SOLEMN Study - Synergy Optical Coherence Tomography in Left Main PCI
Phase: NA
Conditions: Percutaneous Coronary Intervention, Optical Coherence Tomography, In-stent Coronary Artery Restenosis
Sponsor: Jesse Brown VA Medical Center

SOLEMN Study 
CONFIDENTIAL 
SOLEMN REV. 19 
MLADEN VIDOVICH 
 
1 
STUDY PROTOCOL 
 
Study of Left Main Coronary Artery Healing after PCI with Boston Scientific 
Synergy Bioabsorbable Polymer Stent 
 
 
 
SOLEMN Study (Synergy OCT LEft MaiN) 
 
 
 
 
 
January 2, 2018 
Version 19 
 
 
 
 
This investigational protocol contains confidential information for use by the 
principal investigators and their designated representatives participating in this 
clinical investigation. It should be held confidential and maintained in a secure 
location. It should not be copied or made available for review by any 
unauthorized person or firm. 
 
 
 

SOLEMN Study 
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PROTOCOL SIGNATURE PAGE 
 
Study of Left Main Coronary Artery Healing after PCI with Boston Scientific 
Synergy Bioabsorbable Polymer Stent 
 
 
 
SOLEMN Study (Synergy OCT LEft MaiN) 
 
 
 
I have read this protocol, appendices and amendment(s), if applicable, and agree 
to adhere to the requirements. I will provide copies of this protocol and all pertinent 
information to the study personnel under my supervision. I will discuss this material 
with them and ensure they are fully informed regarding the device and the conduct 
of the study. 
I will conduct the study in accordance with the protocol and Good Clinical Practice 
guidelines, as well as local regulations, and I accept respective revisions to the 
protocol approved by authorized personnel of the Sponsor and by regulatory 
authorities. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary Investigator (print) 
 
 
 
Primary Investigator (signature) 
 
 
Date 
 
Institution Name/Location (print) 
 
 
 

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MLADEN VIDOVICH 
 
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PRINCIPAL INVESTIGATOR: 
 
 
Mladen I. Vidovich, MD 
Associate Professor of Medicine 
University of Illinois at Chicago and Jesse Brown VA Medical Center 
Chicago, IL  
miv@uic.edu 
 
CO-PRINCIPAL INVESTIGATOR: 
 
Sunil V. Rao, MD 
Professor of Medicine 
Duke University and Durham VA Medical Center 
Durham, NC 
sunil.rao@duke.edu 
 
CORE LAB PRINCIPAL INVESTIGATOR: 
 
Akiko Maehara, MD 
Cardiovascular Research Foundation 
New York, NY 
amaehara@crf.org 
 
Contact Information: 
 
Mladen I. Vidovich, MD 
University of Illinois at Chicago 
Jesse Brown VA Medical Center 
820 S Damen Avenue 
Chicago, IL 60612 
Phone 312-413-4951 Fax 312-413-2948 
email miv@uic.edu and mladen.vidovich@va.gov  
 
 
 
1. TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE ...................................................................................... 2 
1. 
Table of Contents ................................................................................................. 3 
2. 
SPECIFIC AIMS ...................................................................................................... 6 
2.1. 
Background .................................................................................................................................................. 6 
2.2. 
Challenges of Left Main Stenting/PCI ............................................................................................... 6 
2.3. 
OCT detection of stent strut coverage .............................................................................................. 7 
2.4. 
Left Main imaging as surrogate endpoint for clinical trial ....................................................... 7 

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2.5. 
Hypothesis .................................................................................................................................................... 7 
2.6. 
Specific Aims ................................................................................................................................................ 9 
3. 
RESEARCH PLAN ................................................................................................... 9 
3.1. 
Trial, Site and Data Infrastructure ................................................................................................... 10 
3.2. 
VA Procedure Volume (2014) ........................................................................................................... 10 
3.3. 
VA PCI Characteristics (2014) ........................................................................................................... 10 
3.4. 
Anticipated VA Study Sites ................................................................................................................. 10 
3.5. 
Core Laboratory Experience .............................................................................................................. 11 
4. 
RESEARCH DESIGN AND METHODS .................................................................... 11 
4.1. 
Experimental Design ............................................................................................................................. 11 
4.2. 
Primary Endpoint ................................................................................................................................... 12 
4.3. 
Secondary Endpoints ............................................................................................................................ 12 
5. 
Study Population ............................................................................................... 12 
5.1. 
Collection of Race and Ethnicity Data ............................................................................................ 12 
5.2. 
Randomization and blinding .............................................................................................................. 13 
5.3. 
Study Duration ......................................................................................................................................... 13 
5.4. 
Patient Withdrawal ................................................................................................................................ 13 
6. 
PRE- AND Post-Procedure Follow-up Assessments ............................................. 13 
6.1. 
Baseline Data ............................................................................................................................................ 14 
6.2. 
Hospital Discharge ................................................................................................................................. 14 
6.3. 
1 month (plus or minus 2 weeks) .................................................................................................... 15 
6.4. 
3 Months (plus or minus 1-month) ................................................................................................. 15 
6.5. 
12 Months (plus or minus 1-month) .............................................................................................. 15 
6.6. 
Additional Visits ...................................................................................................................................... 16 
6.1. 
OCT Data and Clinical Interventions .............................................................................................. 16 
7. 
Post-Procedure Anti-Platelet Medication ........................................................... 16 
7.1. 
Aspirin ......................................................................................................................................................... 16 
7.2. 
Additional Antiplatelet Therapy ...................................................................................................... 17 
8. 
Subject recruitment & selection criteria ............................................................. 18 
9. 
BENEFITS AND RISKS .......................................................................................... 19 
9.1. 
Benefits ........................................................................................................................................................ 19 
9.2. 
Risks ............................................................................................................................................................. 20 
9.3. 
Optical Coherence Tomography (OCT) ......................................................................................... 22 
10. 
TREATMENT ................................................................................................... 22 
10.1. 
Arterial Access Site ................................................................................................................................. 22 
10.2. 
Follow-up assessments:  3 months and 12 months ................................................................. 22 
10.3. 
MACE Definition ...................................................................................................................................... 23 
11. 
Angiography, PCI and OCT .............................................................................. 23 
11.1. 
Baseline angiography and PCI ........................................................................................................... 23 
11.2. 
Baseline and follow-up OCT ............................................................................................................... 23 
11.3. 
Follow-up 3- and 12-month Angiography ................................................................................... 24 
11.4. 
OCT Methodology ................................................................................................................................... 24 
11.5. 
Single LM Stent OCT .............................................................................................................................. 25 
11.6. 
Bifurcation LM Stent OCT .................................................................................................................... 25 

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11.7. 
Quantitative Coronary Angiography (QCA) analyses .............................................................. 25 
11.8. 
Optical Coherence Tomography analyses .................................................................................... 25 
11.9. 
OCT Definitions ........................................................................................................................................ 25 
11.10. 
OCT Strut Coverage (Figure 2.) ................................................................................................... 26 
11.11. 
OCT LASM (Late Acquired Stent Malapposition) ................................................................. 26 
11.12. 
Proposed OCT Measurements ...................................................................................................... 27 
12. 
Safety Evaluations .......................................................................................... 28 
12.1. 
Reporting of Adverse Events ............................................................................................................. 28 
12.2. 
Definitions of Adverse Events ........................................................................................................... 28 
12.3. 
Adverse Event (AE) ................................................................................................................................ 28 
12.4. 
Adverse Device Event (ADE) .............................................................................................................. 28 
12.5. 
Serious Adverse Event (SAE) ............................................................................................................. 28 
12.6. 
Serious Adverse Device Effect (SADE) ........................................................................................... 29 
12.7. 
Unanticipated Serious Adverse Device Effect (USADE) ......................................................... 29 
12.8. 
Unanticipated Adverse Device Effect ............................................................................................. 29 
12.9. 
Device Deficiency (DD) ......................................................................................................................... 29 
12.10. 
Device Malfunction ........................................................................................................................... 29 
13. 
Biostatistical considerations ........................................................................... 29 
13.1. 
Primary Endpoint Analysis ................................................................................................................. 29 
13.2. 
Secondary Endpoint Analyses ........................................................................................................... 30 
13.3. 
Expected treatment effect ................................................................................................................... 30 
13.4. 
Statistical Analysis Sites ....................................................................................................................... 30 
13.5. 
Sample Size considerations ................................................................................................................ 31 
14. 
Safety, DSMB and Complaint Program ........................................................... 31 
14.1. 
Data Safety Monitoring Board (DSMB) ......................................................................................... 31 
14.2. 
Selection and Monitoring of Clinical Sites and Operators ..................................................... 32 
15. 
Monitoring ..................................................................................................... 32 
15.1. 
Monitoring of Critical Data and Processes ................................................................................... 32 
15.2. 
Communication of Centralized Monitoring ................................................................................. 33 
15.3. 
Clinical Events Committee (CEC) ..................................................................................................... 33 
15.4. 
Case report forms (CRF) ...................................................................................................................... 33 
15.5. 
Discontinuation Criteria for the Entire Trial .............................................................................. 34 
15.6. 
Study Termination ................................................................................................................................. 34 
15.7. 
Potential limitations .............................................................................................................................. 34 
16. 
Ethical Aspects of the Proposed Research ...................................................... 34 
17. 
Data Ownership ............................................................................................. 35 
18. 
Institutional Review Board Approval (IRB) ..................................................... 35 
18.1. 
Statement of Compliance ..................................................................................................................... 35 
18.2. 
Signed Informed Consent .................................................................................................................... 35 
18.3. 
Subject Confidentiality ......................................................................................................................... 36 
18.4. 
Retention of Records by the Investigator ..................................................................................... 36 
19. 
IDE Submission ............................................................................................... 36 
20. 
Role of Sponsor (Jesse Brown VA Coordinating Center) .................................. 36 
20.1. 
General Duties .......................................................................................................................................... 36 

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20.2. 
Selection of Investigators .................................................................................................................... 37 
20.3. 
Role of the Investigator ........................................................................................................................ 37 
20.4. 
Delegation of responsibility ............................................................................................................... 39 
20.5. 
Record Maintenance .............................................................................................................................. 39 
20.6. 
Communication with the FDA ........................................................................................................... 40 
20.7. 
Prohibition of Promotion and Other Practices .......................................................................... 40 
20.8. 
Maintaining Records ............................................................................................................................. 40 
20.9. 
Submitting Reports ................................................................................................................................ 40 
21. 
REFERENCES ................................................................................................... 41 
22. 
Appendix A. ................................................................................................... 46 
22.1. 
Case Report Forms ................................................................................................................................. 46 
23. 
Appendix B. ................................................................................................... 46 
23.1. 
CRF Proposal for OCT Analysis ......................................................................................................... 47 
24. 
Appendix C. .................................................................................................... 47 
24.1. 
Jesse Brown VA Consent Form .......................................................................................................... 47 
25. 
Appendix D. ................................................................................................... 47 
25.1. 
MACE Definitions .................................................................................................................................... 47 
25.2. 
Safety Definition ...................................................................................................................................... 49 
 
 
2. SPECIFIC AIMS 
 
2.1. Background 
 
Percutaneous coronary intervention (PCI) is increasingly used to treat 
unprotected left main (LM) coronary artery stenosis.(2) Both protected and 
unprotected  LM PCI are considered standard of care in most centers worldwide 
and in the United States. and LM PCI has been associated with favorable 
outcomes compared to CABG.(3-5) 
 
2.2. Challenges of Left Main Stenting/PCI 
 
However, due to its critical location, stent failure in LM PCI is of particular 
concern. Specifically, stent thrombosis (ST) in this location is associated with 
adverse outcome.(6) Improvement in stent design and introduction of newer 
generation drug-eluting stents has reduced occurrence of ST.(7) 
 
The Boston Scientific Synergy™ stent is a new generation bioabsorbable 
polymer drug-eluting stent (BP-DES) with thinner struts (2.25-2.75mm - 74µm, 
3.0-3.5mm - 79 µm and 4.0mm - 81µm) and an abluminal thin coat of 
bioabsorbable polymer which is fully absorbed over a period of 3 months along 
with the elution of the anti-restenotic drug everolimus. These technical 
characteristics promote a more complete and quick healing process with the 

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Synergy™ stent as it has been shown in previous studies.(8) 
 
2.3. OCT detection of stent strut coverage 
 
Optical Coherence Tomography (OCT) allows for precise determination of stent 
placement, stent expansion and apposition.(9, 10) The pattern of vessel healing 
can be very precisely studied,(11) in particular when immediate post-stent 
implantation OCT data is compared to the 3- or 6-month post-PCI intervals.(8, 
12) OCT-guided PCI is associated with improved outcome (as measured by 
Fractional Flow Reserve – FFR) in high-risk NSTEMI patients without increasing 
periprocedural complications.(13) 
Optimal and consistent vessel healing is particularly important in LM PCI where 
stent thrombosis is a potential complication with serious adverse outcome.(6) In 
the recent PESTO trial, OCT identified the underlying morphological abnormality 
in 97% of cases of ST. There were multiple underlying mechanisms identified - 
strut malapposition, ruptured neoatherosclerosis, and severe 
underexpansion.(14) Imaging-guided PCI in LM PCI (e.g., IVUS) has been 
associated with improved outcomes.(15) Similarly, the CLI-OPCI study 
demonstrated that suboptimal stent deployment as visualized by OCT was 
associated with increased MACE.(9) 
 
2.4. Left Main imaging as surrogate endpoint for clinical trial 
 
Full stent coverage has been associated with reduced MACE and improved 
outcomes.(16) Similarly, ST is felt to be reduced with full stent strut coverage. 
Since contemporary drug-eluting stent, in particular BP-DES may afford faster 
and more complete healing(17) it has been suggested that stent strut coverage 
may be used, in certain domains of care, as a surrogate marker of full stent 
healing and be associated with shortened DAPT duration. 
Temporal trends in stent strut coverage suggest that newer generation drug-
eluting stents have faster stent healing/coverage approaching those observed 
with bare-metal stents.(18) Since shorter DAPT duration is feasible and in routine 
clinical use with BMS we feel that stent strut coverage may be, at least in part, be 
used as a surrogate marker for a clinical trial investigating Synergy stent 
healing.(19, 20) 
 
2.5. Hypothesis 
 
Our main hypothesis is that the healing patterns in LM will be favorable (full and 
rapid strut coverage) with the use on the BP-DES. 
 
Due to the gradual disappearance of the bioabsorbable polymer (BP) on the 
Boston Scientific Synergy™ stent over time, early strut coverage patterns and 
timeline may be different than previously observed in durable polymer (DP) drug-
eluting stents (DES) and bare-metal stents (BMS) stents in LM PCI.(21, 22) 
 

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Late acquired stent malapposition (LASM) is expected to differ from previous 
observations with DP DES.(23, 24) 
 
The unique attributes of the BP technology present on the Synergy™ stent may 
potentially allow for reduction in the duration of the dual antiplatelet therapy 
(DAPT) following LM PCI. BP-DES have been shown to have superior clinical 
outcomes compared to BMS and first-generation DES, while outcomes were 
similar to DP second-generation DES.(25) Therefore, this new information about 
stent healing process with BP-DES is particularly important given the critical 
location of LM PCI procedure. 
 
Additionally, our study will include all-comers, unprotected and protected LM PCI 
allowing for assessment of differences in neointimal hyperplasia (NIH) in LAD 
and LCX.(26) 
 
The additional risk of this study to patients is small given the demonstrated safety 
of OCT.(13) Both angiographic and follow-up has been routinely performed in 
multiple studies and has demonstrated safety in previous studies.(27, 28) 
Therefore, performance of 3- and 12-month follow-up in this study of healing of 
LM is an accepted clinical and research practice. 

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2.6. Specific Aims 
 
We expect to observe early and complete healing of the BP-DES Synergy stent 
in the LM position and a very low percentage of malapposed struts.(8) In 
addition, we expect to observe significant reduction of neointimal hyperplasia. 
3. RESEARCH PLAN 
 
 
Figure 1.  
 
Unapposed stent struts post PCI(1) 
 
 
 

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3.1. Trial, Site and Data Infrastructure 
 
The Department of Veterans Affairs (VA) is the single largest integrated 
healthcare system in the US. The recent national approval and introduction of the 
Boston Scientific Synergy Stent at the VA provides a unique opportunity to 
perform a prospective observational study of this device. 
 
The VA operates an advanced Electronic Medical Record (EMR) that is 
consistent across the whole system, and Clinical Assessment Reporting and 
Tracking (CART) system used by all VA cardiac catheterization laboratories.(29) 
VA offers robust follow greater than 85% of its patients within its own healthcare 
system.(30) 
 
Additionally, the VA serves a highly complex population with significant CAD and 
multiple co-morbidities. This environment is particularly well-suited with 
performance of this trial. 
 
3.2. VA Procedure Volume (2014) 
 
• 78 VA Cardiac Catheterization Laboratories nationwide 
• 37,813 patients with 39,464 diagnostic coronary angiographies 
• 11,013 patients with 12,248 PCIs 
 
3.3. VA PCI Characteristics (2014) 
 
• Indications  
 
 
Stable Angina  
33% 
Unstable Angina  
27% 
NSTEMI 
 
23% 
STEMI  
 
7% 
 
• Arterial Access 
 
Femoral 
 
75% 
 
Radial  
 
25% 
 
3.4. Anticipated VA Study Sites 
 
VA Site 
Principal Investigator 
San Francisco 
Kendrick Shunk 
Oklahoma City 
Faisal Latif 
Minneapolis 
Edward Mcfalls 
Pittsburgh 
Aref Rahman 

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Atlanta 
Kreton Mavromatis 
San Antonio 
Robert Chilton 
Cleveland 
Noah Rosenthal 
Dallas 
Subhash Banerjee 
Chicago 
Mladen Vidovich 
Tucson 
Tam Truong 
Long Beach 
Arnold Seto 
Birmingham 
Masood Leesar 
Denver 
Ehrin Armstrong 
Charleston 
Valerian Fernandes 
 
 
3.5. Core Laboratory Experience 
 
The Clinical Trials Center (CTC) at the Cardiovascular Research Foundation 
(CRF) has contributed to key advances in interventional cardiovascular disease. 
Through the design and execution of clinical trials, the CTC has played a pivotal 
role in bringing innovative new technologies, pharmacologic therapies, and new 
treatment paradigms to patients. Led by thought leaders in clinical research and 
practice, the CTC is uniquely positioned to design clinical research protocols that 
answer the most important questions in cardiovascular medicine. Drawing upon a 
thorough understanding of treatment guidelines, as well as the research and 
regulatory landscape, the CTC works with sponsors to design and execute 
studies that have a profound impact on patient care. The CTC has been involved 
in more than 650 clinical studies with enrollment of over 150,000 subjects, 
including seminal trials that have shaped the field. This high-quality portfolio 
draws small startups, as well as large companies, that seek the expertise, 
passion for innovation, and quality of CRF. 
4. RESEARCH DESIGN AND METHODS 
 
4.1. Experimental Design 
 
The proposed study is a multicenter, observational, prospective, single-arm study 
of stent strut coverage of patients undergoing LM PCI. 
 
Baseline quantitative coronary analysis (QCA) will be performed at the time of 
stent implantation. 
 
Stent coverage in LM PCI will be studied with OCT at 3 and 12 months and 
compared to baseline OCT at the time of stent implantation.(31, 32) 
 
OCT/data will be analyzed in a core lab (CTC CRF) and correlated with clinical 
outcomes at 3 and 12 months. 

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4.2. Primary Endpoint 
• 3-month stent strut coverage in LM PCI 
 
4.3. Secondary Endpoints 
• 12-month stent strut coverage in LM PCI 
• 3-month late acquired stent malapposition (LASM) 
• 12-month late acquired stent malapposition (LASM) 
• One-month LM Synergy stent safety 
• 1-, 3- and 12-month MACE 
• 1-, 3- and 12-month Stent Thrombosis (ST) (ARC definition) 
5. STUDY POPULATION 
 
75 patients undergoing LM PCI (protected or unprotected) with Boston Scientific 
Synergy™ stent. 
 
The goal is to enroll 75 patients from up to 10 VA sites and an enrollment period 
of 3 years, each site is expected to include 7-10 patients during the study period.  
 
After a total of 75 patients are enrolled the study will be closed for further 
enrollment. 
 
Eligible patients will be screened at each participating center and those who had 
undergone LM PCI with Boston Scientific Synergy™ stent and where OCT was 
performed during the index procedure will be eligible. The index procedure may 
be performed by any interventional cardiologist – this is specifically needed in 
order to maintain equipoise on the part of stent choice and use of OCT. 
 
At the end of the study enrollment period, the proportion of patients at each site 
treated with Synergy stents vs. non-Synergy stents and the proportion of patients 
that underwent OCT imaging during LM PCI will be collected. 
 
Eligible patients will be approached and consented for inclusion in the SOLEMN 
trial after the initial procedure. 
  
5.1. Collection of Race and Ethnicity Data 
 
Race and ethnicity will be collected via the CRF at the time the patient is enrolled 
in the trial. For example, several studies have shown that South Asians in North 
America have a higher burden of cardiovascular disease and cardiovascular 
deaths compared to whites and other ethnic groups.(33) Similarly, there are 
differences in cardiovascular outcomes after revascularization in women or 
different ethnicities.(34) 
 

SOLEMN Study 
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The Department of Veterans Affairs population which can be considered for the 
trial consists mainly of male subjects. The ethnic background can vary 
considerably between various sites. Previous studies performed at the VA have 
therefore reported inclusion of populations that may not fully represent the US 
population as a whole. For example, a large VA-sponsored Cooperative Trial 
(PRESERVE) enrolled >90% of a male population which was almost 80% 
white.(35) 
 
Therefore, while the study investigators will maintain records and document 
gender, race and ethnicity, the SOLMEN trial will likely consist of a population 
specific to the environment present at the Department of Veterans Affairs 
Hospitals. These are recognized limitations of all trials performed within the 
Veterans Affairs environment. 
  
 
5.2. Randomization and blinding 
 
This is in single arm study with no randomization or blinding. 
 
5.3. Study Duration  
 
Patients will be followed for 12 months after the index procedure. At one month, 
clinical follow-up will be performed (clinic or telephone). At 3 months, the 
angiography and OCT will be performed. At 12 months, the final angiography and 
OCT will be performed. No further follow-up is planned after completion of the 3- 
and 12-month angiography and OCT. 
 
5.4. Patient Withdrawal 
 
Each patient is free to withdraw from the study at any time and without reason, 
and without influence on their further medical treatment or relationship to their 
physicians. Once the patient is withdrawn, they will be followed per institutional 
standard of care. 
6. PRE- AND POST-PROCEDURE FOLLOW-UP ASSESSMENTS 
 
Baseline, procedure and follow-up assessments will be performed according to 
the schedule described in Figure 2. “Flowchart of the study design”. During each 
specified evaluation, the corresponding Case Report Form (CRF) must be 
completed. 
 
Subject telephone numbers should be obtained to ensure contact is maintained. 
These telephone numbers should include all home numbers, work numbers as 
well as primary physician numbers. A phone number of a relative or friend should 
also be requested.  

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SOLEMN Study 
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• Post-procedure 12-lead ECG: an ECG should be performed 
between 12 – 24 hours post-procedure or prior to discharge if less 
than 12 hours; 
• Record of all cardiovascular medications, including DAPT and anti-
coagulants 
• If the patient enrolled had NSTEMI during the index procedure, 
documentation that the cardiac enzymes were stable and declining 
at the time of the index procedure. No additional biomarker follow-
up as part of the SOLEMN trial is required. 
• The corresponding Hospital Discharge Case Report Form (CRF) 
must be completed; 
• Cardiac Catheterization and Percutaneous Coronary Intervention 
Report(s) for the Index Procedure. 
• Coronary Angiograms (DICOM) 
• OCT Imaging (St. Jude format) 
 
 
6.3. 1 month (plus or minus 2 weeks) 
 
• Telephone assessment or clinic visit; 
• The corresponding 1-month Case Report Form (CRF) must be 
completed; 
• Record of all cardiovascular medications, including DAPT and anti-
coagulants; 
• Record of all adverse events 
 
6.4. 3 Months (plus or minus 1-month) 
 
• Repeat coronary angiography and LM OCT; 
• The corresponding 3-month Case Report Form (CRF) must be 
completed; 
• Record of all cardiovascular medications, including DAPT and anti-
coagulants; 
• Record of all adverse events; 
• ECG; 
• CBC and serum creatinine. 
• Cardiac Catheterization and, if clinically indicated, Percutaneous 
Coronary Intervention Report(s)  
• Coronary Angiograms (DICOM) 
• OCT Imaging (St. Jude format) 
 
 
6.5. 12 Months (plus or minus 1-month) 
 

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• Repeat coronary angiography and LM OCT 
• The corresponding 12-month Case Report Form (CRF) must be 
completed 
• Record of all cardiovascular medications, including DAPT and anti-
coagulants; 
• Record of all adverse events; and 
• ECG; 
• CBC and serum creatinine; 
• Cardiac Catheterization and, if clinically indicated, Percutaneous 
Coronary Intervention Report(s)  
• Coronary Angiograms (DICOM) 
• OCT Imaging (St. Jude format) 
 
6.6. Additional Visits 
 
Under certain circumstances, the Sponsor or Investigator may request an 
evaluation of the Subject either before or after a scheduled visit, i.e., an 
additional visit.  If an additional follow-up is due to concern over a suspected 
adverse event or a suspected device deficiency, the visit must be documented as 
an additional visit. 
 
If the Subject experiences a cardiac event (i.e., Non-STEMI or STEMI) or 
complains of other new or unresolved signs or symptoms, an additional visit is 
required to be documented and reported as an adverse event.  It is the discretion 
of the Investigator to determine other assessments and treatment methods for an 
additional visit. 
 
Data collected at additional visits includes date and reason of follow-up, assess 
for adverse events and any study activities performed. 
 
6.1. OCT Data and Clinical Interventions 
 
Since the benefit of follow-up LM OCT has not been established, we will collect 
data how the operators used the additional imaging data obtained during the 
patient participation in the SOLEMN study. 
 
7. POST-PROCEDURE ANTI-PLATELET MEDICATION 
 
7.1. Aspirin 
 

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Following PCI, subjects with no known aspirin allergy or bleeding risk should 
continue on aspirin (minimum of 75 mg/day up to 162 mg/day or dose per 
standard hospital practice) indefinitely. 
 
7.2. Additional Antiplatelet Therapy 
 
6-month minimum of DAPT (Dual Antiplatelet Therapy) duration 
is recommended in the SOLEMN trial. 
 
Subjects should be treated in accordance with current US guidelines. All 
cardiovascular medications will be recorded for data collection at each visit. 
Please refer to the specific package insert for the designated P2Y12 medication 
e.g., Clopidogrel, Ticlopidine, Ticagrelor or Prasugrel for indications, 
contraindications, warnings and precautions.  
 
SCHEDULE OF EVENTS 
 
PROCEDURE/TEST 
Index 
Procedure 
Screening and 
Baseline 
30 Days 
 
3 
Months 
 
12 
Months 
 
Visit Number 
- 
1 
2 
3 
4 
Range from the index procedure 
-  
+ 
1-2 Days 
+/- 
14 Days 
+/- 
30 Days 
+/- 
30 Days 
Informed Consent Form 
 
X 
 
 
 
12-lead ECG 
 
X 
 
X 
X 
Demographics and Medical 
History 
 
X 
 
 
 
General Clinical State 
 
X 
X 
X 
X 
CBC, Serum creatinine  
 
X 
 
X 
X 
Troponin I  
 
X 
 
X 
X 
Coronary Angiogram (DICOM) 
X 
 
 
X 
X 
LM OCT Imagining 
 (St. Jude format) 
X 
 
 
X 
X 
Cardiac Medication Profile 
 
X 
X 
X 
X 

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Deviations, Adverse Events  
 
X 
X 
X 
X 
 
8. SUBJECT RECRUITMENT & SELECTION CRITERIA 
 
Patients who have undergone clinically-indicated PCI of LM where OCT was 
performed as part of the routine index procedure will be identified by a local study 
investigator or study coordinator and will be screened for eligibility for the study.  
Only patients who have already undergone LM PCI and OCT as part of routine, 
standard care will be approached.  
 
The index LM PCI procedure may be performed by any operator regardless of 
their participation in the SOLEMN study.  
 
The follow-up procedures can be performed by SOLEMN investigators only. 
 
The following criteria will be used: 
 
Inclusion criteria: 
 
• Age 18 years or greater; 
• Left Main CAD, defined as ≥ 50% diameter stenosis and amenable to 
revascularization by PCI;  
• Willing and able to give informed consent. The patients must be able to 
comply with study procedures and follow-up. 
• Ability to comply with minimum of 6 months of DAPT after the index 
procedure. 
• Unprotected Left Main PCI 
a. The IFU for Dragonfly OPTIS Imaging Catheter indicates that the 
catheter is contraindicated for use in patients disqualified for CABG 
surgery. The patients in the SOLEMN trial will have had OCT 
performed with their LM PCI prior to enrollment. The decision to 
perform unprotected LM PCI therefore will have been made prior to 
enrollment in the SOLEMN trial. The initial indication to perform LM 
PCI and LM OCT is at the discretion of the interventional 
cardiologist prior to enrollment into the SOLEMN trial. The 
SOLEMN trial will not allow for enrollment of patients who are 
disqualified for CABG surgery. 
 
• Protected Left Main PCI 
 
a. The IFU for Dragonfly OPTIS Imaging Catheter indicates that it is 
intended for use in vessels 2.0 – 3.5 mm in diameter. The SOLEMN 

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19 
trial specifically allows for imaging of LM vessels that are larger in 
diameter. 
 
b. The IFU for Dragonfly OPTIS Imaging Catheter specifies that it is 
not intended for use in the left main coronary artery or in a target 
vessel which has undergone a previous bypass procedure. The 
SOLEMN trial specifically allows for imaging of protected/bypassed 
LM and/or into the LAD or LCX, as appropriate. 
 
 
Exclusion criteria: 
 
1. Coexisting conditions that limit life expectancy to less than 12 months or 
that could affect patient’s compliance with the protocol; 
2. Serum creatinine greater than 2.0 mg/dL; 
3. Cardiogenic shock; 
4. STEMI; 
5. Non-STEMI, if the cardiac troponin is not stable or starting to decline; 
6. Pregnancy; 
7. Inability to take dual antiplatelet therapy for 6 months; 
8. Any target lesion with previously placed stent. 
9. Patients disqualified for CABG surgery. 
 
Contraindications for OCT use: 
 
1. Bacteremia or sepsis 
2. Major coagulation system abnormalities 
3. Severe hemodynamic instability or shock 
4. Patients diagnosed with coronary artery spasm 
5. Acute renal failure 
 
The study design will be explained to the patients and if they agree to participate 
and they will be asked to sign in the consent form and they will receive a copy of 
the consent form.  
 
9. BENEFITS AND RISKS 
 
9.1. Benefits 
 
• Left main PCI has been widely used as an alternative to CABG in selected 
patients with symptomatic coronary artery disease. The potential benefits 
of the Boston Scientific Synergy™ stent are the low profile, improved 
flexibility and bioabsorbable nature of the polymer. The positive clinical 
outcomes seen from the global and United States experience have 

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20 
demonstrated that the stent is safe and effective in a wide range of 
applications in the coronary tree. 
 
• Optical coherence tomography has been widely used in the coronary 
arteries and has demonstrated exceptional resolution and detail when 
studying native coronary artery disease as well as healing of the metallic 
stent implants. Multiple studies of OCT have demonstrated its 
reproducibility and safety across variety of lesions, anatomies and 
coronary locations. 
 
9.2. Risks 
 
• The risk assessment and management was performed per the ISO EN 
14971 Standard According to the Medical Device Classification (Medical 
Device Directive 93/42/EEC, Rule 13 Annex IX) and Code of Federal 
Regulations (21CFR860.3), the Boston Scientific Synergy™ stent is a 
Class III device, long-term implantable medical device incorporating 
integral medicinal product liable to act in ancillary way on human body. 
 
• As described previously, the potential benefit of the Boston Scientific 
Synergy™ stent in the left main coronary artery are its flexibility, thin-strut 
design and bioabsorbable polymer. Potential risks are all that apply to 
implantation of a drug-eluting stent, placement of the stent in left main 
coronary artery and the fact that Boston Scientific Synergy™ stent has not 
been studied in the left main coronary artery. This study is specifically not 
designed to seek approval of Boston Scientific Synergy™ stent in the left 
main coronary artery. Instead, it is the study of healing of the Boston 
Scientific Synergy™ stent in this location. 
 
• Other risks associated with using this device are those associated with 
percutaneous treatment procedures for a stenotic coronary artery. The 
complications relating to standard PTCA and stenting include, but are not 
limited to the following: 
 
• Abrupt stent closure 
• Abrupt vessel closure or spasm 
• Acute myocardial infarction 
• Allergic reaction to anti-coagulation and/or anti-thrombotic 
therapy, contrast material, or stent and/or delivery system 
materials 
• Aneurysm, pseudo aneurysm, or arteriovenous fistula 
• Arrhythmias (including ventricular fibrillation and ventricular 
tachycardia) 
• Cardiac tamponade 
• Cardiogenic shock 
• Death 

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• Damage to the stent or injury to the artery requiring emergency 
coronary artery bypass grafting (CABG) 
• Dissection, perforation, or rupture of the coronary artery 
• Emboli (blockage), distal (air, tissue or thrombotic emboli) 
• Fever 
• Hematoma at catheter insertion site 
• Hemorrhage requiring transfusion 
• Hypotension / hypertension 
• Increased risk of restenosis of stented segments 
• Infection and/or pain at catheter insertion site 
• Perforation or rupture of the artery 
• Peripheral ischemia / peripheral nerve injury 
• Renal failure 
• Stent migration or embolization 
• Stent thrombosis or occlusion 
• Stroke or transient ischemic attack 
• Total occlusion of coronary artery 
• Unstable angina 
 
• As mentioned above, there are also potential risks that may be associated 
with implantation of Boston Scientific Synergy™ stent which may include, 
but are not limited to the following: 
 
• Allergic/ immunologic reaction to drug 
• Alopecia 
• Anemia 
• Blood product transfusion 
• Chest Heaviness 
• Dizziness 
• Gastrointestinal symptoms 
• Headache 
• Hematologic dyscrasia (including Leukopenia, Neutropenia, 
Thrombocytopenia) 
• Hepatic enzymes change 
• Histological changes in vessel wall, including inflammation, 
cellular damage or necrosis 
• Lymphadenopathy 
• Mouth Ulcers 
• Myalgia/Arthralgia 
• Nausea 
• Peripheral Neuropathy 
• Skin Rash 
 
• The occurrence of the above listed complications may lead to the need for 
a repeat catheterization and/or percutaneous coronary intervention, 
myocardial infarction, stent thrombosis, stroke, emergency bypass 

SOLEMN Study 
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22 
surgery, or death. The risks associated with the Boston Scientific 
Synergy™ stent are believed to be similar, although possibly less due to 
the bioabsorbable nature of the polymer, to those risks associated with 
second generation drug eluting stents currently in use to treat a stenotic 
coronary artery. Additional risks, which are not known at this time, may 
also exist. Appropriate contraindications and warnings are included in the 
Instructions for Use (IFU). 
 
 
9.3. Optical Coherence Tomography (OCT) 
 
• The C7 Dragonfly, Dragonfly DUO, or Dragonfly OPTIS Imaging Catheter 
is not intended for use in the left main coronary artery. Currently, the 
catheter is being used clinically for left main imaging in the United States 
and globally. This study is not designed to seek approval of use of the 
OCT catheter in the left main coronary artery. Additional risks of OCT, 
which are not known at this time, may also exist. Appropriate 
contraindications and warnings are included in the Instructions for Use 
(IFU). 
 
• The following complications have been described with the use of Optical 
Coherence tomography catheters: 
 
§ Coronary artery spasm 
§ Unstable angina 
§ Allergic reaction to the contrast media 
§ Kidney damage due to contrast media 
§ Arterial dissection, injury or perforation 
§ Thrombus formation, abrupt closure or total vessel occlusion 
§ Abnormal heart rhythms 
§ Embolism 
§ Acute myocardial infarction 
§ Death 
§ Catheter entrapment 
 
 
10. 
TREATMENT 
 
10.1. Arterial Access Site 
 
• Follow- up PCI can be performed via the radial artery or the femoral 
artery, as per the site’s usual routine. 
 
10.2. Follow-up assessments:  3 months and 12 months 
 

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23 
The follow-up assessments at 1, 3 months, and 12 months include: 
 
• Patient status and any adverse events; 
• A clinical assessment and physical examination; 
• Complete Blood Count (CBC)  
• Serum Creatinine  
• Cardiac enzymes  
• Record of all medications 
• Angina status 
• Any medical care received 
 
 
10.3. MACE Definition 
 
• MACE (Major adverse cardiac events) will be defined as cardiac death, 
nonfatal myocardial infarction, or target lesion revascularization. 
 
11. 
ANGIOGRAPHY, PCI AND OCT 
 
11.1. Baseline angiography and PCI 
 
• Baseline angiography and PCI will be performed as per clinical routine at 
each participating center.  Adjunctive pharmacologic therapy during and 
immediately after the PCI should be prescribed as per the clinical routine 
at each participating center.  
• Only patients with PCI performed with Boston Scientific Synergy™ stent 
will be eligible for the trial. 
• Covering the entire diseased portion of the lesion with a single drug-eluting 
stent is recommended. 
• Left main bifurcation strategy will be performed per clinical routing at each 
participating center (e.g., culotte, crush, DK-crush, TAP, etc.). 
 
11.2. Baseline and follow-up OCT 
 
Performance of OCT 
 
• OCT should be performed with the St. Jude OCT system. For correct use 
of the OCT catheter and the St. Jude recording system, refer to the 
instructions for use provided by St Jude Medical along with the product. 
• Ensure correct calibration of all equipment. 
• In order to obtain high-quality images, it is strongly advocated to use 
power injection due to the large caliber of the LM and presence of high 
flow. 

SOLEMN Study 
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24 
 
 
11.3. Follow-up 3- and 12-month Angiography 
 
For angiographic assessment, ≥2 unforeshortened views of the LM with 
angiographic projections >30 degrees apart from one another should be obtained 
at the time of 3- and 12-month follow-up procedure(s). It is recommended that at 
follow-up angiography, ≥2 unforeshortened views of the lesion identical to the 
index procedure be obtained. It is recommended that the images be acquired at 
15 to 30 frames per second. 
 
11.4. OCT Methodology 
 
After adjusting for the pullback speed, cross-sections will be analyzed at 0.6-mm 
longitudinal intervals throughout the treated segment. Lumen contours will be 
traced using semiautomatic algorithms. Detection of metallic stent struts will be 
performed automatically with manual adjustments made as necessary. Stent 
area tracings will be automatically performed by interpolated contours connecting 
the center point of the luminal surface of each detected metallic strut. Stent 
expansion will be determined as the minimum stent area divided by the average 
reference lumen area and presented as a percentage. The stent eccentricity 
index will be calculated in every analyzed cross-section as (maximum stent 
diameter – minimum stent diameter) / maximum stent diameter. Neointimal 
hyperplasia (NIH) area will be determined in follow-up examinations as the area 
between the stent and lumen contours. The percentage of NIH obstruction of the 
stented area will be automatically determined in each analyzed cross-section at 
follow-up as (NIH area / stent area) × 100. Incomplete stent apposition (ISA) area 
will be determined as the area between the stent contour and the lumen contour 
at the site of malapposed struts, in a region not overlying a side branch ostium. 
ISA volume will be automatically computed by the Simpson rule. 
 
At the strut level, the strut-to-lumen distance will be automatically measured from 
the center point of the luminal surface of each analyzed strut to the lumen 
contour by a line projected through the gravitational center of the lumen. Covered 
struts will be considered when they have positive strut-to-lumen distances, a 
measure of the NIH thickness covering each strut. Uncovered and malapposed 
struts will be considered when they have negative strut-to-lumen distances. 
Malapposed struts will be differentiated from uncovered struts when the negative 
value of the strut-to-lumen distance is higher than the sum of the strut thickness 
+ a compensation factor of 20 µm to correct for the strut blooming.(36) Thus, a 
cutoff of 101 µm (74 or 79 µm for strut thickness + 20 µm for the compensation 
factor) will be used for determination of stent strut malapposition. The ratio of 
uncovered to total stent struts (RUTTS) will be calculated in each analyzed 
cross-section as the number of uncovered struts divided by the total number of 
struts in that particular cross-section. The number of cross-sections in which the 
RUTTS was >30% will be reported for each time point.(16) 

SOLEMN Study 
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25 
 
11.5. Single LM Stent OCT 
 
For single-stent LM technique it is anticipated to perform imaging of the whole 
length of the stent. If the stent is extending into the LAD or LCX the stented 
segment will be imaged, respectively. 
 
11.6. Bifurcation LM Stent OCT 
 
All bifurcation techniques are allowed in the SOLEMN trial. One- and two-stent 
techniques are allowed. At present time, there are few studies describing OCT of 
LM and bifurcation of LM and these have described a variety of measurement 
methodologies.(37-40) 
 
If the index procedures included OCT imaging of both limbs of the LM bifurcation 
it is recommended that repeat 3- and 12- month OCT imaging be performed to 
allow for strut coverage comparison. 
 
OCT measurements will be performed by: 
 
1) Conventional analysis of the main branch pullback; 
2) Conventional analysis of the side branch pullback; and 
3) If available, 3D OCT reconstruction of the bifurcation will be analyzed. 
 
11.7. Quantitative Coronary Angiography (QCA) analyses 
 
QCA analyses will be performed at CRF. 
 
11.8. Optical Coherence Tomography analyses 
 
OCT analyses will be performed at CRF. 
 
11.9. OCT Definitions 
 
The Indications for Use statement in the labeling for the Dragonfly OPTIS image 
catheter indicates that the device is not intended for use in the left main coronary 
artery. Therefore, the use of the Dragonfly OPTIS catheter in the SOLEMN study 
will be considered an off-label use. Multiple previous studies have described 
protocols for assessing stent strut coverage outside of LM (see below). The 
SOLEMN protocol allows enrollment of patients who underwent single LM stent 
placement and any or the currently accepted LM/LAD/LCX bifurcation strategies. 
Therefore, the OCT Stent Strut Coverage definitions previously described in non-
LM vessels (see below) will be used in the SOLEMN trial. 
 

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SOLEMN Study 
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SOLEMN REV. 19 
MLADEN VIDOVICH 
 
27 
Malapposition will be defined as a measured distance greater than the total 
thickness of the stent metal plus polymer of the stent.  
 
LASM (Late Acquired Stent Malapposition) defined as a malapposition visible 
only at follow-up by comparing follow-up to baseline OCT image 
 
11.12. Proposed OCT Measurements 
 
  
Index 
Procedure 3-month f/u 
 
12-month f/u 
Post-PCI 
  
  
 
 Cross-sectional level analysis 
  
  
 
  Mean lumen area (mm2) 
  
  
 
  Minimal lumen area (mm2) 
  
  
 
  Mean stent length (mm) 
  
  
 
  Intrastent prolapse 
  
  
 
 Strut level analysis 
  
  
 
  Number of stent strut 
  
  
 
  Malapposition 
  
  
 
Follow-up 
  
  
 
 Cross-sectional level analysis 
  
  
 
  Mean lumen area (mm2) 
  
  
 
  Minimal lumen area (mm2) 
  
  
 
  Mean stent length (mm) 
  
  
 
  Mean NIH area (mm2) 
  
  
 
  Percentage of neointimal volume 
obstruction (%) 
  
  
 
  Cross Section with any uncovered 
strut 
  
  
 
  Cross Section with uncovered strut 
> 0.3 
  
  
 
  Cross Section with any malapposed 
strut 
  
  
 
  Presence of thrombi 
  
  
 
 Strut level analysis 
  
  
 
  Number of stent strut 
  
  
 
  Mean Neointimal Thickness (μm) 
  
  
 
  Uncovered strut 
  
  
 
  Malapposed strut 
  
  
 
  Both of malapposed and uncovered 
strut (%) 
  
  
 
 

SOLEMN Study 
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28 
 
 
12. 
SAFETY EVALUATIONS 
 
12.1. Reporting of Adverse Events  
 
Trial personnel must report to the Jesse Brown Central site any adverse event 
within 24 hours of learning of the event. The notification can be performed via e-
mail, fax or phone. Evidence of the initial notification should be captured. Study 
personnel must forward follow-up information and the completed adverse event 
CRF to the Jesse Brown Central site as the event continues and/or resolves.  It is 
the responsibility of the Site Principal Investigator to inform the Institutional Review 
Board (IRB of the adverse event as required by local procedure.  
 
• Safety of the subjects participating in this clinical trial will be 
monitored throughout the trial using the Adverse Event reporting 
process to identify real and potential safety issues. 
 
12.2. Definitions of Adverse Events 
 
12.3. Adverse Event (AE) 
 
• Any untoward medical occurrence, unintended disease or injury or 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons whether or not related to the 
investigational medical device. 
 
12.4. Adverse Device Event (ADE) 
 
• Adverse event related to the use of an investigational medical device. 
 
12.5. Serious Adverse Event (SAE) 
 
• An adverse event that: 
 
1. led to a death, 
2. led to a serious deterioration in the health of the subject that either 
resulted in: 
a) a life-threatening illness or injury, or 
b) a permanent impairment of a body structure or a body function, or 
c) in-patient or prolonged hospitalization, or 

SOLEMN Study 
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29 
d) medical or surgical intervention to prevent life threatening illness or 
injury or permanent impairment to a body structure or a body function. 
 
12.6. Serious Adverse Device Effect (SADE)  
 
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event. 
 
12.7. Unanticipated Serious Adverse Device Effect (USADE)  
 
A serious adverse device effect which by its nature, incidence, severity or 
outcome has not been identified in the current version of the risk analysis report. 
 
12.8. Unanticipated Adverse Device Effect  
 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death 
was not previously identified in nature, severity, or degree of incidence in the risk 
analysis report, or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 
 
12.9. Device Deficiency (DD) 
 
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance. Note: Device deficiencies include malfunctions, 
use errors, and inadequate labeling. 
 
12.10. Device Malfunction 
 
Failure of an investigational medical device to perform in accordance with its 
intended purpose when used in accordance with the instructions for use or CIP. 
 
13. 
BIOSTATISTICAL CONSIDERATIONS 
 
13.1. Primary Endpoint Analysis 
 
The primary endpoint is 3-month stent strut coverage and is specifically defined 
as Percentage of Uncovered Stent Struts. The Percentage of Uncovered Stent 
Struts is the number of struts without distinct overlying tissue, in which the 
luminal reflection of the strut surface is directly interfacing with the lumen, divided 
by total number of analyzable struts. 
 
The null and alternative hypotheses for the primary endpoint are: 
 

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30 
H0: μS3 ³ 0.90 
H1: μS3 < 0.90 
 
where μS3 is the mean percentage of uncovered stent struts for Synergy DES at 
3 months after index procedure. 
 
The one-sided significance level of 0.05 will be used. 
 
Baseline clinical characteristics will be analyzed on the patient level whereas 
OCT data will be analyzed on per-patient, per-lesion, per-segment, and per-strut 
levels. 
 
Categorical variables will be compared with the c2 or the Fisher exact tests. 
 
Continuous variables will be compared with the 2-sample Wilcoxon rank-sum 
test.  
 
For segmental and strut analyses, continuous variables will be compared using 
generalized estimating equations with exchangeable correlation to account for 
the clustering of values within each lesion and subject. 
 
13.2. Secondary Endpoint Analyses 
 
The secondary endpoint or 12-month stent strut coverage and is similarly defined 
as primary endpoint as defined as Percentage of Uncovered Stent Struts. The 
Percentage of Uncovered Stent Struts at time 0, 3-months and 12-months will be 
compared with ANOVA. 
 
The additional secondary endpoints (categorical and continuous) will be analyzed 
as indicated above. 
 
• 3-month late acquired stent malapposition (LASM) 
• 12-month late acquired stent malapposition (LASM) 
• One-month LM Synergy stent safety 
• 1-, 3- and 12-month MACE 
• 1-, 3- and 12-month Stent Thrombosis (ST) (ARC definition) 
 
13.3. Expected treatment effect 
 
We expect >90% strut coverage at 3-months and >95% strut coverage at 12 
months follow-up OCT. 
 
13.4. Statistical Analysis Sites  
 

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31 
Analysis will be undertaken by statisticians at the VA, Duke University and CRF. 
 
13.5. Sample Size considerations 
 
Previous studies have included similar number of patients in OCT follow-up of 
stent strut coverage.  
 
We anticipate some patient attrition during the trial. The ideal assumption is to 
have a full sample 75 patients at baseline, 75 patients at 3-months and 75 
patients at 12-month follow-up. 
 
With attrition due to unforeseeable and clinically-driven events, we anticipate an 
inclusion of 75 patients at baseline, 65 patients at 3 months and 50 patients at 
12-month follow-up. 
 
14. 
SAFETY, DSMB AND COMPLAINT PROGRAM 
 
Safety will be performed by IRB standards at each study site. 
 
The central Jesse Brown VA site will perform electronic chart monitoring of a 
random sample of 10% of the study participants. 
 
Electronic central monitoring will collect a random sample of: 
 
• Informed consent forms 
• Site Records 
• Source Data (for verification and corroboration) 
 
Safety of the subjects participating in this clinical trial will be monitored 
throughout the trial using the Adverse Event reporting process to identify real and 
potential safety issues. 
 
14.1. Data Safety Monitoring Board (DSMB) 
 
A Data and Safety Monitoring Board (DSMB) will be appointed to periodically 
review the conduct of the proposed trial for safety. The committee members will 
be cardiologists with experience in clinical research who will not be participating 
in the trial as investigators.  Potential financial or intellectual conflicts of interest 
will be assessed prior to appointing the members. The DSMB will meet prior to 
the enrollment of the first subject to review the trial protocol, informed consent 
documents and plans for safety and data monitoring of the study. The DSMB will 
determine the risks and benefits to research subjects, protection and safety of 
the subjects and to offer suggestions for improving the study design. In addition, 
the DSMB will determine which data will be required for periodic review. The 

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32 
DSMB will meet every 6 months to: determine adherence to study plan; review 
interim analysis, if applicable, and determine specific data to be analyzed; review 
protocol violations and deviations to assess adequacy of study; ensure 
documentation of informed consent; review enrollment followed eligibility criteria, 
enrollment numbers, visit compliance, or screening failure information; discuss 
investigator or key personnel changes; review completeness and quality of data 
collection forms; evaluate the aggregate analysis of adverse events/serious 
adverse events; review vital signs, clinical tests, etc.; and review confidentiality. 
At the end of each meeting the DSMB will give a recommendation to continue the 
trial unchanged, modify the protocols and/or consent form, or terminate the trial. 
 
14.2. Selection and Monitoring of Clinical Sites and Operators 
 
In the selection of study investigators, the PI requires each physician to have 
adequate experience with investigational devices, demonstrate commitment to 
patient safety and consistency in adherence to study protocols. 
 
Monitoring will be conducted by the PI and/or designee. These responsibilities 
include collecting and tracking data forms and instituting quality control measures 
for data entry verification and trial compliance. 
15. 
MONITORING  
 
Monitoring procedure will be performed based on the following FDA guidance 
and recommendations:   
 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation
/Guidances/UCM269919.pdf.  
 
Centralized monitoring of the VA sites will be conducted for the SOLEMN trial. 
 
• Data quality will be routinely monitored by a routine review of submitted 
data (CRF), angiograms, and OCT images. Follow-up on missing data, 
inconsistent data, data outliers and potential deviations will be provided to 
the sites when such occurrences are identified. 
• Site performance metrics (enrollment numbers, high frequency of protocol 
deviations, delays in data submission) will be routinely performed. 
• Completion of administrative and regulatory tasks will be performed, for 
example, compliance with local institutional review board (IRB) 
requirements or other appropriate local regulatory requirements. 
 
 
15.1. Monitoring of Critical Data and Processes  
 

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In order to provide highest level of protection of human subjects the following 
data and processes will be continuously monitored and feedback provided to the 
sites: 
 
• Adherence to protocol eligibility criteria (inclusion/exclusion criteria) 
• Ongoing evaluation, documentation and reporting of serious adverse 
events and unanticipated adverse device effects, subject deaths, subject 
withdrawals, especially when a withdrawal may be related to an adverse 
event 
• Specifically, use of OCT in LM coronary artery will be continuously 
monitored to ascertain safety throughout the trial 
 
With continuous monitoring, if a risk associated with the SOLEMN trial is 
identified, the principal investigator, study investigators and DSMB will act to 
remove the source of identified risk. Study monitoring will be adjusted 
accordingly in such instance to effectively oversee the identified risks. 
 
 
15.2. Communication of Centralized Monitoring 
 
Written communication between the central monitoring site (Jesse Brown VA) 
and the local VA sites will be performed via encrypted government email systems 
only. Additionally, teleconferences, videoconferencing will be provided through 
secured VA government systems only. 
 
 
15.3. Clinical Events Committee (CEC) 
 
The CEC is a group of 3 physicians with pertinent experience to review safety 
event data from the SOLEMN clinical study. This committee adjudicates 
individual AEs, which occur in the study. The CEC will also review and validate 
adverse events that occur over the course of the study and the subsequent 
classification of these adverse events as related to the device or procedure. 
 
15.4. Case report forms (CRF)  
 
Case Report Forms will be collected via facsimile and sent to the central location 
at Jesse Brown VA Medical Center. 
 
All information required and entered in the CRFs will be also available for later 
verification and confirmation in the VA electronic medical records (CPRS) should 
later confirmation be necessary. 
 

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The designated facsimile line for the SOLEMN trial only (312-569-7203) is in a 
locked and secured office with access only by the PI and Jesse Brown Research 
study personnel assigned to the SOLEMN protocol. 
 
15.5. Discontinuation Criteria for the Entire Trial 
 
If the Sponsor, Data Safety and Monitoring Board, Clinical Events Committee, 
Regulatory Agency, and/or the Principal Investigator discover conditions during 
the study that indicate the investigation should be terminated for patient safety 
reasons, an appropriate schedule for termination will be instituted. 
 
15.6. Study Termination 
 
If the study is terminated prior to the completion of expected enrollment for any 
reason, all participating centers will be notified within five working days. All 
patients already enrolled will continue to be followed for the planned course of 
study described in this protocol. 
 
15.7. Potential limitations  
 
The main limitation of the proposed trial is absence of randomization and single 
arm design. 
 
Additionally, due to logistical and financial considerations the sample size will be 
inadequate to determine the impact of Synergy on LM MACE. 
 
We anticipate some patient attrition during the trial. The assumption is to have a 
full sample 75 patients at baseline, 75 patients at 3-months and 75 patients at 
12-month follow-up. 
 
 
16. 
ETHICAL ASPECTS OF THE PROPOSED RESEARCH 
 
Angiographic follow-up of LM PCI has been routinely performed in the past in 
research and clinical settings.(27) ACC/AHA PCI guidelines consider use of 
intracoronary imaging guidance with IVUS a Class IIb recommendation, 
supporting the use of OCT as an intracoronary imaging method during the index 
procedure.(4) 
 
Lastly, stent strut coverage after PCI has been assessed in numerous studies in 
the past supporting its safety and underlying the scientific rational for use.(11, 17, 
41, 42) 
 

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Although participation in our study carries a small risk (related to performance of 
repeat invasive angiography and OCT we will make every effort to minimize it. To 
minimize the risk associated with angiography and OCT, patients at high risk for 
vascular access complications, allergy to contrast dye or other contraindications 
for repeat cardiac catheterization will be excluded from the study. Also patients 
will be monitored closely with clinic visits or phone follow-up as indicated in the 
protocol. To minimize the risk from cardiac catheterization and invasive OCT 
assessment, patients at high risk for complications, such as patients with 
peripheral vascular disease and renal failure, will also be excluded. All 
angiographic OCT imaging procedures will be performed by experienced, high-
volume, interventional cardiologists. 
 
17. 
DATA OWNERSHIP 
 
Department of Veterans Affairs 
 
18. 
INSTITUTIONAL REVIEW BOARD APPROVAL (IRB) 
 
Local IRB will be obtained at each of the participating sites.  
 
The local site investigators must obtain appropriate IRB approval before the 
study can be initiated. A copy of the written approval from the IRB and a copy 
of the approved informed consent form must be sent to the Jesse Brown VA 
Central Site. 
 
18.1. Statement of Compliance 
 
This study will be conducted in accordance with relevant parts of the Code of 
Federal Regulation (CFR), ISO 14155: Clinical Investigation of Medical 
Devices for Human Subjects-Good Clinical Practices, the relevant parts of the 
ICH Guidelines for Good Clinical Practices, ethical principles that have their 
origins in the Declaration of Helsinki, and pertinent individual country laws 
and regulations. The study shall not begin until the required 
approval/favorable opinion from the IRB/EC and/or regulatory authority has 
been obtained, if appropriate. Any additional requirements imposed by the 
IRB/EC or regulatory authority shall be followed, if appropriate. 
 
 
18.2. Signed Informed Consent 
 
Signed informed consent forms (or copies) are to be maintained in the study 
file and must be available for verification by monitors or inspectors. 
 

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18.3. Subject Confidentiality 
 
The coordinating Jesse Brown site and the local sites will maintain the 
confidentiality of the identity of subjects enrolled in the study and the 
information contained in their study records. The records will be made 
available as required for review by governing regulatory agency such as FDA 
and a reviewing IRB; the subject’s identity will not be disclosed. All data used 
in the analysis and reporting of this evaluation will be used in a manner 
without identifiable reference to the subject. 
 
18.4. Retention of Records by the Investigator 
 
Investigators will retain records for a period of 3 years following the 
completion of the study, or as per local requirements, whatever is stricter.  
 
19. 
IDE SUBMISSION  
 
• IDE submission will be prepared in collaboration with: 
 
Alexandra Scrymgeour, MS, PharmD 
Acting Chief, Regulatory and Clinical Compliance Clinical Research 
Pharmacy Coordinating Center VA Cooperative Studies Program 
Phone: (505)248-3203 
Fax: (505)248-3205 
Email: Alexandra.Scrymgeour@va.gov 
 
 
20. 
ROLE OF SPONSOR (JESSE BROWN VA COORDINATING 
CENTER) 
 
As the sponsor of this clinical study, the central coordinating site at Jesse 
Brown VA Medical Center will hold the overall responsibility to conduct of 
the study. 
 
20.1. General Duties 
 
The central coordinating site at Jesse Brown VA Medical Center general 
duties consist of submitting applications and information to the FDA, 
obtaining regulatory and IRB approvals prior to allowing study 
commencement at selected sites, selecting investigators, ensuring proper 
investigational site monitoring and ensuring subject informed consent is 
obtained. 
 

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20.2. Selection of Investigators 
 
The central coordinating site at Jesse Brown VA Medical Center will be 
involved in: 
 
• Assuring selection of investigators qualified by training and experience 
 
• Obtaining a signed investigator's agreement containing: 
o investigator's curriculum vitae 
o statement of investigator's relevant experience, including date, 
location, extent, and type of experience 
o if an investigator was involved in an investigation or other research 
that was terminated, an explanation of the circumstances that led to 
the termination 
• statement of the investigator's commitment to conduct the investigation in 
accordance with the investigational plan and any conditions of approval 
imposed by the IRB or FDA 
• ensure that the requirements for informed consent are met  
• Providing investigators with the necessary information to conduct the 
investigation including, but not necessarily limited to: 
o the investigational plan 
o the report of prior investigations 
 
20.3. Role of the Investigator 
 
The Principal Investigator of an investigational site is responsible for ensuring that 
the study is conducted in accordance with the Clinical Study Agreement, the 
clinical investigation plan, ISO 14155, ethical principles that have their origins in 
the Declaration of Helsinki, any conditions of approval imposed by the reviewing 
IRB/EC, and prevailing local and/or country laws and/or regulations, whichever 
affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the 
following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with 
the Investigator responsibilities as described in such Agreement.   
• Prior to beginning the study, sign the Investigator Brochure Signature Page and 
Protocol Signature page documenting his/her agreement to conduct the study 
in accordance with the protocol. 
• Provide his/her qualifications and experience to assume responsibility for the 
proper conduct of the study and that of key members of the site team through 
up-to-date curriculum vitae or other relevant documentation and disclose 
potential conflicts of interest, including financial, that may interfere with the 
conduct of the clinical study or interpretation of results. 

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• Make no changes in or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any 
deviation from the approved protocol that occurred during the course of the 
clinical investigation. 
• Create and maintain source documents throughout the clinical study and 
ensure their availability with direct access during monitoring visits or audits; 
ensure that all clinical-investigation-related records are retained per 
requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data 
reported to the sponsor in the CRFs and in all required reports. 
• Record, 
report, 
and 
assess 
(seriousness 
and 
relationship 
to 
the 
device/procedure) every adverse event as applicable per the protocol and 
observed device deficiency. 
• Report to sponsor, per the protocol requirements, all SAEs and device 
deficiencies that could have led to a SADE and potential/USADE or UADE. 
• Report to the IRB/EC and regulatory authorities any SAEs and device 
deficiencies that could have led to a SADE and potential/USADE or UADE, if 
required by the national regulations or this protocol or by the IRB/EC, and 
supply Coordinating center with any additional requested information related to 
the safety reporting of a particular event. 
• Maintain the device accountability records and control of the device, ensuring 
that the investigational device is used only by authorized/designated users and 
in accordance with this protocol and instructions/directions for use. 
• Allow the sponsor to perform monitoring and auditing activities, and be 
accessible to the clinical research monitor or auditor and respond to questions 
during monitoring visits or audit(s). 
• Allow and support regulatory authorities and the IRB/EC when performing 
auditing activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, 
this protocol and local IRB/EC requirements. 
• Provide adequate medical care to a subject during and after a subject’s 
participation in a clinical study in the case of adverse events, as described in 
the Informed Consent Form (ICF). 
• Inform the subject of the nature and possible cause of any adverse events 
experienced. 
• As applicable, provide the subject with necessary instructions on proper use, 
handling, storage, and return of the investigational device when it is 
used/operated by the subject. 

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• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be 
required. 
• Provide the subject with well-defined procedures for possible emergency 
situations related to the clinical study, and make the necessary arrangements 
for emergency treatment, including decoding procedures for blinded/masked 
clinical investigations, as needed. 
• Ensure that clinical medical records are clearly marked to indicate that the 
subject is enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are 
provided with some means of showing their participation in the clinical 
investigation, together with identification and compliance information for 
concomitant treatment measures (contact address and telephone numbers 
shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, 
the subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are 
maintained and documented during the clinical investigation. 
• Ensure that maintenance and calibration of the equipment relevant for the 
assessment of the clinical investigation is appropriately performed and 
documented, where applicable. 
 
20.4. Delegation of responsibility 
 
When specific tasks are delegated by an investigator, including but not limited to 
conducting the informed consent process, the Principal Investigator is responsible 
for providing appropriate training and adequate supervision of those to whom tasks 
are delegated. The investigator is accountable for regulatory violations resulting 
from failure to adequately supervise the conduct of the clinical study. 
 
20.5. Record Maintenance 
 
The central coordinating site at Jesse Brown VA Medical Center will maintain 
copies of correspondence, data, shipment of 
studies, UADEs and other records related to this clinical study as required under 
local, VA and national regulations. 
 

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20.6. Communication with the FDA 
 
The central coordinating site, Jesse Brown VA, will submit reports as required 
by the FDA regulations. 
 
20.7. Prohibition of Promotion and Other Practices  
 
The IDE regulations prohibit the promotion and commercialization of a device 
that has not been first cleared or approved for marketing by FDA. As indicated in 
the SOLEMN protocol, the SOLEMN trial is not designed to seek FDA approval 
for the Synergy stent for use in LM PCI nor it is designed to seek FDA approval 
for use of OCT in LM. 
 
The central coordinating site, Jesse Brown VA, will actively monitor and prevent 
prolonging the SOLEMN trial beyond the point needed to collect data required to 
complete the trial. 
 
20.8. Maintaining Records  
 
The central coordinating site, Jesse Brown VA, shall maintain the following 
accurate, complete, and current records relating to the SOLEMN trial: 
 
• Correspondence (including reports) with another sponsor, monitor, 
investigators, an IRB or FDA 
• Records of investigational study images shipment 
• Signed investigator agreements 
• Adverse device effects (whether anticipated or unanticipated) and 
complaints 
• Any other records that FDA requires by regulation or by specific 
requirement for a category of investigation or a particular 
investigation 
•  
20.9. Submitting Reports 
 
The central coordinating site, Jesse Brown VA shall prepare and submit 
the following complete, accurate, and timely reports: 
 
• Unanticipated adverse device effects (with evaluation) to FDA, all 
IRBs, and investigators within 10 working days after notification by 
the investigator. Subsequent reports on the effect may be required 
by FDA. 
• Withdrawal of IRB approval 
• Withdrawal of FDA approval 
• Annual progress report  
• Final report  

SOLEMN Study 
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41 
• Other reports as requested by the IRB or FDA 
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2015;11 Suppl V:V64-70. 

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SOLEMN Study 
CONFIDENTIAL 
SOLEMN REV. 19 
MLADEN VIDOVICH 
 
47 
23.1. CRF Proposal for OCT Analysis 
 
24. 
APPENDIX C. 
 
24.1. Jesse Brown VA Consent Form 
 
25. 
APPENDIX D. 
 
25.1. MACE Definitions 
 
Death is defined as all cause death.  Cardiac death is defined as any sudden 
death, death related to acute myocardial infarction, arrhythmia or congestive 
heart failure, death secondary to a cerebrovascular accident, or death directly 
related to PCI or CABG, even if the ultimate cause of death is not clearly a 
cardiac event (e.g., infection).  Non-cardiac death is any death which is not 
clearly cardiac in etiology. 
 
Myocardial infarction is defined in two ways, depending on whether or not it is 
PCI or CABG-related or a spontaneous event, as recently described in the 
literature.(43) 
Spontaneous myocardial infarction (>48 hours after PCI or CABG): 
Detection of rise and/or fall of cardiac biomarkers (CK-MB or troponin) 
with at least one value above the 99th percentile of the upper reference 
limit (URL) together with evidence of myocardial ischemia with at least one 
of the following: 
• Symptoms of ischemia 
• ECG changes indicative of new ischemia [new ST-T changes or new, 
persistent, non rate-related left bundle branch block (LBBB)] 
• Development of pathological Q waves (≥ 0.03 seconds in duration and 
≥ 1 mm in depth) in ≥ 2 contiguous precordial leads or ≥ 2 adjacent 
limb leads of the ECG  
• Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality 
 
PCI or CABG-related MI (<48 hours after PCI or CABG):  
 
Elevation of the cardiac troponin value > 10 x 99th percentile of the URL in 
patients with a normal baseline reference level, or an increase of > 20%, if 
the baseline values are elevated, but are stable or falling.  In addition, at 
least one of the following:  
(i) 
new pathologic Q waves or new left bundle branch block 
(ii) 
angiographic documented new graft or new native coronary 
occlusion 

SOLEMN Study 
CONFIDENTIAL 
SOLEMN REV. 19 
MLADEN VIDOVICH 
 
48 
(iii) 
imaging demonstration of new loss of viable myocardium or new 
regional wall motion abnormalities  
is required. 
 
Stroke (cerebrovascular accident or CVA) is the rapid onset of a focal or 
global neurological deficit.  If the duration is <24 hours, the event is deemed a 
transient ischemic attack (TIA), except if an intervention is performed as defined 
below.  If the duration is ≥24 hours, it is deemed a stroke.  Stroke is subdivided 
as ischemic, hemorrhagic, or undetermined.  Ischemic stroke refers to acute 
symptomatic episode of focal cerebral, spinal, or retinal dysfunction caused by an 
infarction of the central nervous system tissue.  Hemorrhagic stroke is an acute 
symptomatic episode of focal or global cerebral or spinal dysfunction caused by 
nontraumatic intraparenchymal, intraventricular or subarachnoid hemorrhage.  
Undetermined stroke is one with insufficient information to allow categorization 
as either of the above two.  
Stroke is diagnosed when the following criteria are met: 
1. Rapid onset of a focal/global neurological deficit with at least one of the 
following: 
- 
Change in level of consciousness 
- 
Hemiplegia 
- 
Hemiparesis 
- 
Numbness or sensory loss affecting one side of the body 
- 
Dysphagia/aphasia 
- 
Hemianopia 
- 
Amaurosis fugax 
- 
Other new neurological sing(s)/symptom(s) consistent with 
stroke 
2. Duration of focal/global neurological deficit is ≥24 hours, or it can be <24 
hours if a therapeutic intervention is performed, brain imaging clearly 
documents a new hemorrhage or infarct, or the neurological deficit results 
in death. 
3. Confirmation of the diagnosis by at least one of the following: 
- 
Neurology or neurosurgical specialist 
- 
Brain imaging (CT, MRI, or cerebral vessel angiography) 
- 
Lumbar puncture diagnostic of intracranial hemorrhage 
Urgent revascularization is defined as an unplanned hospitalization for an 
acute coronary syndrome which results in revascularization during the 
hospitalization. 
Repeat revascularization is defined as any unplanned (elective or urgent) 
revascularization, whether PCI or CABG.  Planned staged PCI procedures do not 
qualify. 

SOLEMN Study 
CONFIDENTIAL 
SOLEMN REV. 19 
MLADEN VIDOVICH 
 
49 
Bleeding is defined as per the Bleeding Academic Research Consortium 
(BARC).(44) Other descriptions of bleeding, such as TIMI, may be applied as 
well. 
Stent thrombosis is defined as per the Academic Research Consortium.(45)  
Rehospitalization is defined as a hospital stay of >24 hours 
 
25.2. Safety Definition 
One-month LM Synergy stent safety is defined as a composite of cardiac death 
and target vessel MI at 1 month after index PCI. 
Cardiac death. Any death due to proximate cardiac cause (e.g., MI, low-output 
failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all 
procedure-related deaths including those related to concomitant treatment. 
Target vessel MI will be defined as all as MIs that occur in the distribution of the 
LM, LAD, and LCX coronary arteries.