Robotically Assisted PCI in Ostial Lesions
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Corindus Inc.

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Protocol title: 
 
ROBotically assisted PCI in OSTIAL lesions: 
the ROB-OSTIAL study 
 
Version A  
23 November 2022 
 
 
 
 
Sponsor  
Corindus, Inc. dba Siemens Healthineers 
Endovascular Robotics 
 
 
 
 
275 Grove Street, 
Newton, MA  02466 
 
 
This protocol is the confidential intellectual property of Corindus, Inc. dba Siemens 
Healthineers Endovascular Robotics “Sponsor”. The use of any unpublished material 
presented in this document must be restricted to the recipient for the agreed purpose 
and must not be disclosed to unauthorized persons without the written consent of the 
Sponsor. 
 

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PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
I have read and agree to adhere to the clinical investigation plan and all 
regulatory requirements applicable in conducting this clinical investigation. 
 
 
Principal Investigator 
 
Printed name: ROBERTO NERLA 
Site: MARIA CECILIA HOSPITAL – COTIGNOLA (RA) 
Signature: 
Date: 
 
 
 

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SPONSOR SIGNATURE PAGE 
 
 
Printed name: Colleen Smith 
Title: Clinical Operations Manager, Corindus, Inc. dba Siemens Healthineers 
Endovascular Robotics 
Signature: 
Date: 
 
 
 

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GENERAL INFORMATION 
Clinical Study Proposal 
Study Design 
 
Sponsored Study, Prospective, single-center, randomized 
Title - Acronym 
Robotically assisted PCI in ostial lesions:  
the ROB-OSTIAL study 
Sponsor 
Corindus, Inc. dba Siemens Healthineers Endovascular Robotics 
Funding address  
275 Grove Street 
Newton, MA  02466 
Primary 
Investigator (PI) 
Roberto Nerla  MD 
Institution 
Maria Cecilia Hospital – GVM Care and Research Cotignola (IT) 
Version 
A 
Projected Dates of 
Study 
Estimated First patient in: February 2023 
Expected Time to Complete Enrollment: August 2024 (18 months) 
Expected Time of each Subject to Complete the Study: 1 month 
Total Expected Duration of the Study: 21 months 
Estimated study end: November 2024 
GCP Statement 
The study will be conducted in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki and 
are consistent with ICH Good Clinical Practice as well as regulatory 
requirements 
Confidential 
This protocol is the property of the Sponsor and may not – in full 
or in part – be passed on, reproduced, published or otherwise used 
without permission 
* ICH: The International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
 
 

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SYNOPSIS 
Research Topic: 
Robotically assisted PCI in ostial lesions:  
the ROB-OSTIAL study 
Summary of Proposal: 
To assess accuracy of robotic-assisted PCI in obtaining full 
ostial lesion coverage and minimal protrusion compared to 
manual PCI. 
Robotically assisted PCI offers the opportunity of performing 
minimal device movements (up to a minimum of 1 mm) in a 
stable and reproducible setting. This feature may be of great 
help when dealing with ostial lesions, whose treatment 
requires a precise stent positioning to avoid strut protrusion 
but also geographic miss of the lesion. Robotic-assisted PCI for 
ostial lesions showed encouraging results in large 
observational registries, but no study compared this approach 
with manual PCI.  
We aim to perform a randomized (1:1) study comparing 
manual (n=33) and robotic-assisted PCI (n=33) in obtaining 
full lesion coverage when treating ostial lesions (ostial left 
main will be excluded).  
Primary endpoint of the study will be full ostial coverage as 
assessed by IVUS imaging, while secondary endpoints will be 
procedural success, vessel damage and number of protruding 
struts in the donor vessel as assessed by IVUS imaging. 
 
Summary of Timeline: 
Starting in 2023 (after EC approval), approximate duration 21 
months 
 
 
 
 
 
 
 
 
 
 

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STUDY TABLE OF ASSESSMENTS  
 
Assessment 
 
Enrollment 
 
 
Procedure 
 
Discharge 
 
1M FU 
(± 7 days) 
Eligibility criteria 
X 
X 
 
 
Informed consent 
X 
 
 
 
Medical and Cardiac history 
X 
 
 
 
Canadian Cardiovascular 
Society (CCS) Angina Grade 
X 
 
X 
X 
Hemoglobin/hematocrit 
X 
 
 
X 
CK and/or CK-MB and 
troponin 
X 
 
X 
 
Total Cholesterol 
X 
 
 
X 
Creatinine and Glomerular 
filtration rate 
X 
 
X 
X 
 
12-lead ECG 
X 
 
X 
X 
Concomitant Therapy 
X 
 
X 
X 
Procedure: 
Coronary angiography 
 
X 
 
 
Procedure: Percutaneous 
Coronary Intervention (PCI) 
 
X 
 
 
Procedure: Intravascular 
Ultrasound (IVUS) 
 
X 
 
 
 
MACE - MAE 
 
 
X 
X 
 
Adverse event 
 
X 
X 
X 
 
 
 
 

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STUDY FLOW CHART 
 

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1. 
RATIONALE 
Robotic PCI is known to reduce geographical miss of coronary lesions and increase 
accuracy of stent placement during coronary PCI. Its role may be particularly 
helpful when treating ostial lesions, which require a precise stent positioning in 
order to reduce long-term clinical events. 
1.1 
Clinical need 
Accurate placement of coronary stents in ostial locations is known to be 
challenging (1).  Angiographic ostial location ambiguity, often requiring multiple 
views, and problems with the motion of the stent before deployment are 
considered possible relevant sources of mistakes during PCI (2).  Advancement of 
the stent past the ostium can lead to ''geographic miss'' where suboptimal 
scaffolding of the plaque or lack of coverage of areas exposed to balloon injury 
increase the risk of restenosis (3-5). If the stent is protruding in the donor vessel, 
it may cause difficulties, including 1) The need to re-cannulate the coronary artery, 
2) a possible re-wiring through the side of the stent (in case of re-intervention) 
with subsequent stent deformation, and 3) unopposed struts undergoing an 
irregular process of endothelialization and neointima coverage (6,7). Of note, a 
retrospective analysis of 100 consecutive PCI of aorto-ostial lesions observed 
stent misplacement (defined as a stent deployed > 1 mm from the ostium) in 54% 
of cases, of which proximal and distal misses were equally represented (8). 
Interestingly, a geographic miss was associated with higher rates of restenosis and 
target lesion revascularization (TLR) compared with ‘accurate’ stent placement. 

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The use of robotic PCI is able to offer some advantages compared to manual PCI, 
including the reduction of longitudinal ‘geographic miss’ and the possibility of 
performing 1-mm accommodations in device positioning. In addition, it can 
improve lesion length evaluation as previously reported (9). The adjunct role of 
robotic-PCI in improving lesion coverage during ostial vessels PCI has never been 
previously evaluated.  
1.2 Device Description 
The CorPath® GRX System is intended for use in the remote delivery and 
manipulation of coronary or peripheral guidewires, rapid exchange (RX) devices 
and guide catheters during percutaneous coronary intervention (PCI) procedures. 
 
The complete CorPath GRX System includes the following major components: 
The Bedside Components consist of an Extended Reach Arm, Robotic Drive and 
Single-use Cassette. The Extended Reach Arm is mounted on a bed rail and 
supports the Robotic Drive. 
• Robotic Drive: Receives inputs from the Control Console. These inputs 
actuate mechanical operations in Single-use Cassette as movements to a 
loaded guidewire, RX device, and guide catheter. The Robotic Drive moves 
forward and backwards to advance and retract the guide catheter. A 
Bedside Touchscreen on the Robotic Drive provides the user interface for 
bedside operator during system set-up, loading and device exchanges. 
• Single-use Cassette: Attaches to the Robotic Drive and can be loaded with 
commercially available guide catheters, guidewires, and RX devices. This 

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Single-use Cassette advances, retracts, and rotates the guidewire, advances 
and retracts the RX device, and rotates the guide catheter. 
• Extended Reach Arm: Mounted on the rail of the procedure table and 
supports the Robotic Drive. 
The Interventional Cockpit houses the Control Console, the X-ray Foot Pedal, 
and Monitor(s) to display angiographic and hemodynamic data. It is designed to 
protect the physician from radiation exposure while maneuvering interventional 
devices. 
Control Console: The Control Console enables the physician to remotely 
manipulate the guide catheter, guidewire, and RX device. The Control Console has 
a touchscreen and three joysticks: one joystick for RX device manipulation, one for 
guidewire manipulation, and a third joystick for guide catheter manipulation. 
2 
STUDY DESCRIPTION 
This is Sponsored, prospective, single-center, randomized study. Subjects who 
meet eligibility criteria are randomly assigned (1:1) to manual PCI (n=33) or 
robotically-assisted PCI (n=33). In both arms, the final result will be evaluated by 
IVUS assessment of ostial coverage. 
 
2.1 
Endpoints 
The aim of this study is to (1) compare ostial coverage and (2) strut protrusion, as 
assessed by IVUS, between a strategy of robotic-PCI and a strategy of standard 

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manual PCI in a prospective randomized study including subjects undergoing 
elective PCI at a single high-volume center. 
Primary endpoints:  
1) Evidence of full ostial coverage at angiographic and IVUS assessment 
Secondary endpoints:  
1) Distance from most proximal stent strut and coronary ostium (mm), as 
assessed by IVUS 
2) In-hospital major cardiovascular events 
3) Procedural duration (defined as the duration from when the sheath is 
inserted until it is removed) 
4) Major adverse cardiovascular events at 1 month follow-up 
 
2.2 
 Inclusion criteria 
1. Male or nonpregnant female aged ≥18 years 
2. Coronary ostial lesions suitable for percutaneous coronary intervention (PCI). 
3. The subject has been informed of the nature of the study, agrees to its 
provisions and has provided written informed consent.  
 

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2.3 
Exclusion criteria 
Subject relevant criteria 
1. 
Cardiogenic shock or hemodynamic instability requiring support. 
2. 
ST-elevation myocardial infarction. 
3. 
Ongoing acute renal failure. 
4. 
In the opinion of the investigator, the subject is deemed unsuitable for 
robotic PCI due to clinical status and/or anatomic characteristics 
Lesion relevant criteria 
5. 
Ostial left main disease 
6. 
Chronic Total Occlusion 
 
2.4 
Risks and benefits 
Indications to PCI, PCI itself, and medical management of subjects will follow 
scientific evidence and guidelines. Robotically-assisted PCI did not show safety 
concerns in published studies and is currently conceived as an adjunctive tool to 
improve PCI accuracy. The potential benefits of robotically-assisted PCI in this 
specific setting include a better procedural result (IVUS evidence of full ostium 
coverage with no/minimal protrusion in the donor vessel) with no difference in 
major short-term outcomes. 

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 All materials employed are currently commercially available and CE marked.  
3 
STATISTICAL DESIGN 
The present study is a prospective, randomized 1:1, single-center study. It is 
intended for subjects with indications of coronary revascularization and coronary 
lesions suitable for PCI. Subjects will be randomly assigned to one arm out of two: 
robotic PCI (n=33) or manual PCI (n=33) in a 1:1 ratio.  
Based on previous studies, we estimated an overall incidence of geographic ostial 
miss of 50%. Assuming that the use of robotic PCI can selectively achieve at least 
a 70% reduction of the geographic miss, 66 subjects are required to have an 80% 
chance of detecting, as significant at the 5% level, a 70% decrease of geographic 
miss from manual PCI to robotic PCI arm. 
4 
METHODS FOR ASSESSING AND RECORDING DATA 
Data will be recorded on individual subjects’ case report forms (CRF) within the 
electronic data capture (EDC) system.  
5 
DESCRIPTION OF CLINICAL INVESTIGATION RELATED PROCEDURES 
5.1 
Baseline evaluation, subject enrollment  
All patients admitted and evaluated for coronary angiography and potential PCI 
will be screened at hospital admission for study eligibility by a member of the 
investigational site’s research team that will review the patient’s medical history.  

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At this point and prior to undergoing any study-related procedures, the informed 
consent must be explained and signed. During the consent discussion, the 
investigator or his/her designee must fully illustrate all pertinent aspects and 
risks of the study and related procedures. In particular, the subject must be 
informed that randomization will only be done after coronary angiography and 
coronary lesion suitability assessment. No additional procedure will be performed 
to assess lesion suitability, as the ostial disease will be only defined by 
angiography The subject will be considered enrolled after the coronary 
angiography is complete and the subject is randomized. 
 
5.2 
Screen Failure 
A subject who signs an informed consent form (ICF) and does not undergo 
randomization will be considered a screen failure and should be treated according 
to the standard of care. 
 
5.3 
Coronary angiography 
After a written informed consent form has been obtained, the subject will undergo 
coronary angiography. If the presence of critical coronary lesions eligible for PCI 
is confirmed, lesion-related inclusion/exclusion criteria will be checked to go to 
the next step of randomization. 
 

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5.4 
Randomization 
Once the investigator has determined that the subject and the procedure are 
eligible based on inclusion/exclusion criteria, the subject will be randomized in a 
1:1 fashion to either robotic-assisted PCI or conventional manual PCI. 
Randomization is completed after the primary operator assesses the coronary 
lesion(s). Qualified subjects will be randomized to treatment using an Interactive 
Web-based Randomization System (IWRS). The IWRS will assign treatment arm 
and will be recorded in the CRF.  
 
5.5 
Coronary angioplasty 
Coronary angioplasty will be performed according to common practice and to 
physician choice concerning lesion preparation, stent implantation, need for post-
dilatation or adjunctive treatment strategies. In order to reduce possible 
confounding factors, the same coronary stent (i.e. Resolute Onyx, Medtronic) will 
be used for all subjects. 
In the peri-procedural period, medications will be administered in line with 
applicable guidelines on PCI. In particular, during the index procedure heparin or 
bivalirudin will be used alternately as per the hospital standard of care; while 
GPIIb/IIIa blockers will be left to the discretion of the operator. Accordingly, 
subjects will be adequately loaded with dual antiplatelet therapy (DAPT). 
 

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5.6 
Manual Conversion for Robotic-assisted PCI 
Unplanned manual conversion (UMC), defined as a disengagement of the robotic 
drive to use bedside manipulation of either the guide catheter, guidewire, or 
delivery system and that was due to: 
• Inability to navigate to the target lesion as intended, cross the target lesion 
as intended, treat the target lesion as intended, retract the CorPath GRX 
system as intended, or other CorPath system device malfunction; OR  
• Any clinical condition that requires rapid medical intervention  
In the context of this study, a manual conversion will be considered to have 
occurred if a subject is randomized to robotic-assisted PCI and the operator 
converts from robotic PCI to manual PCI when treating the ostial lesion(s). In both 
study arms, non-target lesion(s) (lesions not located in the ostium) may be treated 
manually or robotically at the primary operator’s discretion. Manual conversion 
can only occur intraprocedural. Reasons for manual conversion should be 
recorded in the eCRF. 
 
5.7 
IVUS assessment 
The secondary endpoint for the clinical study will be the distance from the 
proximal stent edge to the true ostium as measured by IVUS following stent 
deployment. The aorto-ostium will be defined as the plane at which the coronary 
artery joined the aorta sinus. Protrusion of the stent beyond this plane (protruding 
stent) as well as the distance between this plane and the most proximal stent strut 
(geographical miss) will be measured. In the case of side branches (left anterior 

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descending or circumflex) the ostium will be defined as the plane between the side 
branch emerging point and the carina tip. Protrusion of the stent beyond this plane 
(protruding stent) as well as the distance between this plane and the most 
proximal stent strut (geographical miss) will be measured.  
 
5.8 
Drug regimen 
Subjects will receive medications as provided by physicians per standard practice, 
including anti-ischemic and anti-anginal drugs, antithrombotic drugs, and fluid 
administration according to the subject’s general condition (such as cardiac 
function).  
 
5.9 
Post-Procedure 
The following data will be collected 72 hours post-procedure or day of discharge, 
whichever occurs first: 
• Classification of Angina 
• Creatinine and Glomerular filtration rate 
• 12-Lead ECG  
• Adverse Events and Serious Adverse Events 
• Concomitant Therapy 
 
5.10 
Follow-up 
The subject will have a follow-up visit at 1 month (± 7 days) post procedure, in 
which any clinically relevant adverse event will be assessed. In particular, the 

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incidence of major adverse cardiac events (MACE), including death, myocardial 
infarction, and target lesion revascularization, will be checked for secondary 
endpoints evaluation. 
 
5.11 
Subject Study Completion 
Subject participation in the clinical investigation will conclude upon completion of 
the 30-day visit. Upon completion of subject participation in the clinical 
investigation, the subject will return to the standard of care. 
 
5.12 
Subject Withdrawal 
Subjects must be informed about their right to withdraw from the clinical 
investigation at any time and for any reason without sanction, penalty or loss of 
benefits to which the subject is otherwise entitled. Withdrawal from the clinical 
investigation will not jeopardize their future medical care or relationship with the 
investigator. Subjects will be requested to specify the reason for the request to 
withdraw. The investigator must make all reasonable efforts to retain the subject 
in the clinical investigation until completion of the clinical investigation. 
 
The Principal Investigator has the right to discontinue a subject’s participation in 
the study in the event of an underlying illness, protocol violation, or for 
administrative or other reasons.  Should a subject withdraw, reasonable efforts 
will be undertaken to obtain and report the completed observations as thoroughly 
as possible.  A complete final evaluation at the time of the subject's discontinuation 

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should be made.  The reason for the withdrawal will be recorded in the case report 
form. 
 
When subject withdrawal from the clinical investigation is due to an adverse 
event, the subject will be followed until resolution of that adverse event or 
determination that the subject’s condition is stable. The status of the subject’s 
condition should be documented at the time of withdrawal. 
 
In case of subject withdrawal, the site should make documented attempts to 
schedule the subject for a final study visit prior to study withdrawal. At this final 
study visit, the subject will undergo assessments scheduled for the closest 
protocol-mandated follow-up visit (e.g., 72 hours or discharge or 1 month). 
 
When a subject is withdrawn from the study, all study assessments, with the 
exceptions mentioned above, are immediately stopped.  Any data collected prior 
to withdrawal from the study will be used in descriptive analyses up to the time 
point of withdrawal, and results from that subject shall be censored from further 
analyses thereafter. 
6 
ADVERSE EVENTS AND DEVICE DEFICIENCIES 
6.1 
    Definitions* 
             *MEDDEV 2.7/3rev. 3 May 2015 ; ISO 14155:2011 
Adverse Events 
An adverse event (AE) is any untoward medical occurrence, unintended disease 
or injury, or any untoward clinical signs (including an abnormal laboratory 

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finding) in subjects, users, or other persons (this is restricted to events related to 
the investigational medical device) whether or not related to the investigational 
medical device. This includes events related to the investigational device or the 
comparator. This includes events related to the procedure involved in the 
investigational plan.  
Serious Adverse Events 
An event is considered serious when: 
• led to a death, 
• lead to a serious deterioration in health that either: 
1. resulted in a life-threatening illness or injury, or 
2. resulted in a permanent impairment of a body structure or a body 
function, or 
3. required in-subject hospitalization or prolongation of existing 
hospitalization, or 
4. resulted in medical or surgical intervention to prevent permanent 
life-threatening illness or permanent impairment to a body 
structure or a body function, 
• led to foetal distress, fatal death or a congenital abnormality or birth 
defect. 
This includes device deficiencies that might have led to a serious adverse event if 
a) a suitable action had not been taken or b) intervention had not been made or c) 
if circumstances had been less fortunate. 

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A planned hospitalization for pre-existing conditions, without a serious 
deterioration in health, is not considered to be a serious adverse event. 
Device deficiency 
Inadequacy of a medical device related to its identity, quality, durability, 
reliability, safety or performance, such as malfunction, misuse or use error and 
inadequate labelling. 
In the case where a device has failed, the Investigator must inform the Sponsor 
and make every possible effort to have the Sponsor evaluate the device. 
Major Adverse Cardiovascular Events (MACE) 
Defined as composite of cardiac death, target vessel MI, target vessel 
revascularization (PCI and/or CABG). 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristics 
of a serious adverse event. 
Unanticipated Serious Adverse Device Effects (USADE): 
Serious adverse device effect which by its nature, incidence, severity or outcome 
has not been   identified in the current version of the risk analysis report. 
Anticipated serious adverse device effect (ASADE) is an effect which by its 
nature, incidence, severity or outcome has been identified in the risk analysis 
report. 
6.2 
Reporting 
Sites are encouraged to report promptly: 
• any SAE  

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• any Device Deficiency that might have led to a SAE if a) a suitable action 
had not been taken or b) intervention had not been made or c) if 
circumstances had been less fortunate. 
• New findings/updates in relation to already reported events 
 
No later than 24 hours after the event or after being informed about the 
event the SAE CRF form should be completed in the database. Completing the SAE 
form in the database will automatically trigger an e-mail alert to the monitoring 
staff. 
Reportable events will be reported by the Sponsor, or designee, to the Ethics 
Committees and to the Ministry of Health (MOH) as per current regulation. 
The investigator will promptly report to the Ethics Committee any death, SADE, 
and/or USADE that occurred at the site. 
7 
STUDY ADMINISTRATION 
7.1 
Good Clinical Practice 
The procedures set out in this protocol are designed to ensure that the 
investigator abides by the principles of the Declaration of Helsinki and Good 
Clinical Practice Guidelines (ICH-GCP) in the latest version, in the conduct, 
evaluation, and documentation of the study. A copy of these documents will be 
provided to the center. The study will be carried out in keeping with local legal 
requirements and international regulations. 
 

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7.1.1 Informed Consent of the Subject 
Subjects who meet all inclusion criteria and none of the exclusion criteria are 
deemed eligible. Before being enrolled in the clinical study, the subject must 
provide a written consent form to participate in the study after the nature, scope 
and possible consequences of the clinical study have been explained both orally 
and in writing. Subjects should be aware that if they are enrolled/randomized to 
the study, they will be followed for the study whether or not they undergo invasive 
strategy as allocated. All subjects who signed informed consent form must be 
listed on the Screening Log. 
7.1.2 Approval of the Study Protocol 
Before the start of the study, the study protocol, the informed consent, and other 
appropriate documents must be submitted to and approved by the local Ethics 
Committee (EC) and the appropriate regulatory authorities in accordance with 
local legal requirements. Documentation of Ethics Committee approvals will be 
required before the site is activated to randomize. 
7.2 
Maintenance of Records 
The Investigator agrees to obtain a correctly completed informed consent form for 
each subject included in the study. The investigator will maintain a personal list of 
subject numbers and subject names to enable records to be found at a later date. 
The Investigator must maintain all study records, subject files, and other source 
data for the maximum period of time permitted by the hospital, institution, private 
practice, national regulations, or Sponsor. For trials performed in the European 

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Community, the Investigator is required to arrange for the retention of the subject 
identification codes for at least 15 years after the completion or discontinuation 
of the trial. 
7.3 
Confidentiality 
The Sponsor respects and protects personally identifiable information collected 
or maintained for this clinical investigation. The privacy of each subject and 
confidentiality of his/her information will be preserved in reports and when 
publishing any data. Confidentiality of data will be observed by all parties involved 
at all times throughout the clinical investigation. All data will be secured against 
unauthorized access. 
The Investigator agrees to maintain the confidentiality of the study protocol.  
7.4 
Data Management 
Data will be collected on electronic case report forms (CRFs). The CRF must be 
signed by the investigator or other appropriate individuals who are authorized by 
the investigator. The signing of the ‘Study completion – Investigator’s statement 
CRF’ must be done by the investigator and is considered to be the final 
authorization of the CRFs. 
7.5 
 Source Documentation 
Source data is all information, original records of clinical findings, observations, 
or other activities in a clinical trial necessary for the reconstruction and evaluation 
of the trial. Source data are contained in source documents. Examples of these 
original documents, and data records include: hospital records, clinical and office 

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charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate and complete, 
X-rays, subject files, and records kept at the pharmacy, at the laboratories, and at 
medico-technical departments involved in the clinical trial. 
 
The site will make available all source documents for inspection. The following 
information should be included in the subject’s medical record: 
• Subject’s name and contact information 
• The fact that the subject is participating in an approved clinical 
investigation 
• The clinical investigation title and reference number 
• The date the subject was enrolled into the trial and the subject ID 
number 
• A statement that written informed consent was obtained 
• Date of procedure and device lot number 
• Dates of all visits 
• Lists of medications 
• Documentation of Adverse Events 
• Date subject exited the clinical investigation, and a notation as to 
whether the subject completed the clinical investigation or 
discontinued, with the reason for early termination 
 

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7.6 
Protocol Deviations 
A deviation is defined as an instance(s) of failure to follow, intentionally or 
unintentionally, the requirements of the protocol. The investigator should not 
deviate from the protocol. 
 
In some cases, failure to comply with the protocol may impact the integrity of the 
study data or be considered failure to protect the rights, safety, and well-being of 
subjects. These deviations are considered Major Deviations, and include: 
• Failure to obtain informed consent 
• Enrollment of a subject that did not meet the inclusion/exclusion 
criteria  
 
The PI must maintain accurate, complete, and current records, including 
documents showing the date of and reason for each deviation from the protocol. 
Relevant information for each deviation will be documented as soon as possible 
on the applicable eCRF. The site will submit the eCRF to the Sponsor. 
 
The PI is required to adhere to local regulatory requirements for reporting 
deviations to EC. 
 
An investigator shall notify the Sponsor and the reviewing EC of any deviation 
from the investigational plan to protect the life or physical well-being of a subject 
in an emergency. Such notice shall be given as soon as possible, but in no event 
later than 5 working days after the emergency occurred. Except in such an 

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emergency, prior approval by the Sponsor is required for changes in or 
deviations from the investigational plan, and if these changes or deviations may 
affect the scientific soundness of the plan or the rights, safety, or welfare of 
human subjects, FDA and EC approval are also required. 
8 
DATA PROTECTION 
All information related to the participation of a subject in this study will be treated 
with the utmost confidentiality, in accordance with good clinical practice (Decree 
of the Ministry of Health of 15 July 1997, and subsequent amendments and 
additions) and regulations on the protection of personal data: Information and 
Consent pursuant to Legislative Decree no. 196 of 30/06/2003 and the European 
General Data Protection Regulation (GDPR - General Data Protection Regulation), 
which came into force on 25 May 2018. 
9 
MONITORING 
It is the responsibility of the Sponsor to ensure the clinical investigation is 
conducted, recorded and reported according to the approved protocol, 
subsequent amendment(s), applicable regulations and guidance documents. 
Monitoring of this study will be conducted according to the study-specific 
Monitoring Plan.  
 
Prior to beginning the clinical investigation, the Sponsor will contact the 
investigator or designee to discuss the clinical investigation and data 

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requirements. A designated monitor will periodically review the subject records 
and associated source documents. The investigator shall make subject and clinical 
investigation records available to the clinical monitor for monitoring. The study 
monitor(s) will audit study records, CRFs, source documents, and other data 
relating to the study. The Investigator may redact such records, source documents, 
and other data to the extent reasonably necessary to protect subject 
confidentiality. 
10 COMPLIANCE 
10.1 
Quality Assurance Audits and Regulatory Inspections 
The investigator and/or delegate should contact the Sponsor immediately upon 
notification of a regulatory authority inspection at the site. A monitor or designee 
will assist the investigator and/or delegate in preparing for the audit. The Sponsor 
may perform quality assurance audits, as required. 
 
The Principal Investigator or institution will provide direct access to source data 
during and after the clinical investigation for monitoring, audits, EC review, and 
regulatory authority inspections, as required. The Principal Investigator or 
institution will obtain permission for direct access to source documents from the 
subject, hospital administration, and national regulatory authorities before 
starting the clinical investigation. 
 

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10.2 
Repeated and Serious Non-Compliance 
In the event of repeated non-compliance or a one-time serious non-compliance, as 
determined by the Sponsor, a monitor or designee will attempt to secure 
compliance by one or more of the following actions: 
• Visiting the investigator 
• Contacting the investigator by telephone 
• Contacting the investigator in writing 
• Retraining of the investigator 
 
If an investigator is found to be repeatedly non-compliant with the signed 
agreement, the CIP, or any other conditions of the clinical investigation, the 
Sponsor will either secure compliance or, at its sole discretion, terminate the 
investigator’s participation in the clinical investigation. In case of termination, the 
Sponsor will inform the responsible regulatory authority, as required, and ensure 
that the EC is notified, either by the Principal Investigator or by the Sponsor. 
11  SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL 
INVESTIGATION 
The Sponsor reserves the right to terminate the clinical investigation at any stage, 
with appropriate written notice to the investigators, ECs, and relevant Regulatory 
authorities, if required.  
 

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A Principal Investigator, EC, or regulatory authority may suspend or prematurely 
terminate participation in a clinical investigation at the investigational sites for 
which they are responsible. The investigators will follow the requirements 
specified in the Clinical Trial Agreement.  
 
If suspicion of an unacceptable risk to subjects arises during the clinical 
investigation or when so instructed by the EC or regulatory authority, the Sponsor 
may suspend the clinical investigation while the risk is assessed. The Sponsor will 
terminate the clinical investigation if an unacceptable risk is confirmed. If the 
Sponsor completes an analysis of the reasons for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, the 
Sponsor will inform the Principal Investigators, EC, or regulatory authority, where 
appropriate, of the rationale, providing them with the relevant data supporting 
this decision. Approval from the EC or regulatory authority, where appropriate, 
will be obtained before the clinical investigation resumes. If subjects have been 
informed of the suspension, the Principal Investigator or authorized designee will 
inform them of the reasons for resumption. 
 
If the Sponsor suspends or prematurely terminates the clinical investigation at an 
individual investigational site in the interest of safety, the Sponsor will inform all 
other Principal Investigators. 
 

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If suspension or premature termination occurs, the Sponsor will remain 
responsible for providing resources to fulfill the obligations from the CIP and 
existing agreements for following up the subjects enrolled in the clinical 
investigation, and the Principal Investigator or authorized designee will promptly 
inform the enrolled subjects at his/her investigational site, if appropriate. 
12 CLINICAL INVESTIGATION CONCLUSION 
The clinical investigation will be concluded when: 
• All sites are closed AND 
• The final report has been provided to investigators or the Sponsor has 
provided formal documentation of clinical investigation closure. 
13 PUBLICATION POLICY 
Publication planning and authorship determinations will be overseen by the 
Sponsor, and investigators will be notified via email about the dissemination of 
study 
data 
and 
opportunities 
for 
involvement 
as 
authors 
on 
publications/presentations.  
14 REFERENCES 
1. Medina A, Suarez de Lezo J, Pan M. A new classification of coronary 
bifurcation lesions. Rev Esp Cardiol. 2006;59:183. 
2. Kwan TW, James D, Huang Y, Liou M, Wong S, Coppola J. Perfection of 
precise ostial stent placement. J Invasive Cardiol. 2012;24:354-358. 
3. Zampieri P, Colombo A, Almagor Y, Maiello L, Finci L. Results of coronary 
stenting of ostial lesions. Am J Cardiol. 1994;73:901-903. 

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used without the express written consent of Siemens Healthineers. 
4. Mathias DW, Mooney JF, Lange HW, Goldenberg IF, Gobel FL Mooney MR. 
Frequency of success and complications of coronary angioplasty of a 
stenosis at the ostium of a branch vessel. Am J Cardiol. 1991;67:491-495. 
5. Dishmon DA, Elhaddi A, Packard K, Gupta V, Fischell TA. High incidence of 
inaccurate stent placement in the treatment of coronary aorta-ostial 
disease. J Invasive Cardiol. 2011;23:322-326. 
6. Attizzani GF, Capodanno D, Ohno Y, Tamburino C. Mechanisms, 
pathophysiology, and clinical aspects of incomplete stent apposition. J Am 
Coll Cardiol. 2014;63:1355-1367. 
7. Chetcuti SJ, Moscucci M. Double-wire technique for access into a protruding 
aorto-ostial stent for treatment of in-stent restenosis. Catheter Cardiovasc 
Interv. 2004;62:214-217. 
8. Dishmon DA, Elhaddi A, Packard K, Gupta V, Fischell TA. High incidence of 
inaccurate stent placement in the treatment of coronary aorto-ostial disease. J 
Invasive Cardiol 2011;23:322-326. 
9. Rajaraman P, Doody MM, Yu CL, et al. Journal Club: Cancer risks in U.S. 
radiologic 
technologists 
working 
with 
fluoroscopically 
guided 
interventional 
procedures 
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AJR 
Am 
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Roentgenol 
2016;206:1101-9.