A Prospective Global Randomized Trial Assessing the Safety and Efficacy of the BuMA Supreme™ Biodegradable Drug Coated Coronary Stent System for Coronary Revascularization in Patients With Stable Coronary Artery Disease or Non-ST Segment Elevation Acute Coronary Syndromes
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Sino Medical Sciences Technology Inc.

The PIONEER III Trial [SIN-US-001] 
    Sino Medical Sciences Technology, Inc. 
Version 8.0 – 26MAR2020 
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The PIONEER III Trial 
A Prospective Multicenter Global Randomized Controlled Trial 
Assessing the Safety and Efficacy of the BuMA Supreme™ 
Biodegradable Drug Coated Coronary Stent System for Coronary 
Revascularization in Patients with Stable Coronary Artery Disease 
or Non-ST Segment Elevation Acute Coronary Syndromes 
Protocol # SIN-US-001 
Clinical Investigation Plan 
Version 8.0 
26 March 2020  
Sponsor: 
Sino Medical Sciences Technology, Inc. (SINOMED) 
2nd Floor, Building B, TEDA BioPharm Res., #5 
Tianjin 300457, People’s Republic of China 
US Agent: 
NOVA Vascular, Inc. 
25 Mauchly, Suite 301 
Irvine, CA 92618 USA  
NOTICE: The information contained in this document is CONFIDENTIAL and PROPRIETARY to SINOMED, and 
should not be disclosed to any anyone who is not a recipient or reviewer of this protocol without express prior 
written consent of SINOMED. 

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Table of Contents 
1.0 DOCUMENT CONTROL ......................................................................................................................................... 4 
1.1 VERSION HISTORY ........................................................................................................................................................... 4 
1.2 PROTOCOL APPROVAL PAGE ............................................................................................................................................. 7 
1.3 INVESTIGATOR SIGNATURE PAGE ....................................................................................................................................... 8 
2.0 STUDY CONTACTS ................................................................................................................................................ 9 
3.0 PROTOCOL SYNOPSIS .......................................................................................................................................... 12 
4.0 BACKGROUND ..................................................................................................................................................... 20 
4.1 CLINICAL BACKGROUND ................................................................................................................................................. 20 
4.2 INVESTIGATIONAL DEVICE ............................................................................................................................................... 21 
4.3 CONTROL DEVICE .......................................................................................................................................................... 24 
4.4 RATIONALE .................................................................................................................................................................. 25 
5.0 STUDY DESIGN .................................................................................................................................................... 25 
5.1 STUDY DESIGN OVERVIEW .............................................................................................................................................. 25 
5.2 STUDY OBJECTIVE ......................................................................................................................................................... 26 
5.3 ENDPOINTS .................................................................................................................................................................. 26 
6.0 SUBJECT SELECTION AND WITHDRAWAL............................................................................................................. 27 
6.1 PATIENT POPULATION.................................................................................................................................................... 27 
6.2 ELIGIBILITY CRITERIA ...................................................................................................................................................... 27 
6.3 SUBJECT SCREENING ...................................................................................................................................................... 29 
6.4 INFORMED CONSENT ..................................................................................................................................................... 29 
6.5 SUBJECT ENROLLMENT ................................................................................................................................................... 30 
6.6 WITHDRAWAL AND REPLACEMENT OF SUBJECTS ................................................................................................................. 30 
6.7 PROTOCOL DEVIATIONS ................................................................................................................................................. 31 
7.0 STUDY PROCEDURES AND ASSESSMENTS ........................................................................................................... 32 
7.1 SCHEDULE OF PROCEDURES AND ASSESSMENTS .................................................................................................................. 32 
7.2 SCREENING / BASELINE .................................................................................................................................................. 33 
7.3 INDEX PROCEDURE ........................................................................................................................................................ 34 
7.4 POST-PROCEDURE / PRE-DISCHARGE FOLLOW-UP ............................................................................................................... 36 
7.5 30-DAY FOLLOW-UP (CLINIC VISIT) .................................................................................................................................. 36 
7.6 SIX-MONTH FOLLOW-UP (TELEPHONE CONTACT/CLINIC VISIT) .............................................................................................. 37 
7.7 TWELVE-MONTH FOLLOW-UP (CLINIC VISIT OR OPTIONAL TELEPHONE CONTACT / VIRTUAL VISIT*) ............................................. 37 
7.8 ANNUAL FOLLOW-UP AT 2, 3, 4, AND 5 YEARS (TELEPHONE CONTACT/CLINIC VISIT) ................................................................ 39 
8.0 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ............................................................................................. 39 
8.1 ADVERSE EVENTS (AE) .................................................................................................................................................. 39 
8.2 SERIOUS ADVERSE EVENTS (SAE) .................................................................................................................................... 40 
8.3 ADVERSE DEVICE EFFECT (ADE) ...................................................................................................................................... 40 
8.4 SERIOUS ADVERSE DEVICE EFFECT (SADE) ........................................................................................................................ 40 
8.5 UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ............................................................................................................. 40 
8.6 DEVICE DEFICIENCIES, MALFUNCTIONS, AND USE ERROR...................................................................................................... 40 
8.7 DOCUMENTATION ......................................................................................................................................................... 41 
8.8 REPORTING.................................................................................................................................................................. 42 
8.9 EXPECTED ADVERSE EVENTS ........................................................................................................................................... 44 
9.0 BENEFIT: RISK ANALYSIS ...................................................................................................................................... 46 

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9.1 POTENTIAL BENEFITS ..................................................................................................................................................... 46 
9.2 POTENTIAL RISKS AND DISCOMFORTS ............................................................................................................................ 46 
9.3 METHODS TO MINIMIZE RISKS ........................................................................................................................................ 46 
10.0 STUDY COMMITTEES ........................................................................................................................................... 46 
10.1 EXECUTIVE COMMITTEE ............................................................................................................................................... 46 
10.2 CLINICAL EVENTS COMMITTEE (CEC) ............................................................................................................................. 46 
10.3 DATA SAFETY MONITORING COMMITTEE (DSMC) ........................................................................................................... 47 
11.0 STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN .......................................................................................... 47 
11.1 HYPOTHESES .............................................................................................................................................................. 47 
11.2 ANALYSIS POPULATIONS .............................................................................................................................................. 48 
11.3 SAMPLE SIZE CALCULATION AND ASSUMPTIONS ............................................................................................................... 48 
11.4 METHOD OF ANALYSIS & REPORTING ............................................................................................................................. 51 
11.5 MEASURES TO MINIMIZE BIAS ...................................................................................................................................... 54 
12.0 PUBLICATION POLICY .......................................................................................................................................... 54 
13.0 DATA COLLECTION AND MONITORING ............................................................................................................... 55 
13.1 DATA COLLECTION AND MONITORING ............................................................................................................................ 55 
13.2 SOURCE DOCUMENTATION ........................................................................................................................................... 55 
13.3 AUDITING ................................................................................................................................................................. 56 
14.0 DEVICE ACCOUNTABILITY .................................................................................................................................... 56 
15.0 ETHICAL AND REGULATORY CONSIDERATIONS ................................................................................................... 57 
15.1 APPLICABLE REGULATIONS ........................................................................................................................................... 57 
15.2 INSTITUTIONAL REVIEW BOARD / ETHICS COMMITTEE ....................................................................................................... 57 
15.3 INSURANCE ............................................................................................................................................................... 57 
15.4 REGULATORY APPROVAL .............................................................................................................................................. 57 
15.5 TRIAL REGISTRATION ................................................................................................................................................... 58 
15.6 RECORDS AND REPORTS ............................................................................................................................................... 58 
15.7 PROTOCOL AMENDMENTS ............................................................................................................................................ 59 
15.8 INFORMED CONSENT ................................................................................................................................................... 59 
15.9 TERMINATION OF THE STUDY ........................................................................................................................................ 59 
15.10 PATIENT PRIVACY ..................................................................................................................................................... 59 
16.0 REFERENCES ........................................................................................................................................................ 60 
17.0 APPENDICES ........................................................................................................................................................ 68 
17.1 APPENDIX A: DEFINITIONS ........................................................................................................................................... 68 
17.2 APPENDIX B: ACRONYMS ............................................................................................................................................. 78 
17.3 APPENDIX C: ANGIOGRAPHIC IMAGING ACQUISITION GUIDELINES ....................................................................................... 81 
 
 
 

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5.0 (27 April 2018) 
Minor modifications and clarifications to study eligibility criteria, including: 
Added upper age limit of 99 years to general inclusion criteria; added that 
when treatment of 2 target lesions in a single vessel is planned, there must 
be adequate separation between lesions to ensure a gap of ≥10 mm 
between study stents; clarified that known other medical illness or known 
history of substance abuse that may cause non-compliance with 
prescribed medications excludes a potential subject from study 
participation; clarified that lesions accessed via arterial or saphenous vein 
grafts are not eligible target lesions; clarified that vascular brachytherapy 
is not permitted as part of the index procedure treatment plan. 
Minor modifications to study procedures and assessments, including: 
Clarified that assessments performed as part of standard medical care 
prior to study enrollment are valid sources of data for verifying study 
eligibility and (after informed consent has been obtained) collecting 
baseline study data; clarified that laboratory testing of CBC and serum 
creatinine should be performed only if part of the site standard of care; 
clarified that antiplatelet therapy loading dose, loading dose timing, and 
maintenance dosage may vary based on applicable regional guidelines; 
clarified that a major protocol deviation is any deviation that may affect the 
scientific soundness of the protocol or the rights, safety, or welfare of the 
patients, and that the stated examples of major protocol deviations are not 
exhaustive. 
Minor administrative updates and editorial corrections, including: Editorial 
correction for consistency of study title; updated anticipated study 
timelines; updated study contacts; updated Angiographic Core Laboratory 
submission information. 
6.0 (19 February 2019) 
Not implemented. 
Modified BuMA DES stent size matrix (4.0 mm diameter stent added), with 
corresponding changes to angiographic inclusion criteria (visually 
estimated reference vessel diameter now ≥2.25 mm to ≤4.00 mm) and 
intended use statement. Anticipated study timelines updated. 
7.0 (29 May 2019) 
Includes all changes from Version 6.0 (as approved by US FDA), with the 
following additional minor changes: 
• 
Time frame for 30-day follow up clinic visit modified from “30 days 
(+ 7 days) post-procedure” to “30 days (± 7 days) post-procedure” 
due to operational considerations 
• 
Updated anticipated study timelines 
• 
Updated Angiographic Core Laboratory contact email 

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8.0 (26 March 2020) 
Protocol revised to permit telephone or virtual follow-up visits at 12 months 
if necessary to assure the safety of trial participants in the context of the 
Coronavirus Disease 2019 pandemic. Modified protocol sections include: 
• 
Section 5.1 (Study Design Overview) 
• 
Section 7.1 (Schedule of Procedures and Assessments) 
• 
Section 7.7 (Twelve-Month Follow-up [Clinic Visit or Optional 
Telephone Contact / Virtual Visit]) 
 
 

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by randomized comparison with commercially-available durable polymer everolimus-
eluting stent systems. 
Study Design 
This prospective, multicenter study will enroll up to 1632 subjects at up to 130 
investigational sites in North America, Japan, and Europe. Patients presenting with 
symptomatic ischemic heart disease (including chronic stable angina with evidence of 
ischemia, unstable angina, or non-ST segment elevation myocardial infarction) who 
require elective or urgent percutaneous coronary intervention (PCI) to treat up to 3 
native coronary artery lesions in up to 2 major coronary arteries, in vessel diameters 
of ≥2.25 mm to ≤4.00 mm and lesion lengths ≤31 mm, and who meet all eligibility 
criteria will be enrolled in the study and randomized 2:1 (stratified by presentation 
[acute coronary syndrome vs. non-ACS], diabetes status [with vs. without medically-
treated diabetes mellitus], and study site) to the following treatment groups:  
• 
Intervention: Coronary revascularization with the BuMA SupremeTM 
Biodegradable Drug Coated Coronary Stent System (BuMA DES) 
• 
Control: Coronary revascularization with commercially-available durable 
polymer everolimus-eluting stent systems (DP EES) 
Subjects will have clinical follow-up in-hospital and at 30 days, 6 months, 12 months, 
and 2, 3, 4, and 5 years. Follow-up at 30 days and 12 months* will be clinic visits, while 
the 6-month follow-up and annual follow-up at 2-5 years will be via telephone contact 
(or optional clinic visit). Subjects in whom no study stent is implanted will be followed 
to 12 months only. 
*NOTE: For the duration of the Coronavirus Disease 2019 (COVID-19) pandemic, 
phone follow-up or virtual visit at 12 months is permitted if necessary to assure the 
safety of trial participants.  
Sites and 
Geography 
Up to 130 sites in North America, Japan, and Europe. A minimum of 50% of subjects 
will be enrolled at North American sites, and no single center will enroll more than 10% 
of all subjects. 
Primary 
Safety and 
Efficacy 
Endpoint  
Target lesion failure at 12 months 
Target lesion failure (TLF) is defined as the composite of cardiac death, target vessel-
related 
myocardial 
infarction 
(TV-MI), 
and 
clinically-driven 
target 
lesion 
revascularization (TLR). 
Secondary 
Endpoints 
All secondary endpoints will be compared in the BuMA DES group versus the DP EES 
group. All endpoints will be evaluated in-hospital and at 30 days, 6 months, 12 months, 
and 2, 3, 4, and 5 years unless specified otherwise. 
Powered Secondary Endpoint 
Long-term Safety and Efficacy, defined as target lesion failure (TLF) between 
12 months and 5 years by landmark analysis. TLF is defined as the composite 
of cardiac death, target vessel-related myocardial infarction (TV-MI), and 
clinically-driven target lesion revascularization (TLR). 
Secondary Safety Endpoints  
1. Major adverse cardiac events (MACE), defined as a composite of all-cause 
death, myocardial infarction, and target vessel revascularization  

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2. Mortality, classified as cardiac or non-cardiac, and reported cumulatively and 
individually 
3. Myocardial infarction (MI), defined according to the modified Third Universal 
Definition  
4. Stent thrombosis, definite or probable (ARC-defined), classified as early, late, 
or very late 
5. Bleeding complications (BARC definitions), evaluated as components and as 
a composite of BARC Type 3 and 5 bleeding  
Secondary Efficacy Endpoints 
1. Lesion success, defined as attainment of <30% residual stenosis, as 
measured 
by 
quantitative 
coronary 
angiography 
(QCA) 
using 
any 
percutaneous method [evaluated post-procedure] 
2. Device success, defined as attainment of <30% residual stenosis of the target 
lesion measured by QCA using the assigned device [evaluated post-procedure] 
3. Procedure success, defined as lesion success without the occurrence of in-
hospital MACE [evaluated in-hospital] 
4. Clinically-driven target lesion revascularization (TLR) [evaluated in-
hospital and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years] 
5. Clinically-driven target vessel revascularization (TVR) [evaluated in-
hospital and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years] 
6. Target vessel failure (TVF), defined as cardiac death, target vessel-related 
MI, or clinically-driven target vessel revascularization [evaluated in-hospital 
and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years] 
7. Target Lesion Failure (TLF), defined as cardiac death, target vessel-related 
MI, or clinically-driven target lesion revascularization [evaluated in-hospital and 
at 30 days, 6 months, and 2, 3, 4, and 5 years] 
Patient 
Population 
The patient population will consist of up to 1632 male and female adults presenting 
with symptomatic ischemic heart disease, including chronic stable angina with 
evidence of ischemia or acute coronary syndromes (UA or NSTEMI), requiring elective 
or urgent percutaneous coronary intervention (PCI) with drug-eluting stents. Patients 
meeting all inclusion and no exclusion criteria will be enrolled and randomized 2:1 to 
coronary revascularization with the BuMA DES or DP EES. 
Subject 
Follow-up 
Subjects will have clinical follow-up prior to discharge from the index intervention and 
at 30 days, 6 months, 12 months*, and 2, 3, 4, and 5 years. Follow-up at 30 days and 
12 months will be clinic visits, while the 6-month follow-up and annual follow-up at 2-5 
years will be via telephone contact (or optional clinic visit). Subjects in whom no study 
stent is implanted will be followed to 12 months only. *NOTE: For the duration of the 
Coronavirus Disease 2019 (COVID-19) pandemic, phone follow-up or virtual visit at 12 
months is permitted if necessary to assure the safety of trial participants. 

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Study 
Committees 
Clinical Events Committee 
An independent Clinical Events Committee (CEC) will adjudicate all site-reported 
adverse events that represent a potential endpoint event in an ongoing fashion during 
the trial. Relationship of these events to the study device will also be adjudicated.  
Data Safety Monitoring Committee 
An independent Data Safety Monitoring Committee (DSMC) will be responsible for the 
oversight and safety monitoring of the study. The DSMC will advise the Sponsor 
regarding the continuing safety of the trial subjects and those yet to be recruited to the 
trial, as well as the continuing validity and scientific merit of the trial. 
Antiplatelet 
Therapy 
Dual antiplatelet therapy (DAPT) will be administered according to physician 
preference in accordance with published guidelines1, 2 and local standards of care. 
Patients with stable ischemic heart disease will be required to receive DAPT for at 
least 6 months in the absence of contraindications; discontinuation of DAPT after 3 
months is permitted (but not required) in patients with a high risk of bleeding. Patients 
with ACS will be required to receive DAPT for at least 12 months in the absence of 
contraindications; discontinuation of DAPT after 6 months is permitted (but not 
required) in patients with a high risk of bleeding.  
The following doses are recommended: 
• 
ASA 300 to 325 mg oral or 250 mg IV loading dose and ASA 75-100 mg 
maintenance dose indefinitely. NOTE: Aspirin loading is recommended 
regardless of whether or not the patient was receiving chronic aspirin therapy 
prior to the procedure. 
 AND 
• 
Clopidogrel 600 mg loading dose before procedure and 75 mg daily 
maintenance dose OR prasugrel 60 mg loading dose and 10 mg daily OR 
ticagrelor 180 mg loading dose and 90 mg twice daily. NOTE: For patients 
receiving chronic clopidogrel therapy prior to the procedure, pre-procedure re-
loading with clopidogrel (600 mg) is recommended. For patients receiving 
chronic prasugrel or ticagrelor therapy prior to the procedure, re-loading is at 
the discretion of the operator.  
Recommended loading dose, loading dose timing, and maintenance dosage may vary 
based on physician discretion and applicable regional clinical guidelines. Approved 
adjunctive therapies (e.g., GP IIb/IIIa inhibitors, cangrelor) may be used according to 
physician preference in accordance with local standards of care.  
Each site is encouraged to commit to a consistent antiplatelet regimen to be applied 
to all subjects enrolled in the trial, independent of treatment group. 
Inclusion 
Criteria 
Potential subjects must meet ALL of the following criteria to be eligible for inclusion in 
the study: 
General Inclusion Criteria 
1. The patient is a male or non-pregnant female ≥20 years of age and not greater 
than 99 years of age 

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2. The patient has symptomatic ischemic heart disease, including chronic stable 
angina (and/or objective evidence of myocardial ischemia on functional study or 
invasive fractional flow reserve [FFR] measurement) or acute coronary 
syndromes (UA or NSTEMI), that requires elective or urgent percutaneous 
coronary intervention (PCI). 
3. The patient is an acceptable candidate for percutaneous coronary intervention 
(PCI) with drug-eluting stents, and for emergent coronary bypass graft (CABG) 
surgery 
4. The patient is willing to comply with specified follow-up evaluations 
5. The patient or legally authorized representative has been informed of the nature 
of the study, agrees to its provisions, and has been provided written informed 
consent approved by the appropriate Institutional Review Board (IRB) or Ethics 
Committee (EC) 
Angiographic Inclusion Criteria 
1. Target vessel(s) must be major coronary artery or branch vessels with a 
visually estimated reference diameter of ≥2.25 mm to ≤4.00 mm. Treatment is 
limited to a maximum of 2 target vessels per subject, a maximum of 2 target 
lesions per epicardial vessel, and a maximum of 3 target lesions per subject. 
2. Target lesion(s) must be de novo or previously unstented restenotic native 
coronary artery lesions (no in-stent restenotic lesions permitted) 
3. Target lesion(s) must have a visually estimated diameter stenosis of >50% and 
<100% 
4. Target lesion(s) must measure 31 mm or less in length by visual estimation, 
and must be treatable with a single study stent. 
5. In subjects in whom treatment of 2 target lesions in a single epicardial vessel 
is planned, there must be adequate separation between lesions to ensure a 
gap of ≥10 mm between study stents 
Exclusion 
Criteria 
Potential subjects will be excluded if ANY of the following conditions apply:  
General Exclusion Criteria 
1. Pregnant or nursing patients and those who plan pregnancy in the period up to 
1 year following index procedure. Female patients of childbearing potential 
must have a negative pregnancy test done within 7 days prior to index 
procedure per site standard test. 
2. Patients with a history of bleeding diathesis or coagulopathy, contraindications 
to anti-platelet and/or anticoagulant therapy, or who will refuse transfusion 
3. Patients who are receiving or will require chronic anticoagulation therapy for 
any reason 
4. Known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, ADP 
receptor antagonists (clopidogrel, prasugrel, ticagrelor, ticlopidine), cobalt 
chromium, 316L stainless steel or platinum, sirolimus or its analogues, and/or 
contrast sensitivity that cannot be adequately pre-medicated 

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5. ST-segment elevation myocardial infarction (STEMI) at index presentation or 
within 7 days prior to randomization  
6. Known LVEF <30% or cardiogenic shock requiring pressors or mechanical 
circulatory assistance (e.g., intra-aortic balloon pump, left ventricular assist 
device, other temporary cardiac support blood pump) 
7. Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 
mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation or 
Cockcroft-Gault  formula) or dialysis at the time of screening 
8. Target vessel percutaneous coronary intervention with stent placement in the 
previous 3 months 
9. Planned elective surgery that would require discontinuation of DAPT within 6 
months of the index procedure 
10. Past or pending heart or any other organ transplant, or on the waiting list for 
any organ transplant 
11. Patients who are receiving immunosuppressant therapy, or who have known 
immunosuppressive or severe autoimmune disease that will require chronic 
immunosuppressive therapy. NOTE: Corticosteroid use is permitted. 
12. Known other medical illness or known history of substance abuse that may 
cause non-compliance with the protocol or prescribed medications, confound 
data interpretation, or is associated with a life expectancy of less than 1 year 
13. Current participation in another investigational drug or device study 
Angiographic Exclusion Criteria 
1. Target lesion contains a total occlusion (TIMI 0 flow) 
2. Target lesion is in an unprotected left main coronary artery location 
3. Target lesion is located within an arterial or saphenous vein graft or graft 
anastomosis, or in a native artery location that requires traversal of an arterial 
or saphenous vein graft to access 
4. Target lesion involves a previously stented segment (in-stent restenosis) or is 
≤10 mm from a previously implanted stent  
5. Target lesion involves a bifurcation in which 2-vessel stenting is planned    
6. Index procedure treatment plan for the target lesion includes stent overlapping 
7. Index procedure treatment plan for the target vessel includes treatment of 2 
target lesions that would result in 2 study stents placed <10 mm apart   
8. Index procedure treatment plan for the target vessel includes vessel 
preparation other than balloon pre-dilatation (e.g., cutting balloon, 
atherectomy, thrombectomy, excimer laser angioplasty, brachytherapy) 
9. Treatment plan includes repeat intervention (staged procedure)  
Blinding 
This is a single-blind study. The following individuals will be blinded to the subject’s 
treatment allocation: 

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• 
Subject and his/her family members 
• 
Site personnel conducting follow-up evaluations will not have access to 
randomization eCRFs, and every effort will be made to ensure that 
medical records use a non-specific term to identify the treatment device 
(e.g., “DES”) to avoid revealing treatment group assignment  
• 
Members of the Clinical Events Committee 
• 
Angiographic Core Laboratory technicians performing the analysis 
Un-blinding will occur only after the database has been locked for the analysis of the 
primary endpoint or to protect subject rights, welfare, or well-being at the request of 
the DSMC. A site investigator may also reveal treatment allocation to an individual 
subject if deemed necessary due to complication or injury. 
Analysis Plan Primary Endpoint Analysis 
The primary analysis will be a test for non-inferiority of the BuMA DES compared with 
DP EES for the primary endpoint of TLF at 12 months, performed in the Per Protocol 
(PP) and Intention to Treat (ITT) populations using the Farrington-Manning test. The 
PP population is defined as subjects who meet all inclusion criteria and no exclusion 
criteria, have provided written informed consent, and in whom an assigned study stent 
has been implanted. The ITT population is defined as all subjects enrolled in the study, 
analyzed by assigned treatment, regardless of the treatment actually received.  
A total of 1551 evaluable subjects (1034 Intervention: 517 Control) will provide 80% 
power to demonstrate non-inferiority of the BuMA DES, assuming a 6.5% rate of TLF 
at 12 months in the DP EES group, no difference between treatments, a one-sided 
alpha of 0.025, and an absolute non-inferiority margin of 3.575%. The sample size has 
been increased to 1632 subjects (1088 Intervention: 544 Control) to account for an 
expected 5% loss to follow-up at 12 months, inclusive of dropout from the PP analysis 
population. If non-inferiority for the primary endpoint is met and superiority for the 
powered secondary endpoint is met, formal superiority testing will be performed for the 
primary endpoint. 
The primary endpoint will be evaluated in both the PP and ITT populations. For the 
primary analyses, only subjects who experienced a primary endpoint event or who had 
at least 11 months follow-up (1 year minus the allowable 30 day window) and who 
meet the applicable analysis population definition will be included in the analysis. As 
an additional analysis, to account for any missing data in the primary endpoint, a 
tipping point analysis will be conducted. A sensitivity analysis for the primary endpoint 
will also be conducted according to various alternate biomarker thresholds for PCI-
related MI. 
In addition, to assess the appropriateness of pooling results between study regions 
(North America vs. Japan vs. Europe), an assessment of the effect of region on the 
primary endpoint will be carried out in the PP population using interaction testing from 
the logistic regression with a 0.15 level of significance. 
Secondary Endpoints Analysis 
Powered Secondary Endpoint 
The powered secondary endpoint of long-term safety and efficacy, defined as TLF 
between 12 months and 5 years by landmark Kaplan-Meier analysis, will be a test for 

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superiority of the BuMA DES group to the DP EES group via the log-rank test in the 
ITT population. The analysis will be performed when the last enrolled subject has 
completed his/her 5 year clinical follow-up visit, and will be performed only if non-
inferiority for the primary endpoint has been met. 
Assuming a TLF rate of 8% between 12 months and 5 years in the DP EES group and 
a hazard ratio (HR) of 0.52 in the BuMA DES group compared with the DP EES group, 
the study sample size of 1444 evaluable subjects at 1 year (accounting for an 
estimated 5% loss to follow-up at 1 year, a 6.5% rate of TLF prior to 1 year, and a 
continued annual loss to follow-up of 5%) will provide approximately 80% power to 
demonstrate superiority of the BuMA DES. 
Secondary Safety Endpoints  
All secondary safety endpoints will be evaluated in the ITT population using 
appropriate descriptive statistics. No formal hypothesis testing will be performed. 
Statistics for continuous variables will include mean, median, standard deviation, 
minimum, maximum, and sample size for each treatment group. Binary variables will 
be summarized using frequencies, percentages, and sample size for each treatment 
group.  
As a secondary analysis, all secondary safety endpoints will be evaluated in the PP 
population.  
Secondary Efficacy Endpoints 
All secondary efficacy endpoints will be evaluated in the ITT population using 
appropriate descriptive statistics. No formal hypothesis testing will be performed. 
Statistics for continuous variables will include mean, median, standard deviation, 
minimum, maximum, and sample size for each treatment group. Binary variables will 
be summarized using frequencies, percentages, and sample size for each treatment 
group.  
As a secondary analysis, all secondary efficacy endpoints will be evaluated in the PP 
population. 
Subgroup Analyses: 
Subgroup analyses will be performed for all primary and secondary endpoints in their 
respective primary analysis populations for the following subgroups: 
• 
Enrollment region (North America vs. Japan vs. Europe) 
• 
Presentation (stable coronary artery disease vs. acute coronary syndromes) 
• 
Single- versus multi-vessel disease (1 vs. 2 target vessels) 
• 
Diabetes status (subjects with vs. without medically-treated diabetes mellitus) 
• 
Subject gender (male vs. female) 
Anticipated 
Timelines 
First subject enrolled:  
October 2017 
Last subject enrolled: 
August 2019 
30 day follow-up: 
September 2019 
6 month follow-up: 
February 2020 
12 month follow-up: 
August 2020 
2 year follow-up: 
August 2021 

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3 year follow-up: 
August 2022 
4 year follow-up: 
August 2023 
5 year follow-up: 
August 2024 
4.0 Background 
4.1 Clinical Background 
Percutaneous coronary intervention (PCI) with drug eluting stents (DES) is a mainstay of treatment for 
patients with coronary artery disease (CAD), including stable angina, silent ischemia, and acute coronary 
syndromes (ACS).1, 3-5 Compared with bare metal stents (BMS), DES reduce restenosis and the 
consequent need for repeat revascularization via the inhibition of neointimal hyperplasia.6 However, even 
with the use of DES repeat intervention is required in >10% of all patients within 1 year,7 and DES use 
has been associated with a small incremental risk of late (>30 days to 1 year post-implantation) and very 
late (>1 year post-implantation) stent thrombosis. Although rare, stent thrombosis is a devastating 
complication, usually associated with myocardial infarction or death.8 Extended duration dual antiplatelet 
therapy (DAPT) is required after DES implantation, with an attendant risk of bleeding complications;2 
however, the risk of stent thrombosis persists following DAPT discontinuation.9  
DES are also associated with delayed vascular healing, as evidenced by histologic data from autopsy 
studies of stent thrombosis that reveal persistent fibrin deposition and poor re-endothelialization.10, 11 
While the mechanisms by which DES cause a prolongation of arterial healing are incompletely 
understood, the permanent presence of a non-erodable polymer drug release matrix is thought to be a 
contributor to both late stent thrombosis and late restenosis.12 The polymer has also been implicated in 
localized hypersensitivity reactions and adverse late vessel wall remodeling.13, 14 Although second-
generation DES with more biocompatible polymers and reduced strut dimensions have improved the 
extent of endothelialization, concerns regarding late stent thrombosis and delayed vascular healing 
remain,15 and a persistent inflammatory response continues to be observed.16, 17  
To address the issue of permanent polymer as a contributor to inflammation, stent thrombosis, and 
restenosis, DES using erodible polymers for drug delivery have been developed. Long-term follow-up 
has demonstrated that this technology is capable of reducing (but not eliminating) the occurrence of very 
late stent thrombosis; however, major adverse cardiac event rates are comparable to those observed 
with durable polymer DES.18, 19 In addition, limitations remain in the implementation of erodible polymers 
in currently available DES. The polymer composition required for biodegradation conflicts with the optimal 
adhesive and mechanical properties of balloon-expandable coronary stent coatings, creating the 
potential for cracking and delamination upon stent placement and over time as the polymer degrades; 
these effects may impair re-endothelialization and serve as a substrate for the observed thrombosis and 
inflammation.20, 21 Furthermore, optimization of the timeframes for drug elution and polymer resorption 
have the potential to improve early vascular healing and thereby reduce long-term adverse events.22 
For these reasons, the development of new-generation DES that incorporate erodible polymers to 
prevent restenosis, while improving the speed and completeness of re-endothelialization and restoration 
of normal vascular function, is desirable to improve the outcomes of patients undergoing PCI for the 
treatment of CAD.   

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4.2 Investigational Device  
4.2.1 Name of the Investigational Device  
The BuMA Supreme™ Biodegradable Drug Coated Coronary Stent System, herein referred to as the 
“BuMA DES.” The BuMA DES is manufactured by Sino Medical Sciences Technology, Inc. (Tianjin, 
People’s Republic of China). 
4.2.2 Intended Use 
The BuMA Supreme Biodegradable Drug Coated Coronary Stent System is indicated for improving 
coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary 
artery lesions (length ≤ 31 mm) with reference vessel diameters of 2.25 mm to 4.0 mm. 
4.2.3 Regulatory Status 
The BuMA DES is for investigational use only. 
4.2.4 Device Description 
The following is a summary description of the Investigational Device. For additional information, please 
refer to the Instructions for Use.  
4.2.4.1 Overview 
The BuMA Supreme Biodegradable Drug Coated Coronary Stent System is a device / drug combination 
product consisting of a drug-coated balloon expandable stent and a rapid exchange delivery system. The 
cobalt chromium (CoCr) stent is coated with a very thin, non-erodable layer of poly n-butyl methacrylate 
(PBMA) that is covalently bonded to the metal surface through a proprietary electro-grafting (eG™) 
process. A topcoat is then applied that contains sirolimus, the active ingredient, embedded in a 
biodegradable polymer, poly lactic co-glycolic acid (PLGA). In addition to the stent, the BuMA Supreme 
system includes a rapid exchange balloon expandable delivery system. 
The BuMA DES is designed to de-couple the therapeutic goals of restenosis prevention and optimal 
vascular healing by providing controlled and complete drug delivery via a biodegradable polymer matrix, 
leaving behind a stent with an extremely thin and uniform coating that promotes early and complete re-
endothelialization.  
4.2.4.2 Stent Platform 
The BuMA DES stent platform is a laser-cut L605 CoCr alloy tube, subjected to acid descaling and then 
electro-polished to a nominal strut thickness of 80 µm. Figure 1 shows an image of an expanded BuMA 
DES. 

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Figure 2. Coating Structure of the BuMA DES 
The PBMA base layer is covalently bonded to the CoCr stent surface using SINOMED’s proprietary 
electro-grafting (eG) technology. The very thin durable base layer is designed to secure adhesion of the 
topcoat, preventing cracking and delamination upon initial stent expansion and over time, in addition to 
suppressing corrosion and heavy metal ion release, while maintaining a thin strut profile and optimal 
surface properties to facilitate rapid re-endothelialization. The topcoat (3-10 µm thick) consists of a PLGA 
carrier matrix containing sirolimus; the polymer is completely resorbed within 2-3 months. PMBA has 
been widely used in FDA approved drug eluting stents, and PLGA is a well-characterized bioabsorbable 
biomaterial used in FDA-approved vascular implants. 
4.2.4.4 Drug Component 
The stent coating elutes the drug sirolimus (rapamycin), a macrocyclic lactone produced by the bacterium 
Streptomyces hygroscopicus. Sirolimus is widely used in drug eluting stents for the suppression of 
neointimal hyperplasia, and its safety and effectiveness in this application have been demonstrated 
during more than 14 years of commercial experience. 
The sirolimus dose is approximately 1.2 µg/mm2, with total dose per stent ranging from 59 µg (2.25 mm 
X 10 mm) to 285 µg (4.0 mm X 35 mm). The drug is fully eluted from the carrier matrix within 
approximately 45 days.   
4.2.4.5 Delivery System 
The BuMA DES is delivered using a rapid exchange balloon expandable delivery system with 145 cm 
working length, compatible with guide wires ≤ 0.014” and guide catheter inner diameters ≥ 5 F (0.056”). 
Radiopaque markers located on the catheter shaft indicate the working length of the balloon. A schematic 
of the delivery system is provided in Figure 3.  
 
Figure 3. BuMA DES delivery system. 1. Balloon Tip; 2. Protective sleeve; 3. Balloon; 4. BuMA Supreme stent; 5. 
Radiopaque marker bands; 6. Catheter tubing; 7. Hypotube shaft; 8. Anti-kink protective tubing; 9. Luer lock. 

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XIENCE PROX 
2.0, 2.25, 2.5, 2.75, 3.0, 3.25, 3.5, 
4.0 
8, 12, 15, 18, 23, 28, 33, 38 
PROMUS Element Plus 
2.25, 2.5, 2.75, 3.0, 3.5, 4.0 
8, 12, 16, 20, 24, 28, 32, 38 
Promus PREMIER 
2.25, 2.5, 2.75, 3.0, 3.5, 4.0 
8, 12, 16, 20, 24, 28, 32, 38 
4.4 Rationale 
The BuMA DES is designed to provide the benefits of conventional DES for the prevention of restenosis 
while facilitating early and complete vascular healing to prevent long-term adverse events. This study will 
evaluate the safety and effectiveness of the BuMA DES at 1 year by randomized comparison with state-
of-the-art commercially available durable polymer DES, and will also evaluate the potential benefits of 
BuMA DES for the reduction of late adverse events.  
5.0 Study Design 
5.1 Study Design Overview 
This prospective, multicenter study will enroll up to 1632 subjects at up to 130 investigational sites in 
North America, Japan, and Europe. A minimum of 50% of subjects will be enrolled at North American 
sites, and no single center will be permitted to enroll more than 10% of all subjects. 
Patients presenting with symptomatic ischemic heart disease (including chronic stable angina with 
evidence of ischemia, unstable angina, or non-ST segment elevation myocardial infarction) who require 
elective or urgent percutaneous coronary intervention (PCI) to treat up to 3 native coronary artery lesions 
in up to 2 major coronary arteries, in vessel diameters of ≥2.25 mm to ≤4.00 mm and lesion lengths ≤31 
mm, and who meet all eligibility criteria will be enrolled in the study and randomized 2:1 (stratified by 
presentation [acute coronary syndrome vs. non-ACS], diabetes status [with vs. without medically-treated 
diabetes mellitus], and study site) to the following treatment groups:  
• 
Intervention: Coronary revascularization with the BuMA Supreme Biodegradable Drug Coated 
Coronary Stent System (BuMA DES) 
• 
Control: Coronary revascularization with the commercially-available durable polymer everolimus-
eluting stent systems (DP EES) 
Subjects will have clinical follow-up in-hospital and at 30 days, 6 months, 12 months*, and 2, 3, 4, and 5 
years. Follow-up at 30 days and 12 months will be clinic visits, while 6-month follow-up and annual follow-
up at 2-5 years will be via telephone contact (or optional clinic visit). Subjects in whom no study stent is 
implanted will be followed to 12 months only. *NOTE: For the duration of the Coronavirus Disease 2019 
(COVID-19) pandemic, phone follow-up or virtual visit at 12 months is permitted if necessary to assure 
the safety of trial participants. 
The primary analysis will be a non-inferiority test comparing BuMA DES to DP EES for the primary safety 
and efficacy endpoint of target lesion failure at 12 months in the Intention to Treat and Per Protocol patient 
populations. As a secondary hypothesis-driven analysis, a superiority test comparing BuMA DES to DP 
EES will be performed for the powered secondary endpoint of long-term safety and efficacy, defined as 
target lesion failure between 12 months and 5 years by landmark analysis. The study will also report 
additional secondary safety and efficacy endpoints.  
Clinical endpoint data will be adjudicated by an independent Clinical Event Committee, and an 
independent Data Safety Monitoring Committee will monitor the safety of subjects throughout the trial. 
Index procedure and event-driven angiographic data will be analyzed by an independent Angiographic 
Core Laboratory.  

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5.2 Study Objective 
The primary objective of the trial is to evaluate the safety and efficacy of the BuMA DES in patients with 
functionally significant ischemia requiring percutaneous coronary intervention (PCI) with implantation of 
drug eluting stents for the treatment of stable coronary artery disease or acute coronary syndromes 
without ST-segment elevation (unstable angina [UA] and non-ST-segment elevation myocardial infarction 
[NSTEMI]) by randomized comparison with commercially-available durable polymer everolimus-eluting 
stent systems.  
5.3 Endpoints 
5.3.1 Primary Endpoint 
The primary safety and efficacy endpoint of the study is target lesion failure at 12 months. Target lesion 
failure (TLF) is defined as the composite of cardiac death, target vessel-related myocardial infarction (TV-
MI), and clinically-driven target lesion revascularization (TLR). 
5.3.2 Secondary Powered Endpoint 
The powered secondary hypothesis-driven endpoint is long-term safety and efficacy, defined as target 
lesion failure (TLF) between 12 months and 5 years by landmark analysis. TLF is defined as the 
composite of cardiac death, target vessel-related myocardial infarction (TV-MI), and clinically-driven 
target lesion revascularization (TLR).  
5.3.3 Additional Secondary Endpoints 
All endpoints will be evaluated in-hospital and at 30 days, 6 months, 12 months, and 2, 3, 4, and 5 years 
unless specified otherwise. 
5.3.3.1 Secondary Safety Endpoints  
5.3.3.1.1 Major adverse cardiac events (MACE), defined as a composite of all-cause 
death, myocardial infarction, and target vessel revascularization  
5.3.3.1.2 Mortality, classified as cardiac or non-cardiac, and reported cumulatively and 
individually 
5.3.3.1.3 Myocardial infarction (MI), defined according to the modified Third Universal 
Definition  
5.3.3.1.4 Stent thrombosis, definite or probable (ARC-defined), classified as early, late, 
or very late 
5.3.3.1.5 Bleeding complications (BARC definitions), evaluated as components and as 
a composite of BARC Type 3 and 5 bleeding  
5.3.3.2 Secondary Efficacy Endpoints 
5.3.3.2.1 Lesion success, defined as attainment of <30% residual stenosis, as measured 
by quantitative coronary angiography (QCA) using any percutaneous method [evaluated 
post-procedure] 
5.3.3.2.2 Device success, defined as attainment of <30% residual stenosis of the target 
lesion measured by QCA using the assigned device [evaluated post-procedure] 
5.3.3.2.3 Procedure success, defined as lesion success without the occurrence of in-
hospital MACE [evaluated in-hospital] 
5.3.3.2.4 Clinically-driven target lesion revascularization (TLR) [evaluated in-hospital 
and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years] 

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5.3.3.2.5 Clinically-driven target vessel revascularization (TVR) [evaluated in-hospital 
and at 30 days, 6 months, and 1, 2, 3, 4, and 5 years] 
5.3.3.2.6 Target vessel failure (TVF), defined as cardiac death, target vessel-related MI, 
or clinically-driven target vessel revascularization [evaluated in-hospital and at 30 days, 6 
months, and 1, 2, 3, 4, and 5 years] 
5.3.3.2.7 Target Lesion Failure (TLF), defined as cardiac death, target vessel-related MI, 
or clinically-driven target lesion revascularization [evaluated in-hospital and at 30 days, 6 
months, and 2, 3, 4, and 5 years] 
6.0 Subject Selection and Withdrawal  
6.1 Patient Population 
The patient population from which subjects for this trial will be recruited consists of male and female 
adults in the general interventional cardiology population. The trial will enroll up to 1632 subjects 
presenting with symptomatic ischemic heart disease, including chronic stable angina with evidence of 
ischemia or acute coronary syndromes (UA or NSTEMI), requiring elective or urgent percutaneous 
coronary intervention (PCI) with drug-eluting stents.  
6.2 Eligibility Criteria 
6.2.1 Inclusion Criteria 
Potential subjects must meet ALL of the following criteria to be eligible for enrollment into the study: 
6.2.1.1 General Inclusion Criteria 
6.2.1.1.1 The patient is a male or non-pregnant female ≥20 years of age and not greater 
than 99 years of age 
6.2.1.1.2 The patient has symptomatic ischemic heart disease, including chronic stable 
angina (and/or objective evidence of myocardial ischemia on functional study or invasive 
fractional flow reserve [FFR] measurement) or acute coronary syndromes (UA or 
NSTEMI), that requires elective or urgent percutaneous coronary intervention (PCI). 
6.2.1.1.3 The patient is an acceptable candidate for percutaneous coronary intervention 
(PCI) with drug-eluting stents, and for emergent coronary bypass graft (CABG) surgery 
6.2.1.1.4 The patient is willing to comply with specified follow-up evaluations 
6.2.1.1.5 The patient or legally authorized representative has been informed of the nature 
of the study, agrees to its provisions, and has been provided written informed consent 
approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC) 
6.2.1.2 Angiographic Inclusion Criteria 
6.2.1.2.1 Target vessel(s) must be major coronary artery or branch vessels with a visually 
estimated reference diameter of ≥2.25 mm to ≤4.00 mm. Treatment is limited to a 
maximum of 2 target vessels per subject, a maximum of 2 target lesions per epicardial 
vessel, and a maximum of 3 target lesions per subject. 
6.2.1.2.2 Target lesion(s) must be de novo or previously unstented restenotic native 
coronary artery lesions (no in-stent restenotic lesions permitted) 
6.2.1.2.3 Target lesion(s) must have a visually estimated diameter stenosis of ≥50% and 
<100% 

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6.2.1.2.4 Target lesion(s) must measure 31 mm or less in length by visual estimation, and 
must be treatable with a single study stent. 
6.2.1.2.5 In subjects in whom treatment of 2 target lesions in a single epicardial vessel is 
planned, there must be adequate separation between lesions to ensure a gap of ≥10 mm 
between study stents 
6.2.2 Exclusion Criteria 
Potential subjects will be excluded if ANY of the following criteria apply: 
6.2.2.1 General Exclusion Criteria 
6.2.2.1.1 Pregnant or nursing patients and those who plan pregnancy in the period up to 
1 year following index procedure. Female patients of childbearing potential must have a 
negative pregnancy test done within 7 days prior to index procedure per site standard test. 
6.2.2.1.2 Patients with a history of bleeding diathesis or coagulopathy, contraindications 
to anti-platelet and/or anticoagulant therapy, or who will refuse transfusion 
6.2.2.1.3 Patients who are receiving or will require chronic oral anticoagulation therapy for 
any reason 
6.2.2.1.4 Known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, ADP 
receptor antagonists (clopidogrel, prasugrel, ticagrelor, ticlopidine), cobalt chromium, 
316L stainless steel or platinum, sirolimus or its analogues, and/or contrast sensitivity that 
cannot be adequately pre-medicated 
6.2.2.1.5 ST-segment elevation myocardial infarction (STEMI) at index presentation or 
within 7 days prior to randomization   
6.2.2.1.6 Known LVEF <30% or cardiogenic shock requiring pressors or mechanical 
circulatory assistance (e.g., intra-aortic balloon pump, left ventricular assist device, other 
temporary cardiac support blood pump) 
6.2.2.1.7 Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) <30 
mL/min/1.73 m2 (by the Modification of Diet in Renal Disease equation or Cockcroft-Gault 
formula) or dialysis at the time of screening 
6.2.2.1.8 Target vessel percutaneous coronary intervention with stent placement in the 
previous 3 months 
6.2.2.1.9 Planned elective surgery that would require discontinuation of DAPT within 6 
months of the index procedure 
6.2.2.1.10 Past or pending heart or any other organ transplant, or on the waiting list for 
any organ transplant 
6.2.2.1.11 Patients who are receiving immunosuppressant therapy, or who have known 
immunosuppressive or severe autoimmune disease that will require chronic 
immunosuppressive therapy. NOTE: Corticosteroid use is permitted. 
6.2.2.1.12 Known other medical illness or known history of substance abuse that may 
cause non-compliance with the protocol or prescribed medications, confound data 
interpretation, or is associated with a life expectancy of less than 1 year 
6.2.2.1.13 Current participation in another investigational drug or device study 
6.2.2.2 Angiographic Exclusion Criteria 
6.2.2.2.1 Target lesion contains a total occlusion (TIMI 0 flow) 

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6.2.2.2.2 Target lesion is in an unprotected left main coronary artery location 
6.2.2.2.3 Target lesion is located within an arterial or saphenous vein graft or graft 
anastomosis, or in a native artery location that requires traversal of an arterial or 
saphenous vein graft to access 
6.2.2.2.4 Target lesion involves a previously stented segment (in-stent restenosis) or is 
≤10 mm from a previously implanted stent  
6.2.2.2.5 Target lesion involves a bifurcation in which 2-vessel stenting is planned    
6.2.2.2.6 Index procedure treatment plan for the target lesion includes stent overlapping 
6.2.2.2.7  Index procedure treatment plan for the target vessel includes treatment of 2 
target lesions that would result in 2 study stents placed <10 mm apart 
6.2.2.2.8 Index procedure treatment plan for the target vessel includes vessel preparation 
other than balloon pre-dilatation (e.g., cutting balloon, atherectomy, thrombectomy, 
excimer laser angioplasty, brachytherapy) 
6.2.2.2.9 Treatment plan includes repeat intervention (staged procedure) 
6.3 Subject Screening 
Patients requiring elective or urgent PCI will be pre-screened by a member of the research team who has 
received training on this Clinical Investigation Plan, including a review of the patient’s medical history and 
any testing that has been performed as a part of the patient’s routine medical care, to determine whether 
the patient meets general eligibility criteria (inclusion and exclusion) for participation in the trial. 
Potentially eligible subjects will undergo the process of informed consent (§6.4) prior to the performance 
of any study-specific assessments. After informed consent has been obtained, screening / baseline tests 
and examinations will be performed to verify eligibility and to collect baseline study data. Assessments 
performed as part of standard medical care prior to study enrollment are valid sources of data for verifying 
study eligibility and collecting baseline study data, provided that the previously performed assessments 
comply with applicable protocol requirements. Potentially eligible subjects will be randomized to a 
treatment group and enrolled in the study only after it has been confirmed (at the time of the index 
procedure cardiac catheterization) that the patient meets all angiographic inclusion criteria and no 
angiographic exclusion criteria, and after treatment of any non-target lesion has been completed 
successfully without complication. 
A screening log will be maintained to document the enrollment and subject number, or reason for non-
enrollment of subjects screened but not enrolled in the study. Subjects who receive any study stent during 
the index procedure (BuMA DES or DP EES) must complete all assigned follow-up assessments (to 5 
years); subjects who do not receive any study stent during the index procedure will be followed to 12 
months only for safety.  
6.4 Informed Consent 
Relevant study information will be summarized on a Patient Information and Consent Form (“Informed 
Consent Form [ICF]”) that has been approved by applicable regulatory authorities. This document, or a 
modification based on local IRB/EC recommendations, must be approved by the applicable IRB/EC and 
signed by each subject or his/her legal representative prior to the performance of any study-specific 
procedures or assessments. 
Prior to obtaining informed consent, the investigator (or designee) should provide the relevant study 
information to the patient in both oral and written form, in a language and at a level of complexity 
understandable to the patient. Patients should not be coerced, persuaded, or unduly influenced to 
participate or remain in the trial. The patient or his/her legal representative must be given ample time and 

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opportunity to inquire about details of the trial, and all questions about the trial should be answered to the 
satisfaction of the patient or the representative. 
The written informed consent form should be signed and personally dated by the subject or his/her legal 
representative, and by the person who conducted the informed consent discussion (investigator or 
designee), prior to the subject’s participation in the trial. If the subject or his/her legal representative is 
unable to read the consent form, a witness should be present during the entire informed consent 
discussion. After the informed consent form is read to the subject and signed by the subject or his/her 
legal representative, the witness should also sign the consent form, attesting that informed consent was 
freely given by the subject or his/her legal representative. For non-English speaking subjects, the written 
informed consent should be translated into the subject’s native language, or a short form (including the 
elements of informed consent translated into the subject’s native language) should be used. The informed 
consent process should be documented in each subject’s medical record.   
The subject or his/her legal representative must be provided with a copy of the signed and dated informed 
consent form. 
The Investigator shall inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required, that may be relevant 
to the subject and his/her willingness to continue participation in the study. The consent form should be 
updated or amended whenever such new information becomes available and updated consent shall be 
recorded. 
6.5 Subject Enrollment 
Potentially eligible subjects who meet all general inclusion criteria and no general exclusion criteria and 
who have consented to participate in the trial will undergo screening/baseline assessments. At the index 
procedure cardiac catheterization, the target lesions(s), target vessel(s), and index procedure treatment 
plan will be evaluated to confirm that all angiographic inclusion criteria (§6.2.1.2) and no angiographic 
exclusion criteria (§6.2.2.2) are met.  
If the subject meets all inclusion and no exclusion criteria, and treatment of any non-target lesion has 
been completed successfully without complication, the subject will be randomized to a treatment arm 
(BuMA DES or DP EES in a 2:1 ratio) and enrolled in the trial. Randomization will be stratified by the 
presence of acute coronary syndrome (i.e., patients with stable angina or silent ischemia versus patients 
with unstable angina or non-ST segment elevation myocardial infarction), by diabetes status (i.e., 
subjects with vs. without medically-treated diabetes mellitus), as well as by study center. All target 
lesion(s) should be treated with the assigned stent type. 
The point of enrollment is the moment of randomization. All enrolled subjects will be assigned a study-
specific patient identification number via the database system.  
No single site will be permitted to enroll more than 10% of the total number of subjects in the trial (i.e., 
no single site may enroll more than 163 subjects). 
6.6 Withdrawal and Replacement of Subjects 
Subjects can withdraw from the study at any time; the reason(s) for withdrawal (if given) will be 
documented. All data available at the time of withdrawal (if any) will be used for analysis, unless the 
subject has explicitly forbid the use of such data and has documented this preference in accordance with 
local regulatory requirements. With the exception of ascertainment of survival status (in accordance with 
applicable legal and ethical considerations), there will be no further follow-up (per this study protocol) on 
a subject who has withdrawn. Subjects who withdraw from the study will not be replaced. The withdrawal 
of a subject can be initiated by the Investigator if he/she determines it is in the best interest of the patient. 

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6.7 Protocol Deviations 
All deviations from the requirements of this Clinical Investigation Plan will be considered protocol 
deviations. In the event of a protocol deviation, a Protocol Deviation form should be completed in the 
eCRF and submitted to the Sponsor and to the relevant regulatory body (if required by local regulations). 
Protocol deviations that will be collected include, but are not limited to: 
• 
Failure to obtain informed consent, or failure to obtain informed consent prior to the performance 
of study-specific procedures or assessments 
• 
Enrollment of a subject who did not meet all study inclusion criteria, or who met one or more 
study exclusion criteria 
• 
Failure to complete protocol-specified assessments  
A major protocol deviation is a protocol deviation that may affect the scientific soundness of the protocol 
or the rights, safety, or welfare of the patients. Major protocol deviations include, but are not limited to: 
failure to obtain informed consent, enrollment of a subject not meeting study eligibility criteria, and 
implantation of a study stent in a patient who has not reached the point of enrollment. Major protocol 
deviations require immediate reporting to the Study Monitor and the Institutional Review Board/Ethics 
Committee.  
Site-level deviations are those that occur at the study center but are not directly related to a specific 
patient. The Sponsor reserves the right to terminate the study participation of a site with excessive 
protocol deviations, or to suspend the site’s participation until an adequate system to reduce further 
deviations has been implemented.   
 
 

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ischemia (for example, due to new ischemic ECG changes [such as ischemic ST changes or new pathological Q 
waves] or new LBBB, angiographic evidence of a flow-limiting complication, or imaging evidence of new loss of 
viable myocardium or new regional wall motion abnormality), serial measurements should be taken every 6 to 12 
hours until a decline is noted.   
6 Angiographic eligibility criteria must be confirmed at the time of the index procedure. All angiographic films for the 
index procedure and any repeat intervention or repeat diagnostic cardiac catheterization must be forwarded to the 
Angiographic Core Laboratory (§17.3). 
7 Procedural angiographic images, ECG data, and the results of laboratory testing should be submitted for all 
repeat revascularizations. For all adverse events that represent a potential endpoint event, all relevant medical 
information (including clinically relevant imaging data, ECG data, and the results of relevant laboratory testing 
performed as part of the standard of care) should be collected and retained as part of the research file to support 
adverse event analysis and adjudication.  
8 Subjects who do not receive a study stent during the index procedure will be followed to 12 months only. 
9 For the duration of the Coronavirus Disease 2019 (COVID-19) pandemic, phone follow-up or virtual visit at 12 
months is permitted if necessary to assure the safety of trial participants. The reason for the conduct of the phone 
follow-up should be documented in the eCRF. Phone follow-ups conducted for other reasons (e.g., to collect all 
available data in a subject otherwise lost to follow-up) should continue to be recorded as protocol deviations, and 
details of the protocol deviation must be captured in the appropriate eCRF. Please refer to Section 7.7 for 
additional considerations related to alternate assessment methods. 
10 For subjects who underwent a phone follow-up at the 12-month time point for any reason, it is preferable that the 
2-year follow-up be conducted as an in-clinic visit. 
7.2 Screening / Baseline 
The following tests and examinations must be performed prior to the procedure to verify eligibility and to 
collect baseline study data. Note that assessments performed as part of standard medical care prior to 
study enrollment are valid sources of data for verifying study eligibility and collecting baseline study data, 
provided that the previously performed assessments comply with applicable protocol requirements. 
• 
Review of general inclusion and exclusion criteria.  
• 
Female patients of childbearing potential must have a pregnancy test performed within 7 days 
prior to the procedure 
• 
Relevant medical history and patient demographic information 
• 
Physical examination  
• 
Anginal status (CCS, Braunwald classification of unstable angina, or silent ischemia) 
• 
Documentation of all concomitant medications 
• 
A 12-lead electrocardiogram (ECG). The ECG may be performed up to 21 days prior to procedure, 
except when there is evidence of acute or recent MI or UA, in which case the ECG must be 
performed within 24 hours prior to the index procedure.  
Laboratory testing per site standard practice; if laboratory testing is part of the standard of care 
and includes CBC and serum creatinine, these should be recorded. The results of any additional 
tests performed per site standard practice should also be collected. 
• 
The blood draw for cardiac biomarkers testing (preferably cTn I or T; if not available, then CKMB 
is acceptable) may be performed within 48 hours prior to the index procedure, except when there 
is evidence of acute or recent (<7 days) MI or UA, in which case the draw must be performed 
within 24 hours prior to the index procedure. If the subject does not have a known diagnosis of 
acute MI or UA within 96 hours prior to the index procedure, assessment of cardiac biomarkers 
may be obtained after the start of the index procedure but prior to device implantation. 

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7.3 Index Procedure  
7.3.1 Angiographic Imaging 
The imaging protocol includes angiography pre-intervention, post-stent implantation, and after any post-
dilatation (if any), in addition to documentation of any procedural complications. For details, please refer 
to the Angiographic Imaging Acquisition Guidelines (§17.3). All procedural angiographic imaging should 
be forwarded to the Angiographic Core Laboratory for analysis. 
7.3.2 Eligibility Confirmation 
At the time of the index procedure, the investigator should confirm the following before the patient is 
randomized to a treatment arm and enrolled in the trial: 
1) The target vessel(s), target lesion(s), and treatment plan meet all angiographic inclusion criteria 
and no exclusion criteria; AND 
2) Treatment of a non-target lesion (if performed) has been successfully completed without 
complications (see §7.3.3) 
7.3.3 Treatment of Non-target Lesion 
Treatment of a single non-target lesion that does not meet study angiographic eligibility criteria during 
the index procedure is permitted, provided that all the following conditions are met: 
1) The non-target lesion is treated first, prior to randomization. 
2) The non-target lesion is located in a separate epicardial vessel from the target lesion(s). The 
epicardial vessels are defined as the LAD, LCx, and RCA, each including its respective branches; 
e.g., a patient with a target lesion in the LAD would not be eligible for treatment of a non-target 
lesion in a diagonal branch. The ramus intermedius is considered a branch of the LCx. 
3) The non-target lesion is treated with an approved (FDA-approved, CE-marked, or PMDA-
approved, as applicable) commercially available device. 
4) Treatment of the non-target lesion was successful, defined as: 
a. Final % diameter stenosis (%DS) ≤30% with final TIMI 3 flow AND 
b. Without the following complications 
i. Residual dissection (NHLBI grade ≥ type B) 
ii. Angiographic complications (e.g., distal embolization, side branch closure) 
iii. Chest pain lasting > 5 minutes 
iv. ST segment elevation or depression lasting > 5 minutes. 
If all the above conditions have been met, the patient may be randomized to a treatment arm and enrolled 
in the trial. The non-target lesion will not be considered in the primary analyses. 
7.3.4 Treatment of Target Lesion(s) 
Implantation of the assigned study stent(s) in the designated target lesion(s) should be performed per 
site standard practice in accordance with each manufacturer’s Instructions for Use. All target lesions 
should be treated with the assigned study stent type. 
Pre-dilatation of the target lesion(s) with an appropriately sized angioplasty balloon is recommended, and 
should be documented on the eCRF. 

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The investigator should choose the appropriate diameter and length of the stent(s) to be implanted by 
visual estimate, ensuring that the selected stent length allows complete coverage of the target lesion with 
1-2 mm of healthy vessel overlap at each end. If the stent is under-dilated following initial expansion, 
post-dilation should be performed with an appropriately sized balloon.  
In the event of a need for a bailout device at the target lesion (e.g., edge dissection, unplanned additional 
device required to cover target lesion), the same device as the implanted device should be used (i.e., 
BuMA DES for BuMA DES-treated lesions, DP EES for DP EES-treated lesions), with 1-2 mm overlap of 
the bailout and implanted stents. 
Procedural details should be entered into the eCRF. ACT should be measured at the onset of the 
procedure and at regular intervals throughout the procedure per routine hospital practice. 
7.3.5 Unplanned Staged Procedures 
Subjects with planned staged procedures are not eligible for enrollment in the study (refer to Angiographic 
Exclusion Criterion #9, §6.2.2.2.9). However, if index procedure complications (excessive contrast load 
or radiation exposure, blood loss, or patient intolerance) necessitate discontinuation of the procedure, 
staged treatment of a target lesion is permitted provided the staged procedure is performed >72 hours 
and <14 days after the index procedure. The same device as the previously implanted device(s) must be 
used (i.e., BuMA DES for BuMA DES-treated subjects, DP EES for DP EES-treated subjects). 
7.3.6 Concomitant Medical Therapy 
Dual antiplatelet therapy (DAPT) will be administered according to physician standard practice in 
accordance with published guidelines1 and local standards of care. Patients with stable ischemic heart 
disease will be required to receive DAPT for at least 6 months in the absence of contraindications; 
discontinuation of DAPT after 3 months is permitted (but not required) in patients with a high risk of 
bleeding. Patients with ACS will be required to receive DAPT for at least 12 months in the absence of 
contraindications; discontinuation of DAPT after 6 months is permitted (but not required) in patients with 
a high risk of bleeding.  
The following doses are recommended: 
• 
ASA 300 to 325 mg oral or 250 mg IV loading dose and ASA 75-100 mg maintenance dose 
indefinitely. NOTE: Aspirin loading is recommended regardless of whether or not the patient was 
receiving chronic aspirin therapy prior to the procedure.  
AND 
• 
Clopidogrel 600 mg loading dose before procedure and 75 mg daily maintenance dose OR 
prasugrel 60 mg loading dose and 10 mg daily OR ticagrelor 180 mg loading dose and 90 mg 
twice daily. NOTE: For patients receiving chronic clopidogrel therapy prior to the procedure, pre-
procedure re-loading with clopidogrel (600 mg) is recommended. For patients receiving chronic 
prasugrel or ticagrelor therapy prior to the procedure, re-loading is at the discretion of the operator.  
Recommended loading dose, loading dose timing, and maintenance dosage may vary based on 
physician’s discretion and applicable regional clinical guidelines. Approved adjunctive therapies (e.g., GP 
IIb/IIIa inhibitors, cangrelor) may be used according to physician preference in accordance with local 
standards of care. Each site is encouraged to commit to a consistent antiplatelet regimen to be applied 
to all subjects enrolled in the trial, independent of treatment group. 
Procedural anticoagulation therapy should be administered according to physician standard practice in 
accordance with published guidelines and local standards of care.    
All medications administered, including the dose and timing, should be recorded in the patient’s medical 
record and the CRF.  

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7.4 Post-procedure / Pre-discharge Follow-up 
The procedure is complete once the last guiding catheter has been removed from the patient. Thereafter, 
if a guiding catheter is re-introduced, this is considered a repeat intervention, which must be documented. 
The post-procedure follow-up must include: 
• 
Anginal status (CCS, Braunwald classification of unstable angina, or silent ischemia) 
• 
Current concomitant medications documentation. If DAPT has been interrupted or terminated 
the stop date (and resumption date, if applicable) and the reason for interruption/termination 
should be recorded. 
• 
A 12-lead electrocardiogram (ECG), to be completed within 24 hours post-procedure or prior 
to hospital discharge (whichever occurs first) 
• 
Laboratory testing per site standard practice; if laboratory testing is part of the standard of 
care and includes CBC and serum creatinine, these should be recorded. The results of any 
additional tests performed per site standard practice should also be collected. 
• 
Cardiac biomarkers (preferably cTn I or T; if not available, then CKMB is acceptable) should 
be measured 2 to 6 (up to 12) hours postprocedure. If cardiac biomarkers are elevated and 
there is a clinical suspicion of myocardial ischemia (for example, due to new ischemic ECG 
changes [such as ischemic ST changes or new pathological Q waves] or new LBBB, 
angiographic evidence of a flow-limiting complication, or imaging evidence of new loss of 
viable myocardium or new regional wall motion abnormality), serial measurements should be 
taken every 6 to 12 hours until a decline is noted. 
• 
Documentation of any adverse events/ serious adverse events occurring since the point of 
enrollment. All clinically significant adverse events should be carefully documented by the 
research staff using the adverse event data forms. In the event of repeat intervention after the 
index procedure or repeat diagnostic cardiac catheterization (regardless of whether 
revascularization was performed), procedural angiographic images should be forwarded to 
the Angiographic Core Laboratory. For all adverse events that represent a potential endpoint 
event, all relevant medical information (including clinically relevant imaging data, ECG data, 
and the results of relevant laboratory testing performed as part of the standard of care) should 
be collected and retained as part of the research file to support adverse event analysis and 
adjudication. 
Prior to hospital discharge, research staff should review the follow-up requirements with the subject to 
help ensure that he or she returns to the clinic for the 30-day follow-up visit. Telephone numbers should 
be obtained from the subject to ensure the ability to contact him or her at the required time. These phone 
numbers should include all home numbers, work numbers and primary physician numbers. A phone 
number of a relative or friend should also be requested.  
7.5 30-day Follow-up (Clinic Visit) 
All subjects will return to the clinic at 30 days (± 7 days) post-procedure for a clinical evaluation. The 30-
day follow up visit will include the following assessments: 
• 
Anginal status (CCS, Braunwald classification of unstable angina, or silent ischemia) 
• 
Current concomitant medication documentation. If DAPT has been interrupted or terminated 
the stop date (and resumption date, if applicable) and the reason for interruption/termination 
should be recorded.  
• 
A 12-lead electrocardiogram (ECG) 

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• 
Laboratory testing per site standard practice; if laboratory testing is part of the standard of 
care and includes CBC and serum creatinine, these should be recorded. The results of any 
additional tests performed per site standard practice should also be collected. 
• 
Documentation of any adverse events/ serious adverse events occurring since the previous 
evaluation. All clinically significant adverse events should be carefully documented by the 
research staff using the adverse event data forms. In the event of repeat intervention after the 
index procedure or repeat diagnostic cardiac catheterization (regardless of whether 
revascularization was performed), procedural angiographic images should be forwarded to 
the Angiographic Core Laboratory. For all adverse events that represent a potential endpoint 
event, all relevant medical information (including clinically relevant imaging data, ECG data, 
and the results of relevant laboratory testing performed as part of the standard of care) should 
be collected and retained as part of the research file to support adverse event analysis and 
adjudication. 
Prior to concluding the visit, research staff should also review the follow-up requirements with the subject 
to help ensure that the patient can be reached for the required telephone contact at 6 months, and that 
the patient returns to the clinic for the 12-month follow-up visit.  
7.6 Six-month Follow-up (Telephone Contact/Clinic Visit) 
All subjects will be contacted by telephone at 6 months (± 30 days) post-procedure for additional follow-
up, to include the following assessments: 
• 
Anginal status (CCS, Braunwald classification of unstable angina, or silent ischemia) 
• 
Current concomitant medication documentation. If DAPT has been interrupted or terminated 
the stop date (and resumption date, if applicable) and the reason for interruption/termination 
should be recorded. 
• 
Documentation of any adverse events/ serious adverse events occurring since the previous 
evaluation. All clinically significant adverse events should be carefully documented by the 
research staff using the adverse event data forms. In the event of repeat intervention after the 
index procedure or repeat diagnostic cardiac catheterization (regardless of whether 
revascularization was performed), procedural angiographic images should be forwarded to 
the Angiographic Core Laboratory. For all adverse events that represent a potential endpoint 
event, all relevant medical information (including clinically relevant imaging data, ECG data, 
and the results of relevant laboratory testing performed as part of the standard of care) should 
be collected and retained as part of the research file to support adverse event analysis and 
adjudication. 
If a clinic visit occurs as part of the subject’s regular medical care during the specified follow-up 
window, the follow-up assessment may be conducted during this visit, and no separate telephone 
contact is necessary. 
7.7 Twelve-month Follow-up (Clinic Visit or Optional Telephone Contact / 
Virtual Visit*) 
All subjects will return to the clinic at 12 months (± 30 days) post-procedure for a clinical evaluation with 
the following exceptions: 
• 
For the duration of the Coronavirus Disease 2019 (COVID-19) pandemic, phone follow-up or 
virtual visit at 12 months is permitted if necessary to assure the safety of trial participants. The 
reason for the conduct of the phone follow-up should be documented in the eCRF.  
The 12-month follow up visit will include the following assessments: 

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• 
Anginal status (CCS, Braunwald classification of unstable angina, or silent ischemia). 
o For subjects undergoing this assessment via phone or virtual visit, anginal status 
should be documented according to patient reporting. 
• 
Current concomitant medication documentation. If DAPT has been interrupted or terminated 
the stop date (and resumption date, if applicable) and the reason for interruption/termination 
should be recorded. 
o For subjects undergoing this assessment via phone or virtual visit, concomitant 
medications should be documented according to patient reporting. 
• 
A 12-lead electrocardiogram (ECG). 
o For subjects undergoing this assessment via phone or virtual visit, the patient should 
be asked about any recent or planned visits to a healthcare provider. If yes, contact 
information should be requested and the provider should be contacted to provide any 
relevant documentation. All documentation should be reviewed with the site Principal 
Investigator and, if deemed valid, entered into the EDC by the site. 
• 
Laboratory testing per site standard practice; if laboratory testing is part of the standard of 
care and includes CBC and serum creatinine, these should be recorded. The results of any 
additional tests performed per site standard practice should also be collected. 
• 
For subjects being assessed by phone or virtual visit, this data will not be collected. 
• 
Documentation of any adverse events/ serious adverse events occurring since the previous 
evaluation. All clinically significant adverse events should be carefully documented by the 
research staff using the adverse event data forms. In the event of repeat intervention after the 
index procedure or repeat diagnostic cardiac catheterization (regardless of whether 
revascularization was performed), procedural angiographic images should be forwarded to 
the Angiographic Core Laboratory. For all adverse events that represent a potential endpoint 
event, all relevant medical information (including clinically relevant imaging data, ECG data, 
and the results of relevant laboratory testing performed as part of the standard of care) should 
be collected and retained as part of the research file to support adverse event analysis and 
adjudication. 
o For subjects undergoing this assessment via phone or virtual visit, if potential SAEs or 
AEs are reported, the subject should be asked about any associated healthcare visits; 
if applicable visits are reported, contact information should be sought and the provider 
contacted to provide relevant source documentation (including angiographic films, as 
applicable). All source documentation must be reviewed with the site PI and, if deemed 
valid, entered into the EDC by the site. All collected angiographic films are provided to 
the Angiographic Core Laboratory for analysis.  
Prior to concluding the visit, research staff should also review the follow-up requirements with the subject 
to help ensure that the patient can be reached for the required telephone contact (or optional clinic visit) 
follow-ups at 2, 3, 4, and 5 years. Telephone numbers, including all home, work, and primary physician 
numbers, should be confirmed.  
Note: For subjects who did not receive any study stent during the index procedure (BuMA DES or DP-
EES), the 12-month follow-up will be the final follow-up assessment for this protocol. 

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7.8 Annual Follow-up at 2, 3, 4, and 5 Years (Telephone Contact/Clinic 
Visit) 
All subjects who received any study stent during the index procedure will be contacted by telephone (or 
optional in-clinic assessment) annually at 2, 3, 4, and 5 years post-procedure for additional follow-up, to 
include the following assessments: 
• 
Anginal status (CCS, Braunwald classification of unstable angina, or silent ischemia) 
• 
Current concomitant medication documentation. If DAPT has been interrupted or terminated 
the stop date (and resumption date, if applicable) and the reason for interruption/termination 
should be recorded. 
• 
Documentation of any adverse events/ serious adverse events occurring since the previous 
evaluation. All clinically significant adverse events should be carefully documented by the 
research staff using the adverse event data forms. In the event of repeat intervention after the 
index procedure or repeat diagnostic cardiac catheterization (regardless of whether 
revascularization was performed), procedural angiographic images should be forwarded to 
the Angiographic Core Laboratory. For all adverse events that represent a potential endpoint 
event, all relevant medical information (including clinically relevant imaging data, ECG data, 
and the results of relevant laboratory testing performed as part of the standard of care) should 
be collected and retained as part of the research file to support adverse event analysis and 
adjudication. 
NOTE: For subjects who underwent a phone follow-up at the 12-month time point for any reason, it is 
preferable that the 2-year follow-up be conducted as an in-clinic visit. For all other subjects, if a clinic visit 
occurs as part of the subject’s regular medical care during the specified follow-up window, the annual 
follow-up assessment may be conducted during this visit, and no separate telephone contact is 
necessary.  
8.0 Adverse Events and Serious Adverse Events 
In this study, patients should be encouraged to report adverse events (AEs) spontaneously or in response 
to general, non-directed questioning. Any time during the study, the patient may volunteer information 
that resembles an adverse event (AE). If it is determined that a clinically significant AE has occurred, the 
investigator should obtain all the information required to complete the AE CRFs. Non-clinically-significant 
adverse events will not be required post discharge from the initial study procedure. 
8.1 Adverse Events (AE) 
An adverse event is any untoward medical occurrence, unintended disease or injury or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or other persons, whether or 
not related to the study device.  
NOTE: This definition includes events related to the study device or to the procedures involved, but does 
not imply that there is a relationship between the adverse event and the study device.  
Pre-Existing Conditions: 
Pre-existing medical conditions or a repeat of symptoms reported prior to the procedure will not be 
recorded as an AE. Pre-existing conditions that worsen during a study are to be considered adverse 
events. For users or other persons, this classification is restricted to events related to the study device. 

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8.2 Serious Adverse Events (SAE) 
A serious adverse event is an adverse event that: 
1. Led to a death 
2. Led to a serious deterioration in the health of the subject that: 
a. Resulted in a life-threatening illness or injury 
b. Resulted in a permanent impairment of a body structure or a body function 
c. Required in-patient hospitalization or prolongation of existing hospitalization 
d. Resulted in medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to body structure or a body function. 
3. Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
8.3 Adverse Device Effect (ADE) 
An adverse device effect is an adverse event related to the use of a medical device. This includes: 
• 
Any adverse event resulting from insufficiencies or inadequacies in the Instructions for Use, the 
deployment, the implantation, the installation, the operation, or any malfunction of the medical 
device 
• 
Any event that is a result of a use error or intentional misuse 
8.4 Serious Adverse Device Effect (SADE) 
A serious adverse device effect is an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event.  
8.5 Unanticipated Adverse Device Effect (UADE) 
An unanticipated adverse device effect is any serious adverse effect on the 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 investigational plan or 
application (including a supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety or welfare of subjects. 
NOTE: An anticipated serious adverse device effect (ASADE) is a serious adverse device effect which 
by its nature, incidence, severity, or outcome has been identified in the investigational plan or application 
(including a supplementary plan or application).  
8.6 Device Deficiencies, Malfunctions, and Use Error 
Investigators are instructed to report all possible device deficiencies, malfunctions, misuse or use error 
observed during the course of the trial. These incidents will be documented in the case report form 
provided as follows: 
• 
Device deficiency: Inadequacy of a medical device related to its identity, quality, durability, 
reliability, safety or performance. NOTE: Device deficiencies include malfunction, use error, and 
inadequate labeling. They may or may not affect device performance or lead to an adverse event. 
o 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 protocol. NOTE: A device malfunction occurs when the device is used in 

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• 
The AE CRF must be reviewed by the investigator 
For adverse events not meeting the criteria for an SAE or (potential) UADE, the Sponsor recommends 
that the Investigator notify the Sponsor within 10 working days of first learning of the AE using the 
electronic data capture (EDC) CRF. If necessary, the Investigator may be requested to provide de-
identified copies of source documentation (e.g., physician/nurse notes or summaries) regarding the 
event. 
The Investigator must also notify the responsible IRB/EC regarding new and significant safety information 
and any events identified by SINOMED that require expedited FDA or other regulatory authority reporting 
as serious, unexpected, and related to the investigational device. It is the responsibility of the investigator 
to ensure site-specific IRB/EC reporting requirement are met. 
The sponsor is responsible for reporting SAEs and device deficiencies to regulatory authorities in line 
with applicable regulatory requirements and for reviewing the risk analysis, determining the need for 
corrective or preventative action, and informing investigators and regulatory authorities accordingly. 
8.8.2 Serious Adverse Events 
The Sponsor recommends that the Investigator notify SINOMED within 3 working days of first learning of 
any SAE using the EDC CRF. If necessary, the Investigator may be requested to provide copies of de-
identified source documentation (e.g., physician/nurse notes or summaries) regarding the event. The 
Sponsor will conduct an evaluation of the event and, if it is determined by the Sponsor to be a UADE, it 
will be reported as described in the following section. 
At EU sites, Serious Adverse Device Effects (SADEs) must be reported to the Safety Monitor (Europe) 
within 48 hours of knowledge if required by local or national regulations; contact details are provided in 
§2.0.  
It is the responsibility of each Investigator to report all serious adverse events and/or serious adverse 
device effects and device deficiencies that could have led to a serious adverse device effect to the 
IRB/EC, according to national regulations and IRB/EC requirements. If required by national regulations, 
the Investigator may also be required to report SAEs to the applicable regulatory authority. 
8.8.3 Unanticipated Adverse Device Effects 
Investigators must report any (potential) unanticipated adverse device effects to the Sponsor and their 
IRB/EC as soon as possible but no later than within 5 working days after the investigator first learns of 
the event [21 CFR 812.150]. UADEs should be reported immediately on the eCRF and via telephone to 
the Sponsor Clinical Project Lead; contact details are provided in §2.0. 
Investigators should consider the device labeling and the listing of expected adverse events (§8.9) in 
determining whether an event may qualify as “unanticipated.” 
If an event is determined by SINOMED to be a UADE, the Sponsor will report the event to the FDA, 
relevant Competent Authorities and/or other regulatory authorities, and the European Databank on 
Medical Devices in accordance with MEDDEV 2.12-1, as applicable. The Sponsor will also report all 
UADEs to all investigators to enable reporting to their respective IRB/EC. The Sponsor will provide this 
notification within 10 days after first receiving notice of the effect [21 CFR 812.150].  
If the Sponsor and the DSMC determine that the event presents an unreasonable risk to participating 
subjects, the Sponsor must terminate all investigations or parts of investigations presenting the risk in 
the clinical trial not more than 5 working days after making that determination, and not more than 15 
working days after the sponsor first received notice of the effect [21 CFR 812.26]. Follow-up visits for 
enrolled subjects will continue according to the schedule of assessments. 

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8.9 Expected Adverse Events 
The following adverse events have been identified as actual or potential complications associated with 
percutaneous coronary intervention with drug-eluting stents, categorized below by their estimated 
frequency at 1 year. It is expected that the nature and frequency of the risks observed with the use of 
BuMA DES and DP EES in this trial will be similar. 
Very common (≥10%) 
• 
Angina pectoris (stable or unstable) 
Common (1.0% to <10%) 
• 
Access site complications (including pain, hematoma, or hemorrhage) 
• 
Arrhythmia (atrial, ventricular) 
• 
Cardiac, pulmonary, or renal failure 
• 
Coronary artery dissection 
• 
Hypertension 
• 
Hypotension  
• 
Myocardial infarction 
• 
Nausea and vomiting 
• 
Restenosis 
• 
Vascular complications (including access site vascular complications) that may require vessel 
repair 
Uncommon (0.1% to <1.0%) 
• 
Allergic or hypersensitivity reactions (to contrast agent, procedural medications, or device 
materials) 
• 
Bleeding complications (which may require transfusion) 
• 
Cardiac arrest 
• 
Coronary artery perforation 
• 
Coronary artery spasm 
• 
Distal embolization 
• 
Fever 
• 
Myocardial ischemia (silent) 
• 
Pain or infection at the catheter site 
• 
Palpitations 
• 
Pericarditis 
• 
Peripheral ischemia (due to vascular injury) 
• 
Pseudoaneurysm 
• 
Pulmonary edema 

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• 
Requirement for surgery (emergent or non-emergent) 
• 
Stroke or transient ischemic attack 
• 
Total occlusion of a coronary artery 
• 
Ventricular tachycardia 
• 
Ventricular fibrillation 
• 
Vessel dissection 
Rare (0.01% to <0.1%) 
• 
Arterial injury 
• 
Arteriovenous fistula 
• 
Cardiac tamponade 
• 
Coronary artery embolism 
• 
Nausea (procedural) 
• 
Pericardial effusion 
• 
Peripheral artery dissection 
• 
Peripheral nerve injury 
• 
Renal insufficiency 
• 
Shock 
Very rare (<0.01%) 
• 
Abrupt coronary artery closure 
• 
Arterial rupture 
• 
Coronary artery aneurysm 
The nature and frequency of potential adverse events specifically related to the sirolimus drug component 
as incorporated into the BuMA DES are not known, but are expected to be rare and may include but are 
not limited to:  
• 
Abnormal liver function tests 
• 
Anemia 
• 
Diarrhea 
• 
Hypercholesterolemia 
• 
Hypersensitivity, including anaphylactic / anaphylactoid type reactions 
• 
Hypertriglyceridemia 
• 
Infections 
• 
Leucopenia 
• 
Pseudoaneurysm 
• 
Renal failure 

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• 
Thrombocytopenia 
9.0 Benefit: Risk Analysis 
9.1 Potential Benefits 
The targeted patient population consists of patients presenting with symptomatic ischemic heart disease, 
including chronic stable angina with evidence of ischemia or acute coronary syndromes, planned to 
undergo PCI with DES for the treatment of CAD. Compared with traditional durable polymer DES, the 
combination of a thin durable base layer with a biodegradable polymer drug delivery matrix featured in 
the BuMA DES may offer improved re-endothelialization, reducing the risk of long-term adverse events.  
Subjects in the BuMA US IDE trial may not derive any direct benefit from their participation in the trial; 
however, subjects may gain satisfaction from having made an altruistic contribution to medical science, 
and the results of the trial may contribute to improved treatments that could benefit future patients who 
require PCI for the treatment of CAD. 
The potential benefits and risks of study participation will be evaluated on an individual basis and 
discussed with each patient prior to enrollment in the study. 
9.2 Potential Risks and Discomforts 
Enrollment in the trial involves exposure to some risks. The risks of trial participation are not expected to 
be materially different from those encountered by an individual undergoing PCI with DES outside the 
context of the trial (§8.9). The use of the BuMA DES may pose additional potential risks of an unknown 
nature or frequency.  
9.3 Methods to Minimize Risks 
The clinical investigation plan is specifically designed to manage and minimize risks through careful 
subject selection, thorough training of investigators, adherence to pre-determined time points to assess 
subject clinical status, and regular clinical monitoring visits by Sponsor-appointed monitoring personnel. 
In addition, an independent Data Safety Monitoring Committee will meet regularly throughout the trial to 
monitor the safety of subjects.  
10.0 Study Committees 
10.1 Executive Committee 
The Executive Committee will be comprised of the Study Chairman, the Principle Investigators and Co-
Principal Investigators from the US, Europe, and Japan, and one or more Sponsor Representatives. The 
Executive Committee will be responsible for scientific and operational management of the trial, and will 
meet regularly prior to and during the trial to monitor trial progress.  
10.2 Clinical Events Committee (CEC) 
An independent Clinical Events Committee (CEC) will adjudicate all site-reported adverse events that 
represent a potential endpoint event in an ongoing fashion during the trial. Relationship of these events 
to the study device and procedure will also be adjudicated.  
The CEC will include cardiologists and/or interventional cardiologists experienced in clinical trials who 
are otherwise independent of the Sponsor and the conduct of the study. Members will not have scientific, 
financial or other conflicts of interest related to SINOMED or the Investigators. The CEC will operate and 

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conduct all meetings and event reviews independent of the Sponsor unless specific expert knowledge 
regarding the characteristics or function of the study device is requested by the CEC from the Sponsor.  
The CEC will meet regularly throughout the study to adjudicate events in an ongoing and timely fashion. 
The adjudication process, event definitions and required source document materials for each type of 
event will be pre-specified in the CEC Charter prior to the onset of the trial. The adjudication process will 
include CEC member review of data collected from all relevant medical records, as well as all imaging 
studies, associated with an event. All adjudication decisions will be made by the CEC in an independent 
fashion based upon review of all available medical evidence. 
10.3 Data Safety Monitoring Committee (DSMC) 
An independent Data Safety Monitoring Committee (DSMC) will be responsible for the oversight and 
safety monitoring of the study. The DSMC will advise the Sponsor regarding the continuing safety of the 
trial subjects and those yet to be recruited to the trial, as well as the continuing validity and scientific merit 
of the trial. The DSMC will be composed of leading experts in interventional cardiology and biostatistics 
who are not participating in the trial and have no affiliation with the Sponsor. 
During the enrollment phase of the trial, the DSMC will review accumulating safety data to monitor for 
the incidence of serious adverse events that would warrant modification or termination of the trial. Any 
DSMC recommendations for study modification or termination prompted by concerns regarding subject 
safety or issues relating to data monitoring or quality control will be submitted in writing to the Sponsor 
for consideration and final decision. However, if the DSMC at any time determines that a potential serious 
risk exists to subjects in this trial, the DSMC chairman will immediately notify the Sponsor. 
The DSMC will meet at regular intervals to review the safety data. DSMC responsibilities, membership, 
meeting frequencies, and procedures will be outlined in the DSMC charter prior to the onset of the trial.  
11.0 Statistical Considerations and Analysis Plan 
11.1 Hypotheses 
 
11.1.1 Primary Safety and Efficacy Hypothesis 
The primary hypothesis is that the rate of TLF in the Intervention group is not inferior to the rate of TLF 
in the Control group by greater than or equal to the pre-specified non-inferiority margin (Δ). Specifically, 
the null and alternative hypotheses are: 
H0: pI - pC ≥ Δ  
HA: pI - pC < Δ  
Where: 
pI = the true rate of TLF in the Intervention group at 12 months  
pC = the true rate of TLF in the Control group at 12 months 
Δ = non-inferiority margin 
The non-inferiority criterion is met if the upper bound of the 95% confidence interval (97.5% one-sided 
confidence interval) of the difference between the Intervention and Control group event rates is less than 
the specified delta, using the Farrington-Manning approach.  
If non-inferiority is demonstrated in the both the Per Protocol (PP) and Intention to Treat (ITT) populations, 
the trial will be declared a success. Because both analysis populations will be considered simultaneously, 
no adjustment for alpha is necessary.  

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11.1.2 Secondary Powered Endpoint Hypothesis 
If the primary non-inferiority hypothesis is confirmed, the secondary powered endpoint hypothesis will be 
tested. The secondary powered endpoint hypothesis is that the rate of TLF in the treatment group is 
superior to the rate of TLF in the control group over the period between 1 and 5 years postprocedure in 
a landmark analysis. Specifically, the null and alternative hypotheses are: 
H0: SI(t) = SC(t) for all t  
HA: SI(t) ≠ SC(t)  
Where: 
SI(t) = the survival distribution in the Intervention group and SC(t) = the survival distribution in the 
Control group  
Superiority will be demonstrated if the survival distributions are not equal using the log-rank test in the 
Intention to Treat patient population.  
11.2 Analysis Populations 
11.2.1 Intention to Treat (ITT) Analysis Population 
The Intention to Treat (ITT) analysis population is defined as all subjects enrolled in the study, by 
assigned treatment, regardless of the treatment actually received. 
The ITT population will be the co-primary analysis population for the primary safety and efficacy endpoint, 
the primary analysis population for the powered secondary endpoint, and the primary analysis population 
for all additional secondary safety endpoints and secondary efficacy endpoints.  
11.2.2 Per Protocol (PP) Analysis Population 
The Per Protocol (PP) analysis population is defined as subjects enrolled in the trial who meet all inclusion 
criteria and no exclusion criteria, have provided written informed consent, and in whom an assigned study 
stent has been implanted.  
The PP population will be the co-primary analysis population for the primary safety and efficacy endpoint 
and the secondary analysis population for all secondary endpoints.  
11.3 Sample Size Calculation and Assumptions 
11.3.1 Primary Endpoint  
The primary safety and efficacy endpoint of the trial is target lesion failure (TLF), defined as the per-
subject hierarchical composite of cardiac death, target vessel-related myocardial infarction (TV-MI), and 
clinically-driven target lesion revascularization (TLR), evaluated at 12 months. 
We assume:  
• 
Randomization ratio is 2:1 (BuMA DES: DP EES) 
• 
The true rate of TLF in the Control group at 12 months = 6.5% (§11.3.3.1) 
• 
No difference between treatments (the true rate of TLF in the Intervention group at 12 months = 
6.5%) 
• 
Non-inferiority margin (Δ) = 3.575% (§11.3.3.3) 
• 
Loss to follow-up at 1 year (inclusive of dropout from co-primary PP analysis population) = 5% (a 
standard assumption for contemporary trials of coronary stents) 
• 
α = 0.025 (one-sided) 

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Given these assumptions, a sample size of 1551 evaluable subjects (1034 Intervention: 517 Control) will 
provide 80% power to demonstrate non-inferiority of the BuMA DES to DP EES using the Farrington-
Manning approach. The sample size has been increased to 1632 subjects (1088 Intervention: 544 
Control) to account for an expected 5% loss to follow-up at 12 months. 
11.3.2 Secondary Powered Endpoint  
The powered secondary endpoint of the trial is long-term safety and efficacy, defined as TLF between 12 
months and 5 years by landmark analysis. The analysis will be performed when the last enrolled subject 
has completed his/her 5 year clinical follow-up visit. 
We assume: 
• 
Randomization ratio is 2:1 (BuMA DES: DP EES) 
• 
The landmark (between 12 months and 5 years) TLF rate in the Control group  = 8% (§11.3.3.2) 
• 
The rate of TLF in the control group at 12 months = 6.5% (§11.3.3.1) 
• 
A constant Hazard Ratio in the Intervention group compared to the Control Group = 0.52 
• 
Loss to follow-up = 5% per year (a standard assumption for contemporary trials of coronary stents) 
• 
α = 0.05 (two-sided) 
Given these assumptions, the planned study sample size of 1444 evaluable subjects at 1 year 
(accounting for an estimated 5% loss to follow-up at 1 year, a 6.5% rate of TLF prior to 1 year, and a 
continued annual loss to follow-up of 5%) will provide approximately 80% power to demonstrate 
superiority of the BuMA DES to DP EES using the log-rank test. 
11.3.3 Rationale for Assumptions  
11.3.3.1 Expected Control Event Rate – Primary Endpoint  
The expected event rate of the primary endpoint (target lesion failure [TLF] at 12 months) in the Control 
group was estimated based on published data from randomized controlled trials of commercially-
available durable polymer everolimus-eluting coronary stent systems (DP EES).  
A bibliographic scientific database search (MEDLINE, EMBASE, Cochrane Central Register of Controlled 
Trials [CENTRAL]) was conducted to identify relevant published clinical data according to the following 
criteria:  
1. Randomized controlled trials (RCTs) 
2. Commercially available durable polymer everolimus-eluting coronary stent systems as an 
investigational device or active comparator, including the XIENCE family of cobalt-chromium 
everolimus-eluting stent systems (XIENCE EES; including XIENCE V, XIENCE NANO, XIENCE 
PRIME, XIENCE PRIME LL, XIENCE XPEDITION, XIENCE XPEDITION SV, XIENCE 
XPEDITION LL, XIENCE Alpine; studies in which a subset of patients in the everolimus-eluting 
stent arm received cobalt-chromium Promus stents were included) and the PROMUS Element 
family of everolimus-eluting platinum chromium stent systems (including PROMUS Element, 
PROMUS Element Plus, and Promus PREMIER). 
3. Treatment of native vessel coronary artery disease; studies that were limited solely to the 
treatment of acute myocardial infarction, chronic total occlusion, in-stent restenosis, or 
unprotected left main coronary artery disease were excluded. 
4. Clinical data reported at ≥12 months 
5. Subjects = humans, adults ≥18 years of age 
6. NDP EES ≥200 

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Weighted average 
-- 
6.01 
Meta-analytic average 
(inverse variance method) 
-- 
6.50 
Therefore, based on published literature reporting TLF at 1 year in subjects treated with DP EES, the 
expected event rate for the primary efficacy endpoint in the control group is estimated to be 6.5%.  
11.3.3.2 Expected Control Event Rate – Secondary Powered Endpoint 
The powered secondary long-term device safety and efficacy endpoint is long-term safety and efficacy, 
defined as target lesion failure (TLF) between 12 months and 5 years by landmark analysis. 
Of the 14 selected randomized trials reporting TLF rates in DP EES at 1 year (§11.2), 8 trials  reported 
data at one or more time points between 2 and 5 years postprocedure (SPIRIT III, SPIRIT IV, RESOLUTE 
AC, SORT OUT IV, TWENTE, RESET, ISAR TEST 4, and NEXT). Based on this data, a landmark 
(between 12 months and 5 years) TLF event rate in the control group of 8% was estimated (2% annually).  
11.3.3.3 Non-inferiority Margin 
A meta-analysis of historical trials determined that a conservative estimate (lower bound of the 90% CI) 
for the treatment effect of the Control comparator (DP EES) compared to bare metal stents (BMS) was 
9.0% for the primary endpoint of TLF at 1 year.100 The selected non-inferiority margin of 3.575% therefore 
preserves >60% of the risk reduction provided by the Control using the fixed margin approach. This 
clinical margin is more conservative than the usual practice in cardiovascular outcomes studies of 
selecting a non-inferiority margin that preserves 50% of the Control effect size.101 
11.4 Method of Analysis & Reporting  
11.4.1 General Approach 
Non-inferiority testing for the primary safety and efficacy endpoint will be one-sided and performed at a 
0.025 significance level for the comparison of the BuMA DES arm with the DP EES arm. Superiority tests 
on the secondary powered endpoint of long-term safety and efficacy (if the primary non-inferiority 
endpoint is met) and the primary safety and efficacy endpoint (if the secondary superiority endpoint is 
met) will be performed at a two-sided 0.05 significance level.  
Analysis of all additional safety and efficacy endpoint results will be summarized using descriptive 
statistics. For binary variables, descriptive statistics will include counts, percentages, and sample size for 
each treatment group; p-values may be presented for hypothesis-generating purposes. For continuous 
variables, descriptive statistics include mean, median, standard deviation, quartiles, minimum, maximum, 
and sample size for each treatment group. Binary variables will be summarized using frequencies, 
percentages, and sample size for each treatment group. For time-to-event data, Kaplan-Meier estimates 
at the indicated time points will be displayed graphically.  
Analysis will be conducted using SAS (version 9.3 or greater), unless otherwise noted. Please refer to 
the formal Statistical Analysis Plan (SAP) for additional details. 
11.4.2 Baseline Characteristics 
The following data will be summarized using descriptive statistics and presented by treatment group for 
the ITT and PP populations:  
• 
Baseline demographics  
• 
Baseline comorbidities, risk factors, and medical history  
• 
Cardiac risk factors, angina status, and cardiac history  
• 
Procedural characteristics  

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• 
Device details 
11.4.3 Primary Endpoint Analysis 
The primary analysis will be a test for non-inferiority of the BuMA DES compared with DP EES for the 
primary endpoint of TLF at 12 months, performed in the Per Protocol (PP) and Intention to Treat (ITT) 
populations using the Farrington-Manning test. If non-inferiority for the primary endpoint is met and 
superiority for the powered secondary endpoint is met, formal superiority testing will be performed for the 
primary endpoint. 
The primary endpoint will be evaluated in both the PP and ITT populations. For the primary analyses, 
only subjects who experienced a primary endpoint event or who had at least 11 months follow-up (1 year 
minus the allowable 30 day window) and who meet the applicable analysis population definition will be 
included in the analysis. Analysis is at the subject level. A subject will be considered a failure for TLF if 
the subject experiences a cardiac death, a target vessel-related myocardial infarction (TV-MI) in any 
target vessel, or clinically-driven target lesion revascularization (TLR) in any study target lesion. 
As an additional analysis, to account for any missing data in the primary endpoint, a tipping point analysis 
will be conducted. A sensitivity analysis for the primary endpoint will also be conducted according to the 
pre-specified alternate biomarker thresholds for PCI-related MI (§17.1). 
In addition, to assess the appropriateness of pooling results between study regions (North America vs. 
Japan vs. Europe), an assessment of the effect of region on the primary endpoint will be carried out in 
the PP and ITT populations using interaction testing from the logistic regression with a 0.15 level of 
significance. A non-significant result for region will support the pooling of patients across regions for the 
primary safety and efficacy analysis. A significant result will require further inspection of the by-region 
results to assess if poolability is appropriate. 
11.4.4 Secondary Powered Endpoint Analysis 
The powered secondary endpoint of long-term safety and efficacy, defined as TLF between 12 months 
and 5 years by landmark Kaplan-Meier analysis, will be a test for superiority of the BuMA DES group to 
the DP EES group via the log-rank test in the ITT population. Subjects who experience TLF prior to 12 
months will be excluded from this analysis. The analysis will be performed when the last enrolled subject 
has completed his/her 5 year clinical follow-up visit, and will be performed only if non-inferiority for the 
primary endpoint has been met. 
11.4.5 Additional Secondary Endpoints Analysis  
11.4.5.1 Secondary Safety Endpoints 
All secondary safety endpoints will be evaluated in the ITT population using appropriate descriptive 
statistics. No formal hypothesis testing will be performed. Statistics for continuous variables will include 
mean, median, standard deviation, minimum, maximum, and sample size for each treatment group. 
Binary variables will be summarized using frequencies, percentages, and sample size for each treatment 
group.  
As a secondary analysis, all secondary safety endpoints will be evaluated in the PP population.  
11.4.5.2 Secondary Efficacy Endpoints 
All secondary efficacy endpoints will be evaluated in the ITT population using appropriate descriptive 
statistics. No formal hypothesis testing will be performed. Statistics for continuous variables will include 
mean, median, standard deviation, minimum, maximum, and sample size for each treatment group. 
Binary variables will be summarized using frequencies, percentages, and sample size for each treatment 
group.  
As a secondary analysis, all secondary efficacy endpoints will be evaluated in the PP population. 

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11.4.6 Subgroup Analyses 
Subgroup analyses will be performed for all primary and secondary endpoints in their respective primary 
analysis populations for the following subgroups, and results will be reported by treatment group using 
descriptive statistics: 
• 
Enrollment region (North America vs. Japan vs. Europe) 
• 
Presentation (stable coronary artery disease vs. acute coronary syndromes) 
• 
Single- versus multi-vessel disease (1 vs. 2 target vessels) 
• 
Diabetes status (subjects with vs. without medically-treated diabetes mellitus)  
• 
Subject gender (male vs. female) 
The interaction p-value for the subgroup by treatment effect will be presented.  
11.4.7 Additional Analyses 
The following data will be summarized using descriptive statistics presented by treatment group in the 
ITT and PP populations:  
• 
Subject enrollment and data compliance by site and visit (data compliance at each visit is the 
percentage of patients whose data forms have been collected and entered divided by the 
percentage of patients whose forms should have been collected and entered)  
• 
Frequency (number and percentage of patients) with each type of concomitant medication  
• 
Frequency (number and percentage of patients) with each site-reported Treatment Emergent AE 
overall and by MedDRA system organ class and preferred term (a treatment emergent AE is an 
AE that started or worsened during or after the index procedure)  
• 
Frequency (number and percent of patients) with each site-reported Treatment Emergent Serious 
AE overall and by MedDRA system organ class and preferred term  
• 
Frequency (number and percent of patients) with each site-reported Treatment Emergent AE or 
SAE, by CEC-adjudicated relationship to the investigational device or procedure  
• 
Protocol deviations (number and percentage of patients with each deviation type) 
• 
Detailed listings on primary and secondary endpoints, site-reported AE, and protocol deviations 
11.4.8 Handling of Multiplicity Issues 
The primary safety and efficacy endpoint will be evaluated simultaneously in the co-primary PP and ITT 
populations, and trial success requires meeting the non-inferiority criterion in both analyses. Therefore, 
adjustment for Type I error is not necessary.  
The secondary powered endpoint hypothesis will only be tested if the primary endpoint non-inferiority 
hypothesis is met. Superiority for the primary endpoint will be tested if the secondary powered endpoint 
hypothesis is confirmed. 
11.4.9 Multicenter Studies 
The appropriateness of pooling data across sites will be assessed by including a random effect for site 
in a random effects model assessing the primary endpoint using the logit link. If a test of the variance 
from the mixed effects model is significant at alpha=0.15, then it will be determined that heterogeneity by 
site exists. If this occurs, the primary endpoint results will be presented by site and the final analysis will 
be stratified by site. Sites with less than 10 subjects will be pooled according to study region as defined 
previously. 

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11.5 Measures to Minimize Bias 
11.5.1 Randomization 
Subjects will be randomly assigned to a treatment group in a 2:1 ratio (BuMA DES : DP EES) after 
eligibility criteria have been confirmed (at the time of the index procedure). Randomization will be stratified 
by presentation (acute coronary syndrome vs. non-ACS) and diabetes status (subjects with vs. without 
medically-treated diabetes mellitus) given the influence of clinical presentation and diabetes status on 
the outcome of subjects with CAD. Randomization will also be stratified by study site to avoid introducing 
bias as a result of site-specific factors.  
11.5.2 Blinding 
This is a single-blind study. The following individuals will be blinded to the subject’s treatment allocation: 
• 
Subject and his/her family members 
• 
Site personnel conducting follow-up evaluations will not have access to randomization 
eCRFs, and every effort will be made to ensure that medical records use a non-specific term 
to identify the treatment device (e.g., “DES”) to avoid revealing treatment group assignment  
• 
Members of the Clinical Events Committee 
• 
Angiographic Core Laboratory technicians performing the analysis 
Un-blinding will occur only after the database has been locked for the analysis of the primary endpoint or 
to protect subject rights, welfare, or well-being at the request of the DSMC. 
If a site investigator determines it is necessary to reveal treatment allocation to the subject as a result of 
complication or injury, he or she is requested to notify the Sponsor. 
11.5.3 Independent Assessments 
To decrease the variability of clinical outcome measurements, all adverse events, including all potential 
endpoint events, will be adjudicated by an independent CEC according to standardized endpoint 
definitions, and the relationship of these events to the study device will also be adjudicated. In addition, 
an independent Angiographic Core Laboratory analysis will be performed by technicians who are blinded 
to subject treatment assignment to provide accurate and unbiased determinations of lesion and device 
success, as well as to determine if revascularizations meet the diameter stenosis criteria for classification 
as clinically-driven.  
12.0 Publication Policy 
The Sponsor and the Principal Investigators are committed to the publication and widespread 
dissemination of the results of the study in the scientific community. This study represents a joint effort 
between the Sponsor and the Principal Investigators and Co-Principal Investigators; as such, the parties 
agree that the recommendation of any party concerning manuscript or text shall be taken into 
consideration in the preparation of final scientific documents for publication or presentation.  
All parties agree that the Investigators will do publications and/or presentations. The number of authors 
will be determined according to the rules of the addressed scientific journal and by decision of the 
Executive Committee. Abstracts and articles shall be submitted to the Sponsor in advance of their 
publication. An agreement on the final form of abstracts and articles shall be obtained within an 
appropriate time frame of 60 days. In the event that diverging opinions on presentation of the data cannot 
be reconciled, the Executive Committee will make a final decision.  

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Any and all information supplied or obtained during this study by or on behalf of any party involved in the 
study (in whatever form) shall be treated as confidential, shall not be disclosed to any third party unless 
with the prior written consent of the Sponsor in each case. Any documents, papers, drawings or other 
materials which are released or created by any party involved in this study are and shall remain at all 
times the property of the Sponsor excluding publications which are approved in writing by the Sponsor. 
Such materials shall not be reproduced in any form without the prior written consent of the Sponsor and 
must be returned to the Sponsor immediately upon request, or upon completion of the evaluation of such 
materials, whichever occurs first. 
All clinical data or any other information gathered during or after this study related to the study, the people 
involved, or the materials involved will be considered confidential. Confidential information will remain 
confidential for a period of 36 months following study completion. 
13.0 Data Collection and Monitoring 
13.1 Data Collection and Monitoring 
All required data for this study will be collected on standardized Case Report Forms (CRFs) using an 
electronic data capture system (EDC). The investigator (or designated hospital staff) will assure primary 
data collection based on source-documented hospital chart reviews. 
Independent monitoring will be performed to ensure that the investigator and his/her study team conduct 
the clinical investigation in accordance with contract specifications, this protocol, the Declaration of 
Helsinki, ICH-GCP, ISO 14155, 21 CFR Part 812, and other applicable FDA and local regulations, and 
to ensure adequate protection of the rights and safety of subjects and the quality and integrity of the 
resulting data. Submitted trial data will be verified against patient charts and other sources containing 
original records of patient data. Source document verification will occur in accordance with the pre-
specified Monitoring Plan.  
Progress of the trial will be monitored by: 
• 
On-site review, as deemed appropriate by the Sponsor 
• 
Telephone communications between site personnel (e.g., Site Investigator, Trial Coordinator) and 
trial monitors 
• 
Review of CRFs and associated clinical records 
• 
Review of regulatory documents 
Entities responsible for monitoring in the US, Europe, and Japan are listed in §2.0.   
If a monitor becomes aware that an Investigator is not complying with the requirements mentioned above, 
the sponsor will be notified by the monitor. The Sponsor will evaluate the non-compliance and if 
necessary, immediately either secure compliance or discontinue shipments of the investigational device 
to the Investigator and terminate the Investigator’s participation in continued enrollment in the 
investigation. The Investigator will be required to return all unused devices to the Sponsor.  
13.2 Source Documentation 
Auditors, monitors, IRBs/ECs, the Sponsor, and the FDA and other regulatory authorities may have 
access to the medical records related to this study. Original or certified copies of all relevant clinical 
findings, observations, and other activities throughout the clinical investigation must be recorded and 
maintained in the medical file of each enrolled patient (no source documentation will be recorded directly 
on the CRF). At a minimum, the following must be included in each patient’s file: 

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• 
Sufficient medical history and current physical condition, including any medication(s) the patient 
is taking at the time of the procedure to assess the patient’s eligibility; 
• 
The medical file should reveal the patient’s participation in this study, including documentation of 
written informed consent; 
• 
Dated report of the index procedure including medication, material usage, and complications, if 
applicable; 
• 
Dated reports of the post-procedure / pre-discharge and follow-up assessments; 
• 
Dated results of required laboratory tests; 
• 
Any adverse event(s), the resultant action or treatment, and outcome, if applicable; and 
• 
In the case of withdrawal of patient consent, the reason and patient status at time of withdrawal. 
The Site Investigator will permit study-related monitoring, audits, IRB/EC review, and FDA and other 
applicable regulatory authority inspections by allowing direct access to the source data. 
In case of electronic source data, periodic access will be allowed for full safety review. The review will be 
specific to study subjects and the records that would contain potential safety data. Dated print-outs are 
acceptable for preliminary review of safety information. Print-outs will not be limited to cardiac data only, 
but should include all available data related to the identified patient(s). 
13.3 Auditing 
As a quality assurance measure, investigational sites may be audited during the trial or following trial 
completion. The purpose of an audit is to provide an independent evaluation of trial conduct and protocol 
and GCP compliance, separate from routine monitoring and quality control functions. The audit may be 
conducted by SINOMED personnel (or designee), the FDA, or another regulatory body.  
Site Investigators are requested to notify the Sponsor if the FDA or another regulatory body requests an 
audit. The site investigator and/or institution shall permit SINOMED and regulatory bodies direct access 
to source data and all other relevant documents.  
14.0 Device Accountability 
The Site Principal Investigator is responsible for device accountability at his/her trial site and must 
maintain associated trial records according to 21 CFR Part 812.140. The investigator may assign the 
responsibility for device accountability to an appropriate study staff member, but remains the final 
responsible person. 
The Principal Investigator or designed research staff must store all investigational product in a secure 
location and in compliance with Institutional Policies, and access to the investigational product must be 
monitored and limited to research staff. The investigator will maintain device use/disposition records that 
document device delivery to the trial site, the inventory at the site, administration to each patient as well 
as any device that was opened but not used. These records must include dates, quantities, batch/serial 
numbers, expiration dates, and the unique code numbers assigned to the trial patients. The investigator 
must maintain records that adequately document which device was used (or exposed to the circulation) 
of each subject and any device malfunctions. 
At the trial closeout visit, the Investigator must return to the Sponsor any unused devices and a copy of 
the completed device inventory. The Investigator’s copy of the device reconciliation records must 
document all device usage (including devices that were opened but not used) and any unused devices 
that have been returned to the Sponsor. 

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15.0 Ethical and Regulatory Considerations 
15.1 Applicable Regulations 
This trial will be conducted in compliance with this protocol, the Sponsor’s standard operating procedures 
and/or guidelines, FDA regulations, PMDA regulations, local regulations where applicable, ICH GCP 
guidelines, the Declaration of Helsinki, Annex X of the European Medical Devices Directive, and EN/ISO 
14155:2011. In the event of conflict between provisions of the cited regulations, the applicable regional 
or national law or regulation shall prevail.   
15.2 Institutional Review Board / Ethics Committee 
This trial will be conducted in accordance with 21 CFR 56 Institutional Review Boards. The investigator 
will assure that an appropriately constituted Institutional Review Board (IRB) or Ethics Committee (EC) 
complies with the requirements of the International Conference on Harmonization Guideline. Prior to 
initiation of the study, the investigator will forward copies of the protocol, Investigators Brochure, informed 
consent form and all other appendices to be used for the study to the IRB/EC for its review and approval. 
A copy of the written IRB/EC approval must be provided to the Sponsor (or designee) and should include 
the following: 
• 
A statement of IRB/EC approval for the proposed study at the institution; 
• 
The date the study was approved and the duration of approval (if applicable); 
• 
Identification of the approved documents including version dates and/or other references. At a 
minimum, the following documents should be listed: 
o Study protocol  
o Patient information and consent form 
o Any additional written information to be provided to the patient 
• 
A listing of any conditions attached to the approval (if applicable); 
• 
Identification of the approved primary investigator; 
• 
The signature of the IRB/EC chairperson; 
• 
Acknowledgement of the sub-Investigators. 
Any amendments to the protocol, as well as possible associated information and consent form changes, 
will be submitted to the IRB/EC and written approval obtained prior to implementation. Substantive 
changes will be submitted to the FDA (and other local regulatory authorities as applicable) for approval 
prior to implementation, and the FDA (and other local regulatory authorities as applicable) will be notified 
of any changes not requiring approval according to applicable guidelines. 
15.3 Insurance 
The Sponsor will maintain clinical trial insurance coverage for the duration of the study in accordance 
with applicable local laws and regulations. Details of insurance, indemnity, compensation, and 
reimbursement shall be addressed in a separate agreement approved by the interested parties.  
15.4 Regulatory Approval 
The Sponsor is responsible for notifying the study to the FDA and any other relevant authorities (as 
applicable) according to regulatory requirements. Investigators may not commence enrollment of 

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subjects until they have met any local IRB/EC and hospital management requirements and have received 
confirmation from the Sponsor that the appropriate regulatory approvals have been obtained. 
15.5 Trial Registration 
This trial meets the definition of an “applicable clinical trial” according to Section 801 of the Food and 
Drug Administration Amendments Act. The Sponsor affirms that it will serve as the Responsible Party 
and fulfill all requirements regarding trial registration, the provision of clinical trial information, and results 
reporting through the ClinicalTrials.gov registry data bank.  
Clinical trial information will be submitted no more than 21 days after the first subject is enrolled in the 
trial, and results information will be submitted no later than 1 year after completion of the trial or no later 
than 30 days after the device is approved, licensed, or cleared by the FDA.  
15.6 Records and Reports 
Sponsor and investigator will maintain records related to this study for 7 years (or longer according to 
local requirements) after the end of this study.  
Records maintained by the Sponsor will include: 
• 
All essential correspondence related to the clinical trial 
• 
Signed Investigator Agreement 
• 
Curriculum vitae for each Investigator 
• 
Records of device shipment and disposition (shipping receipts, material destruct records, etc.) 
• 
Adverse event information 
• 
Complaint documentation 
• 
All data forms prepared and signed by the Investigators and all received source documentation 
and core laboratory reports 
• 
Clinical Investigation Plan (CIP) and any amendments 
• 
Investigators Brochure / Report of Prior Investigations  
• 
Site monitoring reports 
• 
Financial disclosure information 
Records maintained by each Site Investigator (the investigator may delegate responsibility for record 
maintenance to a member of his/her study team, but remains the ultimate responsible person) will include: 
• 
All essential correspondence related to the clinical trial 
• 
Device use/disposition records 
• 
Records of each subject’s case history and exposure to the device. Case histories include the 
CRFs and supporting data (source documentation). 
• 
Signed Investigator Agreement 
• 
Curriculum vitae  
• 
Clinical Investigation Plan (CIP) and any amendments 

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The Sponsor and Site Investigators are each responsible for the preparation, review, and submission of 
all required reports in accordance with local laws and regulations, the requirements of the FDA and other 
regulatory authorities as applicable, and the requirements of local IRB/ECs.  
15.7 Protocol Amendments 
Any protocol amendments will be approved by the Sponsor, the Principal Investigators, the IRB/EC and 
any necessary regulatory body before it can be implemented. Substantive changes will be submitted to 
the FDA (and other regulatory authorities as applicable) for approval prior to implementation, and the 
FDA (and other regulatory authorities as applicable) will be notified of any changes not requiring approval 
in accordance with relevant guidelines. 
15.8 Informed Consent 
Informed consent will be obtained and documented as described in §6.4 prior to the performance of any 
study-specific procedures or assessments in accordance with 21 CFR Part 50, other applicable laws and 
regulations, and local IRB/EC requirements.  
15.9 Termination of the Study 
The Sponsor reserves the right to terminate the study but intends only to exercise this right for valid 
scientific or administrative reasons and reasons related to protection of patients. Possible reasons for 
early trial termination include: 
• 
Unanticipated Adverse Device Effects (UADEs) present an unreasonable risk to patients 
• 
Recommendation from the DSMC 
If the trial is terminated early, the Sponsor will provide a written statement to the Investigators to enable 
notification of the IRBs/ECs. The Sponsor will also inform the FDA (and the relevant Competent Authority 
and/or other regulatory authorities where required). In the case of early termination of trial enrollment, 
follow-up visits will continue for all enrolled subjects. 
The Sponsor may terminate an investigator’s or site’s participation in the study if there is evidence of an 
investigator’s failure to maintain adequate clinical standards or evidence of an investigator or staff’s 
failure to comply with the protocol. Should investigator or site participation be considered for termination, 
the Sponsor (or designee) will ensure appropriate follow-up for any subjects enrolled, including transferal 
to the supervision of an approved investigator and approval of transfer of subject oversight and follow-up 
by the appropriate IRB/EC. Notification of study site suspension or termination will occur no later than 
five (5) working days after the Sponsor makes the determination. A suspended or terminated study site 
may not be reinitiated without approval of the reviewing IRB/EC. The investigator should notify the IRB/EC 
in writing as soon as possible but no later than within 10 days if the premature termination is related to 
safety or compliance issues. The same procedure will be applied to the Competent Authority and other 
applicable regulatory authorities where required. 
15.10 Patient Privacy 
The Sponsor affirms and upholds the principle of patient confidentiality. Throughout this study, all data 
provided to SINOMED or its designee(s) will only be identified by a study-specific subject identification 
number. “Protected Health Information” will be maintained in compliance with the Health Insurance 
Portability and Accountability Act of 1996 (HIPAA) and applicable local regulations. 
The investigator agrees that representatives of SINOMED, its designee(s), and regulatory authorities 
may inspect included patients’ records to verify trial data, provide the data are treated as confidential and 
that the subject’s privacy is maintained. 

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16.0 References 
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2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 
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efficacy in drug-eluting stents with and without permanent polymer. JACC Cardiovasc Interv. 2009;2:291-9. 

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13. 
Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O and 
Kolodgie FD. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: 
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Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J, Davidson CJ, McKoy JM, 
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18. 
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W, Morice MC, Di Mario C, Corti R, Antoni D, Sohn HY, Eerdmans P, Rademaker-Havinga T, van Es GA, Meier 
B, Juni P and Windecker S. Improved safety and reduction in stent thrombosis associated with biodegradable 
polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with 
coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable 
Stent Coating) randomized, noninferiority trial. JACC Cardiovasc Interv. 2013;6:777-89. 
19. 
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durable polymer sirolimus-eluting stents: an update meta-analysis. Cardiology. 2015;130:96-105. 
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Kolodgie FD, Virmani R and Joner M. Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent 
Relative to Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex Vivo in a 
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21. 
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G, Mancone M, Genereux P and Stone GW. Clinical outcomes with bioabsorbable polymer- versus durable 
polymer-based drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. J Am 
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22. 
Xu B, Gao R, Yang Y, Cao X, Qin L, Li Y, Li Z, Li X, Lin H, Guo Y, Ma Y, Wang J, Nie S, Xu L, Cao E, 
Guan C and Stone GW. Biodegradable Polymer-Based Sirolimus-Eluting Stents With Differing Elution and 
Absorption Kinetics: The PANDA III Trial. J Am Coll Cardiol. 2016;67:2249-58. 
23. 
Qian J, Zhang YJ, Xu B, Yang YJ, Yan HB, Sun ZW, Zhao YL, Tang YD, Gao Z, Chen J, Cui JG, Mintz 
GS and Gao RL. Optical coherence tomography assessment of a PLGA-polymer with electro-grafting base layer 
versus a PLA-polymer sirolimus-eluting stent at three-month follow-up: the BuMA-OCT randomised trial. 
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24. 
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and Stone GW. 5-year results of a randomized comparison of XIENCE V everolimus-eluting and TAXUS 
Paclitaxel-eluting stents: final results from the SPIRIT III trial (clinical evaluation of the XIENCE V everolimus 
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Cardiovasc Interv. 2013;6:1263-6. 
25. 
Brener SJ, Kereiakes DJ, Simonton CA, Rizvi A, Newman W, Mastali K, Wang JC, Caputo R, Smith RS, 
Jr., Ying SW, Cutlip DE and Stone GW. Everolimus-eluting stents in patients undergoing percutaneous coronary 
intervention: final 3-year results of the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent 
System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions trial. Am Heart J. 
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26. 
Iqbal J, Serruys PW, Silber S, Kelbaek H, Richardt G, Morel MA, Negoita M, Buszman PE and Windecker 
S. Comparison of zotarolimus- and everolimus-eluting coronary stents: final 5-year report of the RESOLUTE all-
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27. 
Stone GW, Teirstein PS, Meredith IT, Farah B, Dubois CL, Feldman RL, Dens J, Hagiwara N, Allocco DJ 
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Serruys PW, Ruygrok P, Neuzner J, Piek JJ, Seth A, Schofer JJ, Richardt G, Wiemer M, Carrie D, 
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Kaiser C, Galatius S, Jeger R, Gilgen N, Skov Jensen J, Naber C, Alber H, Wanitschek M, Eberli F, Kurz 
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Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Lee JY, Kang SJ, Lee SW, Lee CW, Park SW, Choo SJ, 
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Kim U, Lee CH, Jo JH, Lee HW, Choi YJ, Son JW, Lee SH, Park JS, Shin DG, Kim YJ, Jeong MH, Cho 
MC, Bae JH, Lee JH, Kang TS, Jung KT, Jung KH, Lee SW, Cho JH, Kim W, Hur SH, Kim KS, Park HS, Kim MH, 
Hwang JY, Kim DI and Kim TI. A prospective, randomized comparison of promus everolimus-eluting and TAXUS 
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17.0 Appendices 
17.1 Appendix A: Definitions 
Adverse Device Effect 
(ADE) 
An adverse device effect is an adverse event related to the use of a 
medical device. This includes: 
• 
Any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any 
malfunction of the medical device 
• 
Any event that is a result of a use error or intentional misuse 
Anticipated Serious 
Adverse Device Effect 
(ASADE) 
An anticipated serious adverse device effect is a serious adverse 
device effect which by its nature, incidence, severity, or outcome has 
been identified in the investigational plan or application (including a 
supplementary plan or application).  
Bleeding 
Defined according to the following BARC definitions102 
Type 0: no bleeding 
Type 1: bleeding that is not actionable and does not cause the 
patient to seek unscheduled performance of studies, hospitalization, 
or treatment by a healthcare professional; may include episodes 
leading to self-discontinuation of medical therapy by the patient 
without consulting a healthcare professional 
Type 2: any overt, actionable sign of hemorrhage (e.g., more 
bleeding than would be expected for a clinical circumstance, 
including bleeding found by imaging alone) that does not fit the 
criteria for type 3, 4, or 5 but does meet at least one of the following 
criteria: (1) requiring nonsurgical, medical intervention by a 
healthcare professional, (2) leading to hospitalization or increased 
level of care, or (3) prompting evaluation 
Type 3 
Type 3a 
Over bleeding plus hemoglobin drop of 3 to <5 g/dL* 
(provided hemoglobin drop is related to bleed) 
Any transfusion with over bleeding 
Type 3b 
Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided 
hemoglobin drop is related to bleed) 
Cardiac tamponade 
Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid) 
Bleeding requiring intravenous vasoactive agents 
Type 3c 

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Intracranial hemorrhage (does not include microbleeds or 
hemorrhagic transformation, does include intraspinal) 
Subcategories confirmed by autopsy or imaging or lumbar 
puncture 
Intraocular bleed comprising vision 
Type 4: CABG-related bleeding 
Perioperative intracranial bleeding within 48 h 
Reoperation after closure of sternotomy for the purpose of 
controlling bleeding 
Transfusion of ≥5 U whole blood or packed red blood cells within 
a 48-h period (NOTE: cell saver products are not counted) 
Chest tube output ≥2L within a 24-h period 
Type 5: fatal bleeding 
Type 5a 
Probable fatal bleeding; no autopsy or imaging confirmation 
but clinically suspicious 
Type 5b 
Definite fatal bleeding; overt bleeding or autopsy or imaging 
confirmation 
NOTES:  
Platelet transfusions should be recorded and reported but are not 
included in these definitions until further information is obtained 
about the relationship to outcomes. If a CABG-related bleed is not 
adjudicated as at least a type 3 severity event, it will be classified as 
not a bleeding event. If a bleeding event occurs with a clear temporal 
relationship to CABG (i.e., within a 48-h time frame) but does not 
meet type 4 severity criteria, it will be classified as not a bleeding 
event.  
* Corrected for transfusion (1 U packed red blood cells or 1 U whole 
blood = 1 g/dL hemoglobin) 
Braunwald classification of 
unstable angina 
Class I: New onset of severe or accelerated angina. Patients with 
new onset (< 2 months in duration) exertional angina 
pectoris that is severe or frequent (> 3 episodes/day) or 
patients with chronic stable angina who develop 
accelerated angina (that is, angina distinctly more frequent, 
severe, longer in duration, or precipitated by distinctly less 
exertion than previously) but who have not experienced 
pain at rest during the preceding 2 months. 
Class II: Angina at rest, subacute. Patients with one or more 
episodes of angina at rest during the preceding month but 
not within the preceding 48 hours. 

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Class III: Angina at rest, acute. Patients with one or more episodes 
of angina at rest within the preceding 48 hours. 
Canadian Cardiovascular 
Society (CCS) classification 
of stable angina 
Class I: Ordinary physical activity, such as walking and climbing 
stairs, does not cause angina. Angina with strenuous, rapid, 
or prolonged exertion at work or recreation. 
Class II: Slight limitation of ordinary activity. Walking or climbing 
stairs rapidly, walking up hill, walking or stair climbing after 
meals, in cold, in wind, or when under emotional stress or 
during the first few hours after awakening may cause pain. 
Walking more than two blocks on the level and climbing 
more than one flight of stairs at a normal pace and in 
normal conditions. 
Class III: Marked limitation of ordinary physical activity. Walking 
one-two blocks on a level and climbing one flight of stairs at 
normal pace results in angina. 
Class IV: Inability to carry on any physical activity without 
discomfort. Anginal syndrome may be present at rest. 
Cardiac death 
See “death” 
Clinically-driven 
revascularization 
A revascularization is considered clinically driven if angiography at 
follow-up shows a percent diameter stenosis ≥ 70% (by core lab 
quantitative coronary angiography assessment) OR percent diameter 
stenosis ≥ 50% accompanied by one of the following:103 
(1) a positive history of recurrent angina pectoris, presumably 
related to the target vessel; 
(2) objective signs of ischemia at rest (ECG changes) or during 
exercise test (or equivalent) presumably related to the target 
vessel; 
(3) abnormal results of any invasive functional diagnostic test 
(e.g., Doppler flow velocity reserve, fractional flow reserve) 
Death 
Classified as cardiac, vascular, or noncardiovascular according to 
the following ARC definitions.69 All deaths are considered cardiac 
unless an unequivocal noncardiac cause can be established. 
Specifically, any unexpected death even in patients with coexisting 
potentially fatal noncardiac disease (e.g., cancer, infection) should 
be classified as cardiac. 
• 
Cardiac death: Any death due to proximate cardiac cause 
(e.g., MI, low-output failure, fatal arrhythmia), unwitnessed 
death and death of unknown cause, and all procedure-
related deaths, including those related to concomitant 
treatment, will be classified as cardiac death.  
• 
Vascular death: Death caused by noncoronary vascular 
causes, such as cerebrovascular disease, pulmonary 
embolism, ruptured aortic aneurysm, dissecting aneurysm, 
or other vascular diseases.  

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In instances of myocardial injury with necrosis where a condition other than CAD contributes to an imbalance 
between myocardial oxygen supply and/or demand, e.g. coronary endothelial dysfunction, coronary artery 
spasm, coronary embolism, tachy-/brady-arrhythmias, anemia, respiratory failure, hypotension, and 
hypertension with or without LVH. 
Type 3: Myocardial infarction resulting in death when biomarker values are unavailable 
Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes 
or new LBBB, but death occurring before blood samples could be obtained, before cardiac biomarker could 
rise, or in rare cases when cardiac biomarkers were not collected. 
Type 4a: Myocardial infarction related to percutaneous coronary intervention (PCI) 
Myocardial infarction associated with PCI is arbitrarily defined by elevation of cTn values >5 × 99th percentile 
URL in patients with normal baseline values (<99th percentile URL), or a rise of cTn values >20% if the 
baseline values are elevated and are stable or falling, within 48 hours of the procedure.* In addition, either (i) 
new ischemic ECG changes (e.g., ischemic ST changes or new pathological Q waves) or new LBBB, or (ii) 
angiographic loss of patency of a major coronary artery or a side branch or persistent slow- or no-flow or 
embolization, or (iii) imaging demonstration of new loss of viable myocardium or new regional wall motion 
abnormality are required. 
Type 4b: Myocardial infarction related to stent thrombosis 
Myocardial infarction associated with stent thrombosis is detected by coronary angiography or autopsy in the 
setting of myocardial ischemia and with a rise and/ or fall of cardiac biomarkers values with at least one 
value above the 99th percentile URL. 
Type 5: Myocardial infarction related to coronary artery bypass grafting (CABG) 
Myocardial infarction associated with CABG is arbitrarily defined by elevation of cardiac biomarker values >10 
× 99th percentile URL within 48 hours of the procedure in patients with normal baseline biomarker values 
(≤99th percentile URL).* In addition, either (i) new pathological Q waves or new LBBB, or (ii) angiographic 
documented new graft or new native coronary artery occlusion, or (iii) imaging evidence of new loss of viable 
myocardium or new regional wall motion abnormality are required. 
*If cTn is not available, CKMB (measured by mass assay) is an acceptable alternative. The CKMB threshold for 
the diagnosis of PCI-related MI is >5 × 99th percentile URL in patients with normal baseline values. 
CABG = coronary artery bypass grafting; CAD = coronary artery disease; CKMB = creatine kinase MB isoform; 
cTn = cardiac troponin; ECG = electrocardiogram; LBBB = left bundle branch block; LVH = left ventricular 
hypertrophy; MI = myocardial infarction; PCI = percutaneous coronary intervention; ST–T = ST-segment–T wave; 
URL = upper reference limit 
 
 
Per Protocol (PP) 
population  
Subjects who meet all inclusion criteria and no exclusion criteria, 
have provided written informed consent, and in whom an assigned 
study stent has been implanted 
Procedure success 
Lesion success (see definition above) without the occurrence of 
major adverse cardiac events (see definition above) during the index 
procedure hospital stay (maximum of 7 days). In the setting of 
multiple target lesions, all lesions must meet the lesion success 
criteria to have a patient-level procedure success. 
Serious Adverse Device 
Effect (SADE) 
A serious adverse device effect is an adverse device effect that has 
resulted in any of the consequences characteristic of a serious 
adverse event.  
Serious Adverse Event 
(SAE) 
A serious adverse event is an adverse event that: 
1. Led to a death 
2. Led to a serious deterioration in the health of the subject that: 

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a. Resulted in a life-threatening illness or injury 
b. Resulted in a permanent impairment of a body 
structure or a body function 
c. Required in-patient hospitalization or prolongation of 
existing hospitalization 
d. Resulted in medical or surgical intervention to prevent 
life-threatening 
illness 
or 
injury 
or 
permanent 
impairment to body structure or a body function 
Led to fetal distress, fetal death or a congenital abnormality or birth 
defect. 
Stent thrombosis 
Defined as definite, probable, or possible according to the following 
ARC definitions, and classified as early, late, or very late according 
to the timing criteria below:103 
• 
Definite stent thrombosis: Confirmed by angiographic or 
pathological evidence:  
o Angiographic confirmation of stent thrombosis: The 
presence of an intracoronary thrombus that originates 
in the stent or in the segment 5 mm proximal or distal 
to the stent and presence of at least 1 of the following 
criteria within a 48-hour time window: 
 
Acute onset of ischemic symptoms at rest 
 
New ischemic ECG changes that suggest 
acute ischemia 
 
Typical rise and fall in cardiac biomarkers 
(refer to definition of spontaneous MI) 
 
Nonocclusive thrombus. Intracoronary 
thrombus is defined as a (spheric, ovoid, or 
irregular) noncalcified filling defect or lucency 
surrounded by contrast material (on 3 sides or 
within a coronary stenosis) seen in multiple 
projects, or persistence of contrast material 
within the lumen, or a visible embolization of 
intraluminal material downstream.  
 
Occlusive thrombus: TIMI 0 or 1 instrastent or 
proximal to a stent up to the most adjacent 
proximal side branch or main branch (if 
originating from the side branch) 
NOTE: The incidental angiographic 
documentation of stent occlusion in the absence 
of clinical signs or symptoms is not considered a 
confirmed stent thrombosis (silent occlusion). 
o Pathologic confirmation of stent thrombosis: Evidence 
of recent thrombus within the stent determined at 

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autopsy or via examination of tissue retrieved 
following thrombectomy.  
• 
Probable stent thrombosis: Clinical definition of probably 
stent thrombosis is considered to have occurred after 
intracoronary stenting in the following cases: 
o Any unexplained death within the first 30 days  
o Irrespective of the time after the index procedure, any 
MI that is related to documented acute ischemia in 
the territory of the implanted stent without 
angiographic confirmation of stent thrombosis and in 
the absence of any other obvious cause 
• 
Possible stent thrombosis: Clinical definition of possible stent 
thrombosis is considered to have occurred with any 
unexplained death from 30 days after intracoronary stenting 
until end of trial follow-up 
Stent thrombosis timing: 
• 
Early stent thrombosis: 0 to 30 days after stent implantation 
• 
Late stent thrombosis: >30 days to 1 year after stent 
implantation. 
• 
Very late stent thrombosis: >1 year after stent implantation. 
NOTE: Late and very late stent thrombosis include primary as 
well as secondary late stent thrombosis; secondary late stent 
thrombosis is a stent thrombosis after a target lesion 
revascularization.  
Target lesion failure (TLF) 
The composite of cardiac death, target vessel-related myocardial 
infarction, and clinically-driven target lesion revascularization 
Target lesion 
revascularization (TLR) 
Any repeat percutaneous intervention of the target lesion or bypass 
surgery of the target vessel performed for restenosis or other 
complication of the target lesion. The target lesion is defined as the 
treated segment from 5 mm proximal to the stent and to 5 mm distal 
to the stent. 
A revascularization is considered clinically driven if angiography at 
follow-up shows a percent diameter stenosis ≥ 70% (by core lab 
quantitative coronary angiography assessment) OR percent diameter 
stenosis ≥ 50% (by core lab quantitative coronary angiography 
assessment) accompanied by one of the following:103 
(1) a positive history of recurrent angina pectoris, presumably 
related to the target vessel; 
(2) objective signs of ischemia at rest (ECG changes) or during 
exercise test (or equivalent) presumably related to the target 
vessel; 
(3) abnormal results of any invasive functional diagnostic test 
(e.g., Doppler flow velocity reserve, fractional flow reserve). 

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All TLR should be prospectively classified as clinically-driven or non-
clinically-driven by the investigator prior to angiography. Where 
independent core laboratory quantitative coronary angiography (QCA) 
and the investigator assessment differ with respect to whether percent 
diameter stenosis requirements are met, the QCA judgment shall 
prevail. 
Target vessel-related 
myocardial infarction (TV-
MI) 
Any myocardial infarction (see definition) not clearly attributable to a 
non-target vessel 
Target vessel failure (TVF) 
The composite of cardiac death, target vessel-related myocardial 
infarction, and clinically-driven target vessel revascularization 
Target vessel 
revascularization (TVR) 
Any repeat percutaneous intervention or surgical bypass of any 
segment of the target vessel. The target vessel is defined as the entire 
major coronary vessel proximal and distal to the target lesion, which 
includes upstream and downstream branches and the target lesion 
itself.   
A revascularization is considered clinically driven if angiography at 
follow-up shows a percent diameter stenosis ≥ 70% (by core lab 
quantitative coronary angiography assessment) OR percent diameter 
stenosis ≥ 50% (by core lab quantitative coronary angiography 
assessment) accompanied by one of the following:103 
(1) a positive history of recurrent angina pectoris, presumably 
related to the target vessel; 
(2) objective signs of ischemia at rest (ECG changes) or during 
exercise test (or equivalent) presumably related to the target 
vessel; 
(3) abnormal results of any invasive functional diagnostic test 
(e.g., Doppler flow velocity reserve, fractional flow reserve). 
Where 
independent 
core 
laboratory 
quantitative 
coronary 
angiography (QCA) and the investigator assessment differ with 
respect to whether percent diameter stenosis requirements are met, 
the QCA judgment shall prevail. 
Total Occlusion 
An occlusion with no antegrade filling of contrast to the distal segment 
(TIMI grade 0) 
Unanticipated Adverse 
Device Effect (UADE) 
An unanticipated adverse device effect is any serious adverse effect 
on the 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 investigational plan or application (including a supplementary plan 
or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety or welfare of subjects. 
NOTE: An anticipated serious adverse device effect (ASADE) is a 
serious adverse device effect which by its nature, incidence, severity, 
or outcome has been identified in the investigational plan or 
application (including a supplementary plan or application).   

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Use Error 
Act or omission of an act that results in a different medical device 
response than intended by the manufacturer or expected by the user.  
NOTE 1: Use error includes slips, lapses and mistakes. 
NOTE 2: An unexpected physiological response of the patient does 
not itself constitute a use error. 
 
 
 
 

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17.2 Appendix B: Acronyms 
AE  
adverse event 
ACS 
acute coronary syndromes 
ADE  
adverse device effect 
ADP 
adenosine diphosphate 
AMI 
acute myocardial infarction 
ARC 
Academic Research Consortium 
ASA  
acetylsalicylic acid 
ASADE 
anticipated serious adverse device effect 
BARC 
Bleeding Academic Research Consortium 
BuMA DES 
BuMA Supreme biodegradable drug coated coronary stent system 
CABG 
coronary artery bypass graft surgery 
CAD 
coronary artery disease 
CCS 
Canadian Cardiovascular Society (grading scale of angina pectoris) 
CEC 
clinical events committee 
CI 
confidence interval 
CIP 
clinical investigation plan 
CK  
creatine kinase 
CKMB 
creatine kinase MB isoform 
CRF  
case report form 
cTn 
cardiac troponin 
DAPT  
dual antiplatelet therapy 
DES 
drug eluting stent 
DICOM  
Digital Imaging and Communications in Medicine 
DP EES 
durable polymer everolimus-eluting stents 
DSMC 
data safety monitoring committee 

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EC  
ethics committee 
ECG  
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture (system) 
eGFR 
estimated glomerular filtration rate 
F 
French (catheter scale system) 
FDA 
U.S. Food and Drug Administration 
FFR 
fractional flow reserve 
GCP  
good clinical practices 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IRB  
institutional review board 
ISO 
International Organization for Standardization 
ITT  
intention to treat 
IV  
intravenous 
LAD 
left anterior descending coronary artery 
LAO 
left anterior oblique 
LBBB 
left bundle branch block 
LCx 
left circumflex coronary artery 
LVEF 
left ventricular ejection fraction 
MACE 
major adverse cardiac events 
MI  
myocardial infarction 
NSTEMI 
non-ST-segment elevation myocardial infarction 
PCI  
percutaneous coronary intervention 
PBMA 
poly n-butyl methacrylate 

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PLGA 
poly lactic co-glycolic acid 
PMDA 
Pharmaceuticals and Medical Devices Agency (Japan) 
PP  
per protocol 
QCA 
quantitative coronary angiography 
RAO 
right anterior oblique 
RCA 
right coronary artery 
RCT 
randomized controlled trial 
SADE  
serious adverse device effect 
SAE  
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
STEMI 
ST-segment elevation myocardial infarction 
TBD 
to be determined 
TIMI 
Thrombolysis in Myocardial Infarction (flow grade) 
TLF 
target lesion failure 
TLR 
target lesion revascularization 
TV-MI 
target vessel-related myocardial infarction 
TVF 
target vessel failure 
TVR 
target vessel revascularization 
UA 
unstable angina 
UADE  
unanticipated adverse device effect 
URL  
upper reference limit 
US 
United States 
XIENCE EES 
Xience family of durable polymer cobalt chromium everolimus-eluting 
coronary stent systems 
 
 
 

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17.3 Appendix C: Angiographic Imaging Acquisition Guidelines 

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