The Drift-Reduction for Improved Fractional Flow Reserve (FFR) Using Fiberoptic Technology (DRIFT) Study
Phase: NA
Conditions: Left Anterior Descending Coronary Artery Stenosis
Sponsor: Columbia University

The Drift-Reduction for Improved FFR using Fiberoptic Technology 
(DRIFT) study 
Version 4.1 
November 20, 2018 
NCT03848650

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Version 4.1 dated 11/20/2018 
Table of Contents 
1.
Protocol Summary .............................................................................................................................. 5
2.
Additional Summary Information .................................................................................................... 7
3.
Background ......................................................................................................................................... 8
3.1. 
Fractional Flow Reserve  ............................................................................................................. 8 
3.2. 
Rationale for Study Endpoints and Cut-Off Values .................................................................... 8 
     3.2.1.     Angiographically intermediate LAD lesions ......................................................................... 8 
     3.2.2.     Correlation of Pre-PCI OCT MLA with Pre-PCI FFR .......................................................... 9 
     3.2.3.     Resting Gradient .................................................................................................................... 9 
     3.2.4.     Pullback Measurements ......................................................................................................... 9 
     3.2.5.     Post-PCI OCT Assessment .................................................................................................... 9 
     3.2.6.     Post-PCI FFR ......................................................................................................................... 9 
     3.2.7.     Discrepancy between FFR and resting physiology indices ................................................... 9 
3.3. 
Study Device: OpSens Medical OptoWire Deux Pressure Wire ............................................... 10 
4.
Study Objectives ............................................................................................................................... 11
4.1. 
Study Objectives  ....................................................................................................................... 11 
4.2. 
Primary Endpoint  ...................................................................................................................... 11 
4.3. 
Secondary Endpoints  ................................................................................................................ 11 
5.
Study Design and Population ........................................................................................................... 12
5.1. 
Determination of Study Eligibility  ............................................................................................ 12 
5.2. 
Inclusion Criteria  ...................................................................................................................... 12 
5.3. 
Exclusion Criteria  ..................................................................................................................... 12 
5.4. 
Subject Screening and Informed Consent  ................................................................................. 13 
5.5. 
Subject Enrollment  ................................................................................................................... 13 
5.6. 
Subject Withdrawal  .................................................................................................................. 13 
6.
Procedures and Assessments ........................................................................................................... 14
6.1. 
Schedule of Events  ................................................................................................................... 14 
6.2. 
Baseline Procedures  .................................................................................................................. 14 
6.3. 
Procedural Protocol ................................................................................................................... 14 
6.4. 
Procedural Information  ............................................................................................................. 14 
6.5. 
Shipment of Materials to the Core Lab  ..................................................................................... 15 
7.
Study Risk Determination................................................................................................................ 15
8.
Statistical Considerations................................................................................................................. 15
      8.1        Statistical Analysis and Analysis Sets  ...................................................................................... 15 
      8.2        Analysis of Baseline Demographics and Procedural Characteristics  ........................................ 15 
9.
Definitions  ........................................................................................................................................ 15
10.
Reporting Responsibilities ............................................................................................................... 16
11.
Data Submission Requirements  ................................................................................................. 16
11.1. 
Required Data  ........................................................................................................................... 16 
11.2. 
Data Collection  ......................................................................................................................... 16 
11.3. 
Data Collection and Tracking  ................................................................................................... 17 
11.4. 
Time Windows for Expected Completion of Electronic Case Report Forms/Reports  .............. 17 
12.
Study Steering Committees  ........................................................................................................ 17
13.
Ethical and Regulatory Considerations  ..................................................................................... 17
13.1. 
Subject Confidentiality  ............................................................................................................. 17 

 
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13.2. 
Selection of Investigators  ......................................................................................................... 18 
13.3. 
Initiation of Study Sites  ............................................................................................................ 18 
13.4. 
Study Closeout Visit  ................................................................................................................. 18 
13.5. 
Maintaining Records  ................................................................................................................. 18 
13.6. 
Submitting Reports  ................................................................................................................... 18 
13.7. 
Site Record Retention Policy  .................................................................................................... 19 
14. 
Risks to the Subjects  ................................................................................................................... 19 
14.1. 
Human Subjects Involvement and Characteristics  .................................................................... 19 
14.2. 
Sources of Materials  ................................................................................................................. 19 
14.3. 
Potential Risks  .......................................................................................................................... 19 
14.4. 
Confidentiality of Subject Medical Information  ....................................................................... 19 
15. 
References  .................................................................................................................................... 21 
 
 
 
List of Tables 
Table 1: Schedule of Events ........................................................................................................................ 14 
Table 2: Investigator Reporting Responsibilities ........................................................................................ 16 
Table 3: Sponsor Reporting Responsibilities .............................................................................................. 16 
Table 4: Responsibilities and Guidance for Submitting Reports and Other Data ....................................... 17 
Table 5: List of Acronyms .......................................................................................................................... 20 
 
 
 
List of Figures 
Figure 1: Guidewire Construction ............................................................................................................... 10

 
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Version 4.1 dated 11/20/2018 
1. Protocol Summary  
Study Title 
The Drift-Reduction for Improved FFR using Fiberoptic Technology 
(DRIFT) study 
Device Description 
OpSens Medical OptoWire Duex Pressure Wire 
Study Design 
Prospective, observational, multi-center, single-arm, clinical registry 
Objectives 
The primary objective of this study is to assess the accuracy, efficacy 
and durability of the OpSens Medical OptoWire Deux Pressure Wire 
in the assessment of angiographically intermediate proximal left 
anterior descending (LAD) stenosis in clinical practice.  
Subject Population 
Subjects with stable angina, unstable angina, or non–ST segment 
elevation myocardial infarction (if the LAD lesion is the non-culprit 
lesion) who are referred to coronary angiography and have an 
angiographically intermediate proximal LAD stenosis with anatomy 
amenable to percutaneous intervention. Patients meeting enrollment 
criteria and had fractional flow reserve (FFR) with the OpSens FFR 
system and optical coherence tomography (OCT) of the LAD as part 
of their routine care using a standard of care technique will be 
eligible for enrollment in this study. 
Number of Subjects 
and Sites 
This study will enroll a total of 60 patients at Columbia University 
Medical Center and St. Francis Hospital. 
Primary Endpoint 
The primary endpoint is the rate of significant drift, defined as Pd/Pa 
<0.97 or >1.03 in the pre-percutaneous coronary intervention (PCI) 
FFR recording. 
Secondary Endpoint 
Secondary efficacy endpoints:  
1. The rate of pre-PCI positive FFR (≤0.80) in angiographically 
intermediate proximal LAD lesions. 
 
2. The rate of pre-PCI resting Pd/Pa (≤0.92) in angiographically 
intermediate proximal LAD lesions. 
 
3. The rate of significant drift defined as Pd/Pa <0.97 or >1.03 
with post-PCI FFR recording.  
 
4. Pre-PCI OCT correlation (minimum lumen area [MLA]<2.5 
mm2) with FFR (≤0.80).  
 
5. Pre-PCI OCT correlation with the pullback for distinguishing 
focal (step-up ≥0.03) versus diffuse disease defined by pre-
PCI resting Pd/Pa pullback.  
 
6. Post-PCI OCT correlation (edge dissection [lumen area 
within the dissection ≤4.5 mm2], stent underexpansion [≤4.5 

 
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mm2 in 3 mm vessel or ≤ distal reference lumen area], 
residual disease outside of stent [minimum lumen area <4.5 
mm2]) with the pullback for distinguishing focal (step-up 
≥0.03) versus diffuse disease defined by post-PCI resting 
Pd/Pa pullback.  
 
7. The rate of discrepancy between FFR and resting physiology 
indices and its correlation with an OCT derived MLA. 
 
Secondary economic endpoints: 
8. Total number of OptoWires used during the procedure.  
 
9. Frequency of use of alternative guidewire (workhorse wire) 
for the procedure.  
 
10. Total duration of the procedure. 
 
11. Duration of FFR procedure. 
Procedural Protocol 
Patients with an angiographically intermediate proximal LAD 
lesion, who meet the inclusion and exclusion criteria will be 
eligible for enrollment in this observational study post-procedure.  
Inclusion Criteria 
1. Male or female subjects, > 18 years of age.  
2. Patients with stable angina, unstable angina or non-ST 
segment elevation myocardial infarction (if the LAD lesion is 
the non-culprit lesion) and in whom an intermediate proximal 
LAD stenosis (30-80%) with TIMI flow 3 has been identified 
on angiography.  
NOTE: Patients with multi-vessel disease can be enrolled. 
3. Patients have had FFR and OCT of the LAD with the OpSens 
FFR system as part of their routine evaluation as standard of 
care procedure. 
4. Provides written, informed consent and HIPPA consent to use 
data in a clinical study. 
Exclusion Criteria 
General exclusion criteria:  
1. Patients presented with non-ST segment elevation myocardial 
infarction (NSTEMI) with the LAD involved as the culprit 
lesion  
2. ST-elevation myocardial infarction within the past 30 days. 
3. Hemodynamic instability requiring vasopressor or mechanical 
circulatory support. 
4. Prior heart transplant. 
5. Known left ventricular ejection fraction ≤40% 

 
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6. LAD supplying akinetic or severely hypokinetic territories if 
already known based on prior imaging. 
7. Patients is enrolled in another clinical study that may impact 
the results of this study. 
8. FFR not acquired per the instructions for use (IFU) for the 
OpSens wire. 
9. LAD Lesion not assessed with OCT. 
 
Angiographic exclusion criteria:  
1. TIMI grade 2 or lower at baseline angiography. 
2. Target lesion involves left main (>50% by visual estimation). 
3. Presence of a chronic total occlusion in any vessel. 
4. Presence of a side branch ≥2.75 mm with ≥70% stenosis in the 
LAD.  
5. Bifurcation lesion that resulted in the stent implantation of a 
side branch. 
Expected Start Date 
February 2018 
Enrollment  
The enrollment duration is expected to last 5 months. 
Follow-up 
There is no clinical follow-up. 
Regulatory Status 
OpSens Pressure Wire received 510(k) clearance from U.S. Food 
and Drug Administration in March 2016. 
 
 
 

 
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2. Additional Summary Information 
 
 
CO -PRINCIPAL INVESTIGATOR 
Manish A. Parikh, MD 
Columbia University Medical Center 
New York, NY 
USA 
 
CO-PRINCIPAL INVESTIGATOR 
Jeffrey W. Moses, MD 
Columbia University Medical Center 
New York, NY 
USA 
 
DATA COORDINATING CENTER 
Cardiovascular Research Foundation 
1700 Broadway, 9th Floor 
New York, NY 10019 
646-434-4500 
 
FFR, OCT AND ANGIOGRAPHIC CORE LABS 
Cardiovascular Research Foundation 
1700 Broadway, 9th Floor 
New York, NY 10019 
646-434-4500 
 
DEVICE MANUFACTURER 
OpSens Medical 
750, Boul. du Parc Technologique 
Québec, QC Canada G1P 4S3 
418.781.0333 
 
STUDY SPONSOR 
Manish Parikh, MD 
 
STUDY CORRESPONDENT 
Lauren Privitera, MPH, MS-Bioethics 
Email: lp2183@cumc.columbia.edu 
Phone: 347-271-0901  
 
 
 
 
 
 
 
 
 

 
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3. Background 
 
3.1. Fractional flow reserve 
 
Fractional flow reserve (FFR) is an index that quantifies the hemodynamic significance of 
coronary artery stenosis. FFR is obtained by measuring the ratio between pressure distal to 
a stenosis and proximally using specialized pressure-measuring guidewires during maximal 
hyperemia.1-3 FFR is considered the standard of reference for clinical decision-making. Clinical 
outcome studies have shown that medical therapy is preferred for non-hemodynamically 
significant lesions (FFR >0.80), while coronary revascularization should be considered in cases 
of significant functional stenosis (FFR ≤0.80).4-11 Society guidelines reflect the importance of 
physiology-guided revascularization, with the ACCF/AHA/SCAI guidelines recommending 
that FFR is used to guide the treatment strategy in stable coronary lesions.12 Furthermore, the 
most recent appropriate use criteria advocates for expanded use of intracoronary physiologic 
testing.13,14 
 
Nevertheless, for a variety of practical reasons, FFR measurements remain underutilized. 
Conventional pressure guidewires are limited by three main factors. First, pressure-measuring 
guidewires have a more complex design than standard guidewires used in percutaneous 
coronary interventions (PCI). Consequently, traditional pressure guidewires have handling, 
torquability and lesion crossing characteristics that are suboptimal compared to the mechanical 
performance of workhorse guidewires. In the FFR cohort in the DEFINE-FLAIR study, only 
30.7% of PCI procedures were performed with a pressure wire.15 A pressure wire with improved 
handling characteristics to permit use as a workhorse guidewire during interventions fills an 
important void and improves the likelihood an operator assesses post-intervention FFR by 
avoiding the need to cross with an additional wire. 
 
Secondly, pressure drift can lead to unreliable FFR values and is a prominent limitation with 
conventional pressure wires. Drift can occur when air bubbles become trapped in the cavity of 
the pressure sensor coupled with the inherent thermal and electrical instability of pressure 
sensors.16 Signal drift has been reported to occur in as many as 17.5% of FFR cases.17 Lastly, 
contrast agents and blood can affect connectivity with conventional pressure wires, reducing its 
reliability post-stenting. 
 
Therefore, the ability to derive accurate FFR values reliably with minimal drift and with 
durability to work throughout an entire intervention coupled with the mechanical performance 
of a workhorse guidewire could have an important impact on daily clinical practice by 
increasing utilization of FFR both pre- and post-PCI. 
 
The introduction of fiber optic wires can address these issues and improve the performance of 
FFR wires. The design of the OpSens Medical OptoWire Deux pressure wire combines optimal 
guidewire performance with the ability to perform FFR measurements. Fiber optic pressure 
wires may reduce drift, decreasing the number of repeat FFR recordings as well as reducing the 
number of wire changes. Using the FFR pressure wire for the PCI, thereby avoiding multiple 
wire exchanges, may have both economic and clinical benefits. 
 
3.2. Rationale for study endpoints and cutoff values 
3.2.1. Angiographically intermediate LAD lesions 
Lesions in the intermediate range involving the LAD are often undertreated.  

 
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Physiologic assessment of these lesions can ensure that the treatment of these 
lesions is selected and deferred appropriately.  
 
3.2.2. Correlation of Pre-PCI OCT MLA with Pre-PCI FFR  
OCT provides accurate and reproducible quantitative assessment of coronary 
lesions.18 Prior to revascularization, an OCT MLA <2.5 mm2 can be used to 
predict FFR ≤0.80 in the proximal LAD location.19-21 Correlation of MLA with 
a positive FFR value is associated with improved accuracy in the proximal LAD 
region compared to other coronary segments.20  
 
3.2.3. Resting gradient 
Resting gradients can be used to predict physiologic significance, however a 
large discrepancy exists between FFR and resting gradients in locations which 
supply a large myocardial territory including the left main coronary artery and 
proximal left anterior descending artery.  A resting Pd/Pa ≤0.92 can be used to 
predict a significant FFR based on results from the RESOLVE study with a 
positive predictive value of 89.2% and overall accuracy of 81.5%.22 
 
3.2.4. Pullback measurements 
Repetitive pullback recordings are a safe and effective method to localize lesions 
for revascularization.23, 24 A pullback recording with a pressure wire can also 
help distinguish the presence of a focal lesion versus diffuse disease. A gradual 
change in the recording indicates diffuse disease, whereas an abrupt change 
indicates a focal lesion, and the stenosis can be localized with angiography.  A 
pressure step-up of 0.03 or greater on resting Pd/Pa pullback represents a 
significant and focal stenosis.25 Sparse data exists correlating changes in 
coronary pressure pullback with intravascular ultrasound (IVUS) or OCT lesion 
assessment.26  
 
3.2.5. Post-PCI OCT Assessment 
Use of post-PCI MSA as a predictor for future events has been validated in the 
CLI-OPCI II study.  Suboptimal stent deployment based on specific OCT criteria 
is associated with increased risk for future events.  OCT assessment post-PCI 
with an MSA <4.5 mm2 is an independent predictor of major adverse cardiac 
events. Edge dissection >200 µm at the distal stent edge and reference lumen 
area <4.5 mm2 at either the distal or proximal stent edge is also an independent 
predictor of worse outcomes.27  
 
3.2.6. Post-PCI FFR 
Post-PCI FFR may be a useful indicator of optimal PCI, with post-PCI FFR ≥0.9 
associated with a lower risk of repeat PCI and major adverse cardiac events.28 
Data regarding the correlation between post-PCT FFR and intravascular imaging 
is limited.29 
 
3.2.7. Discrepancy between FFR and resting physiology indices  
Discordance exists between FFR and resting indices such as iFR is related to 
lesion location.  This discordance is most evident in areas of highest flow, 
including the proximal LAD.30  Deferring revascularization in the LAD based on 

 
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iFR values is associated with significantly decreased events compared with 
FFR.31 The correlation between OCT derived MLA and physiologic 
measurements, in lesions with discordant FFR and resting gradients, has not been 
previously investigated.      
 
3.3. Study Device: OpSens Medical OptoWire Deux Pressure Wire 
 
The OptoWire Deux pressure wire (OpSens Medical, Quebec, Canada) is a novel technology 
utilizing optical coherence technology to enhance FFR assessment of the coronaries. The 
OptoWire and OptoMonitor system design allows for simultaneous acquisition of distal pressure 
from the fiber optic sensor embedded in the OptoWire and aortic pressure from an external pressure 
transducer to determine an FFR value. The concentric guidewire construction allows for high fidelity 
pressure measurements during the entire procedure with good steerability and torquability. It is the 
first hybrid nitinol and stainless steel-based FFR wire designed to improve support for PCI tool 
delivery and resist kinks. The design of the guidewire allows the OptoWire to function as a workhorse 
guidewire (Figure 1. Guidewire construction). The optical contact is not affected by blood and allows 
immediate and reliable signal transmission for FFR measurements. The pressure wire calculates a 
lesion specific physiological index to determine the hemodynamic severity of an intracoronary lesion. 
 
The OptoWire is FDA approved to measure pressure in coronary vessels during diagnostic 
angiography and coronary interventions. Anecdotal data suggest fiber optic pressure wires are 
associated with a significant reduction in signal drift; however, this has yet to be thoroughly validated 
in clinical practice.16 
 
 
Figure 1. Guidewire construction. 
 

 
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4. Study Objectives 
 
4.1. Study Objectives 
 
The primary objective of this study is to assess the accuracy, efficacy, and durability of the 
OpSens Medical OptoWire Deux pressure wire in the assessment of angiographically 
intermediate proximal left anterior descending coronary artery (LAD) stenoses in clinical 
practice.  
 
4.2. Primary Endpoint 
 
The primary endpoint is the rate of significant drift, defined as Pd/Pa <0.97 or >1.03 with the 
pre-PCI FFR recording. 
 
4.3. Secondary Endpoints 
 
Secondary efficacy endpoints: 
 
1. The rate of pre-PCI positive FFR (≤0.80) in angiographically intermediate proximal LAD 
lesions. 
 
2. The rate of pre-PCI resting Pd/Pa (≤0.92) in angiographically intermediate proximal LAD 
lesions. 
 
3. The rate of significant drift defined as Pd/Pa <0.97 or >1.03 with post-PCI FFR 
recording. 
 
4. Pre-PCI OCT correlation (MLA <2.5 mm2) with FFR (≤0.80). 
 
5. Pre-PCI OCT correlation with the pullback for distinguishing focal (step-up ≥0.03) versus 
diffuse disease defined by pre-PCI resting Pd/Pa pullback. 
 
6. Post-PCI OCT correlation (edge dissection [lumen area within the dissection ≤4.5 mm2], 
stent underexpansion [≤4.5 mm2 in 3-mm vessel or ≤ distal reference lumen area], 
residual disease outside of stent [minimum lumen area <4.5 mm2]) with the pullback for 
distinguishing focal (step-up ≥0.03) versus diffuse disease defined by post-PCI resting 
Pd/Pa pullback. 
 
7. The rate of discrepancy between FFR and resting physiology indices and its correlation 
with an OCT derived MLA. 
 
 
Secondary economic endpoints: 
 
8. Total number of OptoWires used during the procedure. 
 
9. Frequency of use of alternative guidewire (workhorse wire) for the procedure.  
 
10. Total duration of the procedure  
 

 
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11. Duration of the FFR procedure  
 
 
5. Study Design and Population 
 
This study is designed as a prospective, observational, multi-center, single-arm, clinical registry 
to estimate the ischemic burden of angiographically intermediate proximal LAD stenosis in 
clinical practice using the OpSens Medical OptoWire Deux FFR system. Subjects with stable 
angina or unstable angina who are found to have an intermediate proximal LAD stenosis on 
coronary angiography with anatomy amenable to PCI and underwent physiological lesion 
assessment with the OptoWire Deux pressure wire and OCT as part of their routine procedures 
using standard of care techniques will be enrolled. Patients meeting enrollment criteria will be 
offered the opportunity to enroll in this observational registry post-procedure.  All patients 
enrolled in this study are expected to be evaluated and treated using a standard of care technique. 
This study will enroll a total of 60 patients at Columbia University Medical Center and St. Francis 
Hospital. 
 
5.1. Determination of Study Eligibility 
 
Subjects eligible for initial study screening are patients with stable angina, unstable angina or 
NSTEMI (if the LAD lesions is the non-culprit lesion), who are referred to coronary 
angiography and have had an invasive FFR measurement and OCT in the LAD artery. Subjects 
will need to read and sign the required informed consent document and fulfill the necessary 
eligibility criteria, as described below, to be enrolled in the study.  
 
5.2. Inclusion Criteria 
1. Male or female subjects, >18 years of age. 
2. Patients with stable angina, unstable angina or non-ST segment elevation myocardial 
infarction (if the LAD lesion is the non-culprit lesion) and in whom an intermediate 
proximal LAD stenosis (30-80%) with TIMI flow 3 has been identified on angiography. 
NOTE: Patients with multi-vessel disease can be enrolled.  
3. Patients have had FFR and OCT of the LAD with the OpSens FFR system as part of their 
routine evaluation as standard of care procedure 
4. Provides written, informed consent and HIPAA consent to use the data in a clinical study. 
 
5.3. Exclusion Criteria 
 
General exclusion criteria 
1. Patients presented with NSTEMI with the LAD involved as the culprit lesion  
2. Any ST-elevation myocardial infarction within the past 30 days. 
3. Hemodynamic instability requiring vasopressor or mechanical circulatory support. 
4. Prior heart transplant. 
5. Known left ventricular ejection fraction ≤40%. 
6. LAD supplying akinetic or severely hypokinetic territories if already known based on 
prior imaging. 

 
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7. Patient is enrolled in another clinical study that may impact the results of this study.  
8. FFR not acquired per the IFU for the OpSens Wire. 
9. LAD Lesion not assessed with OCT 
 
Angiographic exclusion criteria 
1. TIMI grade 2 or lower at baseline angiography.  
2. Target lesion involves left main (stenosis >50%). 
3. Presence of chronic total occlusion in any vessel. 
4. Presence of a side branch≥2.75 mm with ≥70% stenosis in the LAD. 
5. Bifurcation lesion that resulted in the stent implantation of a side branch. 
 
5.4. Subject Screening and Informed Consent 
 
At the investigational centers (Columbia University Medical Center and St. Francis Hospital), a 
qualified Investigator or his designee will approach individual patients who are potential 
candidates for participation after the patient has fully recovered from the procedure and will 
explain the purpose, procedures,   risks, benefits, and intent of the study to each. Interested 
subjects will be invited to join the study and asked to provide written informed consent as 
well as HIPAA consent to use the data for research purposes.  
 
The informed consent form used must be approved by the IRB/EC and other local regulatory 
bodies (as appropriate). The approved consent form should clearly reflect the IRB/EC 
approval date. 
 
Failure to obtain a signed and hand-dated informed consent form will preclude enrollment 
in this registry. 
 
All subjects who begin the study screening process will be tracked by utilizing a study screening 
log. The screening log documents the screening effort to enroll consecutively eligible subjects 
in this study. 
 
5.5. Subject Enrollment 
 
Subjects will be recruited consecutively at Columbia University Medical Center and St. Francis 
Hospital. This is intended to ensure that the range of FFR values in the sample will represent 
that of the intended use population. Subjects who fail to meet the clinical inclusion and 
exclusion criteria will not be included in this study. Subjects will only be formally enrolled in 
the study after all clinical and angiographic criteria are met and the subject provides informed 
consent and HIPAA consent. 
 
5.6. Subject Withdrawal 
 
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the study personnel or institution. 
 

 
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6. Procedures and Assessments 
 
6.1. Schedule of Events 
 
Table 1: Schedule of Events 
 
Study Requirement 
Post-procedure 
Informed consent and HIPAA consent to use data 
X 
Demographics 
X 
Medical history and baseline medication 
X 
Collection of procedural information 
X 
 
 
6.2. Baseline Procedures 
 
The following data must be collected for all patients post-procedure, unless otherwise 
specified: 
 
♦ 
Subject demographics 
♦ 
Medical history 
♦ 
Baseline medications 
♦ 
Clinical assessment 
♦ 
Procedural information 
 
 
6.3. Procedural Protocol 
 
In patients with an angiographically intermediate proximal LAD lesion, eligible for enrollment 
in the study whom an OptoWire Deux was used for physiologic lesion assessment in addition to 
OCT as standard of care, will be offered consent for enrolling in this observational study post-
procedure.  
 
6.4. Procedural Information 
 
The following procedural information will be collected: 
 
♦ 
Number of OptoWire Deux used 
♦ 
Number of workhorse wires used 
♦ 
Total duration of procedure 
♦ 
Duration of FFR measurement 
♦ 
Coronary angiogram (DICOM) 
♦ 
OCT images  
♦ 
Cine marking the position of the FFR wire pressure sensor (DICOM) 
♦ 
Physiology tracing (resting Pd/Pa, FFR, pullback)  
 
6.5. Shipment of Materials to the Core Lab 

 
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The following documentation should be forwarded to the Core Lab: 
 
♦ 
Coronary angiogram (saved on a CD labeled with patient ID) 
♦ 
FFR tracings 
♦ 
OCT images 
♦ 
Study worksheet (Appendix B) 
♦ 
Catheterization report 
 
 
Cardiovascular Research Foundation Core Lab 
Trial Identifier: OpSens FFR Trial 
1700 Broadway, 9th Floor 
New York, NY 10019 
USA 
 
7. Study Risk Determination 
 Participation in this study presents no medical risk to the patient (data collection only). 
 
 
8. Statistical Considerations 
 
This is a prospective, observational, multi-center, clinical study designed to estimate the ischemic 
burden of angiographically intermediate proximal LAD stenosis using FFR. Efficacy will be 
measured using the OpSens FFR system. 
 
The study’s primary endpoint is the rate of significant drift, defined as FFR <0.97 or >1.03 with 
the pre-PCI FFR recording using the OpSens OptoWire Deux pressure wire system.  
 
8.1. Statistical Analysis and Analysis Sets 
 
All statistical analyses will be performed using SAS (SAS Institute Inc., Cary, NC). Patient 
data listings and tabular presentations of results will be provided listing the mean, standard 
deviation, median, minimum, maximum, and number of subjects for continuous data, or in 
tables listing count and percentage for categorical data, where appropriate. 
 
8.2. Analysis of Baseline Demographics and Procedural Characteristics 
 
All clinically relevant baseline variables will be tabulated using descriptive statistics. 
Descriptive statistics for categorical variables will include the number and percentage of 
subjects, with 2-sided 95% confidence intervals of the percentage of subjects. 
 
9. Definitions 
 
REFERENCE VESSEL DIAMETER 
Defined as the average of normal segments within 10 mm proximal and distal to the target lesion 
from 2 orthogonal views using quantitative coronary angiography. 
 
TIMI CLASSIFICATION 
 

 
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TIMI 0: No perfusion. 
TIMI 1: Penetration with minimal perfusion. Contrast fails to opacify the entire bed distal 
to the stenosis for the duration of the cine run. 
TIMI 2: Partial perfusion. Contrast opacifies the entire coronary bed distal to the stenosis; 
however, the rate of entry and/or clearance is slower in the coronary bed distal to 
the obstruction than in comparable areas not perfused by the dilated vessel. 
TIMI 3: Complete perfusion. Filling and clearance of contrast equally rapid in the coronary 
bed distal to stenosis as in other coronary beds. 
  
10. Reporting Responsibilities 
 
Table 2: Investigator Reporting Responsibilities 
 
Type of Report 
Prepared For 
Time Frame 
Withdrawal of IRB/EC approval 
or other action on part of the 
IRB/EC that affects the study 
Sponsor 
Written – Within 5 working days of IRB/EC 
decision. 
Progress Reports 
IRB/EC 
At regular intervals. 
Final Report 
Sponsor and 
IRB/EC 
Within 3 months after termination or completion 
of study or termination of site’s participation. 
 
Table 3: Sponsor Reporting Responsibilities 
 
Type of Report 
Prepared For 
Time Frame 
Withdrawal of IRB/EC 
Approval. 
Investigators, all 
other reviewing 
IRBs/ECs and 
appropriate 
regulatory bodies 
Written – Within 5 working days. 
 
11. Data Submission Requirements 
 
11.1. 
Required Data 
 
All required data for this study will be collected via case report form. 
 
11.2. 
Data Collection 
 
Case Report Form Development, Modification, and Maintenance: 
 
The final set of case report form is designed to accommodate the specific features of the trial 
design. Modification of case report form will only be made if deemed necessary by the sponsor. 
All core lab raw data will be sent to the core labs at the Cardiovascular Research Foundation at 
the address listed in Section 2: Additional Summary Information. This information is 
documented and the data are transmitted to the data center at Cardiovascular Research 
Foundation for integration into the study database. 

 
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Components of the case report form: 
 
1. Enrollment screening and subject eligibility 
2. Baseline demographics, medical history, and clinical presentation 
3. Procedural and lesion data 
 
11.3. 
Data Collection and Tracking 
 
Research coordinators at each clinical site will perform primary data collection from source 
document (e.g., hospital chart, office record) reviews. Data will be entered by the site personnel 
into case report forms. The Sponsor or its designee will provide clinical monitoring, including 
review of case report form with verification to the source documentation. This will include case 
report documentation and hospital charts/office records. 
 
11.4. 
Time Windows for Expected Completion of Case Report Forms 
 
The case report form data submission detailed in the following table should be completed 
as follows: 
 
Table 4. Responsibilities and Guidance for Submitting Reports and Other Data 
 
Type of 
Notification/Report/Other 
Data 
Submitted to 
Time Window for Submission 
Coronary angiogram 
Angiographic Core Lab 
Monthly 
FFR 
FFR Core Lab 
Monthly 
Withdrawal of IRB approval 
Notify sponsor 
Within 5 working days of 
withdrawal 
Final report 
Sponsor, IRB/EC 
Within 3 months of study 
completion or termination 
 
 
12. Study Steering Committees 
 
The Steering Committee is composed of the PIs, several other leading physician experts, and a 
Sponsor representative. The Steering Committee participates in regularly scheduled meetings to 
review study progress and conduct and to provide feedback to the Sponsor on an ad hoc basis. 
Steering Committee membership will be decided by the sponsor. 
 
13. Ethical and Regulatory Considerations 
 
This study will be conducted in accordance with the principles outlined in the Declaration of 
Helsinki and all local Good Clinical Practice requirements. 
 
13.1. 
Subject Confidentiality 
 

 
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Subject confidentiality will be maintained throughout the clinical study in a way that assures 
that data can always be tracked back to the source data. For this purpose, a unique subject 
identification code (ID number and subject name code) will be used that allows identification 
of all data reported for each subject. 
 
Data relating to the study might be made available to third parties (for example in case of an 
audit performed by regulatory authorities) provided the data are treated confidential and that 
the subject’s privacy is guaranteed. 
 
“Protected Health Information” will be treated and maintained in compliance with the HIPAA 
Privacy rule with regard to the processing of personal data and on the free movement of such 
data. 
 
The duration of the storage time of the personal data at the investigational sites, will be in 
accordance with the national regulations. 
 
13.2. 
Selection of Investigators 
 
The sponsor and its designees will select qualified investigators, obtain signed study agreements, 
and provide the investigators with the information necessary to conduct the study. 
 
13.3. 
Initiation of Study Sites 
 
Prior to subject enrollment, a study initiation visit will be completed at the investigational site to 
ensure the following: IRB/EC approval has been obtained and documented prior to subject 
screening, the investigators and study personnel are appropriately trained and clearly understand 
the study, the investigators and study personnel accept the obligations incurred in undertaking 
this clinical investigation. 
 
13.4. 
Study Closeout Visit 
 
Upon completion of the clinical study, all data have been entered into the case report form, 
all queries have been resolved, and final signatures have been obtained), a study closeout 
visit will be performed. The study monitor will ensure that the Investigator’s regulatory files 
are current and complete, and that any outstanding issues from previous visits have been 
resolved. Other issues that will be reviewed with site personnel at this visit include: discussing 
retention of study files, the possibility of site audits, publication policy, and to ensure that the 
Investigator will notify the site’s IRB/EC regarding study closure. 
 
13.5. 
Maintaining Records 
 
The sponsor and/or its designees will maintain copies to include all trial-related correspondence, 
regulatory documents, data, and other records related to the clinical trial. The sponsor and/or 
its designees will maintain records related to the signed Investigator Agreements. 
 
13.6. 
Submitting Reports 
 
The sponsor reporting responsibilities are detailed in Table 3. 

 
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The site will notify the ponsor within 24 hours of the time the Investigator becomes aware of 
withdrawal of IRB/EC approval. The Investigator reporting responsibilities are detailed in 
Table 2. 
 
13.7. 
Site Record Retention Policy 
 
All core laboratories and the clinical sites will maintain study records until the sponsor 
notifies them and the reviewing regulatory authorities that research is completed or terminated 
under the clinical investigation in compliance with United States Food and Drug regulations.  
 
 
14. Risks to the Subjects 
 
14.1. 
Human Subjects Involvement and Characteristics 
 
This study will enroll a total of 60 subjects. The inclusion and exclusion criteria are described 
above in Sections 5.2. and 5.3. Vulnerable populations, specifically prisoners, and 
institutionalized individuals will not be targeted for recruitment. 
 
14.2. 
Sources of Materials 
 
Research material obtained from study participants includes health information obtained 
through medical history, physical and angiographic examination.  
 
Copies of data obtained as part of the study will be retained by the sites, with appropriate source 
documentation, on all subjects that sign informed consent. The data utilized in this study are 
described above and consist of information from subject interview and examination, medical 
records, or study-specified measures and interventions. 
 
14.3. 
Potential Risks 
 
There are no medical risks associated with this study (data collection only). 
 
14.4. 
Confidentiality of Subject Medical Information 
 
Confidentiality of subject medical information will be ensured by providing unique identifiers 
for data transmitted from the enrolling centers. The sponsor and the core laboratories will not 
receive identifiable subject information. The sponsor  and the core laboratories will receive 
case report forms that are already encoded with study identifiers, thus preventing 
knowledge of any subject-identifying information. All diagnostic tests performed at the core 
labs will be labeled to obscure subject-identifying information and provide specific fields in 
which to encode subject identifiers (using the same set of subject initials and numbers 
encoded on the case report forms). This process ensures that the core lab data is eventually 
incorporated with the main subject file held by the sponsor, Dr. Manish Parikh. All direct 
subject contact (informed consent, subject screening and study procedures) and relevant 
confidentiality protections are the responsibility of the sponsor. 
 

 
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Table 6: List of Acronyms 
 
Acronym 
Term 
CFR 
Code of Federal Regulations 
EC 
Ethics committee 
EDC 
Electronic data capture 
FFR 
Fractional flow reserve 
HIPAA 
Health Insurance Portability and Accountability Act 
iFR 
Instantaneous wave-free ratio 
IFU 
Instructions for use 
IRB 
Institutional review board 
IVUS 
Intravascular ultrasound 
LAD 
Left anterior descending coronary artery 
MLA 
Minimum lumen area 
OCT 
Optical coherence tomography 
PCI 
Percutaneous coronary intervention 
PI 
Principal investigator 
TIMI 
Thrombolysis in Myocardial Infarction 
 

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