Dynamic Coronary Roadmap for Contrast Reduction
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Philips Clinical & Medical Affairs Global



 
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Revision History 
Revision 
Revision Date 
Author
Changes/Comments
00 
2018 Apr 05 
Initial version
01 
2019 Jun 05 
Protocol updated based on feedback from 
investigators and study coordinators at the 
potential sites: 
 Target patient population extended from 
elective PCI to elective + ad hoc PCI; 
rephrased inclusion/exclusion criteria, 
objectives, endpoints and study procedures to 
accommodate this change (see Summary 
section, Chapter 5, 6, and 7) 
 Chapter 9: Changed such that all (also non 
significant) changes of the clinical study 
protocol shall be notified to, or approved by the 
MEC and where appropriate regulatory 
authorities. 
 Appendix I: Updated list of investigators, sites, 
and third parties involved in the study 
 Appendix II: Updated list of monitors/clinical 
scientists, clinical study managers 
02 
2019 Jul 04 
Protocol updated based on FDA pre-submission 
meeting feedback: 
 The secondary objective on the iodinated 
contrast volume used per vessel PCI has been 
moved to the Exploratory objectives. 
 Updated the sample size justification for the 
secondary objective resulting in 394 subjects 
required for the study (360 previously).  
 Added site effect analysis for the primary 
endpoint to assess poolability of data. 
 Added sensitivity analysis for the primary 
endpoint to perform worst-case analysis for 
missing data. 
 
Open Issues 
None 
 

 
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Table of Contents 
 
Approval ......................................................................................................................................................... 1 
Revision History .............................................................................................................................................. 2 
Open Issues ................................................................................................................................................... 2 
Table of Contents ........................................................................................................................................... 3 
1. 
Document Introduction ............................................................................................................................ 5 
1.1. 
Purpose ........................................................................................................................................... 5 
1.2. 
Scope .............................................................................................................................................. 5 
1.3. 
References ...................................................................................................................................... 5 
1.4. 
Definitions & Abbreviations ............................................................................................................. 6 
2. 
Summary ................................................................................................................................................ 7 
3. 
Device Description ................................................................................................................................ 10 
3.1. 
Summary description of the study device ...................................................................................... 10 
3.2. 
Intended Purpose .......................................................................................................................... 10 
3.2.1. 
Indications for Use / Medical Purpose ................................................................................... 10 
3.2.2. 
Intended operator profile ....................................................................................................... 10 
3.2.3. 
Clinical environment .............................................................................................................. 11 
3.2.4. 
General safety and effectiveness .......................................................................................... 11 
3.2.5. 
Operating principle ................................................................................................................ 11 
3.3. 
Necessary training and experience needed to use the research device ........................................ 11 
3.4. 
Materials that will be in contact with tissues or body fluids ............................................................ 11 
3.5. 
Device Traceability ........................................................................................................................ 11 
4. 
Justification for the design of the study ................................................................................................. 11 
4.1. 
Clinical background ....................................................................................................................... 11 
4.2. 
Clinical study results ..................................................................................................................... 12 
4.3. 
DCR4Contrast trial justification ...................................................................................................... 12 
5. 
Objectives and hypotheses ................................................................................................................... 13 
5.1. 
Primary objective ........................................................................................................................... 13 
5.2. 
Secondary objective ...................................................................................................................... 13 
5.3. 
Exploratory objectives ................................................................................................................... 13 
6. 
Study Design......................................................................................................................................... 13 
6.1. 
General ......................................................................................................................................... 13 
6.2. 
Maintenance and calibration ......................................................................................................... 14 
6.3. 
Study device exposure and comparators ...................................................................................... 14 
6.4. 
Subjects ........................................................................................................................................ 14 
6.4.1. 
In- and exclusion criteria ........................................................................................................ 14 
6.4.2. 
Duration ................................................................................................................................. 15 
6.4.3. 
Enrollment ............................................................................................................................. 15 
6.4.4. 
Number of subjects ............................................................................................................... 15 
6.4.5. 
Procedure for the replacement of subjects ............................................................................ 15 
6.4.6. 
Subject withdrawal or discontinuation .................................................................................... 15 
6.5. 
Procedures .................................................................................................................................... 16 
6.6. 
Monitoring Plan ............................................................................................................................. 16 
7. 
Statistical considerations ....................................................................................................................... 17 
7.1. 
Sample Size Justification Primary Endpoint .................................................................................. 17 
7.1.1. 
Sample Size Justification Secondary Endpoint ...................................................................... 18 
7.2. 
General Considerations ................................................................................................................. 18 
7.3. 
Poolability ...................................................................................................................................... 19 
7.4. 
Subject Disposition ........................................................................................................................ 19 
7.5. 
Demographics and Baseline Characteristics ................................................................................. 19 
7.6. 
Primary objective ........................................................................................................................... 21 
7.7. 
Secondary objective ...................................................................................................................... 21 
7.7.1. 
Secondary objective: Number of Angiograms ........................................................................ 21 
7.8. 
Exploratory objectives ................................................................................................................... 22 
7.8.1. 
Exploratory objective: Contrast Volume per Vessel PCI ........................................................ 22 

 
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7.8.2. 
Exploratory objective: Contrast Volume per Stratification Group (1, 2, 3 or more vessel PCI) 22 
7.8.3. 
Exploratory objective: Contrast Volume per Simple, Intermediate, Complex PCI subgroup .. 22 
7.8.4. 
Exploratory objective: AKI Incidence ..................................................................................... 23 
7.8.5. 
Exploratory objective: Contrast Usage Variability .................................................................. 24 
7.8.6. 
Exploratory objective: Fluoro & Procedure Time ................................................................... 25 
7.8.7. 
Exploratory objective: X-ray Dose ......................................................................................... 25 
7.8.8. 
Exploratory objective: Procedural Success ............................................................................ 25 
7.8.9. 
Exploratory objective: In-hospital MACCE ............................................................................. 26 
7.8.10. 
Sensitivity Analysis for the Primary Endpoint ......................................................................... 26 
8. 
Data management ................................................................................................................................ 26 
8.1. 
Retention period ............................................................................................................................ 26 
9. 
Amendments to the Clinical Study Protocol .......................................................................................... 27 
10. 
Deviations from the Clinical Study Protocol ....................................................................................... 27 
11. 
Device accountability ........................................................................................................................ 27 
12. 
Statements of compliance ................................................................................................................. 27 
13. 
Informed consent process ................................................................................................................. 27 
14. 
Safety reporting ................................................................................................................................. 28 
15. 
Early termination or suspension of the Clinical study ........................................................................ 28 
16. 
Publication policy .............................................................................................................................. 28 
17. 
Bibliography ...................................................................................................................................... 29 
Appendix I. List of Investigators and Sites .................................................................................................... 32 
Appendix II. List of Monitors/Clinical Scientists/Clinical Study Manager ........................................................ 33 
 

 
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1. 
Document Introduction 
1.1. 
Purpose 
This document is intended to be used as a template for the Post-Market Clinical Study Protocol for clinical 
studies. The document describes the minimum amount of information to be included in this clinical study 
protocol based on the regulations.  
1.2. 
Scope 
This post-market study protocol applies to the clinical evidence study Dynamic Coronary Roadmap for 
Contrast Reduction (DCR4Contrast trial). 
1.3. 
References 
Reference 
Identification 
Title / additional remarks 
[CER] 
DHF287327 
Clinical Evaluation Report Dynamic Coronary Roadmap 
[IFU] 
4522 203 59903 
IFU Dynamic Coronary Roadmap R2.0 
[FDA] 
K172307 
FDA 510(k) clearance Dynamic Coronary Roadmap R2.0 
 
The following documents that are not controlled by Philips are referred to in this document: 
 
[MEDDEV] 
MEDDEV 2.7/1 
MEDDEV 2.7/1 rev 4 - Clinical Evaluation: a guide for 
manufacturers and notified bodies under directives 
93/42/EEC and 90/385 EEC 
[MDD] 
EU MDD 93/42/EEC 
Council Directive 93/42/EEC concerning medical devices. 
Amended by Medical Device Directive as amended by 
2007/47/EC 
[MDR] 
EU MDR 2017/745 
Regulation (EU) 2017/745 of the European Parliament 
and of the Council of 5 April 2017 on medical devices 
[ISO14155] 
EN ISO 14155  
EN ISO 14155:2011 – Clinical Investigation of medical 
devices

 
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1.4. 
Definitions & Abbreviations 
Term 
Description 
AF 
Atrial Fibrillation 
AK 
Air Kerma 
AKI 
Acute Kidney Injury 
AKI-D 
AKI requiring dialysis 
AKIN 
Acute Kidney Injury Network (definitions) 
C(I)N 
Contrast (Induced) Nephropathy 
CABG 
Coronary Artery Bypass Grafting 
CE 
Conformité Européenne (European Conformity)
CFR 
Code of Federal Regulation 
CI 
Confidence Interval 
CI-AKI 
Contrast Induced AKI 
CKD 
Chronic Kidney Disease 
CRF 
Case Report Form 
CRO 
Contract Research Organization
DAP 
Dose Area Product 
DCR 
Dynamic Coronary Roadmap 
eCRF 
Electronic Case Report Form 
eGFR 
estimated Glomerular Filtration Rate 
eGFR 
Estimated Glomerular Filtration Rate 
FDA 
Food and Drug Administration
FFR 
Fractional Flow Reserve 
GFR 
Glomerular Filtration Rate 
HTA 
Health Tech Assessment 
IDMS 
Isotope Dilution Mass Spectrometry 
iFR 
instantaneous wave-Free Ratio 
IFU 
Instructions for Use
IQR 
Interquartile Range 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ISR 
In-Stent Restenosis 
IVUS 
IntraVascular UltraSound 
LMCA 
Left Main Coronary Artery
MDD 
Medical Device Directive 
MDR 
Medical Device Reporting 
MEC 
Medical Ethic Committee 
MI 
Myocardial Infarction 
MVD 
Multi Vessel Disease 
NRD 
Nephropathy requiring dialysis
NSTEMI 
Non-ST segment Elevation Myocardial Infarction 
NYHA 
New York Heart Association classification 
OCT 
Optical Coherence Tomography 
PCI 
Percutaneous Coronary Interventions 
RCA 
Right Coronary Artery 
SCr 
Serum Creatinine
SD 
Standard Deviation 
TIMI 
Thrombolysis In Myocardial Infarction 
UA 
Unstable Angina 

 
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Secondary endpoint: 
 
The average total number of contrast enhanced cine angiographic X-ray runs (angiograms) per 
PCI (from first positioning the interventional guiding catheter in stable coronary position till end of 
PCI procedure) determined via visual assessment (e.g., on the Philips X-ray system). 
  
Main inclusion criteria
 
Subject is undergoing Percutaneous Coronary Intervention (PCI) with a degree of complexity that 
anticipates the need for more than 25ml of iodinated contrast volume  
 
Subject has signed informed consent 
 
Subject is 18 years of age or older, or of legal age to give informed consent per state or national 
law 
Main exclusion criteria 
 
Subject undergoing emergency PCI 
 
Subject with ST-segment Elevation Myocardial Infarction (STEMI) 
 
Subject with Chronic Total Occlusion (CTO) 
 
Subject undergoing PCI for isolated ostial disease of Left Main Coronary Artery (LMCA) or Right 
Coronary Artery (RCA) 
 
Subject undergoing PCI with Optical Coherence Tomography (OCT) support 
 
Subject undergoing PCI with rotational or orbital atherectomy 
 
Subject with Chronic Kidney Disease (CKD) stage V (eGFR < 15 ml/min/1.73 m2) 
 
Subject with contrast allergy that cannot be adequately pre-medicated 
 
Subject participates in a potentially confounding drug or device trial during the course of the study. 
 
Subject is under 18 years of age, or pregnant woman, or breast feeding woman, or meets an 
exclusion criteria according to national law 
 
No. of subjects 
In total 394 subjects will be enrolled in the study during an expected enrollment period of 9 months. 
 
Study procedures 
Physician investigators participating in this study are expected to follow their normal clinical practice in 
treating and following up patients with Coronary Artery Disease (CAD). Patients randomized to the DCR 
group will undergo a PCI procedure during which DCR is used while those randomized to the control 
group will undergo PCI without the use of DCR. The preparation of the PCI procedure, the procedure itself 
and follow up will be performed following standard of care. 
 
Screening 
Patients scheduled for PCI will be screened on inclusion and exclusion criteria by the principal investigator 
or delegated and trained study personnel. When a patient is eligible study information and the informed 
consent form is provided to the patient and after providing ample time to consider participation the patient 
is asked for signed consent.  
 
PCI procedure 
The investigator will perform PCI using standard of care procedures. 
 
Standard of care PCI entails (deviations allowed up to investigator’s discretion): 
 In case of elective PCI: Randomization before procedure  
 
Arterial access (femoral or radial; preferably perform femoral angiography of preclose device at 
this moment) 
 
In case of ad hoc PCI: Diagnostic Coronary Angiography 
 In case of ad hoc PCI: Randomization upon decision to go for PCI 
 
First positioning of interventional guiding catheter in stable coronary position 
 Record the contrast volume used up to that moment 
 
Coronary Angiography [DCR group: DCR started automatically] 
 
Position guidewire 

 
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 
Position balloon + inflate balloon 
 
Position stent + deploy stent  
 
Check PCI result by Coronary Angiography (potentially combined with e.g. Stent Boost, IVUS) 
 
Repeat above steps when necessary, e.g. post-dilate stent or perform PCI in different vessel 
 Record the total contrast volume used 
 
The principal investigator or his delegates on the study team will enter data in a pre-designed e-CRF. This 
will include patient demographics, relevant past medical history, specific target CAD data along with pre-
procedural/screening imaging details, PCI procedure data and follow-up data until patient discharge. 
 
Figure 1 Clinical workflow of the DCR4Contrast trial following standard of care for PCI (ad hoc 
and elective) 
Follow up 
The subjects will be followed-up until discharge following standard clinical care. 
Duration of the study 
The total duration of the study is expected to take 9 months. 
 
 
 
 

 
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3. 
Device Description 
3.1. 
Summary description of the study device 
The Dynamic Coronary Roadmap is a commercially available (CE labeled, FDA 510(k) cleared: K170130 for 
Dynamic Coronary Roadmap R1, and K172307 for Dynamic Coronary Roadmap R2) product developed by 
Philips Medical Systems, a Philips Healthcare company. Dynamic Coronary Roadmap is a software medical 
device intended to provide a real-time and dynamic angiographic roadmap of coronary arteries. The 
angiographic roadmap is automatically generated from previously acquired coronary angiograms during the 
same procedure. Dynamic Coronary Roadmap overlays the angiographic roadmap on live 2D fluoroscopic 
images, thereby assisting the physician in navigating devices, e.g. (guide) wires, catheters, through the 
coronary arteries. 
Dynamic Coronary Roadmap is to be used in combination with a Philips interventional X-ray system. 
 
Dynamic Coronary Roadmap R1 and R2 are completely equivalent since Dynamic Coronary Roadmap R2 
embodies the exact same algorithm as Dynamic Coronary Roadmap R1 and therefore no difference in the 
intended use [FDA]. Both versions R1 & R2 are commercially released products. The difference between R1 
and R2 is the FFR/iFR Roadmap feature added to R2, which is not subject of the current study. The coronary 
roadmapping features of R1 and R2 are identical and the use of R1 and R2 in this study is not impacting 
study results. As a result both R1 and R2 of Dynamic Coronary Roadmap can be used for the purpose of this 
clinical evidence study. 
 
The manufacturer of the study device is: 
Philips Medical Systems Nederland B.V., a Philips Healthcare company 
Veenpluis 6  
5684 PC Best  
The Netherlands 
3.2. 
Intended Purpose  
Since this study will be using the commercially available Dynamic Coronary Roadmap product also the 
related commercially available instruction for use [IFU] will be used. This manual contains safety precautions 
and handling of the study device and contains more features than the coronary roadmapping feature 
required for this study.  
3.2.1. 
Indications for Use / Medical Purpose 
Dynamic Coronary Roadmap is intended to assist the physician during percutaneous coronary interventions 
in correlating the device position to the coronary vasculature, by providing a motion compensated overlay of 
this coronary vasculature.  
 
The FFR/iFR Roadmap feature1 is intended to assist the physician during percutaneous coronary 
interventions in relating the intravascular blood pressure measurement to its anatomical location. FFR/iFR 
roadmap visualizes the position of the pressure wire and the coronary artery on an X-ray image at the 
moment that an intravascular blood pressure measurement was performed as well as the intravascular blood 
pressure measurement values themselves. 
 
Dynamic Coronary Roadmap is suitable for use with the entire adult human population. 
3.2.2. 
Intended operator profile 
Dynamic Coronary Roadmap is intended to be used and operated by: adequately trained, qualified, and 
authorized healthcare professionals who have understanding of the safety information and emergency 
procedures as defined by local laws and regulations for radiation workers and staff. 
                                                    
1 The FFR/iFR Roadmap feature is not subject of the current study and not to be used. 

 
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3.2.3. 
Clinical environment 
Dynamic Coronary Roadmap is intended to be used in the catheterization laboratorium, interventional suite 
or hybrid operating room. The software medical device is connected to a Philips interventional X-ray system. 
Additionally it may also be connected to a compatible intravascular blood pressure measurement system. 
3.2.4. 
General safety and effectiveness 
To facilitate safe and effective operation of the system by a trained healthcare professional, instructions for 
use are provided as part of the device labeling.  
 
Dynamic Coronary Roadmap is a software medical device and does not come in contact with a human 
subject. 
3.2.5. 
Operating principle 
The software medical device uses X-ray generated data as input data and image processing for medical 
imaging and/or pressure data from a compatible intravascular blood pressure measurement system. 
The software medical device provides visual feedback. 
3.3. 
Necessary training and experience needed to use the research device 
There will be no change in the normal operation of the study device/system. Therefore, minimal training is 
needed for the use of Dynamic Coronary Roadmap. 
 
Operators that have no experience with Dynamic Coronary Roadmap should first familiarize themselves with 
the tool for at least 10 interventions before participating in the study. 
3.4. 
Materials that will be in contact with tissues or body fluids 
No materials of the study device will be in contact with tissue or body fluids. 
3.5. 
Device Traceability 
The study device includes a name, including software version and accessories to permit full identification. 
Device traceability will be maintained by Philips. Records shall be kept to document when the device is 
received, installed or uninstalled at the hospital. 
4. 
Justification for the design of the study 
4.1. 
Clinical background 
The most common cardiovascular disease is Coronary Artery Disease (CAD) [Abubakar 2013] and can be 
treated (when severe) via minimally invasive Percutaneous Coronary Interventions (PCI) or Coronary Artery 
Bypass Grafting (CABG). Intraprocedural complication rate in PCI has been consistently low at around 1-2% 
over the past years [Meinertz 2013, Waldo 2018]. 
 
However, some risks still remain and are inevitable in PCI such as the use of toxic iodinated contrast agent 
used to visualize the coronary lumen patency and to assist when navigating devices through the coronary 
tree. Contrast is associated one of the risk factors for contrast induced Acute Kidney Injury (AKI), especially 
to patients with preprocedural renal impairment [Tehrani 2013]. AKI comes with economic burden (longer 
hospitalization and higher readmission rate) next to increased morbidity and mortality [Subramanian 2007, 
Tsai 2014, Koulouridis 2015].  
 
Dynamic Coronary Roadmap provides automatic navigation guidance via a real-time and dynamic 
angiographic roadmap of the coronary arteries. Because of the continuous roadmap DCR has the potential 
to reduce for example the number contrast puffs (small contrast injections) normally required to help device 
navigation through the coronaries. 

 
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4.2. 
Clinical study results 
The clinical evaluation of Dynamic Coronary Roadmap has been covered by the Clinical Evaluation Report 
[CER], including a review of the relevant scientific literature published. 
 
Pilot studies [Dannenberg 2016, Piayda 2018] using DCR in PCI confirmed safety and performance. Other 
recent pilot studies also indicated the potential of DCR to reduce iodinated contrast use: 
 
[Rajappan 2017]: Single center, non-randomized, prospective study showed a contrast reduction of 
26% after introduction of DCR in elective PCI (n=84). The number of contrast enhanced cine runs 
(angiograms) per procedure was reduced by 26% in this study. 
 
[Yabe 2018]: Single center, non-randomized, retrospective study showed to achieve 21.9% contrast 
reduction using Dynamic Coronary Roadmap in PCI (n=43 DCR group, n=103 control group). 
 
Both pilot studies reported that contrast usage is potentially reduced by Dynamic Coronary Roadmap as 
continuously showing the automatic dynamic coronary roadmap reduces: 
 
the need to perform small contrast injections (“puffs”); 
 
the need to perform redo contrast enhanced cine runs (angiograms) to refresh the mental map of the 
coronary arteries; 
 
the need to perform contrast enhanced angiograms when returning to earlier angiogram positions by 
automatically showing the earlier created angiographic roadmap. 
4.3. 
DCR4Contrast trial justification 
We designed this trial in order to confirm the initial pilot study results [Rajappan 2017, Yabe 2018] that 
showed that DCR can potentially lower the amount of iodinated contrast used during PCI procedures. To this 
end a randomized controlled investigation is required according to the clinical evaluation and post-market 
clinical follow-up Annex XIV of the EU Medical Device Regulation [MDR]. Furthermore to be able to report 
out on generalizable results a multi-center approach is chosen. Therefore, the DCR4Contrast trial will be a 
multi-center, prospective, unblinded, stratified 1:1 randomized controlled trial to assess whether using 
Dynamic Coronary Roadmap reduces the total iodinated contrast volume related to PCI compared to the 
control group without Dynamic Coronary Roadmap (see Figure 2). 
 
 
Figure 2 DCR provides a real-time motion compensated coronary roadmap on fluoro for PCI 
guidance. The DCR4Contrast trial aims to assess whether using DCR reduces the total 
iodinated contrast volume related to PCI compared to the control group without Dynamic 
Coronary Roadmap. 
 
 

 
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5. 
Objectives and hypotheses 
5.1. 
Primary objective  
The primary objective of this clinical study is:  
 
To assess whether using Dynamic Coronary Roadmap reduces the total iodinated contrast volume 
related to PCI compared to the control group without Dynamic Coronary Roadmap. 
 
The primary hypothesis is that using Dynamic Coronary Roadmap reduces the total iodinated contrast 
volume related to PCI compared to the control group without Dynamic Coronary Roadmap. 
5.2. 
Secondary objective 
The secondary objective is: 
 
To assess the total number of contrast enhanced cine angiographic X-ray runs (angiograms) related 
to PCI in the Dynamic Coronary Roadmap and control group 
5.3. 
Exploratory objectives 
The exploratory objectives are: 
 
To assess the iodinated contrast volume used per vessel PCI in the Dynamic Coronary Roadmap 
and control group  
 
To assess the total iodinated contrast volume related to PCI per stratification group, i.e., 1 vessel 
PCI, 2 vessel PCI and 3 or more vessel PCI, in the Dynamic Coronary Roadmap and control group 
 
To assess the total iodinated contrast volume related to PCI in subgroups of simple, intermediate 
and complex PCI (where the SYNTAX score for the vessel(s) treated with PCI will be used as an 
index for complexity) in the Dynamic Coronary Roadmap and control group 
 
To assess the incidence of Acute Kidney Injury (AKI) in the Dynamic Coronary Roadmap and control 
group (at discharge following standard clinical care) 
 
To assess the variability of the total iodinated contrast volume related to PCI in the Dynamic 
Coronary Roadmap and control group 
 
To assess the total fluoroscopy & procedure time related to PCI in the Dynamic Coronary Roadmap 
and control group 
 
To assess the total X-ray dose (DAP, AK) related to PCI in the Dynamic Coronary Roadmap and 
control group 
 
To assess the procedural success in the Dynamic Coronary Roadmap and control group 
 
To register in-hospital Major Adverse Cardiovascular and Cerebral Events (MACCE) in the Dynamic 
Coronary Roadmap and control group  
6. 
Study Design  
6.1. 
General 
This is a multi-center, prospective, unblinded, stratified 1:1 randomized controlled trial to assess whether 
using Dynamic Coronary Roadmap reduces the total iodinated contrast volume related to PCI compared to 
the control group without Dynamic Coronary Roadmap. In the randomization process all subjects within each 
type of PCI (ad hoc or elective) will be stratified according to the number of vessels to be treated via PCI, i.e., 
1, 2, or 3 or more vessel PCI. 
 
A prospective multi-center study has been chosen to observe standard of care with the study device, see 
Figure 3 for the DCR4Contrast trial flow.  
 

 
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Figure 3 Clinical workflow of the DCR4Contrast trial following standard of care for PCI (ad hoc and 
elective) 
6.2. 
Maintenance and calibration 
The equipment relevant for the assessment of the clinical study is the Dynamic Coronary Roadmap study 
device and automatic contrast injector for accurate iodinated contrast volume measurement. Maintenance 
and calibration of this equipment will be monitored if this is appropriately performed and documented. The 
contrast agents used within the study will be used according to the legally approved dosing and intended 
use. 
6.3. 
Study device exposure and comparators 
During the PCI procedure the Dynamic Coronary Roadmap study device will be used for the randomly 
selected subjects in the DCR group, see Figure 3. For the randomly selected subjects in the control group 
Dynamic Coronary Roadmap will not be used in order to serve as the comparator to measure the effect of 
Dynamic Coronary Roadmap. Standard of care will be applied to all subjects. 
 
There are no additional devices or medications required for the study. 
6.4. 
Subjects 
6.4.1. In- and exclusion criteria 
Subjects participating in the study will be carefully selected based on the next inclusion and exclusion 
criteria. 
6.4.1.1. Inclusion criteria 
 
Subject is undergoing Percutaneous Coronary Intervention (PCI) with a degree of complexity that 
anticipates the need for more than 25ml of iodinated contrast volume  
 
Subject has signed informed consent 
 
Subject is 18 years of age or older, or of legal age to give informed consent per state or national law 
6.4.1.2. Exclusion criteria 
 
Subject undergoing emergency PCI 
 
Subject with ST-segment Elevation Myocardial Infarction (STEMI) 
 
Subject with Chronic Total Occlusion (CTO) 
 
Subject undergoing PCI for isolated ostial disease of Left Main Coronary Artery (LMCA) or Right 
Coronary Artery (RCA) 
 
Subject undergoing PCI with Optical Coherence Tomography (OCT) support 
 
Subject undergoing PCI with rotational or orbital atherectomy 

 
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 
Subject with Chronic Kidney Disease (CKD) stage V (eGFR < 15 ml/min/1.73 m2) 
 
Subject with contrast allergy that cannot be adequately pre-medicated 
 
Subject participates in a potentially confounding drug or device trial during the course of the study. 
 
Subject is under 18 years of age, or pregnant woman, or breast feeding woman, or meets an 
exclusion criteria according to national law 
 
The domain of the study is ad hoc and elective PCI patients: 
 
Patients scheduled for ad hoc PCI are patients potentially treated via PCI immediately following the 
diagnostic catheterization with diagnostic coronary angiography. 
 
Patients scheduled for elective PCI have recently undergone diagnostic catheterization with 
diagnostic coronary angiography that is still valid for the elective PCI and does not need to be 
redone. Elective PCI is not an emergency intervention and are often also referred to as secondary 
PCI as opposed to primary PCI, which are emergency interventions. 
 
Patients receiving a very straightforward PCI that does not require navigation guidance are not included 
based on the anticipated need for more than 25ml of iodinated contrast volume. This threshold has been 
determined based on standard PCI practice: In PCI typically one contrast enhanced angiogram run is 
performed at the start of the intervention to confirm the C-arm working position and typically two contrast 
injected runs are performed after stent placement to check wall apposition and for documentation purposes. 
Each run typically accounts for 7ml of iodinated contrast, therefore a very straightforward PCI not requiring 
navigation guidance will be performed under 25ml total. 
6.4.2. Duration 
The total duration of the study is expected to take 9 months. 
 
We target to limit the enrollment duration of the 394 subjects to a 9 months maximum, which translates to 
minimally 10 subject inclusions per week overall. Based on a typical PCI procedure volume and the inclusion 
and exclusion criteria it is feasible to enroll at least 2 subjects per week per center, i.e., at least 5 centers are 
required. 
6.4.3. Enrollment 
Subjects are considered to be enrolled in the study after they have signed the informed consent form and 
met all the inclusion and exclusion criteria. No study procedures will be performed before this moment.  
 
The subjects will be followed-up until discharge following standard clinical care.  
6.4.4. Number of subjects  
In total 394 subjects will be enrolled in the study during an expected enrollment period of 9 months. 
 
See section 7 Statistical considerations for more detail on the number of sample size calculation. 
6.4.5. Procedure for the replacement of subjects 
In enrolled subjects the investigator preprocedurally deemed no usage of OCT and/or the rotational or orbital 
atherectomy is required. During the PCI procedure usage of OCT and/or rotational or orbital atherectomy is 
left to the investigator’s discretion. In the case OCT and/or rotational or orbital atherectomy is used in 
enrolled subjects, these subjects will be replaced. 
Thus, the following subjects will be replaced: 
 
Subjects undergoing PCI supported by OCT will be replaced. 
 
Subjects undergoing PCI supported by rotational or orbital atherectomy will be replaced. 
6.4.6. Subject withdrawal or discontinuation 
Subjects can withdraw informed consent at any time during the study.  

 
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6.5. 
Procedures 
Physician investigators participating in this study are expected to follow their normal clinical practice in 
treating and following up patients with Coronary Artery Disease (CAD). Patients randomized to the DCR 
group will undergo a PCI procedure during which DCR is used while those randomized to the control group 
will undergo PCI without the use of DCR. The preparation of the PCI procedure, the procedure itself and 
follow up will be performed following standard of care. 
 
Screening 
Patients scheduled for PCI will be screened on inclusion and exclusion criteria by the principal investigator or 
delegated and trained study personnel. When a patient is eligible study information and the informed consent 
form is provided to the patient and after providing ample time to consider participation the patient is asked for 
signed consent.  
 
PCI procedure 
The investigator will perform PCI using standard of care procedures. 
 
Standard of care PCI entails (deviations allowed up to investigator’s discretion): 
 In case of elective PCI: Randomization before procedure  
 
Arterial access (femoral or radial; preferably perform femoral angiography of preclose device at this 
moment) 
 
In case of ad hoc PCI: Diagnostic Coronary Angiography 
 In case of ad hoc PCI: Randomization upon decision to go for PCI 
 
First positioning of interventional guiding catheter in stable coronary position 
 Record the contrast volume used up to that moment 
 
Coronary Angiography [DCR group: DCR started automatically] 
 
Position guidewire 
 
Position balloon + inflate balloon 
 
Position stent + deploy stent  
 
Check PCI result by Coronary Angiography (potentially combined with e.g. Stent Boost, IVUS) 
 
Repeat above steps when necessary, e.g. post-dilate stent or perform PCI in different vessel 
 Record the total contrast volume used 
 
The principal investigator or his delegates on the study team will enter data in a pre-designed e-CRF. This 
will include patient demographics, relevant past medical history, specific target CAD data along with pre-
procedural/screening imaging details, PCI procedure data and follow-up data until patient discharge. 
6.6. 
Monitoring Plan 
A detailed plan for monitoring arrangement will be separate from this Clinical Protocol. 
 
Monitoring will be performed by a trained person appointed by Philips to ensure compliance with the clinical 
study protocol, applicable national regulations and international standards, patient safety and data validity. 
The Sponsor may designate one or more individuals to monitor the progress of a clinical study. The Sponsor 
may also delegate the monitoring responsibilities to a third party. However, the Sponsor remains ultimately 
responsible for the conduct of the study. The Institution is responsible for the appropriate de-identification of 
subject data. The investigational site should provide access to the source data of the subjects. 
 
All regulatory documents (e.g. MEC/IRB approval, contracts, etc.) will be reviewed for each actively 
participating center. 
 
In accordance to ISO 14155 Clinical investigation of medical devices for human subjects standard before, 
during and after the clinical investigation on-site monitoring is required. After site initiation the first visit will 
occur as soon as possible after the first subject is enrolled at each study site. The monitoring schedule is 
based on the following considerations: enrollment rate, study compliance at the center, magnitude of data 
corrections required, complexity of the study, IRB/MEC request, audit/inspection. 
 
The monitor activities include: 

 
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 
Check that the study is conducted, recorded and reported in compliance with this clinical study 
protocol, and applicable regulations. Acts to oversee the progress of the study. 
 
Check signed and dated informed consent of the subjects and check that this is signed before any 
study-related procedures are undertaken. 
 
Ensure that essential documents (e.g. contract, MEC approval) are maintained in the Site Regulatory 
File. 
 
Ensure recording of deviations from protocol and store in Site Regulatory File or CRF. 
 
Ensure that all adverse events and device deficiencies are reported to the sponsor, and all serious 
adverse events and device deficiencies that could have led to a serious adverse device effect are 
reported to the sponsor without unjustified delay. 
 
Ensure that adverse events and device deficiency are reported to the MEC/IRB, if required. 
 
Ensure that the principal investigator is informed and knowledgeable of all relevant document 
updates concerning the clinical study (e.g. clinical study protocol).  
 
Ensure that amendments to the protocol are provided to the MEC/IRB by the principal investigator.  
 
Ensure device accountability. 
 
Verification of source data.  
 
Critical data and processes will be monitored for this study prior to clinical report completion based on a risk 
based monitoring approach. Dependent on the risk a high or lower sample will be monitored.  
The monitor will review critical clinical data that affect study endpoints. Data collection for reasons other than 
to support the protocol-defined endpoints will not be monitored. 
 
A close-out visit for sites that have enrolled subjects will be conducted once the site has completed collecting 
data for the study. 
 
Names of the monitor(s) can be found in Appendix II. List of Monitors of this protocol. An update of this list 
can be provided to the site under separate cover.  
7. 
Statistical considerations 
Any deviation from the planned analysis described below will be documented with justification in the final 
clinical end report. 
7.1. 
Sample Size Justification Primary Endpoint 
A recent single center, non-randomized, retrospective study [Yabe 2018] has shown to achieve 21.9% 
contrast reduction when using Dynamic Coronary Roadmap compared to the control group without using 
Dynamic Coronary Roadmap, see Table 1.  
 
  
Control group
DCR group 
Number of patients 
103 
43 
Iodinated contrast volume 
(ml) average ± standard 
deviation 
152.1 ± 73.0 
118.8 ± 49.7 
Table 1 Results of a recent pilot study [Yabe 2018] 
To determine the sample size for the primary endpoint of this study we used the Yabe study outcomes as 
input with a margin of 7% for the contrast reduction, i.e., the sample size calculation is performed to reliably 
show a 15% contrast reduction in the DCR group compared to the control group not using Dynamic Coronary 
Roadmap. 
  
For the sample size and power calculations we have set: 
 
Estimated mean for the Control group = 152.1 (based on [Yabe 2018]) 
 
Estimated mean for the DCR group = 129.3 (15% reduction) 
 
Estimated standard deviation = 73.0 (based on [Yabe 2018]) 

 
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 
Effect size (standardized difference): (152.1 – 129.3)/73.0 = 0.3123 
 
Significance: one-sided α = 0.025 (the type I error, i.e., probability of rejecting a true null hypothesis) 
 
Power (1-β) = 80% 
 
Sample sizes of 162 for each group achieves 80% power to reject the null hypothesis of equal means when 
the population mean difference is 15% with a standard deviation of 73.0 for both groups and with a 
significance level (alpha) of 0.025 using a one-sided two-sample equal-variance t-test (calculated by PASS 
16.0.3 software). 
 
Finally the percentage of subjects that are expected to be lost at random during the course of the study 
(drop-out rate) and for whom no response data will be collected (i.e., will be treated as "missing") needs to 
be taken into account. A drop-out rate of 10% (DR=0.1) is assumed, meaning that 162/(1-DR)=180 patients 
are needed in each group totaling 360 patients for the primary endpoint. 
 
The study will be a multi-center trial in which per center a maximum of three investigators will be participating 
and each investigator is required to include at least 20 patients in the study, which indirectly sets the 
minimum number of subjects to be included per center. 
7.1.1. 
Sample Size Justification Secondary Endpoint 
A recent single center, non-randomized, prospective study [Rajappan 2017] showed a 25.6% reduction in the 
total number of cine X-ray runs after introduction of Dynamic Coronary Roadmap, see Table 2. 
 
 
Enrollment group 1 
Enrollment group 4 
Number of patients 
21 
21 
Number of cine X-ray runs 
Average: 46.2 
SD: 22.4 
Median: 43.0 
IQR: 31-54 
Average: 34.6 
SD: 21.2 
Median: 32.0 
IQR: 20-43 
Number of stents 
Average: 1.76 
SD: 0.89 
Average: 1.67 
SD: 0.86 
Table 2 Results of a recent pilot study [Rajappan 2017] 
 
For the sample size and power calculations we have set based on [Rajappan 2017]: 
 
Estimated mean for the Control group = 46.2  
 
Estimated mean for the DCR group = 34.6  
 
Estimated median for the Control group = 43.0  
 
Estimated median for the DCR group = 32.0  
 
Significance: one-sided α = 0.025 (the type I error, i.e., probability of rejecting a true null hypothesis) 
 
Power (1-β) = 80% 
 
Sample sizes of 177 for each group achieves 80% power to reject the null hypothesis of equal population 
distributions with a significance level (alpha) of 0.025 using a one-sided Wilcoxon-Mann-Whitney test, since 
the number of angiographic X-ray runs is discrete and is likely to be not normally distributed (calculated by 
SAS software). 
 
This means for the secondary endpoint on Number of Angiograms that 177/(1-DR)=197 patients are needed 
in each group, so 394 in total which is higher than the total number of patients (360) required for the primary 
endpoint, so a total of 394 subjects are required for this study. 
7.2. 
General Considerations 
All results will be summarized using descriptive statistics, i.e., using frequencies and percentages or 
summary statistics like averages and medians (including confidence intervals and interquartile ranges). 

 
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Subgroup analyses (e.g., for 1, 2, 3 or more vessel PCI, and anatomical complexity via SYNTAX score) will 
be performed and presented. Methods to correct for missing data will be used like, e.g., worst case scenario 
analysis, multiple imputation methods [Rubin 2004]. Analyses to determine whether there is an effect based 
on e.g. intervention difficulty, lesion characteristics, patient demographics, physician experience, center 
effect etc. will be performed. If an effect is found applying adjustment analysis will be considered. An 
independent angiographic committee of experts may be consulted to blindly analyze cases to check for 
validity of exclusion and inclusion criteria and other relevant aspects of the study, and potential adjustment 
analysis will be considered. Statistical analysis will be performed using SAS (SAS Institute, Cary, North 
Carolina) and/or R statistical software (https://www.r-project.org/).  
7.3. 
Poolability 
A site effect analysis will be conducted on the primary endpoint to assess poolability of data. Adjustment 
analysis will be considered if sites are not homogeneous. 
7.4. 
Subject Disposition 
Subject disposition, including the total number of subjects evaluated will be presented. In addition, a listing 
will be provided with the reasons for why the subject was not evaluated. 
7.5. 
Demographics and Baseline Characteristics 
Basic subject characteristics such as age, gender, height and weight will be summarized. In addition, the 
SYNTAX score [Sianos 2005, Neumann 2018] will be determined for the vessel(s) treated with PCI as an 
index for anatomical complexity, the number of lesions treated in the PCI, the location of the lesion, etc., see 
Figure 4: 
 

 
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Figure 4 Steps to determine SYNTAX score as an index for anatomical complexity of the PCI [from 
Neumann 2018] 

 
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7.6. 
Primary objective 
Objective 
To assess whether using Dynamic Coronary Roadmap reduces the total iodinated contrast volume related to 
PCI compared to the control group without Dynamic Coronary Roadmap. 
 
Endpoint 
The primary endpoint of the study is the average total undiluted iodinated contrast volume (in ml) used per 
PCI (from first positioning the interventional guiding catheter in stable coronary position till end of PCI 
procedure) measured by an automatic contrast injector. 
 
Hypothesis 
Dynamic Coronary Roadmap reduces the total iodinated contrast volume used on average per PCI.  
 
H0: µControl1 - µDCR1 ≤ 0 
Ha: µControl1 - µDCR1 > 0 
 
Where µControl1 is the average total iodinated contrast volume usage per PCI for the Control group, and µDCR1 
is the average total iodinated contrast volume usage per PCI for the DCR group. 
 
Rationale for choice of hypothesis 
Based on pilot study results and the working mechanism of DCR this hypothesis is chosen to measure the 
reducing effect of DCR on the total iodinated contrast volume usage in PCI. 
 
Analysis 
The objective will be evaluated using a one-sided two-sample equal-variance t-test. The relative impact of 
the analysis results will be made in comparison to the maximum ratio of contrast volume (in ml) to the 
glomerular filtration rate (in ml/min/1.73m2) being 3.7 for severe CKD (eGFR<30) as recommended by the 
ESC/EACTS Guidlines [Laskey 2007, Neumann 2018]. 
 
All subjects will be included in this analysis. 
7.7. 
Secondary objective 
7.7.1. Secondary objective: Number of Angiograms 
 
Objective 
 
To assess the total number of contrast enhanced cine angiographic X-ray runs (angiograms) related 
to PCI in the Dynamic Coronary Roadmap and control group 
 
Endpoint 
 
The average total number of contrast enhanced cine angiographic X-ray runs (angiograms) per PCI 
(from first positioning the interventional guiding catheter in stable coronary position till end of PCI 
procedure) determined via visual assessment (e.g., on the Philips X-ray system). 
 
Hypothesis 
Dynamic Coronary Roadmap reduces the total number of contrast enhanced cine angiographic X-ray runs 
(angiograms) acquired on average per PCI.  
 
H0: PopControl2 ≤ PopDCR2 
Ha: PopControl2 > PopDCR2 (Control is shifted to the right of DCR) 
 
Where PopControl2 is the population distribution for the number of contrast enhanced cine angiographic X-ray 
runs (angiograms) acquired per PCI for the Control group, and PopDCR2 is the population distribution for the 
number of contrast enhanced cine angiographic X-ray runs (angiograms) acquired per PCI for the DCR 
group. 
 

 
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Rationale for choice of hypothesis 
Based on pilot study results and the working mechanism of DCR this hypothesis is chosen to measure the 
effect of DCR on the number of contrast enhanced cine angiographic X-ray runs (angiograms) acquired in 
PCI. 
 
Analysis 
The number of angiographic X-ray runs is discrete and is likely to be not normally distributed, so the 
objective will be evaluated using a one-sided Wilcoxon-Mann-Whitney test. 
 
All subjects will be included in this analysis. 
7.8. 
Exploratory objectives 
7.8.1. Exploratory objective: Contrast Volume per Vessel PCI 
Objective 
 
To assess the iodinated contrast volume used per vessel PCI in the Dynamic Coronary Roadmap 
and control group  
 
Endpoint 
 
The average undiluted iodinated contrast volume (in ml) used per vessel PCI (from first positioning 
the interventional guiding catheter in stable coronary position till end of PCI procedure) measured by 
an automatic contrast injector. For multi vessel PCI the iodinated contrast volume used per vessel 
PCI will be determined based on the total PCI contrast volume (from first positioning the 
interventional guiding catheter in stable coronary position till end of PCI procedure) divided by the 
number of vessels treated by PCI. 
 
Analysis 
The objective will be evaluated using a two-sample equal-variance t-test and cluster analysis. 
 
All subjects will be included in this analysis. 
7.8.2. Exploratory objective: Contrast Volume per Stratification Group (1, 2, 3 or 
more vessel PCI) 
Objective 
 
To assess the total iodinated contrast volume related to PCI per stratification group, i.e., 1 vessel 
PCI, 2 vessel PCI and 3 or more vessel PCI, in the Dynamic Coronary Roadmap and control group 
  
Endpoint 
 
The average total undiluted iodinated contrast volume (in ml) used per PCI (from first positioning the 
interventional guiding catheter in stable coronary position till end of PCI procedure) measured by an 
automatic contrast injector in each stratification group, i.e., 1 vessel PCI, 2 vessel PCI and 3 or more 
vessel PCI. 
 
Analysis 
The objective will be evaluated using a two-sample equal-variance t-test and cluster analysis.  
 
All subjects will be included in this analysis. 
7.8.3. Exploratory objective: Contrast Volume per Simple, Intermediate, Complex 
PCI subgroup 
Objective 
 
To assess the total iodinated contrast volume related to PCI in subgroups of simple, intermediate 
and complex PCI (where the SYNTAX score for the vessel(s) treated with PCI will be used as an 
index for complexity) in the Dynamic Coronary Roadmap and control group 
  

 
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Endpoint 
 
The average total undiluted iodinated contrast volume (in ml) used per PCI (from first positioning the 
interventional guiding catheter in stable coronary position till end of PCI procedure) measured by an 
automatic injector in subgroups of simple, intermediate and complex PCI. The SYNTAX score for the 
vessel(s) treated with PCI will be calculated to be used as an index for the anatomical complexity of 
the PCI [Sianos 2005].  
 
Analysis 
The objective will be evaluated using a two-sample equal-variance t-test and cluster analysis.  
 
The iodinated contrast volume usage and related contrast volume usage difference will be binned according 
to the anatomical complexity of the PCI procedure using the SYNTAX score for the vessel(s) treated with 
PCI as index for anatomical complexity. 
 
All subjects will be included in this analysis. 
7.8.4. Exploratory objective: AKI Incidence 
Objective 
 
To assess the incidence of Acute Kidney Injury (AKI) in the Dynamic Coronary Roadmap and control 
group (at discharge following standard clinical care) 
 
Endpoint 
 
The total number and percentage of subjects in which AKI, (defined as an absolute SCr increase 
>0.3 mg/dl within 48 hours post PCI or a relative SCr increase >50% within 7 days post PCI, or 
eGFR decrease >25% within 48 hours post PCI) is diagnosed after PCI. 
 
Analysis 
Multiple AKI definitions exist, which are all based on measuring serum creatinine (SCr, measured via isotope 
dilution mass spectrometry (IDMS) [Meyers 2006]) or urine output:  
 
RIFLE (Risk, Injury, Failure, Loss, End stage renal disease) [Bellomo 2004],  
 
Acute Kidney Injury Network (AKIN) [Mehta 2007], and 
 
Kidney Disease Improving Global Outcomes (KDIGO) guidelines [KDIGO guidelines AKI 2012]. 
 
A recent study [Parsh 2016] showed that the combination of an absolute Serum Creatinine (SCr) increase 
>0.3 mg/dl within 48 hours post PCI or a relative SCr increase >50% within 7 days post PCI might be the 
most optimal definition for AKI.  
 
Using the SCr measurement often the estimated GFR (eGFR) is determined as a measure of kidney 
function, which can be calculated according to the Modification of Diet in Renal Disease (MDRD) equation or 
its successor the Chronic Kidney Disease epidemiology (CKD-EPI) equation [Levey 1999, Bellomo 2004, 
Levey 2006, Levey 2009, Van den Brand 2011, Nyman 2014]. The CKD-EPI equation to estimate the 
glomerular filtration rate reads [Levey 2009]: 
 
eGFR = 141 x min(SCr/, 1) x max(SCr/, 1)-1.209 x 0.993Age x 1.018[if female] x 1.159[if black], 
     with =0.7 and =-0.329 if female; 
with =0.9 and =-0.411 if male. 
 
Here min indicates the minimum of SCr/ or 1, and max indicates the maximum of SCr/ or 1. 
 
Based on the eGFR calculation CKD can be classified in 5 stages as indicated in Table 3. 
 
 

 
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CKD classification 
eGFR (ml/min/1.73m2)
Stage I (normal renal function) 
>60 
Stage II (mild – moderate reduction) 
45 – 60 
Stage III (moderate – severe reduction) 
30 – 45 
Stage IV (severe reduction) 
15 - 30 
Stage V (renal failure) 
<15
Table 3 CKD classification based on eGFR [Tsai 2014a] 
 
New AKI biomarkers are being investigated such that both renal function and renal damage can be 
diagnosed early, but even the most promising ones (cystatin C and neutrophil gelatinase-associated lipocalin 
(NGAL)) are rarely routinely used in the hospital [Ostermann 2016]. Serum creatinine measurement and 
eGFR calculation are still most commonly used to diagnose AKI, which we will also adopt using the following 
definition for AKI [Parsh 2016, Bellomo 2004]: 
 
An absolute Serum Creatinine (SCr) increase >0.3 mg/dl within 48 hours post PCI or a relative SCr 
increase >50% within 7 days post PCI 
OR 
 
eGFR decrease >25% within 48 hours post PCI 
 
Note that according to [Guideline NVvR 2017] the measurement of SCr/eGFR is valid for:  
- 
Maximally 7 days when the patient has an acute disease or an acute deterioration of a chronic 
disease;  
- 
Maximally 3 months when the patient has a known chronic disease with stable renal function;  
- 
Approx. 12 months in all other patients  
 
The majority of PCI patients are discharged within 24 hours after the PCI procedure and consequently the 
SCr measurement is performed within 24 hours post PCI while the SCr levels might still be rising and 
diagnosis of AKI may be missed as a result. 
 
Furthermore when considering the incidence of AKI in the patient population of this trial (7.1% incidence, but 
reported from 3% to 19% [Tsai 2014a]) and taking into account the sample size of 394 patients it is not likely 
this trial will find a significant difference in AKI incidence in the DCR group compared to the control group. 
 
As AKI prevention method adequate pre- and post-hydration with isotonic saline (NaCl 0.9%) should be 
applied to patients with GFR<60 ml/min/1.73m2 as recommended by the ESC/EACTS Guidelines: 1 ml/kg/h 
12 h before and continued for 24 h after the procedure (0.5 ml/kg/h if LVEF ≤35% or NYHA >2) [Neumann 
2018]. 
 
The objective will be evaluated using a two-sample equal-variance t-test. 
 
All subjects will be included in this analysis. 
 
 
7.8.5. Exploratory objective: Contrast Usage Variability 
Objective 
 
To assess the variability of the total iodinated contrast volume related to PCI in the Dynamic 
Coronary Roadmap and control group 
 
Endpoint 
 
The standard deviation, Interquartile Range (IQR), quartile coefficient of dispersion ((Q3-
Q1)/(Q3+Q1), where Q1 and Q3 are the first and third quartiles), and relative standard deviation (SD 
divided by the average, also known as coefficient of variation) of the total undiluted iodinated 
contrast volume (in ml) used per PCI (from first positioning the interventional guiding catheter in 
stable coronary position till end of PCI procedure) measured by an automatic contrast.  
 

 
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Analysis 
The objective will be evaluated using a Brown-Forsythe test to test for equal variances in both groups and 
cluster analysis. 
 
All subjects will be included in this analysis. 
7.8.6. Exploratory objective: Fluoro & Procedure Time 
Objective 
 
To assess the total fluoroscopy & procedure time related to PCI in the Dynamic Coronary Roadmap 
and control group 
 
Endpoint 
 
The average fluoroscopy and procedure time per PCI (from first positioning the interventional guiding 
catheter in stable coronary position till end of PCI procedure), where the fluoroscopy time is 
measured by the Philips X-ray system.   
 
Analysis 
The objective will be evaluated using a two-sample equal-variance t-test. 
 
All subjects will be included in this analysis. 
 
7.8.7. Exploratory objective: X-ray Dose 
Objective 
 
To assess the total X-ray dose (DAP, AK) related to PCI in the Dynamic Coronary Roadmap and 
control group 
 
Endpoint 
 
The average total DAP and AK per PCI (from first positioning the interventional guiding catheter in 
stable coronary position till end of PCI procedure) measured by the Philips X-ray system. 
 
Analysis 
The objective will be evaluated using a two-sample equal-variance t-test. 
 
All subjects will be included in this analysis. 
 
7.8.8. Exploratory objective: Procedural Success 
Objective 
 
To assess the procedural success in the Dynamic Coronary Roadmap and control group 
 
Endpoint 
 
The total number and percentage of subjects treated with procedural success. Procedural success is 
defined as an open target vessel with a maximum of 30% residual stenosis and TIMI flow grade 3 
(complete perfusion) [TIMI 1985], e.g. determined via visual inspection of Coronary Angiography. 
 
Analysis 
Since DCR is a tool assisting the physician in navigating devices through the coronary arteries it is not likely 
this trial will find a significant difference in procedural success in the DCR group compared to the control 
group. 
 
The objective will be evaluated using a two-sample equal-variance t-test. 
 
All subjects will be included in this analysis. 
 

 
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7.8.9. Exploratory objective: In-hospital MACCE 
Objective 
To register in-hospital Major Adverse Cardiovascular and Cerebral Events (MACCE) in the Dynamic 
Coronary Roadmap and control group  
 
Endpoint 
 
The total number and percentage of in-hospital. MACCE is defined as all-cause death, acute 
myocardial infarction, coronary artery bypass surgery, repeat coronary revascularization of the target 
lesion, or acute ischemic stroke during hospitalization for the PCI procedure. 
 
Analysis 
Since DCR is a tool assisting the physician in navigating devices through the coronary arteries it is not likely 
this trial will find a significant difference in in-hospital MACCE in the DCR group compared to the control 
group. 
 
The objective will be evaluated using a frequencies and percentages. 
 
All subjects will be included in this analysis. 
7.8.10. Sensitivity Analysis for the Primary Endpoint 
A worst-case analysis will be considered for the primary endpoint [the average total undiluted iodinated 
contrast volume (in ml) used per PCI]. For missing outcomes for the control group, the lower bound of the 
95% confidence interval around the control mean will be imputed. For missing outcomes for the DCR group, 
the upper bound of the 95% confidence interval around the DCR mean will be imputed. The primary endpoint 
will be re-assessed with a complete dataset. 
8. 
Data management 
An e-CRF will be used to collect medical history, subjects demographics, procedure related information, 
protocol deviations, adverse events and device deficiencies. 
 
The e-CRF will be used for data review, data cleaning and issuing and resolving queries. This e-CRF is a 
web-based e-CRF which is password protected and is 21 CFR part 11 compliant. At the end of the study the 
data will be stored as a frozen dataset and will be retained. Interview can be performed separately from the 
e-CRF. 
 
The e-CRF data from the subjects will be key-coded (pseudonomyzed). The information related to the 
subjects (like name) is kept separately in the enrollment log at the hospital. Date and time of the procedure 
and date of discharge will be collected.  
 
All exported (image) data will be de-identified and this data will be collected and stored in a secure location. 
8.1. 
Retention period 
The investigator shall maintain the records related to this study during the investigation and for a period of 2 
years after the latter of the following two dates: The date on which the study is terminated or completed, or 
the date that the records are no longer required for purposes of supporting a premarket approval application 
in the US or a notice of completion of a product development protocol. Or longer if national regulation 
requires this. 
Philips will maintain the records for the same period as the investigator or for a period of device End of Life 
(EoL) plus 15 years, whichever is later.  
 
The sponsor and principal investigator shall take measures to prevent accidental or premature destruction of 
these documents. 

 
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9. 
Amendments to the Clinical Study Protocol 
Amendment to the Clinical Study Protocol shall be notified to, or approved by the MEC and where 
appropriate regulatory authorities. The version number and date of amendments shall be documented. 
Significant changes (such as device modifications, study procedures) shall be discussed with the 
coordinating investigator and principal investigator prior approval. All changes will be documented with a 
justification and described in the latest version of the clinical study protocol.  
10. 
Deviations from the Clinical Study Protocol 
The Investigator is not allowed to deviate from the clinical study protocol or to enroll subjects that do not 
comply with all inclusion and exclusion criteria. Under emergency circumstances, deviations from the clinical 
study protocol to protect the rights, safety and well-being of human subjects may proceed without prior 
approval of the sponsor and the MEC. Such deviations shall be documented and reported to the sponsor and 
the MEC as soon as possible.  
All deviations from the clinical study protocol will be documented with date, subject, reason, actions taken 
and if the deviation affects subject's rights, safety and well being or the scientific integrity of the clinical study. 
The deviation shall be notified to the Sponsor as soon as possible via the e-CRF. Deviations will be reviewed 
by the sponsor and in case of serious or repetitive deviations a corrective action plan may represent a need 
to initiate a corrective action plan with the principal investigator. In some cases, necessitate suspension of 
enrollment at the site or ultimately the principal investigator will be disqualified. 
11. 
Device accountability 
A device that is market released is used in this study, therefore no device accountability (e.g documented 
return and disposal) will be performed.   
12. 
Statements of compliance 
This clinical study shall be conducted in accordance with the clinical study protocol, and with the ethical 
principles that have their origin in the Declaration of Helsinki and all applicable regional and/or national 
regulations. Furthermore, in Europe this clinical study shall be in accordance with the International Standards 
ISO 14155 Clinical investigation of medical devices for human subjects - Good clinical practice [ISO14155], 
and the Medical Device Directive [MDD] and in accordance with [MEDDEV] Clinical Evaluation guidance. 
Furthermore all investigators will complete financial disclosures, as outlined in the CFR 21 part 54 and will 
also comply with part 11. Investigators located in the US shall follow: 21 CFR part 50, 56 and 812. 
 
This study shall not be started prior to obtaining a favorable opinion from a Medical Ethics Committee 
(MEC)/Institutional Review Board (IRB), if required. Any additional requirements imposed by the MEC/IRB 
shall be followed. 
 
Insurance shall be provided for the subjects participating in this clinical trial according to local law. 
13. 
Informed consent process 
Informed consent will be obtained from every subject in writing by the Investigator or his authorized designee 
before any research related procedures are started is started. 
The subject will be informed both orally and in writing about all aspects that are relevant to the subject’s 
decision to participate in the clinical study, including the clinical study procedures. Ample time should be 
provided for the subject to read and understand the informed consent form and to consider participation. The 
informed consent will include personally dated signatures of the subject and the principal investigator or an 
authorized designee responsible for conducting the informed consent process. A copy of the signed and 
dated informed consent form and any other written information will be provided to the subject. 
 
Subjects who are unwilling to provide informed consent will not be included in the Research.  
 
If new information becomes available that might significantly affect the subject’s future health and medical 
care, it shall be provided to the subjects in written form. If relevant, subject shall be asked to reconfirm their 
continuing informed consent in writing.  

 
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14. 
Safety reporting 
The following event should be reported to Philips for Medical Device Reporting (MDR) according to 21 CFR 
part 803: Deaths and serious injuries that a device has or may have caused or contributed to, Caused or 
contributed means that a death or serious injury was or may have been attributed to a medical device, or that 
a medical device was or may have been a factor in a death or serious injury, including events occurring as a 
result of:  (1) Failure; (2) Malfunction; (3) Improper or inadequate design; (4) Manufacture; (5) Labeling; or (6) 
User error. 
Medical Device Reporting shall be reported to the regular Philips Healthcare customer feedback system, i.e. 
contact the local Helpdesk to report these events.  Also report these to the Clinical Study Manager (see 
Appendix II. List of Monitors). 
 
The following incident should be reported to Philips for Vigilance Reporting: 
Any malfunction or deterioration in the characteristics and/or performance of a device, as well as any 
inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead to or might have 
led to the death of a patient, or USER or of other persons or to a serious deterioration in their state of health.  
A serious deterioration in state of health can include according to the definition:  
a) life-threatening illness, 
b) permanent impairment of a body function or permanent damage to a body structure, 
c) a condition necessitating medical or surgical intervention to prevent a) or b). 
Examples: - clinically relevant increase in the duration of a surgical procedure, 
- a condition that requires hospitalization or significant prolongation of existing hospitalization. 
d) any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic test results when used 
within manufacturer’s instructions for use. 
e) foetal distress, foetal death or any congenital abnormality or birth defects. 
Vigilance Reporting shall be reported to the regular Philips Healthcare customer feedback system, i.e. 
contact the local Helpdesk to report these events.  Also report these to the Clinical Study Manager (see 
Appendix II. List of Monitors). 
15. 
Early termination or suspension of the Clinical study 
There are no provisions or interim analyses planned that can result in an early termination of the trial.  
Serious or repetitive occurrence of deviations from study protocol or non-compliance with regulations may 
also be reason for early termination or suspension of a study site.  
16. 
Publication policy 
It is the intention of the investigator and sponsor to submit the clinical study data for publication. Prior to 
submission, claims on intellectual property will be assessed. 
 
This study will also be registered on clinicaltrial.gov before first enrollment. 
 
 
 
 
 
 
 

 
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