Research Centre 
126 University Place 
Glasgow, G12 8TA, United Kingdom  
Tel:+44 (0) 141-330-1671 
       
Date                                         1 August 2016 
 
 
 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 2 of 35 
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or used without the express written consent of St. Jude Medical 
PRINICPAL INVESTIGATOR SIGNATURE PAGE 
Practical Evaluation of Fractional Flow Reserve (FFR) and its Associated Alternate Indices During 
Routine Clinical Procedures 
 
PRESSUREwire Clinical Investigational Plan 
 
Version B 
Reference #: SJM-CIP-10136 
 
I have read and agree to adhere to the clinical investigational plan and all regulatory requirements 
applicable in conducting this clinical study. 
 
 
Principal Investigator 
 
Printed name: ____________________________________ 
Signature:__________________________________________ 
Date:  _____________________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 3 of 35 
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or used without the express written consent of St. Jude Medical 
Clinical Coordinating Investigator/ Regional Investigator 
SIGNATURE PAGE 
 
 
Practical Evaluation of Fractional Flow Reserve (FFR) and its Associated Alternate Indices During 
Routine Clinical Procedures 
 
PRESSUREwire Clinical Investigational Plan 
Version B 
Reference #: SJM-CIP-10136 
 
I have read and agree to adhere to the clinical investigational plan and all regulatory requirements 
applicable in conducting this clinical study.   
 
 
Clinical Coordinating Investigator/ Regional Investigator   
 
Printed name: ____________________________________ 
 
Signature: _________________________________________ 
 
Date:  _____________________________________________ 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 4 of 35 
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or used without the express written consent of St. Jude Medical 
 
Table of Contents                                                                                            Page 
1.1 
STUDY ASSESSMENT SCHEDULE ............................................................................................. 8 
1.2 
STUDY CONTACTS ....................................................................................................................... 8 
3.1 
PURPOSE .................................................................................................................................... 10 
3.2 
STUDY DESIGN AND SCOPE ..................................................................................................... 10 
3.2.1 
Number of subjects required 
10 
3.3 
OBJECTIVES................................................................................................................................ 10 
3.4 
INCLUSION AND EXCLUSION CRITERIA .................................................................................. 11 
3.4.1 
Inclusion Criteria 
11 
3.4.2 
Exclusion Criteria 
11 
3.5 
SUBJECT POPULATION ............................................................................................................. 11 
3.5.1 
Subject Screening 
11 
3.5.2 
Point of Enrollment 
11 
3.6 
INFORMED CONSENT PROCESS ............................................................................................. 12 
3.6.1 
General process 
12 
4.1 
ANTICIPATED CLINICAL BENEFITS .......................................................................................... 12 
4.2 
ANTICIPATED ADVERSE EVENTS AND ADVERSE DEVICE EFFECTS ................................. 12 
4.3 
RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL STUDY ................................ 12 
5.1 
DEVICE DESCRIPTION ............................................................................................................... 13 
6.1 
STUDY FLOW CHART ................................................................................................................. 13 
6.2 
PROCEDURES............................................................................................................................. 13 
6.3 
BASELINE VISIT .......................................................................................................................... 14 
6.4 
PROCEDURE ............................................................................................................................... 15 
6.5 
SCHEDULED FOLLOW-UPS ....................................................................................................... 15 
6.6 
INTERIM VISITS ........................................................................................................................... 15 
6.7 
SUBJECT STUDY COMPLETION ............................................................................................... 15 
6.8 
CRITERIA AND PROCEDURES FOR SUBJECT WITHDRAWAL OR DISCONTINUATION ..... 16 
7.1 
STATEMENTS OF COMPLIANCE ............................................................................................... 16 
7.2 
ADHERENCE TO THE CLINICAL INVESTIGATION PLAN ........................................................ 16 
7.3 
REPEATED AND SERIOUS NON-COMPLIANCE ...................................................................... 18 
8.1 
DEFINITIONS ............................................................................................................................... 18 
8.1.1 
Adverse Event (AE) 
18 
8.1.2 
Serious Adverse Event (SAE) 
18 
8.1.3 
Adverse Device Effect (ADE) 
18 
8.1.4 
Serious Adverse Device Effect (SADE) 
19 
8.2 
PROCEDURE FOR ASSESSING, RECORDING, AND REPORTING ADVERSE EVENTS, DEVICE 
DEFICIENCIES/COMPLAINTS, ADVERSE DEVICE EFFECTS, SERIOUS ADVERSE EVENTS, AND 
SERIOUS ADVERSE DEVICE EFFECTS: .................................................................................. 19 
8.3 
SUBJECT DEATH ........................................................................................................................ 20 
8.3.1 
Procedure for recording and reporting subject death 
20 
8.4 
DEVICE DEFICIENCY (DD)/COMPLAINT ................................................................................... 20 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 5 of 35 
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or used without the express written consent of St. Jude Medical 
9.1 
DATA MANAGEMENT PLAN ....................................................................................................... 21 
9.2 
DOCUMENT AND DATA CONTROL ........................................................................................... 21 
9.2.1 
Traceability of documents and data 
21 
9.2.2 
Recording data 
21 
12.1.1 
Sample Size 
22 
12.1.2 
Analysis Populations 
22 
12.1.3 
Statistical Method and Analysis 
22 
12.1.4 
Additional Analysis 
24 
12.1.5 
Reporting 
24 
15.1 STEERING COMMITTEE ............................................................................................................. 25 
16.1 PREMATURE TERMINATION OF THE WHOLE CLINICAL STUDY OR OF THE CLINICAL STUDY IN 
ONE OR MORE INVESTIGATIONAL SITES ............................................................................... 25 
16.2 RESUMING THE STUDY AFTER TEMPORARY SUSPENSION ............................................... 27 
16.3 STUDY CONCLUSION ................................................................................................................. 27 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 6 of 35 
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or used without the express written consent of St. Jude Medical 
 SYNOPSIS  
 
Title: 
Practical Evaluation of Fractional Flow Reserve (FFR) and its Associated 
Alternate Indices During Routine Clinical Procedures 
 
Acronym: 
PRESSUREwire 
 
Purpose: 
The purpose of this study is to understand routine use of FFR and alternate 
indices in clinical practice. This study will determine the use and clinical 
outcome of FFR-guided PCI in patients presenting with either stable 
coronary artery disease, or in patients presenting with Acute Coronary 
Syndrome (ACS) on culprit and non-culprit lesions as well as during index 
and secondary procedures.  
 
The study will also collect data on the routine use of coronary physiologic 
measurements such as adenosine-induced hyperemia FFR, FFR by 
contrast-induced hyperemia, Pd/Pa, and other alternate indices 
measurements. 
 
Objectives: 
All objectives will be evaluated for all subjects enrolled, ACS subjects and 
stable coronary artery disease subjects separately. 
 
1. Characterize the frequency of change in treatment plan when FFR is 
used compared to the initial decision based on angiography alone. 
 
2. Characterize the 12 month clinical outcomes (MACE) in subjects in 
whom the use of FFR did not lead to a change in treatment decision vs 
subjects in whom the use of FFR led to a change in treatment decision.  
 
3. Characterize the 12 month clinical outcomes (MACE) by FFR values 
and resting indices respectively. 
 
4. Compare resting indices with FFR values.  
 
5. Characterize the 12 month clinical outcomes (MACE) by other 
PressureWire-derived indices (coronary flow reserve (CFR), index of 
microcirculatory resistance (IMR), contrast FFR, resistance reserve ratio 
(RRR)). 
 
6. Compare other PressureWire-derived indices (CFR, IMR, contrast FFR, 
RRR) with FFR values. 
Design: 
This study is a prospective, multicenter, multinational, multicontinental open 
label observational study. 
 
The total duration of the study is expected to be 4 years, which includes 3 
years for enrollment with 12 months of follow-up. 
 
The clinical study will be conducted in approximately 200 centers globally. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
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or used without the express written consent of St. Jude Medical 
Sample Size and 
Planned Analysis 
This is an observational study. No formal power analysis and sample size 
calculations were performed.  Approximately 2000 subjects will be enrolled 
in this study. No single center is allowed to enroll more than 10% of the 
population. A target of 500 ACS patients will be included in the study. This 
sample size allows reasonable enrollment to detect a signal from events at 
12 months. 
Devices used: 
Any commercially available St. Jude Medical PressureWire™ may be used 
for this study. 
 
Study Population 
A patient becomes a subject (enrolled) once he/she has been fully informed 
about the study, has agreed to participate, signed & dated the consent, has 
been determined to meet all inclusion criteria and none of the exclusion 
criteria, and at least one physiologic coronary pressure measurement with 
an SJM PressureWire™ has been recorded.  
 
Since this study is a routine clinical practice observational study, patients 
are allowed to be consented after the procedure, but must be consented 
prior to any data submission. 
 
Specific study population characteristics are defined as follows: 
 
Patients where FFR has been performed or is planned to be performed for 
further evaluation of PCI procedures, as per physician clinical practice. 
 
Inclusion/Exclusio
n Criteria  
Inclusion/Exclusion is defined as follows: 
 
Inclusion Criteria: 
1. Patient is presenting with STEMI, NSTEMI, unstable angina, or 
stable coronary artery disease  
2. Patient is planned to have FFR performed or underwent a cardiac 
catheterization where FFR was performed for further PCI 
consideration 
3. Patient signs and dates written informed consent 
4. Patient is eighteen years of age or older at the time of consent 
 
Exclusion Criteria: 
1. Patient has extremely tortuous or calcified coronary arteries 
2. Patient with a patent coronary artery bypass graft to the target 
vessel 
 
Data Collection 
Data collection will be comprised of baseline demographics and medical 
history, coronary anatomy, procedure, discharge, and 1 year follow up 
phone call for MACE events. 
 
Publication of 
Data 
Data is planned to be analyzed and released at enrollment intervals of 500, 
1000, 1500, and 2000. 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 8 of 35 
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or used without the express written consent of St. Jude Medical 
 
1.1 
STUDY ASSESSMENT SCHEDULE 
 
Baseline 
Procedure 
Discharge 
One Year* 
(± 30 days) 
Interim Visit 
(Subject with potential 
MACE event) 
Medical History, 
Demographics 
and Current 
Clinical Status 
X 
 
 
 
 
Angiography and 
PCI procedure 
Details 
 
X 
 
 
 
Coronary 
Physiologic 
Measurements 
 
X** 
 
 
 
MACE 
Assessment 
 
X 
X 
X 
X 
Medication 
Assessment 
X 
 
X 
X 
X 
*Visit may be conducted via a phone call 
**May occur at index or secondary procedures for patients presenting with ACS 
 
1.2 
STUDY CONTACTS 
Maren Wagner 
Sr. Clinical Manager 
St. Jude Medical 
5050 Nathan Lane North 
Plymouth, MN  55442 
Tel: +1.651.756.5585 
Mobile: +1.612.910.3204 
mwagner2@sjm.com 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 9 of 35 
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or used without the express written consent of St. Jude Medical 
 BACKGROUND AND JUSTIFICATION FOR CLINICAL STUDY 
Fractional flow reserve (FFR) has been demonstrated to be an effective index for determining 
percutaneous coronary intervention (PCI) approach. FFR is defined as the ratio of maximum blood flow 
in a stenotic coronary artery to maximum blood flow if the same artery were completely normal. An FFR 
of 0.80 or less, as measured with the use of a coronary pressure wire during invasive coronary 
angiography, indicates the potential of a specific stenosis to induce myocardial ischemia with an 
accuracy of greater than 90%. Therefore, FFR is recommended for the guidance of coronary 
revascularization.1 
 
Randomized clinical trials have demonstrated that in patients with unstable angina and acute 
myocardial infarction (MI), there are substantial benefits of PCI, including prevention of myocardial 
infarction and reduced mortality rate.2,3 In patients with stable coronary artery disease (CAD), PCI has 
been shown to improve anginal symptoms and quality of life. The FAME (Fractional Flow Reserve 
Versus Angiography for Multivessel Evaluation) 2 year data showed that in patients with mutivessel 
CAD undergoing PCI with drug-eluting stents, routine measurement of FFR as compared with PCI 
guided by angiography alone resulted in a significant reduction of the rate of mortality and myocardial 
infarction.4 
 
Currently, there has been limited research conducted on the use of FFR in ACS patients. According to 
Depta, “a recent study determined that vasodilatory capacity of the microcirculation was similar 
between patients with non-ST elevation myocardial infarction and stable angina. Thus, FFR 
measurement during ACS or AMI may be reliable”.5  While clinical evidence in this setting remains 
sparse and non-conclusive, FFR use in ACS patients is expanding and more research needs to be 
conducted.6 However, recent trials suggest increasing evidence that supports the role of FFR-guided 
strategy in ACS patients.7  
 
For example, Leite notes that, “One of the most important studies about the use of FFR in ACS was 
from Ntalanis et al. 8 who studied 75 acute STEMI patients and 26 NSTEMI patients (<72 h post onset) 
and measured FFR in the non-culprit stenosis immediately following PCI of the culprit vessel and then 
repeated the FFR at 35 + 4 days post initial procedure.  The FFR value remained unchanged between 
the acute and follow-up phases in patients with STEMI (0.78 + 0.10 vs. 0.77 + 0.20, p = NS).  In only 2 
patients, the FFR value was higher than 0.80 at the acute phase and lower than 0.75 at follow-up.  The 
authors stated the data supports that FFR measurements are safe and reliable for evaluating the 
severity of non-culprit stenosis in the acute phase of ACS, even during primary PCI.”9 
 
Alternative indices utilizing pressure wires have also become important to understanding the 
physiologic significance of coronary artery disease.10 Adenosine-induced hyperemia FFR, Pd/Pa, FFR 
by contrast-induced hyperemia, coronary flow reserve (CFR), the index of microcirculatory resistance 
(IMR), as well as other novel indices e.g. resistance reserve ratio (RRR), potentially aid in treatment 
decisions of patients with CAD. 
 
To date, there has not been a large registry study analyzing the use of FFR and alternate indices in 
everyday practice. The PRESSUREwire study looks to expand on the current evidence by collecting 
additional data on the use and clinical outcome of FFR-guided PCI in patients presenting with stable 
coronary artery disease, patients presenting with ACS, as well as those who received routine coronary 
physiologic measurements of adenosine-induced hyperemia FFR, Pd/Pa, FFR by contrast induced 
hyperemia, and other alternate indices measurements. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 10 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
The PRESSUREwire study is an observational study intending to collect additional data on the use and 
clinical outcome of FFR-guided PCI patients presenting with Acute Coronary Syndrome (ACS) on 
culprit and non-culprit lesions at index and secondary procedures. 
 
 STUDY DESIGN 
3.1 
PURPOSE 
The purpose of this clinical study is to understand routine use of FFR and alternate indices in clinical 
practice in the treatment of subjects presenting with either an Acute Coronary Syndrome (ACS) or 
stable coronary artery disease. 
 
3.2 
STUDY DESIGN AND SCOPE 
This study is a prospective, multicenter, multinational, multicontinental open label observational study. 
 
This study will determine the use and clinical outcome of FFR-guided PCI on patients presenting with 
either stable coronary artery disease or ACS both for culprit and non-culprit lesions as well as during 
index and secondary procedures.   
 
The FFR threshold for decision making is anticipated to be 0.80 in line with contemporary guidelines. 
Since the study is observational, there are no mandated thresholds for any of the physiologic 
measurements. 
 
The study will also collect data on the routine use of coronary physiologic measurements such as 
adenosine-induced hyperemia FFR, FFR by contrast-induced hyperemia, Pd/Pa, and other alternate 
indices measurements. 
 
The total duration of the study is expected to be 4 years, which includes 3 years for enrollment with 12 
months of subject follow-up. 
 
The clinical study will be conducted in approximately 200 centers in North America, EMEA, and Asia 
Pacific. 
3.2.1 
Number of subjects required  
Up to 2000 subjects will be enrolled in this study. No single center is allowed to enroll more than 10% of 
the population. A target of 500 ACS patients will be included in the study.  
 
3.3 
OBJECTIVES 
All objectives will be evaluated for all subjects enrolled, ACS subjects and stable coronary artery 
disease subjects separately. 
 
1. Characterize the frequency of change in treatment plan when FFR is used compared to the initial 
decision based on angiography alone. 
 
2. Characterize the 12 month clinical outcomes (MACE) in subjects in whom the use of FFR did not 
lead to a change in treatment decision vs subjects in whom the use of FFR led to a change in 
treatment decision.  

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 11 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
 
3. Characterize the 12 month clinical outcomes (MACE) by FFR values and resting indices 
respectively. 
 
4. Compare resting indices with FFR values.  
 
5. Characterize the 12 month clinical outcomes (MACE) by other PressureWire-derived indices 
(coronary flow reserve (CFR), index of microcirculatory resistance (IMR), contrast FFR, resistance 
reserve ratio (RRR)). 
 
6. Compare other PressureWire-derived indices (CFR, IMR, contrast FFR, RRR) with FFR values. 
 
Refer to section 12.0 for statistical analysis. 
3.4 
INCLUSION AND EXCLUSION CRITERIA 
A subject, who meets all of the inclusion criteria, and none of the exclusion criteria, is eligible to 
participate in this study.  
 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study or lost to 
follow-up) will be accounted for and documented, assigning an identification code. 
 
3.4.1 
Inclusion Criteria 
1. Patient is presenting with STEMI, NSTEMI, unstable angina, or stable coronary artery disease  
2. Patient is planned to have FFR performed or underwent a cardiac catheterization where FFR was 
performed for further PCI consideration 
3. Patient signs and dates written informed consent 
4. Patient is eighteen years of age or older at the time of consent 
 
3.4.2 
Exclusion Criteria 
1. Patient has extremely tortuous or calcified coronary arteries 
2. Patient with a patent coronary artery bypass graft to the target vessel 
 
3.5 
SUBJECT POPULATION 
3.5.1 
Subject Screening 
Potential subjects presenting at the investigational site will be screened by a member of the 
investigational team previously trained on the CIP and delegated to do so. 
 
Subjects who do not meet the inclusion/exclusion criteria will not be eligible to participate in this study. 
 
Subjects meeting the inclusion/exclusion criteria will be fully informed about the study and asked to 
participate in the study. In case the subject agrees, a duly signed and dated Patient Informed Consent 
will be obtained. 
3.5.2 
Point of Enrollment 
A patient becomes a subject (enrolled) once he/she has been fully informed about the study, has 
agreed to participate, signed & dated the consent, has been determined to meet all inclusion criteria 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 12 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
and none of the exclusion criteria, and at least one physiologic coronary pressure measurement with an 
SJM PressureWire™ has been recorded. Refer to section 3.6 for the Informed Consent Process.  
 
3.6 
INFORMED CONSENT PROCESS 
3.6.1 
General process 
Prior to enrolling in the clinical study, all subjects will be consented, as required by applicable 
regulations and the center’s IRB/EC.  Informed consent must be obtained from each subject prior to 
any data collection. The consent form must be signed and dated by the subject and by the person 
obtaining the consent. 
 
Medical circumstances may occur where potential subjects require emergent medical intervention, and 
thus measurements of their FFR and other metrics (i.e. patients experiencing ACS). As a result, and 
since this is a routine clinical practice observational study, subjects are allowed to be consented after 
the procedure, but must be consented prior to any data submission. 
 
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 is 
relevant to the subject’s decision to participate in the clinical study.  
 
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 IRB/EC.  Failure to obtain 
informed consent from a subject prior to study enrollment should be reported to St. Jude Medical within 
5 working days and to the reviewing center’s IRB/EC consistent with the center’s IRB/EC reporting 
requirements.  
 
  RISKS AND BENEFITS OF THE CLINICAL STUDY 
4.1 
ANTICIPATED CLINICAL BENEFITS 
This is a prospective observational study of market-released products. The potential benefit of 
participating in this study with standard of care treatment is that data from this study may enhance 
future treatment for PCI patients. 
There are no direct benefits from participating in the study. 
 
4.2 
ANTICIPATED ADVERSE EVENTS AND ADVERSE DEVICE EFFECTS 
This is a prospective observational study of market-released products. Anticipated adverse events or 
adverse devices effects are the same whether the subject receives the assessment as part of the study 
or outside of the study. 
 
4.3 
RISKS ASSOCIATED WITH PARTICIPATION IN THE CLINICAL STUDY 
The risks of taking part in the PRESSUREwire study and undergoing FFR assessment or alternative 
indices are the same whether the subject receives the assessment as part of the study or outside of the 
study. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 13 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
Refer to the Instructions for Use (IFU) in the package labeling for potential risks associated with an 
SJM PressureWire™. 
 
A risk of study participation is that confidentiality cannot be guaranteed. Investigational site personnel, 
SJM, and SJM representatives will take measures to de-identify study subject personal health 
information in an effort to maintain subject anonymity. 
 DEVICE UNDER INVESTIGATION  
5.1 
DEVICE DESCRIPTION 
Only market-released products will be used in this study. No comparisons are being made between 
devices. 
 
St. Jude Medical pressure wires are guidewires with integrated sensor elements at the tip to enable 
measurements of physiological parameters. These guidewires are uniquely paired with specific 
transmitters and are available in different lengths. 
 
These guidewires are designed to fit inside a percutaneous catheter for the purpose of directing the 
catheter through a vessel. The signal output from the sensor is transmitted to associated equipment for 
analysis, used for calculations, and presentation display of physiological parameters functions or 
indices based on pressure or temperature, e.g. Fractional Flow Reserve (FFR). 
 
Only a commercially available St. Jude Medical PressureWire™ may be utilized for this study. 
 PROCEDURES 
6.1 
STUDY FLOW CHART 
Figure 1: Procedural Flow Chart 
 
 
 
*ADO FFR – IV or IC adenosine, or another suitable agent (Appendix B), for FFR 
 
6.2 
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 clinical study will not commence until St. Jude Medical receives written approval from the IRB/EC 
and relevant regulatory authorities and all required documents have been collected from the site(s). 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 14 of 35 
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or used without the express written consent of St. Jude Medical 
 
Table 1: List of all study specific activities/procedures 
 
Baseline 
Procedure 
Discharge 
One Year* 
(± 30 days) 
Interim Visit 
(Subject with potential MACE event) 
Medical History, 
Demographics and 
Current Clinical 
Status 
X 
 
 
 
 
Angiography and 
PCI procedure 
Details 
 
X 
 
 
 
Coronary 
Physiologic 
Measurements 
 
X** 
 
 
 
MACE 
Assessment 
 
X 
X 
X 
X 
Medication 
Assessment 
X 
 
X 
X 
X 
*Visit may be conducted via a phone call 
**May occur at index or secondary procedures for patients presenting with ACS 
 
A lesion >50% severity by angiographic assessment is considered to be clinically significant. 
 
6.3 
BASELINE VISIT  
The following enrollment activities are performed after the subject has been screened and may occur 
before or after the study procedure/visit. 
 
The principal or delegated study personnel determine subject eligibility for the study 
 
Record enrollment information (name of the study, date of consent and inclusion/exclusion 
information) in the hospital records and complete and submit the Enrollment form in a timely 
manner (recommended within 5 days)  
 
Notification of a consented subject to the sponsor will take place when the sponsor receives the 
baseline form  
 
If a subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject cannot 
participate in the study and cannot be enrolled.  
 
In case the subject was already consented to participate in the study and an FFR was performed, and it 
was determined that they do not meet inclusion/exclusion criteria, the following actions will be taken: 
 
Document enrollment information (name of the study, date of consent and inclusion/exclusion) in 
the hospital records; complete the Baseline and Withdrawal Forms. The form(s) must be 
authorized / approved by the principal or delegated investigator. 
o Inform the subject about the withdrawal.  
o The EC/IRB and Competent Authority should be notified appropriately, as per local 
regulations, about any deviations with regards to obtaining the informed consent. 
 
The following information will be collected at the baseline visit: 
o Medical history 
o Demographics- include subject’s Year of Birth and Gender 
o Current clinical status 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 15 of 35 
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or used without the express written consent of St. Jude Medical 
 
6.4 
PROCEDURE 
Refer to the Instructions For Use (IFU) for procedural steps. 
 
Fractional Flow Reserve (FFR) is an index determining the functional severity of narrowing(s) in the 
coronary arteries. FFR specifically identifies which coronary narrowing(s) are responsible for 
significantly obstructing the flow of blood to the heart muscle.  FFR is used in conjunction with cardiac 
catheterization by placing the pressure wire distal to the coronary lesion and measuring pressure inside 
the artery.  The pressure wire is then retracted until pressure is measured in the entire coronary artery. 
 
The following data points will be collected during the procedure for all evaluated lesions (index or 
secondary procedures): 
• 
Measurements of Pd/Pa 
• 
Measurements of FFR with Adenosine induced hyperemia (IC or IV)  
• 
MACE assessment (required) 
• 
Prospective treatment decisions; initial treatment plan documentation shall be prior to FFR.   
 
Other indices may be collected, according to the investigator’s clinical practice and availability of 
appropriate devices (index or secondary procedures), as follows; 
• 
IMR measurements  
• 
CFR measurements  
• 
Measurements of FFR with Contrast induced hyperemia 
• 
Measurements of any additional novel resting indices (RI) 
6.5 
SCHEDULED FOLLOW-UPS 
Follow-up visits will occur at Discharge and 1-year. 
 
The following assessments will be completed at the Discharge visit: 
• 
MACE assessment 
 
The following assessment will be completed at the 1-Year visit (±30 days): 
• 
MACE assessment 
 
Note: the 1-Year visit may be conducted via a phone call to the subject. 
 
6.6 
INTERIM VISITS 
An Interim Visit is defined as any visit that occurs as a result of a potential MACE event outside the 
windows of the standard assessment schedule.  
 
The following assessments will be completed at an Interim visit: 
• 
MACE assessment 
 
6.7 
SUBJECT STUDY COMPLETION 
When the subject’s participation in the clinical study has been completed after one year follow up, no 
further patient data will be collected. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
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or used without the express written consent of St. Jude Medical 
6.8 
CRITERIA AND PROCEDURES FOR SUBJECT WITHDRAWAL OR DISCONTINUATION 
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: 
 
Subject refuses to continue participating in the study 
 
Subject does not meet the inclusion/exclusion criteria  
 
Subject is deceased (cause must be documented) 
 
Subject’s participation is terminated by the PI or investigator, although the subject consented, 
since participation is no longer medically appropriate 
 
Subject is ‘lost to follow-up’: Subject does not adhere to the scheduled follow up visits but has not 
explicitly requested to be withdrawn from the clinical study. (This does not apply to missed visits). 
Site personnel should at all times make all reasonable efforts to locate and communicate with the 
subject in order to achieve subject compliance to the scheduled follow up visits: 
1.  A subject will be considered ‘Lost to Follow Up’ after a minimum of 2 phone calls of a 
physician or delegate at the investigational site to the subject or contact. These 2 phone calls 
need to be documented in the subject’s hospital records. 
2.  If these attempts are unsuccessful, a letter should be sent to the subject’s last known 
address or general practitioner (GP) and a copy of this letter should be maintained in the 
subject’s hospital records. 
 
If a subject withdraws from the clinical study, the site will record the subject’s reasons for withdrawal, 
on a Withdrawal CRF. 
 
 COMPLIANCE TO CIP 
7.1 
STATEMENTS OF COMPLIANCE 
The investigator will not start enrolling subjects or requesting informed consent from any subject prior 
to obtaining IRB/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 IRB/EC or Competent Authority, those 
requirements will be followed, if appropriate. If any action is taken by an IRB/EC, and regulatory 
requirements with respect to the study, that information will be forwarded to St. Jude Medical. 
 
7.2 
ADHERENCE TO THE CLINICAL INVESTIGATION PLAN 
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 (CIP), 
IRB/EC requirements or the Investigator Agreement. The investigator is not allowed to deviate from the 
CIP, except as specified under emergency circumstances.   

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 17 of 35 
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or used without the express written consent of St. Jude Medical 
 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety and 
well-being of subjects, since the non-compliance exposes subjects to unreasonable risks. For example, 
failure to adhere to the inclusion/exclusion criteria: these criteria are specifically defined by the Sponsor 
to exclude subjects for whom the device is not beneficial and the use involves unreasonable risks. This 
may be considered failure to protect the rights, safety and well-being of the enrolled subject. Similarly, 
failure to perform safety assessments intended to detect adverse events may be considered failure to 
protect the rights, safety and well-being of the enrolled subject. Investigators should seek minimization 
of such risks by adhering to the CIP. 
 
Simultaneously, in the event that adhering to the CIP might expose the subject to unreasonable risks, 
the investigator is also required to protect the rights, safety and well-being of the subject by intentionally 
deviating from the requirements of the CIP, so that subjects are not exposed to unreasonable risks.  
 
It is the responsibility of the investigator to provide adequate medical care to a subject enrolled in a 
study. 
 
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 (CRF). The site 
will submit the CRF to St. Jude Medical. 
 
Regulations require investigators obtain approval from St. Jude Medical and the IRB/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 IRB/EC. Such deviations shall be documented and reported to the sponsor and 
the IRB/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 
St. Jude Medical or designee prior to initiating any changes.   
 
All deviations must be reported to appropriate regulatory authorities in specified timelines (if 
appropriate). 
 
Investigator will notify St. Jude Medical and the reviewing IRB/EC within 5 working days of: 
• Any deviation to protect the life or physical well-being of a subject in an emergency  
• Any failure to obtain informed consent 
 
Investigators or the designee must notify St. Jude Medical, Inc. as soon as possible and complete the 
Deviation CRF. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 18 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
The investigator is required to adhere to local regulatory requirements for reporting deviations to 
IRB/EC. 
 
7.3 
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 
 
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. 
 ADVERSE EVENT, ADVERSE DEVICE EFFECT, DEVICE DEFICIENCY 
8.1 
DEFINITIONS 
8.1.1 
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. 
 
8.1.2 
Serious Adverse Event (SAE) 
An adverse event that led to: 
 
Death 
 
A serious deterioration in the health of the subject, that either resulted in: 
o A life-threatening illness or injury OR 
o A permanent impairment to a body structure or a body function OR 
o An in-patient or prolonged hospitalization OR 
o A medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body OR 
o A malignant tumor 
 
Fetal distress, fetal death or a congenital abnormality or birth defect 
Note:  A planned hospitalization for a pre-existing condition, or a procedure required by the CIP is 
not considered a serious adverse event. 
 
8.1.3 
Adverse Device Effect (ADE) 
An adverse event related to the use of an investigational medical device. 
 
This definition includes adverse events resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the investigational medical 
device. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 19 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
This definition includes any event resulting from the use error or from intentional misuse of the 
investigational medical device. 
 
For this study, ADEs include events related to any St. Jude Medical pressure sensor guidewires.   
 
8.1.4 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse 
event or that might have led to any of these consequences if suitable action had not been taken or 
intervention had not been made or if circumstances had been less opportune.  
 
8.2 
PROCEDURE FOR ASSESSING, RECORDING, AND REPORTING ADVERSE EVENTS, 
DEVICE DEFICIENCIES/COMPLAINTS, ADVERSE DEVICE EFFECTS, SERIOUS ADVERSE 
EVENTS, AND SERIOUS ADVERSE DEVICE EFFECTS:  
Safety surveillance within this study and the safety reporting both performed by the investigator, starts 
as soon as the subject is enrolled in this study. The safety surveillance and the safety reporting will 
continue until the last investigational visit has been performed, the subject is deceased, the 
subject/investigator concludes his participation into the study or the subject/investigator withdraws the 
subject from the study, except as otherwise specified in the CIP. 
 
Events considered reportable to sponsor are:  
 
• 
Major adverse cardiac events (MACE) defined as all cause death, documented non-fatal 
myocardial infarction, and unplanned hospitalization leading to urgent revascularization 
o Myocardial infarction is defined according to the Universal Classification of Myocardial 
Infarction11 (Appendix B) 
o Unplanned hospitalization leading to urgent revascularization is defined as unexpected 
hospitalization due to persisting or increasing complaints of chest pain (with or without 
ST-T changes) AND a revascularization is performed within the same hospitalization. 
• 
Adverse device effects 
 
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. These will be reported to the Sponsor on dedicated case report forms or through 
the EDC system. The Investigator will record all adverse events and device deficiencies on the 
appropriate case report forms 
 
Additional information may be requested, when required, by the Sponsor in order to support the 
reporting of AEs to regulatory authorities. 
 
The Sponsor will ensure that all events and device deficiencies are reported to the relevant authorities 
as per regulations.  
 
Records relating to the subject’s subsequent medical course must be maintained and submitted (as 
applicable) to the Sponsor until the event has subsided or, in case of permanent impairment, until the 
event stabilizes and the overall clinical outcome has been ascertained. Adverse events will be 
monitored until they are adequately resolved.  The status of the subject’s condition should be 
documented at each visit.   
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 20 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
The investigator must notify the IRB/EC, if appropriate, in accordance with national and local laws and 
regulations, of the AEs reported to the Sponsor. 
 
8.3 
SUBJECT DEATH 
8.3.1 
Procedure for recording and reporting subject death 
All subject deaths are to be documented on the Death case report form and reported to the Sponsor 
within 72 hours after becoming aware of the event. 
 
8.4 
DEVICE DEFICIENCY (DD)/COMPLAINT 
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, 
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/complaint does not involve an adverse event, the investigator must notify St. 
Jude Medical as soon as possible after becoming aware of the device deficiency/complaint by emailing 
the information to CAT_VASC_Complaints@sjm.com or calling +1 651.756.5400.  This information will 
not be collected on a CRF for the study.  
 
St. Jude Medical will manage all device deficiencies related to the identity, quality, durability, reliability, 
safety or performance of the study device and the reporting to the appropriate regulatory bodies. 
 DATA MANAGEMENT 
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. 
 
St. Jude Medical respects and protects personally identifiable information collected or maintained for 
this clinical trial. 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 trial.  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, IRB/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. 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 21 of 35 
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or used without the express written consent of St. Jude Medical 
9.1 
DATA MANAGEMENT PLAN 
A detailed Data Management Plan (DMP) will be established to ensure consistency of the data. This 
document will include procedures used for data review, database cleaning, and issuing and resolving 
data queries. 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 St. Jude 
Medical.  
 
Only authorized site personnel will be permitted to enter the CRF data through the electronic data 
capture (EDC) system deployed by St. Jude Medical. An electronic audit trail will be used to track any 
subsequent changes to the entered data. 
 
9.2 
DOCUMENT AND DATA CONTROL 
9.2.1 
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.  
 
9.2.2 
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. 
 
The CRFs will be validated (eCRF) by the authorized site personnel.  
 
 MONITORING  
Centralized monitoring will occur through routine review of real-time data to identify missing data, 
inconsistent data, data outliers, and potential protocol deviations that may be indicative of systemic 
and/or significant errors in data collection and reporting at a site as documented in the Data 
Management Plan. Additionally, copies of event source documents will be reviewed remotely to ensure 
data quality/validity.  
 
On-site monitoring may occur at the discretion of the sponsor.  
 REGULATORY INSPECTIONS 
The investigator and/or delegate should contact St. Jude Medical 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). 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 22 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
 
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 IRB/EC have not been submitted or are incomplete, inaccurate, false or misleading. 
 
 
STATISTICAL CONSIDERATIONS 
12.1.1 Sample Size 
This is an observational study. No formal power analysis and sample size calculations were performed.  
Approximately 2000 subjects will be enrolled in this study. To ensure enrollment balance across study 
centers, no single center will enroll more than 10% of the maximum sample size (200 subjects). A 
target of 500 ACS subjects will be included in the study. 
 
12.1.2 Analysis Populations 
Data from up to 2000 subjects enrolled in this study will be collected and reported. The statistical 
analyses described in this section will be performed for all enrolled subjects, ACS subjects and stable 
coronary artery disease subjects separately.  
 
12.1.3 Statistical Method and Analysis 
This section describes the statistical method and analysis per subject basis unless otherwise specified. 
If more than one lesion is measured for a subject, the data analysis may be performed and presented 
on a per lesion basis, as appropriate. 
 
The following criteria will be used to define the variables per subject level for subject with multiple 
lesions:  
• 
Treatment decision is defined as “changed” if there is at least one decision change based 
on FFR for multiple lesions; if none of the decisions has been changed for the multiple 
lesions, the treatment decision is defined as “unchanged”.   
• 
For all the continuous variables of FFR, resting indices, CFR, contrast FFR, and RRR, we 
will use the lowest value in all lesions as the value for that variable in each subject. For the 
continuous variable of IMR, we will use the highest value in all lesions as the value for IMR 
in each subject.   
 
The following cutoff values will be used to categorize a continuous variable into a binary variable:  
• 
FFR group is defined as “low FFR” if it is equal to or below 0.8 (the cutoff value of 0.8 is 
selected in line with contemporary guidelines and previous findings11). However, since this is 
an observational study, there are no mandated cutoff values for this. Therefore, we will also 
use cutoff value of 0.7512 in the analysis. 
• 
Resting indices group is defined as “low resting indices” if it is equal to or below 0.86 (the 
cutoff value of 0.86 is selected based on previous findings that a baseline  Pd/Pa ≤ 0.86 is 
associated with a positive predictive value of 100% for FFR measurement13). We will also 
use the cutoff value of 0.9214 in the analysis. 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 23 of 35 
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or used without the express written consent of St. Jude Medical 
• 
CFR is defined as “low CRF” if it is below 2.0 (the cutoff value of 2.0 is selected based on 
previous findings15,16). 
• 
IMR is defined as “high IMR” if it is equal to or above 25 (the cutoff value of 25 is selected 
based on previous findings17). 
• 
Contrast FFR is defined as “low Contrast FFR” if it is equal to or below 0.83 (the cutoff value 
of 0.83 is selected based on previous findings18). 
• 
RRR is defined as “low RRR” if it is smaller than 2.0 (the cutoff value of 2.0 is selected 
based on previous foundings19). 
 
The following statistical analysis will be performed for each of the study objectives: 
 
1. Characterize the frequency of change in treatment plan when FFR is used compared to the initial 
decision based on angiography alone  
Frequency and percentage of change in treatment decisions when FFR is used compared to the initial 
decision based on angiography alone will be presented both per subject level and per lesion level. 
 
2. Characterize the 12-month clinical outcomes (MACE) in subjects in whom the use of FFR did not 
lead to a change in treatment decision vs. subjects in whom the use of FFR led to a change in 
treatment decision.  
 
12-month MACE event rate will be summarized using frequency and percentage. Fisher Exact test will 
be performed to evaluate the association between 12-month MACE event and prospective treatment 
decisions, i.e. change or no change, based on FFR measurements. A repeated measures logistic 
regression with generalized estimating equations (GEE) per lesion level will be performed if needed. 
 
3. Characterize the 12 month clinical outcomes (MACE) by FFR values and resting indices 
respectively.  
 
Fisher Exact test will be performed to evaluate the association between 12-month MACE event and 
binary FFR and binary resting indices variables respectively using the following FFR and resting indices 
groups: 
1) Low FFR group (FFR ≤ 0.8) and high FFR group (FFR > 0.8). 
2) Low FFR group (FFR < 0.75) and high FFR group (FFR ≥ 0.75). 
3) Low resting indices group (Pd/Pa ≤ 0.86) and high resting indices group (Pd/Pa > 0.86). 
4) Low resting indices group (Pd/Pa ≤ 0.92) and high resting indices group (Pd/Pa > 0.92). 
 
A repeated measures logistic regression with generalized estimating equations (GEE) per lesion level 
will be performed if needed. 
 
A logistic regression will be performed to evaluate the association between 12-month MACE event and 
continuous FFR and continuous resting indices respectively. A repeated measures logistic regression 
with generalized estimating equations (GEE) per lesion will be performed if needed. 
 
4. Compare resting indices with FFR values. 
 
Kappa coefficient will be used for binary variables, and correlation will be used for continuous variables 
to examine agreement between FFR values and resting indices. 
 
5. Characterize the 12 month clinical outcomes (MACE) by other PressureWire-derived indices (CFR, 
IMR, contrast FFR, RRR).  

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 24 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
 
Fisher Exact test will be used for binary variables, and logistic regression will be used for continuous 
variables to evaluate the association between 12-month MACE event and other PressureWire-derived 
indices (CFR, IMR, contrast FFR, RRR) respectively. 
 
6. Compare other PressureWire-derived indices (CFR, IMR, contrast FFR, RRR) with FFR values 
 
Kappa coefficient will be used for binary variables, and correlation test will be used for continuous 
variables to examine agreement between FFR values and other PressureWire-derived indices (CFR, 
IMR, contrast FFR, RRR) respectively. 
 
12.1.4 Additional Analysis 
Descriptive statistics will be used to summarize each component of MACE rate at 12 months, and FFR, 
Pd/Pa and other PressureWire-derived indices (CFR, IMR, contrast FFR, RRR) measurements during 
index procedure and secondary procedures. 
 
12.1.5 Reporting 
The following data will be summarized and reported after 500, 1000, 1500 subjects complete 12-month 
follow-up visit: 
• 
Investigator sites and enrollment status 
• 
Demographic and baseline characteristics 
• 
Serious Adverse events  
• 
12-month MACE rate 
 
When all enrolled subjects complete 12-month follow-up visit, all statistical analyses described in this 
section will be conducted and a final clinical report will be completed. 
 
 
DOCUMENT RETENTION 
The Principal Investigator  will maintain all clinical study documents from prior to, 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 or 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.  

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 25 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
 
AMENDMENTS TO CLINICAL INVESTIGATIONAL PLAN 
Study related documents such as the CIP, CRFs, Informed Consent form and other subject information, 
and other clinical study documents will be amended as needed throughout the clinical study, and a 
justification statement will be included with each amended section of a document. Proposed 
amendments to the CIP will be agreed upon between the Sponsor and the coordinating investigator (if 
applicable).  
 
The amendments to the CIP and the subject’s Informed Consent will be notified to, or approved by, the 
IRB/EC and regulatory authorities, if required. The version number and date of amendments will be 
documented. 
 
The amendment will identify the changes made, the reason for the changes and if it is mandatory or 
optional to implement the amendment. 
 
Any amendment affecting the subject requires that the subject be informed of the changes and a new 
consent be signed and dated by the investigator at the subject’s next follow up per IRB/EC 
requirements. 
 
Changes to, or formal clarifications of, the CIP will be documented in writing and provided to the 
investigators. This information will be incorporated when an amendment occurs. 
 
 
STUDY COMMITTEES  
15.1 STEERING COMMITTEE 
The Steering Committee (SC) may be used to advise the sponsor during a clinical study, such as in the 
development of the study CIP, during the conduct of the study, during data analysis and/or 
presentation/publication of the study results.  Membership may include National PIs or site investigators 
for the study under review. 
 
 
INVESTIGATION SUSPENSION OR TERMINATION 
16.1 PREMATURE TERMINATION OF THE WHOLE CLINICAL STUDY OR OF THE CLINICAL 
STUDY IN ONE OR MORE INVESTIGATIONAL SITES 
The Sponsor reserves the right to stop the study at any stage, with appropriate written notice to the 
investigator.  
 
Possible reasons for early termination of the study by the Sponsor, either at local, national or 
international level, may include, but are not limited to: 
 
The device /  therapy fails to perform as intended 
 
Occurrence of USADE which cannot be prevented in future cases 
 
Sponsor’s decision 
 
Recommendation from Steering Committee and Sponsor 
 
Request from Regulatory bodies 
 
Request of Ethics Committee(s)  
 
Concern for subject safety and welfare 
 
Failure to secure subject Informed Consent prior to any investigational activity 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 26 of 35 
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or used without the express written consent of St. Jude Medical 
 
Failure to report unanticipated adverse device effects within 72 hours to St. Jude Medical and the 
EC 
 
Repeated non-compliance with this CIP or the Clinical Trial Agreement 
 
Inability to successfully implement this CIP 
 
Violation of the Declaration of Helsinki 2008 (refer to Appendix C) 
 
Violation of applicable national or local laws and regulations 
 
Falsification of data, or any other breach of ethics or scientific principles 
 
The study will be terminated according to applicable regulations. 
 
The investigator may also discontinue participation in the clinical study with appropriate written notice to 
the Sponsor. 
 
Should either of these events occur, the investigator will return all documents to the sponsor; provide a 
written statement as to why the premature termination has taken place and notify the IRB/EC and/or 
the Competent Authority (if applicable). Follow-up for all enrolled subjects will be as per CIP 
requirements. 
 
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in a clinical study at the investigational sites for which they are responsible.   
 
If suspicion of an unacceptable risk to subjects arises during the clinical study or when so instructed by 
the IRB/EC or regulatory authority, St. Jude Medical may suspend the clinical study as appropriate 
while the risk is assessed.  St. Jude Medical will terminate the clinical study if an unacceptable risk is 
confirmed.   
 
St. Jude Medical will consider terminating or suspending the participation of a particular investigational 
site or investigator in the clinical study if monitoring or auditing identifies serious or repeated deviations 
on the part of an investigator.   
 
If suspension or premature termination occurs, the terminating party will justify its decision in writing 
and promptly inform the other parties with whom they are in direct communication.  The Principal 
Investigator and St. Jude Medical will keep each other informed of any communication received from 
IRB/EC or regulatory authority.   
 
If for any reason St. Jude Medical suspends or prematurely terminates the study at an individual 
investigational site, St. Jude Medical will inform the responsible regulatory authority, as appropriate, 
and ensure that the IRB/EC are notified, either by the Principal Investigator or by St. Jude Medical.  If 
the suspension or premature termination was in the interest of safety, St. Jude Medical will inform all 
other Principal Investigators.   
 
If suspension or premature termination occurs, St. Jude Medical 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 study, and the Principal Investigator or authorized designee will promptly inform 
the enrolled subjects at his/her investigational site, if appropriate.   
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 27 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
16.2 RESUMING THE STUDY AFTER TEMPORARY SUSPENSION 
When St. Jude Medical concludes an analysis of the reasons for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, St. Jude Medical will inform 
the Principal Investigators, IRB/EC, or regulatory authority, where appropriate, of the rationale, 
providing them with the relevant data supporting this decision.   
 
Concurrence will be obtained before the clinical study resumes from the IRB/EC or regulatory authority 
where appropriate.   
 
If subjects have been informed of the suspension, the Principal Investigator or authorized designee will 
inform them of the reasons for resumption. 
 
16.3 STUDY CONCLUSION 
The study will be concluded when: 
 
All sites are closed AND 
 
The Final report generated by St. Jude Medical has been provided to sites or St. Jude Medical 
has provided formal documentation of study closure 
 
 
PUBLICATION POLICY 
The results of the clinical study will be submitted for publication. Details of future publication and 
presentations will be outlined in a separate publication policy. 
 
 
BIBLIOGRAPHY  
1. Van Nunen L, Zimmerman F, Tonino P, et. al. Fractional flow reserve versus angiography for 
guidance of PCI in patients with multivessel coronary artery disease (FAME): 5- year follow-up 
of a randomised controlled trial. Lancet. 2015;386:1853-60. 
2. Mehta S, Cannon C, Fox K, Routine vs Selective Invasive Strategies in Patients With Acute 
Coronary Syndromes. A Collaborative Meta-analysis of Randomized Trials. JAMA. 
2005;293:2908-2917. 
3. Keeley E, Boura J, Grines C. Primary angioplasty versus intravenous thrombolytic therapy for 
acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003 Jan 
4;361(9351):13-20. 
4. Pijls N, Fearon W, Tonino P, et. al. Fractional Flow Reserve Versus Angiography for Guiding 
Percutaneous Coronary Intervention in Patients with Multivessel Coronary Artery Disease. 
JACC., 2010; 56(3). doi:10.1016/j.jacc.2010.04.012. 
5. Depta J, Patel J, et. al.  Outcomes of coronary stenosis deferred revascularization for borderline 
versus nonborderline fractional flow reserve values.  The American Journal of Cardiology.  
2014;1788-93  
6. Niccoli G, Falcioni E, Cosentino N, et. al. Physiological Assessment of Nonculprit Stenoses 
During Acute Coronary Syndromes. The American Journal of Cardiology. 2014;114:496. 
7. Hennigan B, Layland J, Fearon WF, et.al. Fractional flow reserve and the index of 
microvascular resistance in patients with acute coronary syndromes. Eurointervention. 2014;10 
Suppl. T:T55-63. 
8. Ntalianis A, Sels J-W, Davidavicius G, et. al. Fractional flow reserve for the assessment of 
nonculprit coronary artery stenosis in patients with acute myocardial infarction. JACC 
Cardiovasc Interv. 2010;3:1274-81. 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 28 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
9. Leite L, Moura Ferreira J, Silva Marques J, et. al. Fractional flow reserve of non-culprit vessel 
post-myocardial infarction: is it reliable?. BMC Cardiovascular Disorders. 2015;15:127. 
10. Pijls N, Bruyne B, Smith L, et. al. Coronary Thermodilution to Assess Flow Reserve; Validation 
in Humans. Circulation. 2002;105:2482-2486. doi:10.1161/01.CIR.000017199.09457.3D. 
11. Thygesen K, Alpert JS, Jaffe AS, et. al. Third Universal Definition of Myocardial Infarction. 
Circulation. 2012;126:2020-2035. 
12. De Bruyne, B., Fearon, WF., Jüni, P. Fractional flow reserve-guided PCI. The New England 
journal of medicine. 2014; 371:1208-1217. 
13. Zimmermann FM, Ferrara A, Johnson NP, et. al. Deferral vs. performance of percutaneous 
coronary intervention of functionally non-significant coronary stenosis: 15-year follow-up of the 
DEFER trial. European Heart Journal. 2015; 36:3182-3188. 
14.  Ammar K. Resting Non-hyperemic Indices and the Goal of 100% Accuracy. J Invasive Cardiol. 
2016; 28:265-270. 
15. Jeremias A, Maehara A, Généreux P, et. al. Multicenter core laboratory comparison of the 
instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE 
study. Journal of the American College of Cardiology. 2014; 63:1253-61. 
16. Lee BK, Lim HS, Fearon WF, et. al. Invasive evaluation of patients with angina in the absence 
of obstructive coronary artery disease. Circulation. 2015; 131:1054-60. 
17. Lee JM, Jung JH, Hwang D, et. al. Coronary flow reserve and microcirculatory resistance in 
patients with intermediate coronary stenosis. Journal of the American College of Cardiology. 
2016; 67:1158-69. 
18. Johnson NP, Jeremias A, Zimmermann FM, et. al. Continuum of vasodilator stress from rest to 
contrast medium to adenosine hyperemia for fractional flow reserve assessment. JACC: 
Cardiovascular Interventions. 2016; 9:757-67. 
19. Layland J, Carrick D, McEntegart M, et. al. Vasodilatory capacity of the coronary 
microcirculation is preserved in selected patients with non-ST-segment-elevation myocardial 
infarction. Circ Cardiovasc Interv.  2013;6:231-236. 
 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 29 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
APPENDIX A: ABBREVIATIONS 
 
Abbreviation 
Term 
ADE 
AE 
CABG 
CIP 
CFR 
CRF 
eCRF 
FFR 
IB 
IC 
IMR 
IFU 
IRB 
NSTEMI 
PCI 
PI 
RDC 
RPI 
RRR 
SADE 
SAE 
SC  
SJM 
STEMI 
USADE 
Adverse Device Effect 
Adverse Event 
Coronary artery bypass graft 
Clinical Investigational Plan 
Coronary flow reserve 
Case Report Form 
Electronic Case Report Form 
Fractional Flow Reserve 
Investigational Brochure 
Informed Consent 
Index of Microcirculatory Resistance 
Instructions For Use 
Institutional Review Board 
Non-ST-elevation myocardial infarction 
Percutaneous coronary intervention 
Principal Investigator 
Remote Data Capture 
Report of Prior Investigation 
Resistance reserve ratio 
Severe Adverse Device Effect 
Severe Adverse Event 
Steering Committee 
St. Jude Medical 
ST-elevation myocardial infarction 
Unanticipated Severe Adverse Device Effect 
 
 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 30 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
APPENDIX B: STUDY GUIDELINES 
 
Universal Classification of Myocardial Infarction 
Type 1: Spontaneous myocardial infarction 
Spontaneous myocardial infarction related to atherosclerotic plaque rupture, ulceration, Assuring, erosion, 
or dissection with resulting intraluminal thrombus in one or more of the coronary arteries leading to 
decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis. The patient may 
have underlying severe CAD but on occasion non-obstructive or no CAD. 
Type 2: Myocardial infarction secondary to an ischemic imbalance 
In instances of myocardial injury with necrosis where a condition other than CAD contributes to an 
imbalance between myocardial oxygen supply and/or demand, e.g. coronary endothelial dysfunction, 
coronary artery spasm, coronary embolism, tachy-/brady-arrhythmias, anemia, respiratory failure, 
hypotension, and hypertension with or without LVH. 
Type 3: Myocardial infarction resulting in death when biomarker values are unavailable 
Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG 
changes or new LBBB, but death occurring before blood samples could be obtained, before cardiac 
biomarker could rise, or in rare cases cardiac biomarkers were not collected. 
Type 4a: Myocardial infarction related to percutaneous coronary intervention (PCI) 
Myocardial infarction associated with PCI is arbitrarily defined by elevation of cTn values >5 x 99th 
percentile URL in patients with normal baseline values (<99thpercentile URL) or a rise of cTn values 
>20% if the baseline values are elevated and are stable or falling. In addition, either (i) symptoms 
suggestive of myocardial ischemia, or (ii) new ischemic ECG changes or new LBBB, or (iii) angiographic 
loss of patency of a major coronary artery or a side branch or persistent slow- or no-flow or embolization, 
or (iv) imaging demonstration of new loss of viable myocardium or new regional wall motion abnormality 
are required. 
Type 4b: Myocardial infarction related to stent thrombosis 
Myocardial infarction associated with stent thrombosis is detected by coronary angiography or autopsy in 
the setting of myocardial ischemia and with a rise and/or fall of cardiac biomarkers values with at least 
one value above the 99th percentile URL. 
Type 5: Myocardial infarction related to coronary artery bypass grafting (CABG) 
Myocardial infarction associated with CABG is arbitrarily defined by elevation of cardiac biomarker values 
>10 x 99th percentile URL in patients with normal baseline cTn values (<99th percentile URL). In addition, 
either (i) new pathological Q waves or new LBBB, or (ii) angiographic documented new graft or new 
native coronary artery occlusion, or (iii) imaging evidence of new loss of viable myocardium or new 
regional wall motion abnormality. 
 
 
Hyperemic agent recommended doses 
Agent 
Recommended dose (IV) 
Recommended dose (IC) 
Adenosine 
140 µg/kg/min 
100 µg for right coronary artery 
200 µg for left coronary artery 
Adenosine 5’-triphosphate (ATP) 
150 ug/kg/min 
N/A 
Nicorandil 
N/A 
2 mg 
Regadenoson 
0.4 mg 
N/A 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 31 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
 
APPENDIX C: CIP REVISION HISTORY 
 
Revision History 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Not 
Applicable 
A 
15APR2016 
First release of CIP 
NA 
1 
B 
22JUL2016 
Clarifications and minor 
enhancements 
NA 
 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 32 of 35 
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or used without the express written consent of St. Jude Medical 
Appendix D: DECLARATION OF HELSINKI 
The most current version of the document will be followed. 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 33 of 35 
This confidential document is the property of St. Jude Medical and shall not be reproduced, distributed, disclosed 
or used without the express written consent of St. Jude Medical 
Appendix E: LIST OF CLINICAL INVESTIGATION SITES AND IRB/EC 
A list of Clinical Investigational sites and IRB/EC will be kept under a separate cover and is available 
upon request.  
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 34 of 35 
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or used without the express written consent of St. Jude Medical 
Appendix F: SAMPLE INFORMED CONSENT 
The study specific informed consent template will be provided under separate cover 
 
 

Study Document No: SJM-CIP-10136      Ver. B 
Study Name: PRESSUREwire 
Clinical Investigational Plan 
 
                                                                                                                       Page 35 of 35 
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or used without the express written consent of St. Jude Medical 
Appendix G: CASE REPORT FORMS 
Final Case Report Forms will be provided under separate cover.