A 2:1 Randomized Trial Comparing the Agent Paclitaxel-Coated PTCA Balloon Catheter vs SeQuent Please Drug Eluting Balloon Catheter for the Treatment of a Small Vessel De Novo Native Coronary Artery Lesion.
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Boston Scientific Corporation

 
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AGENT Japan SV Clinical Trial 
A 2:1 Randomized Trial Comparing the Agent™ Paclitaxel-Coated PTCA Balloon Catheter 
(BSJ016A) vs SeQuent® Please Drug Eluting Balloon Catheter for the Treatment of a Small 
Vessel De Novo Native Coronary Artery Lesion. 
 
 
 
 
CLINICAL INVESTIGATION PLAN 
 
S2313 
 
 
 
 
 
Sponsored By 
Boston Scientific Japan K.K. 
4-10-2, Nakano Nakano-ku 
Tokyo 164-0001, Japan 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their designated 
representatives participating in this clinical investigation. The protocol should be held confidential 
and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
NCT04058990, Date of document: SEP-30-2020 

 
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Contact Information 
Role 
Contact 
Clinical Contact 
 
Sachiyo Sato 
Boston Scientific Japan K.K. 
Clinical Project Manager 
4-10-2 Nakano, Nakano-ku 
Tokyo 164-0001 Japan 
Coordinating Principal 
Investigator  
Masato Nakamura, MD, PhD 
Professor, Division of Cardiovascular Medicine 
Toho University Ohashi Medical Center 
2-22-36, Ohashi Meguro-ku 
Tokyo 153-8515, Japan 
Investigational Centers 
A list of investigational sites is maintained and provided as a separate 
attachment to the protocol. 
Vendors/Labs 
A list of vendors/laboratories is maintained in the manual of operations.  

 
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Original Release: MAY 27, 2019 
Current Version: SEP 30, 2020 
 
Revision 
Version 
Protocol 
Date 
Template 
number and 
version  
Protocol Section Modified  
Summary of Changes  
Justification for 
Modification  
A 
2019/05/27 
90702637 
Rev Ver AL 
N/A 
Initial release  
N/A 
B 
2019/06/19 
90702637 
Rev Ver AL 
・ 
2. Protocol Synopsis: Clinical Inclusion Criteria 
・ 
5.8. Control Device 
・ 
7.1. Scale and Duration: Figure 7.1 1: AGENT Japan SV Study 
Design 
・ 
8.2. Inclusion Criteria: Table 8.2 1: Inclusion Criteria 
・ 
9.1. Point of Enrollment 
・ 
10.3. Informed Consent 
・ 
10.7.5. Treatment of Target Lesion 
・ 
19. Informed Consent 
Refer to the table of change summary 
Revisions to address 
PMDA comments on 
Clinical Trial 
Notification 
・ 
24.2. Definitions; THROMBOSIS 
Description maintenance 
C 
2020/04/24 
90702637 
Rev Ver AL 
・ 
2. Protocol Synopsis: Clinical Inclusion Criteria 
・ 
4. Introduction 
・ 
5. Device Description 
・ 
6. Trial Objectives and Endpoints 
・ 
7. Study Design 
・ 
8. Subject Selection 
・ 
9. Subject Accountability 
・ 
10. Trial Methods 
・ 
11. Statistical Considerations 
・ 
24. Abbreviations and Definitions 
Refer to the table of change summary 
Revisions to add ISR 
substudy and description 
maintenance 
D 
2020/09/30 
90702637 
Rev Ver AN 
・ 
2. Protocol Synopsis: Clinical Inclusion Criteria 
・ 
5.8. Control Device 
Refer to the table of change summary 
Revisions to add 
SeQuent® Please Neo 
Drug Eluting Balloon 
Catheter 
 

 
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2. Protocol Synopsis 
AGENT Japan SV: A 2:1 Randomized Trial Comparing the Agent™ Paclitaxel-Coated 
PTCA Balloon Catheter vs SeQuent® Please Drug Eluting Balloon Catheter for the 
Treatment of a Small Vessel De Novo Native Coronary Artery Lesion.  
Study Objective(s) 
Primary objective is to evaluate the safety and effectiveness of the Agent ™ 
Paclitaxel-Coated PTCA Balloon Catheter for the treatment of Japanese subjects 
with a small vessel de novo native atherosclerotic coronary artery lesion or in-stent 
restenosis (ISR) of a previously treated lesion.  
Planned 
Indication(s) for 
Use 
The Agent™ Paclitaxel-Coated PTCA Balloon Catheter is intended to prevent 
restenosis in subjects with in-stent restenosis (ISR) of a previously treated lesion. If 
reference vessel diameter is less than 3.0 mm, Agent™ Paclitaxel-Coated PTCA 
Balloon Catheter is intended to prevent restenosis in subjects with a small vessel de 
novo native coronary artery lesion as well.  
Study Design 
The AGENT Japan SV trial is composed of the following trials: 
- 
Trial for small vessel de novo native lesion (called “SV trial” hereinafter): This 
is a prospective, multicenter, 2:1 randomized (Agent DCB to SeQuent Please 
DCB), controlled, single-blind, non-inferiority trial.  
- 
Sub-study for ISR (called “ISR substudy” hereinafter): This is a prospective, 
multicenter, single-arm, open-label trial. 
Test Device  
Agent™ Paclitaxel-Coated PTCA Balloon Catheter 
Control Device  
Commercially available SeQuent® Please Drug Eluting Balloon Catheter 
Device Sizes 
The investigational test device and control device matrices consist of the following 
sizes (balloon diameter and balloon length) for SV trial:  
Agent™ Paclitaxel-Coated PTCA Balloon Catheter 
2.00 mm x 12, 15, 20, 30 mm 
2.25 mm x 12, 15, 20, 30 mm 
2.50 mm x 12, 15, 20, 30 mm 
2.75 mm x 12, 15, 20, 30 mm 
3.00 mm x 12, 15, 20, 30 mm 
SeQuent® Please Drug Eluting Balloon Catheter 
Commercially available balloons will be used.  
2.00 mm x 15, 17, 20 mm 
2.50 mm x 10, 15, 17, 20, 26, 30 mm 
2.75 mm x 15, 17, 20, 26 mm 
3.00 mm x 10, 15, 17, 20, 26, 30 mm 
Note : A center may use the SeQuent® Please Neo Drug Eluting Balloon Catheter 
if it is approved and commercially available. 
 
The investigational test device matrices consist of the following sizes (balloon 
diameter and balloon length) for ISR substudy:  
Agent™ Paclitaxel-Coated PTCA Balloon Catheter 
2.00 mm x 12, 15, 20, 30 mm 
2.25 mm x 12, 15, 20, 30 mm 
2.50 mm x 12, 15, 20, 30 mm 
2.75 mm x 12, 15, 20, 30 mm 

 
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3.00 mm x 12, 15, 20, 30 mm 
3.50 mm x 12, 15, 20, 30 mm 
4.00 mm x 12, 15, 20, 30 mm 
Blinding  
The SV trial is conducted as single blind. Subjects will be blinded to treatment 
assigned and treatment received. All subjects must remain blinded until completion 
of 6-month follow-up visits (primary endpoint). 
Packaging of the test Agent DCB and control SeQuent Please DCB devices differ. 
Therefore, the investigator and staff performing the procedure will not be blinded to 
the assigned treatment arm or resulting treatment. The investigator and staffwill be 
trained not to disclose the treatment assignment to the subject in order to minimize 
the potential unblinding of the subjects. 
Core Laboratory personnel and the Clinical Events Committee (CEC) will be 
blinded to a subject’s treatment assignment during the trial. The Biostatistician will 
remain blinded until the primary endpoint analysis.  
The ISR substudy is an open trial and blinding is not applicable. 
Planned Number of 
Subjects  
The following number of subjects are expected to be enrolled: 
- 
SV trial: 150 subjects are expected to be enrolled to support a 2:1 randomization. 
(Investigational test device: Agent DCB, N=100 subjects or Control device: 
SeQuent Please DCB, N=50 subjects)  
- 
ISR substudy: 30 subjects are expected to be enrolled. (Investigational test 
device: Agent DCB) 
Planned Number of 
Investigational 
Sites/ Countries 
The trial is to be conducted in Japan at up to 15 investigational centers.  
Primary Endpoint  
Primary endpoint: Target Lesion Failure (TLF) rate at 6 months post index-
procedure. TLF is defined as any ischemia driven revascularization of the target 
lesion (TLR), myocardial infarction (MI, Q-wave and non–Q-wave) related to the 
target vessel, or cardiac death.  
Additional 
Endpoint  
Clinical endpoints measured at hospital discharge, 30 days, 6 months, 12 months, 
24 months, 36 months, 48 months and 60 months. 
 
Target lesion revascularization (TLR) rate  
 
TLF rate  
 
Target vessel revascularization (TVR) rate  
 
Target vessel failure (TVF) rate  
 
MI (Q-wave and non–Q-wave) rate  
 
Cardiac death rate 
 
Non-cardiac death rate 
 
All death rate  
 
Cardiac death or MI rate  
 
All death or MI rate  
 
All death/MI/TVR rate  
 
Thrombosis related to target lesion rate  
 
Change in Quality of Life: Functional status of general health-related quality of life 
measured by changes in EQ-5D scores at hospital discharge, 6 months, 12 months, 
24 months and 36 months.  
 

 
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Angiographic endpoints at 6 months post-index procedure measured by angiography 
(In lesion/In stent and In segment):  
 
Percent diameter stenosis (%DS)  
 
Late lumen loss 
 
Binary restenosis rate  
 
Minimum lumen diameter (MLD)  
 
Periprocedural endpoints:  
 
Technical success rate  
 
Clinical procedural success rate  
 
Technical success rate: Technical success is the ability to cross and dilate the lesion 
to achieve residual angiographic stenosis no greater than 30% as determined by the 
investigator. The result will be generally confirmed by an angiographic core lab.  
Clinical procedural success rate: Technical success with no death or MI noted within 
24 hours of the index procedure.  
Study Allocation 
If the subject meets clinical inclusion criteria and none of the clinical exclusion 
criteria of both the SV trial and ISR substudy, either an SV lesion or an ISR lesion 
will be enrolled at the investigator’s discretion.  
Please refer to the “Multiple Interventions During Index Procedure”, “Treatment of 
Non-Target Lesions During the Index Procedure” and “Acceptable PCI Devices for 
Non-target Lesion” when the other lesion is treates as a non-target lesion. 
Method of 
Assigning Subjects 
to Treatment (SV 
trial) 
If after consenting, meeting clinical inclusion criteria and none of the clinical 
exclusion criteria and confirmed angiographically significant lesion in a small vessel 
de novo native coronary artery and successful protocol-defined pre-dilation, subjects 
are randomized 2:1 to either an Agent DCB (test) or a SeQuent Please DCB 
(control). 
Subjects will be considered enrolled in the trial after they have been successfully 
randomized (i.e. when a treatment assignment is received by the investigative 
site).  
Note: If the subject is found to meet inclusion and exclusion criteria, the subject will 
be considered a screen failure and not be randomized/enrolled or receive an 
investigational device, nor should the subject be followed postprocedure per 
protocol.  
Method of 
Assigning Subjects 
to Treatment (ISR 
substudy) 
If after consenting, meeting clinical inclusion criteria and none of the clinical 
exclusion criteria and confirmed angiographically significant lesion in an ISR 
coronary artery and successful protocol-defined pre-dilation, subjects will be 
considered enrolled in the ISR substudy. 
Note: If the subject is found to meet inclusion and exclusion criteria, the subject will 
be considered a screen failure and not be enrolled or receive an investigational 
device, nor should the subject be followed postprocedure per protocol.  
Definition of 
successful 
predilation 
Successful predilation occurs when the selected balloon opens vessel entry at 
nominal pressure without major (≥ NHLBI Type D) flow-limiting dissection or need 
for intervention (i.e. stenting), and residual angiographic stenosis no greater than 
30% （visual estimate) as determined by the investigator.  
Follow-up 
Schedule 
Clinical Follow-up visit Schedule: 
 
Clinical follow-up will be required at the following time points: Hospital 
discharge, 30 days, 6 months, 12 months, 24 months, 36 months, 48 months 
and 60 months after the index procedure. 

 
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 
Follow-up office visits will be required at 6 months, 12 months, 24 months and 
36 months after the index procedure. 
 
30 days, 48 months and 60 months follow-up may be performed via telephone 
interview with the subject if the subject is unable to return for an office visit 
within the applicable follow-up window. 
 
Subjects who are enrolled but who do not receive treatment with an 
investigational device will be followed through 30 days only to assess their 
safety. 
Endpoint Assessment: 
 
Assessment of the primary endpoint will occur during the 6-month follow-up 
visit.  
Planned protocol-required invasive testing: 
 
Angiography during the index procedure to assess technical success and 
clinical procedural success. 
 
Follow-up angiography at the 6-months follow-up visit to assess lesion and 
vessel patency. 
 
Subjects requiring reintervention for the target vessel during the 60-month 
follow-up period will undergo angiographic assessment at the time of 
reintervention as standard of care. Angiographic data and images collected 
during the index procedure and through the 60-month follow-up period must 
be forwarded to the Angiographic Core Laboratory for analysis. 
Study Duration  
 
The trial will be considered complete (with regard to the primary endpoint) 
after all enrolled subjects have completed the 6-month follow-up visit, are 
discontinued prior to 6-month follow-up visit, have died, or the last 6-month 
follow-up visit window is closed.  
 
The trial will be considered complete (with regard to all follow-up) after all 
enrolled subjects have completed the 60 months follow-up visit, are 
discontinued prior to 60 months follow-up visit, have died, or the last 60-month 
follow-up visit window is closed. 
 
It is expected to take approximately 12 months to enroll approximately 180 
subjects and 60 months of follow-up is planned. 
 
It is estimated that it will take approximately 6 years to complete this trial.  
Definitions of 
Target Lesion and 
Non-Target Lesion 
(SV Trial) 
Target Lesion 
A target lesion is one that meets the angiographic selection criteria and is to be 
treated with an investigational device during the index procedure. An investigational 
device may be used to treat one de novo lesion.  
If a subject has 2 or more lesions that meet the selection criteria, the target lesion is 
the more severe lesion based on visual estimate of percent diameter stenosis. The 
other lesion can be treated through planned staged PCI procedure before the index 
procedure or as a non-target lesion in the index procedure. 
 
Non-Target Lesion 
A non-target lesion is a lesion treated within a non-target vessel or target vessel 
during the index procedure for which treatment with an investigational device is not 
attempted. If a non-target lesion is located in the target vessel, it should be apart 
more than 15 mm from the target lesion. 
 
Note: Multiple focal stenosis will be considered as a single lesion if they can be 
completely covered with 1 device for PCI. 
Definitions of 
Target Lesion and 
Target Lesion 

 
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Non-Target Lesion 
(ISR substudy) 
A target lesion is one that meets the angiographic selection criteria and is to be 
treated with an investigational device during the index procedure. An investigational 
device may be used to treat one ISR lesion.  
If a subject has 2 or more lesions that meet the selection criteria of ISR, the target 
lesion is the more severe lesion based on visual estimate of percent diameter 
stenosis. The other lesion can be treated through planned staged PCI procedure 
before the index procedure or as a non-target lesion in the index procedure. 
 
Non-Target Lesion 
A non-target lesion is a lesion treated within a non-target vessel during the index 
procedure for which treatment with an investigational device is not attempted. (The 
treatment of the non-target lesion in the target vessel is not allowed for the ISR 
substudy.) 
 
Note: Multiple focal stenosis will be considered as a single lesion if they can be 
completely covered with 1 device for PCI. 
Participant 
Duration 
Subject participation will be 60 months after the index procedure.  
Clinical Inclusion 
Criteria  
CI1. Subject must be at least 20 years of age.  
CI2. Subject understands the trial requirements and the treatment procedures and 
provides written informed consent before any study-specific tests or 
procedures are performed. 
CI3. Subject is eligible for percutaneous coronary intervention (PCI).  
CI4. Subject has documented stable angina pectoris or unstable angina pectoris. If 
subject has documented stable angina pectoris, one of the following criteria 
meet. 
⁃ ≥90% diameter stenosis. 
⁃ Stenosis that is considered a cause of stable effort angina (Only when it's 
without confirmation of significant stenosis).  
⁃ Stenosis that is confirmed a cause of functional ischemia with any test. 
CI5. Subject is an acceptable candidate for coronary artery bypass grafting 
(CABG). 
CI6. Subject is willing to comply with all protocol-required follow-up evaluation. 
CI7. Patients undergoing first or second treatment for ISR lesions for the non-
randomized ISR substudy.  
Angiographic 
Inclusion Criteria 
(visual estimate)  
AI1. The target lesion meets all following criteria. 
⁃ Target lesion length must measure (by visual estimate) ≤28 mm.  
⁃ Target lesion must be a visually estimated reference vessel diameter 
(RVD) ≥2.00mm and <3.00 mm (This applys for SV trial. For ISR 
substudy: RVD ≥2.00mm and ≤4.00 mm.). 
⁃ Target lesion must be a de novo lesion located in a native coronary 
artery with visually estimated stenosis ≥75% and <100% (This applys 
for SV trial. For ISR substudy: Target lesion for ISR must be in-stent 
restenosis of a previously-treated lesion located in a native coronary 
artery with visually estimated stenosis ≥75% and <100%.).  
⁃ Coronary anatomy is likely to allow delivery of an investigational device 
to the lesions. 
⁃ Target lesion must be successfully pre-dilated. 
AI2. Planned treatment of 2 coronary artery lesions in 2 vessels may be treated 
(For SV trial, up to two lesions per vessel can be treated. For ISR substudy, 
single lesion per vessel can be treated.).  

 
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Clinical Exclusion 
Criteria 
CE1. Subject has had an acute myocardial infarction within 72 hours prior to the 
index procedure.  
CE2. Subject has cardiogenic shock, hemodynamic instability requiring inotropic 
or mechanical circulatory support, intractable ventricular arrhythmia, or 
ongoing intractable angina. 
CE3. Subject has severe left ventricular dysfunction with ejection fraction <30%. 
CE4. Subject has received an organ transplant or is on a waiting list for an organ 
transplant.  
CE5. Subject is receiving or scheduled to receive chemotherapy within 30 days 
before or after the index procedure.  
CE6. Subject has renal failure with a serum creatinine of > 2.0mg/dL or who is 
receiving dialysis or chronic immunosuppressant therapy.  
CE7. Subjects has one of the following.  
⁃ Not expected to live for the duration of the study (1 year) by 
investigator’s discretion due to other serious medical illness (e.g. cancer, 
congestive heart failure).  
⁃ Current problems with substance abuse (e.g., alcohol, cocaine, heroin, 
etc.). 
⁃ Planned procedure that may cause non-compliance with the protocol or 
confound data interpretation.  
CE8. Planned PCI (including staged procedures) or CABG after the index 
procedure.  
CE9. Subject previously treated at any time with intravascular brachytherapy.  
CE10. Subject has a known allergy to contrast (that cannot be adequately 
premedicated) and/or the investigational device or protocol-required 
concomitant medications (e.g., paclitaxel, acetyl tributyl citrate (ATBC), 
iopromide, raw materials of Agent DCB and SeQuent Please DCB, P2Y12 
inhibitor or aspirin).  
CE11. Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3.  
CE12. Subject has a white blood cell (WBC) count < 3,000 cells/mm3.  
CE13. Subject has documented or suspected liver disease, including laboratory 
evidence of hepatitis. 
CE14. Subject has a history of bleeding diathesis or coagulopathy or will refuse 
blood transfusions.  
CE15. Subject has had a history of cerebrovascular accident (CVA) or transient 
ischemic attack (TIA) within the past 6 months. 
CE16. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding. 
CE17. Target vessel has been treated with Paclitaxel Eluting Stent or Balloon prior 
to the index procedure.  
CE18. Target vessel has been treated with any type of PCI (e.g. DES, BMS or 
PTCA) within 6 months prior to the index procedure. 
CE19. Target vessel requires the use of adjunctive primary treatment modalities (e.g. 
laser, atherectomy, other debulking devices, etc.) immediately prior to 
investigational device’s treatment. 
CE20. Non-target vessel has been treated with any type of PCI within 24 hours prior 
to the index procedure. 
CE21. Subject is participating in another investigational drug or device clinical trial 
that has not reached its primary endpoint.  
CE22. Subject intends to participate in another investigational drug or device clinical 
trial within 6 months after the index procedure.  

 
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CE23. Subject with known intention to procreate within 6 months after the index 
procedure (women of child-bearing potential who are sexually active must 
agree to use a reliable method of contraception from the time of screening 
through 6 months after the index procedure).  
CE24. Subject is a woman who is pregnant or nursing (a pregnancy test must be 
performed within 7 days prior to the index procedure in women of child-
bearing potential).  
Angiographic 
Exclusion Criteria 
(visual estimate)  
AE1. Target lesion meets any of the following criteria:  
⁃ Left main location. 
⁃ Located within 5 mm of the origin of the left anterior descending (LAD) 
coronary artery or left circumflex (LCX) coronary artery by visual 
estimate.  
⁃ > 50% stenosis of an additional lesion proximal or distal to the target 
lesion (by visual estimate). 
⁃ Located within a saphenous vein graft or an arterial graft. 
⁃ Will be accessed via a saphenous vein graft or an arterial graft.  
⁃ Involves a complex bifurcation (e.g., bifurcations requiring treatment 
with more than 1 stent).  
⁃ TIMI flow 0 (total occlusion) prior to wire crossing.  
⁃ Excessive tortuosity proximal to or within the lesion.  
⁃ Extreme angulation proximal to or within the lesion.  
⁃ Target lesion and/or target vessel proximal to the lesion is severely 
calcified by visual estimate to expect sub-optimal balloon expansion.  
⁃ Target lesion and/or target vessel adjacent to the target lesion presents 
with dissection or aneurysm by visual estimate.  
⁃ Restenosis from previous intervention (This is applicable only to SV 
trial.).  
⁃ PCI within 10 mm proximal or distal to the target lesion (by visual 
estimate) at any time prior to the index procedure （This is applicable 
only to SV trial.）. 
⁃ Planned treatment of a single lesion with more than 1 investigational 
device. 
⁃ In-stent restenosis due to stent fracture or recoil (This is applicable only 
to ISR substudy.). 
AE2.  Non-target lesion to be treated during the index procedure meets any of the 
following criteria:  
⁃ Located in the target vessel (This is applicable only to ISR substudy.).  
⁃ Located within a bypass graft (venous or arterial). 
⁃ Left main location.  
⁃ Chronic total occlusion.  
⁃ Involves a complex bifurcation (e.g., bifurcations requiring treatment 
with more than 1 stent).  
⁃ Located within 15 mm of the proximal or distal shoulder of the target 
lesion by visual estimate in the case of the same vessel with a target 
lesion for SV trial. 
AE3. Subject has unprotected left main coronary artery disease (>50% diameter 
stenosis).  
AE4. Thrombus, or possible thrombus, present in the target vessel.  
AE5. Subject with known coronary artery spasm.  
Adjunctive 
Pharmacologic 
Therapy  
Anticoagulant Therapy 

 
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Anticoagulant therapy (e.g., unfractionated heparin) per local standard of care must 
be administered during the implant procedure, with a recommended target activated 
clotting time of ≥250 seconds during the index procedure.  
 
Anti-Platelet Therapy 
Antiplatelet therapy with aspirin and P2Y12 inhibitor (e.g., clopidogrel, ticlopidine 
prasugrel or ticagrelor) is required to decrease the risk of thrombotic or 
thromboembolic complications.  
Aspirin 
 
For subjects who have not been taking Aspirin at the time of the index 
procedure, the loading dose is required to be administered not more than 2 
hours after the index procedure. 
 
After treatment by investigational device, it is recommended that Aspirin be 
given for at least 3 months in all subjects.  
P2Y12 inhibitor 
 
For subjects who have not been taking P2Y12 inhibitor at the time of the index 
procedure, the loading dose is required to be administered not more than 2 
hours after the index procedure. 
 
After treatment by investigational device, it is recommended that P2Y12 
inhibitor be given for at least 3 months in all subjects. 
Note: Anti-platelet therapy dosing should be according to the local standard care.  
Multiple 
Interventions 
During Index 
Procedure  
During the index procedure, a maximum of 1 target lesion and 1 non-target lesion 
(within target vessel or non-target vessel) may be treated (Treatment in target vessel 
is permitted in SV trial.).  
 
If a non-target lesion is treated, it must be treated before the target lesion is 
treated.  
 
At the time of the index procedure, there must be no revascularizations planned 
for the target or non-target vessels after the index procedure. 
 
In the case of the SV trial, if non-target lesion is located distal to the target 
lesion in the same vessel and in the case that a target lesion needs pre-dilation 
prior to the treatment of non-target lesion to cross a device for the treatment of 
non-target lesion according to investigators decision, protocol-defined pre-
dilation for the target lesion could be done before the treatment of non-target 
lesion. After completing treatment of non-target lesion, remaining treatment for 
target lesion can be performed. After confirming completion of treatment of 
non-target lesion, subjects will be considered enrolled in the trial after they have 
been successfully randomized. 
Treatment of Non-
Target Lesions 
During the Index 
Procedure 
A maximum of 1 non-target lesion within the target vessel or the non-target vessel 
may be treated with a commercial device for non-DCB PCI treatment2) during the 
index procedure as described above under Multiple Interventions During Index 
Procedure. For the subject to be eligible for enrollment into the study, treatment of 
the non-target lesion must:  
 
Not require additional unplanned treatment.  
 
Must be successfully treated (<50% residual stenosis) prior to treatment of the 
target lesion. 
 
Have been completed prior to treatment of the target lesion1).  
 
In the case of the SV trial, when non-target lesion is located distal to the target 
lesion in the same vessel and in the case that target lesion need pre-dilation 
prior to the treatment of non-target lesion to cross the device for non-target 
lesion according to investigators decision, protocol-defined pre-dilation for the 
target lesion could be done before the treatment of non-target lesion. 

 
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Note1: Multiple focal stenosis will be considered as a single lesion if they can be 
completely covered with 1 commercial device for PCI.  
Note2: Inclusion or exclusion criteria do not apply to treatment of non-target lesions 
during the index procedure. See this column and “Acceptable PCI Devices for 
Nontargeted Lesions” for treatment of nontargeted lesions during the study 
procedure. 
Acceptable PCI 
Devices for Non-
target Lesion 
SV trial (treatment of non-target lesion in target vessel or non-target vessel is 
acceptable): 
- 
Non-target lesion in Target vessel: Commercially available DES or DCB 
coated with drug other than paclitaxcel, BMS, or balloon (POBA) 
- 
Non-target lesion in Non-target vessel: Commercially available PCI devices 
except for investigational devices or control devices 
ISR substudy (treatment of non-target lesion in non-target vessel is acceptable): 
Commercially available PCI devices except for investigational devices or control 
devices 
Criteria for Pre-
index Procedures 
Planned staged PCI procedures are allowed prior to the index procedure. Subjects 
are excluded from this study based on prior procedures if they have had any of the 
following. 
 
Previous treatment at any time with coronary intravascular brachytherapy. 
 
Target vessel has been treated with Paclitaxel Eluting Stent or Balloon prior to 
the index procedure.  
 
Target vessel has been treated with any type of PCI (e.g. DES, BMS or PTCA) 
within 6 months prior to the index procedure. 
 
Non-target vessel has been treated with any type of PCI within 24 hours prior 
to the index procedure.  
 
PCI within 10 mm proximal or distal to the target lesion (by visual estimate) at 
any time prior to the index procedure (This is applicable only to SV trial.).  
Statistical Methods  
Primary Statistical 
Hypothesis (SV 
trial) 
The primary endpoint in this trial is 6-month TLF of test group is non-inferior less 
than 13.2% to that of control group. If the resulting p-value become less than 0.025 
(one-sided), it is regarded this endpoint is met. This is corresponding to the exact 
97.5% lower confidence limit exceeding the Non-inferiority margin. The primary 
endpoint (TLF at 6 months) rate for the AGENT DCB is non-inferior to that for 
SeQuent Please DCB.  
Statistical Test 
Method (SV trial) 
The one-sided non-inferiority test of Agent DCB group against SeQuent Please 
group is to be done by The Farrington-Manning score test. 
H0： PAGENT DCB_6MTLF  – PSeQuent Please DCB_6MTLF  ≥ Δ （Inferior） 
H1： PAGENT DCB_6MTLF  – PSeQuent Please DCB_6MTLF  < Δ （Non-inferior） 
Where PAgent DCB 6MTLF and P SeQuentPlease DCB 6MTLF are then 6-months TLF rates for 
the Agent DCB group and SeQuent Please DCB group, respectively, and Δ is the 
non-inferiority margin. Where PAGENT DCB_6MTLF and PSeQuent Please DCB_6MTLF are the 
rates of the primary endpoint for the AGENT DCB group (test) and the SeQuent 
Please DCB group (control), respectively, and Δ (delta) is the non-inferiority 
margin.  
Success Criteria for 
the Study (SV trial) 
If and only if the primary endpoint meets the criterion, the SV trial is declared to 
achieve its purpose.  
Sample Size 
Parameters (SV 
trial) 
A Farrington-Manning standardized test will be used to test the one-sided hypothesis 
of non-inferiority of the Agent DCB versus SeQuent Please DCB: 
 
Agent DCB (test group) expected rate = 3.1% 1) 
 
SeQuent Please DCB (control group) expected rate = 3.1% 1) 

 
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 
Non-inferiority margin（Δ） = 13.2% 
 
Test significance level (α) = 2.5% (1-side) 
 
Statistical Power = 80% 
 
Total evaluable subjects = 144 subjects (Agent DCB (2):SeQuent Please DCB 
(1) =96:48)  
 
Expected attrition rate = Approximately 3% 
 
Total subjects to be enrolment = 150 subjects (100 Agent DCB, 50 SeQuent 
Please DCB)  
With this sample size (144 subjects), if the scientific significant difference falls into 
4.1% (8.3% Agent DCB, 4.2% SeQuent Please DCB), it is still achievable. 
1. The result of a domestically approved SeQuent Please DCB study 
Statistical Test 
Method (ISR 
substudy) 
The descriptive statistics only planned. 
Success Criteria 
for the Study (ISR 
substudy) 
Taking into account the SeQuent Please DCB Japanese study2) TLR event rate was 
5.5% (3/55 lesion). The upper 95% confidence limit of 15.5% is set as the study 
success criteria.  
In this case, 4/28 (14.3%) is regard as study success. 
2)  The result of a domestically approved SeQuent Please DCB ISR study. 
Sample Size 
Parameters (ISR 
substudy) 
The sample size calculation for the primary endpoint of TLF at 6-month is based on 
the following assumptions: 
• 
95% confidence interval with +/-10% accuracy 
• 
Expected TLF event rate  = 3-7% 
• 
Number of evaluable subjects = 28 
• 
Expected attrition rate = 4% 
• 
Number of planned enrollments = 30 subjects 
 

 
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3. Table of Contents 
1. 
Title Page ................................................................................................................................. 1 
2. 
Protocol Synopsis .................................................................................................................. 4 
3. 
Table of Contents .................................................................................................................. 14 
3.1. 
Table of Figures .................................................................................................................. 17 
3.2. 
Table of Tables ................................................................................................................... 17 
4. 
Introduction ........................................................................................................................... 18 
4.1. 
Introduction and Background .............................................................................................. 18 
4.2. 
Clinical Program Development............................................................................................ 18 
4.2.1. 
Agent DCB Platform .......................................................................................... 18 
4.3. 
Trial Rationale ..................................................................................................................... 19 
5. 
Device Description ................................................................................................................ 19 
5.1. 
Agent DCB .......................................................................................................................... 19 
5.2. 
Drug Components Description ............................................................................................ 20 
5.3. 
Manufacturer ....................................................................................................................... 21 
5.4. 
Labeling of Investigational Device ...................................................................................... 21 
5.5. 
Product Receipt and Tracking ............................................................................................. 22 
5.6. 
Investigational Product Storage .......................................................................................... 22 
5.7. 
Product Returns .................................................................................................................. 22 
5.8. 
Control Device ..................................................................................................................... 22 
5.8.1. 
Results of SeQuent Please Japan domestic trial .............................................. 22 
6. 
Trial Objectives and Endpoints ........................................................................................... 23 
6.1. 
Primary Safety Endpoint ..................................................................................................... 23 
6.2. 
Additional Endpoints ........................................................................................................... 23 
7. 
Study Design ......................................................................................................................... 24 
7.1. 
Scale and Duration .............................................................................................................. 24 
7.2. 
Treatment Assignment ........................................................................................................ 28 
7.3. 
Blinding and Unblinding ...................................................................................................... 28 
7.4. 
Target and Non-Target Lesions .......................................................................................... 28 
7.5. 
Justification for the Trial Design .......................................................................................... 29 
8. 
Subject Selection .................................................................................................................. 29 
8.1. 
Trial Population and Eligibility ............................................................................................. 29 
8.2. 
Inclusion Criteria ................................................................................................................. 29 
8.3. 
Exclusion Criteria ................................................................................................................ 30 
9. 
Subject Accountability ......................................................................................................... 32 
9.1. 
Point of Enrollment .............................................................................................................. 32 
9.2. 
Withdrawal........................................................................................................................... 32 
9.3. 
Lost to Follow-Up ................................................................................................................ 33 
9.4. 
End-of-Study Definition ....................................................................................................... 33 
10. Trial Methods ......................................................................................................................... 33 
10.1. Data Collection .................................................................................................................... 33 

 
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10.2. Trial Candidate Screening ................................................................................................... 36 
10.2.1. 
Strategies for Recruitment and Retention ......................................................... 36 
10.3. Informed Consent ................................................................................................................ 36 
10.4. Quality of Life ...................................................................................................................... 36 
10.5. Medications ......................................................................................................................... 36 
10.6. Pre-Procedure Assessments – Within 14 Days Prior to Index Procedure .......................... 37 
10.7. Index Procedure .................................................................................................................. 37 
10.7.1. 
Multiple Interventions During Index Procedure ................................................. 38 
10.7.2. 
Treatment of Non-Target Lesions During the Index Procedure ........................ 38 
10.7.3. 
Criteria for Pre-index Procedures ...................................................................... 38 
10.7.4. 
Randomization/Enrollment ................................................................................ 38 
10.7.5. 
Treatment of Target Lesion ............................................................................... 39 
10.7.6. 
Acceptable PCI Devices for Non-target Lesion ................................................. 40 
10.7.7. 
Post-procedure Angiogram ............................................................................... 40 
10.8. End of the Index Procedure ................................................................................................ 40 
10.9. Postprocedure/ Prehospital Discharge ............................................................................... 40 
10.10. Re-intervention in the target vessel..................................................................................... 41 
10.11. Follow-up Visits ................................................................................................................... 41 
10.11.1. 
30 Day Follow-up Visit (30 ±14 Days) ............................................................... 41 
10.11.2. 
6 Month Follow-up Visit (180 ±30 Days) ........................................................... 42 
10.11.3. 
12 Month Follow-up Visit (365 ±30 Days) ......................................................... 42 
10.11.4. 
24 Month Follow-up Visit (730 ±30 Days) ......................................................... 42 
10.11.5. 
36 Month Follow-up Visit (1095 ±30 Days) ....................................................... 42 
10.11.6. 
48 Month Follow-up Visit (1460 ±30 Days) ....................................................... 43 
10.11.7. 
60 Month Follow-up Visit (1825 ±30 Days) ....................................................... 43 
10.12. Trial Completion .................................................................................................................. 43 
10.13. Missed or Late Visits ........................................................................................................... 43 
10.14. Source Documents .............................................................................................................. 43 
11. Statistical Considerations .................................................................................................... 44 
11.1. Endpoints for SV study ........................................................................................................ 44 
11.1.1. 
Primary Endpoint ............................................................................................... 44 
11.2. Endpoints for ISR substudy ................................................................................................. 45 
11.2.1. 
Primary Endpoint ............................................................................................... 45 
11.3. General Statistical Methods ................................................................................................ 45 
11.3.1. 
Analysis Sets ..................................................................................................... 45 
11.3.2. 
Control of Systematic Error/Bias ....................................................................... 45 
11.3.3. 
Number of Subjects per Investigative Site ........................................................ 46 
11.4. Data Analyses ..................................................................................................................... 46 
11.4.1. 
Other Endpoints/Measurements ....................................................................... 46 
11.4.2. 
Interim Analyses ................................................................................................ 46 
11.4.3. 
Subgroup Analyses ........................................................................................... 46 
11.4.4. 
Justification of Pooling ...................................................................................... 47 
11.4.5. 
Multivariable Analyses ...................................................................................... 47 
11.4.6. 
Other Analyses .................................................................................................. 47 
11.4.7. 
Changes to Planned Analyses .......................................................................... 47 

 
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12. Data Management ................................................................................................................. 47 
12.1. Data Collection, Processing, and Review ........................................................................... 47 
12.2. Data and Record Retention ................................................................................................. 47 
12.3. Core Laboratory .................................................................................................................. 48 
13. Deviations .............................................................................................................................. 48 
14. Device Accountability .......................................................................................................... 48 
15. Compliance ............................................................................................................................ 49 
15.1. Statement of Compliance .................................................................................................... 49 
15.2. Investigator Responsibilities ................................................................................................ 49 
15.2.1. 
Delegation of Responsibility .............................................................................. 50 
15.3. Institutional Review Board ................................................................................................... 50 
15.4. Sponsor Responsibilities ..................................................................................................... 50 
15.4.1. 
Role of Boston Scientific Representatives ........................................................ 51 
15.5. Reimbursement and Compensation ................................................................................... 51 
16. Monitoring.............................................................................................................................. 51 
17. Potential Risks and Benefits ............................................................................................... 52 
17.1. Anticipated Adverse Events and Risks Associated with Use of the Agent DCB ................ 52 
17.2. Risks Associated with the Trial Device(s) Unique to Paclitaxel .......................................... 52 
17.3. Risks associated with Participation in the Clinical Trial ...................................................... 53 
17.4. Possible Interactions with Concomitant Medical Treatments ............................................. 53 
17.5. Risk Minimization Actions ................................................................................................... 53 
17.6. Anticipated Benefits ............................................................................................................ 53 
17.7. Risk to Benefit Rationale ..................................................................................................... 53 
18. Safety Reporting ................................................................................................................... 53 
18.1. Reportable Events by investigational center to Boston Scientific ....................................... 53 
18.2. Definitions and Classification .............................................................................................. 54 
18.3. Relationship to Study Device(s) .......................................................................................... 56 
18.4. Investigator Reporting Requirements ................................................................................. 58 
18.5. Boston Scientific Device Deficiencies ................................................................................. 59 
18.6. Reporting to Regulatory Authorities / IRBs / Investigators .................................................. 59 
19. Informed Consent ................................................................................................................. 59 
20. Committees ........................................................................................................................... 60 
20.1. Executive Committee .......................................................................................................... 60 
20.2. Safety Monitoring Process .................................................................................................. 60 
20.3. Clinical Events Committee .................................................................................................. 61 
21. Suspension or Termination ................................................................................................. 61 
21.1. Premature Termination of the Study ................................................................................... 61 
21.1.1. 
Criteria for Premature Termination of the Study ............................................... 61 
21.2. Termination of Study Participation by the Investigator or Withdrawal of IRB Approval ...... 61 
21.3. Requirements for Documentation and Subject Follow-up................................................... 61 
21.4. Criteria for Suspending/Terminating a Study Center .......................................................... 62 
22. Publication Policy ................................................................................................................. 62 

 
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23. Bibliography .......................................................................................................................... 63 
24. Abbreviations and Definitions ............................................................................................. 64 
24.1. Abbreviations ...................................................................................................................... 64 
24.2. Definitions............................................................................................................................ 66 
 
 
3.1. 
Table of Figures 
Figure 5.1-1: Agent DCB ................................................................................................................ 20 
Figure 5.2-1: Chemical Structure of Paclitaxel .............................................................................. 21 
Figure 5.2-2: Chemical Structure of Acetyltributyl Citrate (ATBC) ................................................. 21 
Figure 7.1-1: AGENT Japan SV Study Design .............................................................................. 25 
Figure 7.1-2: AGENT Japan ISR substudy Design ....................................................................... 27 
 
3.2. 
Table of Tables 
Table 5.1-1: Agent DCB Device Size ............................................................................................. 20 
Table 5.1-2： Paclitaxel Dose per Balloon Diameter and Length ................................................... 20 
Table 5.1-3: Agent DCB Compliance Chart ................................................................................... 20 
Table 8.2-1: Inclusion Criteria ......................................................................................................... 29 
Table 8.3-1: Exclusion Criteria........................................................................................................ 30 
Table 10.1-1: Data Collection Requirements by Visit .................................................................... 34 
Table 18.2-1: Safety Definitions ..................................................................................................... 54 
Table 18.3-1: Criteria for Assessing Relationship of Trial Device or Procedure to Adverse Event 56 
Table 18.3-2: Criteria for Assessing Relationship of Antiplatelet Medication to AE ....................... 57 
Table 18.4-1: Investigator Reporting Requirements ...................................................................... 58 
Table 24.1-1: Abbreviations ............................................................................................................ 64 
Table 24.2-1: Definitions ................................................................................................................ 66 
 
 

 
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4. Introduction 
4.1. 
Introduction and Background 
Coronary artery disease (CAD) is characterized by atherosclerosis in the epicardial coronary arteries. 
Atherosclerotic plaques, the hallmark of atherosclerosis, progressively narrow the coronary artery lumen and 
impair antegrade myocardial blood flow. The reduction in coronary artery flow may be symptomatic or 
asymptomatic, occur with exertion or at rest, and culminate in a myocardial infarction, depending on 
obstruction severity and the rapidity of development. 
Subjects with coronary artery disease have three common therapeutic options 1) medical therapy and risk 
factor modification, 2) coronary artery bypass graft surgery (CABG), and 3) percutaneous coronary 
intervention (PCI). As PCI technology and revascularization procedures evolved, balloon angioplasty, bare 
metal stent (BMS) and drug-eluting stent (DES) succeeded each other as the primary catheter-based 
treatments for coronary artery disease. The optimal management of subjects presenting with not only de 
novo small vessel disease but also in-stent restenosis disease that is a sub study in this study remain unclear.  
Drug delivery via DCB could result in a more homogeneous administration of the drug instead of creating a 
peri-strut gradient,1-5 in reduced vascular smooth muscle cell proliferation6 and in a reduced rate of restenosis 
when compared to uncoated balloon treatment.7 Drug concentrations at the vessel wall with DCB are the 
highest at the time of injury when the neointimal process is the most vigorous. Afterwards, the absence of 
drug and polymer (used in stent technologies) could help to facilitate re-endothelialization, thereby reducing 
the risk of late and very late thrombosis. Another advantage of DCB over DES is the decrease in duration of 
dual antiplatelet therapy (DAPT) when compared to DES, likely resulting in a reduced rate of bleeding 
complications2,5,8. Furthermore, it is an attractive approach in small vessels or in-stent restenosis, respecting 
the original anatomy of the arteries4, thus avoiding further reduction of the lumen diameter with stent struts7 
and avoiding the deployment of a permanent implant/prosthesis that could complicate future 
revascularization efforts2,5.  
4.2. 
Clinical Program Development 
4.2.1. 
Agent DCB Platform 
The Agent paclitaxel-coated balloon is a paclitaxel-coated Percutaneous Transluminal Angioplasty (PTA) 
balloon catheter developed as a collaborative effort between BSC and Hemoteq AG [HTQ, Wuerselen, 
Germany]. The Agent paclitaxel-coated balloon is based on BSC’s well characterized Emerge PTA balloon 
catheters. These catheters are coated with the paclitaxel (active ingredient) drug that is formulated with the 
excipient acetyltributyl citrate (ATBC) to effectively deliver paclitaxel to the vessel wall. Paclitaxel has been 
widely used for both stent and DCB applications as a safe and effective drug to inhibit neointimal 
proliferation and thereby reduce the rate of restenosis. 
Agent paclitaxel-coated balloon was granted a CE mark in July 2014 and is currently marketed in Europe, 
Austria, and other regions and indicated for percutaneous transluminal coronary angioplasty (PTCA) in the 
in-stent restenosis (ISR) and de novo small vessel disease. 
Although clinical studies using Agent DCB for the treatment of a small vessel de novo native coronary artery 
lesion have not been conducted until now, clinical studies (Agent ISR trial and ISAR-DESIRE 3A trial) for 
the treatment of ISR have been conducted as below. 
The Agent ISR trial was designed to evaluate the safety and performance of the Agent paclitaxel-coated 
balloon for the treatment of subjects with an In-Stent Restenosis. The Agent ISR trial is a prospective, 
multicenter, 1:1 randomized Agent paclitaxel-coated balloon versus SeQuent Please paclitaxel-coated 
balloon, controlled trial. The trial enrolled 125 patients, of whom 65 were assigned to Agent DCB, 60 to 
SeQuent Please DCB. The primary endpoint was In-stent late lumen loss at 6 months post-procedure. The 
Agent DCB was shown to be non-inferior to the SeQuent Please DCB for the 6-month primary endpoint (In-
stent late lumen loss). The LL for the Agent DCB group was 0.397 mm and the LL for the SeQuent Please 
DCB group was 0.393 mm. Non-inferiority was concluded because the 2-sided upper 95.0% confidence 
bound on the difference between treatment groups (Agent DCB minus SeQuent Please DCB; 0.004 with an 
upper confidence bound of 0.196) was less than the non-inferiority margin of 0.2 with a P value 0.046. TLF 
in the Agent DCB group and SeQuent Please DCB group was 6.15% and 8.33%, respectively (P=0.9008), 
at 6 months and 9.2% and 11.7%, respectively (P=0.88), at 1 year. All-cause mortality in the Agent DCB 

 
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group and SeQuent Please DCB group was 1.54% and 1.67%, respectively (P=1.0000), at 6 months and 
3.1% and 1.7%, respectively (P>0.99), at 1 year. The incidence of clinical events did not differ between the 
Agent DCB and SeQuent Please DCB groups.9,10 
The ISAR-DESIRE 3A trial was a prospective, multicenter, non-randomized, single arm study with 
comparison against historical control group (SeQuent Please DCB) from ISAR-DESIRE 3 trial for the 
treatment of subjects with a coronary restenosis after implantation of limus-analogue drug-eluting stents 
(DES). The trial enrolled 125 patients were enrolled. The primary endpoint was In-segment percent diameter 
stenosis (%DS) at 6-8 months follow-up angiography. The Agent DCB was shown to be non-inferior to the 
SeQuent Please DCB for the primary endpoint (In-segment percent diameter stenosis). The rate for the Agent 
DCB group was 38.9±17.5% and the rate for the SeQuent Please DCB group was 38.0±21.5% (P=0.0056). 
TLR in the Agent DCB group and SeQuent Please DCB group was 20.6% and 22.1%, respectively (P=0.80), 
at 1 year. All-cause mortality in the Agent DCB group and SeQuent Please DCB group was 0.8% and 2.2%, 
respectively (P=0.39), at 1 year. The incidence of events did not differ between the Agent DCB and SeQuent 
Please DCB groups.11 
4.3. 
Trial Rationale 
PCI is the most common treatment for patients with coronary artery disease. But the optimal management 
of patients presenting with not only de novo small vessel disease but also in-stent restenosis disease that is a 
sub study in this study remain unclear and the need for an alternative therapy exists. The Agent DCB aims 
to address these treatment gaps and clinical outcomes not adequately addressed by POBA, BMS, and DES. 
Agent DCB.incorporates design modifications aimed to improve coating durability and drug transfer 
efficiency, to minimize particulates and systemic PTx levels for patient safety and to optimize arterial PTx 
concentrations with reduced drug dose density (2 µg/mm2 vs 3 µg/mm2) (TransPaxTM Coating Technology).  
 
5. Device Description 
5.1. 
Agent DCB 
The Agent Paclitaxel-Coated PTCA Balloon Catheter (Agent DCB) is a Monorail Percutaneous 
Transluminal Coronary Angioplasty (PTCA) balloon catheter with a semi-compliant balloon coated with a 
formulation of paclitaxel (drug) and an excipient, Acetyl-Tri-n-Butyl citrate (ATBC) (see Figure 5.1-1). The 
Agent balloon catheter is designed to inhibit restenosis by delivering drug to diseased arterial tissue. 
The distal section of the catheter is dual lumen and coaxial. The outer lumen is used for inflation of the 
balloon, and the inner lumen permits the use of guidewires ≤ 0.014 in (0.36 mm) to facilitate advancement 
of the catheter. The proximal section of the catheter is a single-lumen, stainless steel hypotube with a single 
luer port hub for inflation/deflation of the balloon. The balloon is designed to provide an inflatable segment 
of known diameter and length at recommended pressures. A balloon protector is placed over the balloon to 
maintain a low profile and a mandrel is placed into the inner lumen to protect the patency of the catheter. 
The catheter’s tip is tapered to facilitate advancement of the catheter to and through the stenosis. The shaft 
features the ZGlide™ hydrophilic coating, which is located from the guidewire port to just proximal of the 
proximal balloon waist.  
The effective length of the catheter is 144 cm. Marks on the proximal portion of the catheter shaft indicate 
the exit of the balloon catheter tip out of the guide catheter (one at 90 cm and two at 100 cm). Two radiopaque 
marker bands, in conjunction with fluoroscopy, aid in the placement of the catheter’s balloon segment. One 
CLIPIT™ Hypotube Clip is also provided to aid in handling of the catheter. 
The Agent Paclitaxel-Coated PTCA Balloon Catheter is available in a variety of diameters and balloon 
lengths. Device sizes intended for use in this trial are exhibited in Table 5.1-1. Table 5.1.-2 exhibits the dose 
of paclitaxel for each balloon by length and diameter. Table 5.1-3 exhibits the Agent DCB balloon 
compliance chart.  

 
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Figure 5.1-1: Agent DCB 
 
Table 5.1-1: Agent DCB Device Size 
 
Balloon Length (mm)  
2.00 
2.25 
2.50 
2.75 
3.00 
3.50 
4.00 
Balloon 
Diameter 
(mm)  
12 
X 
X 
X 
X 
X 
X 
X 
15 
X 
X 
X 
X 
X 
X 
X 
20 
X 
X 
X 
X 
X 
X 
X 
30 
X 
X 
X 
X 
X 
X 
X 
 
Table 5.1-2： Paclitaxel Dose per Balloon Diameter and Length 
 
Balloon Length (mm)  
2.00 
2.25 
2.50 
2.75 
3.00 
3.50 
4.00 
Balloon 
Diameter 
(mm)  
12 
165 µg 
177 µg 
196 µg 
216 µg 
235 µg 
274 μg 
312 μg 
15 
204 µg 
219 µg 
243 µg 
266 µg 
290 µg 
338 μg 
386 μg 
20 
272 µg 
291 µg 
322 µg 
354 µg 
386 µg 
449 μg 
513 μg 
30 
406 µg 
435 µg 
482 µg 
529 µg 
577 µg 
672 μg 
767 μg 
 
Table 5.1-3: Agent DCB Compliance Chart 
Pressure  
Balloon Diameter (mm)  
atm 
kPa 
2.00 
2.25 
2.50 
2.75 
3.00 
3.50 
4.00 
3.0 
304 
1.86 
2.06 
2.28 
2.53 
2.76 
3.19 
3.66 
4.0 
405 
1.93 
2.14 
2.37 
2.61 
2.85 
3.30 
3.80 
5.0 
507 
1.99 
2.20 
2.44 
2.68 
2.93 
3.39 
3.88 
6.0 
608 
2.03* 
2.26* 
2.50* 
2.75* 
3.00* 
3.46* 
3.96* 
7.0 
709 
2.07 
2.31 
2.55 
2.81 
3.06 
3.52 
4.04 
8.0 
811 
2.10 
2.34 
2.59 
2.85 
3.11 
3.57 
4.09 
9.0 
912 
2.13 
2.38 
2.62 
2.88 
3.15 
3.61 
4.14 
10.0 
1013 
2.15 
2.40 
2.65 
2.91 
3.18 
3.64 
4.18 
11.0 
1115 
2.18 
2.42 
2.67 
2.94 
3.21 
3.68 
4.22 
12.0 
1216 
2.19 
2.44 
2.69 
2.96 
3.23 
3.72** 
4.25** 
13.0 
1317 
2.21 
2.46 
2.72 
2.99 
3.26 
- 
- 
14.0 
1419 
2.23** 
2.48** 
2.74** 
3.02** 
3.28** 
- 
- 
* 
RBP = 6 atm 
** 
RBP = 14 atm 
 
5.2. 
Drug Components Description 
The balloon coating consists of paclitaxel (PTx) and the excipient, acetyltributyl citrate (ATBC).  

 
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Paclitaxel (PTx) is the active pharmaceutical ingredient on the Agent DCB. Paclitaxel is a white powder, 
isolated from a spectrum of TAXUS species and hybrids. It is a terpenoid with a characteristic taxane 
skeleton of 20 carbon atoms, a molecular weight of 853.91 g/mol, and a molecular formula of C47H51NO14. 
It is highly lipophilic and insoluble in water, but is freely soluble in methanol, ethanol, chloroform, ethyl 
acetate, and dimethyl sulfoxide.12,13 The chemical structure of paclitaxel is provided in Figure 5.2-1: 
Chemical Structure of Paclitaxel. 
Paclitaxel is an antiproliferative drug that induces irreversible polymerization of cell microtubules, thus 
inhibiting mitosis. It is widely used in antineoplastic chemotherapy of cancers; however, doses required in 
chemotherapeutic treatment are significantly higher per treatment cycle in cancer patients than in coronary 
artery disease patients.13 Paclitaxel has been shown to inhibit proliferation and migration of smooth muscle 
cells, effectively suppressing neointimal hyperplasia after vessel injury.13,14,15 The drug to excipient 
formulation ratio in Agent DCB is 80:20 PTx/ATBC. The resulting drug dose density (total weight of drug 
per unit of balloon surface area) on the coated balloon is 2 µg/mm2. 
 
Figure 5.2-1: Chemical Structure of Paclitaxel 
 
The coating utilizes the inactive ingredient Acetyl-Tri-n-Butyl Citrate (ATBC) as an excipient to facilitate 
the release and transfer of paclitaxel into the arterial wall. ATBC is a carboxylic acid ester with a molecular 
weight of 402.48 g/mol. ATBC is a colorless, slightly viscous liquid with very faint sweet herbaceous odor. 
The chemical structure of ATBC is provided in Figure 5.2-2.  
 
 
Figure 5.2-2: Chemical Structure of Acetyltributyl Citrate (ATBC) 
5.3. 
Manufacturer 
The Agent DCB is manufactured by BSC and the paclitaxel (drug) and an excipient, Acetyl-Tri-n-Butyl 
citrate (ATBC) are coated on the balloon by Hemoteq AG.  
5.4. 
Labeling of Investigational Device 
The Directions for Use (DFU) for the Agent DCB will be included in the Manual of Operations. The Agent 
DCB is labeled on the front, back and bottom spine of the outer carton, and on the inside sterile pouch. The 
labeling will include the following information in Japanese or in English.  
In Japanese: 

 
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 
Identification number 
 
Sponsor name and address 
 
Storage condition 
 
Exclusively for Clinical Investigations 
In English: 
 
Lot number 
 
Serial number 
 
Balloon dimensions (balloon diameter and length in mm) 
 
Expiration (use by) date  
5.5. 
Product Receipt and Tracking 
In order to allow shipment of investigational product to an investigational center, Boston Scientific (or 
designee) must declare in writing that the investigational center is activated and ready to enroll subjects. The 
investigator agrees not to use a test device or product on any person except subjects who are enrolled into 
the AGENT Japan SV trial. The test product must only be used for the purpose of the clinical trial and in 
compliance to this clinical investigation plan.  
Upon receipt of the test products, the center principal investigator or designated individual will visually 
inspect and notify Boston Scientific (or its designee) of any noted issues or discrepancies. The test product 
will be traced using an investigational product management system (Cenduit LLC), Refer to section 14. 
Device Accountability.  
5.6. 
Investigational Product Storage 
The test products must be stored in a secured and locked location accessible only to those delegated 
individuals who are authorized by the center principal investigator to access them.  
5.7. 
Product Returns 
The test product must be returned to Boston Scientific (or its designee) when it is no longer in use, regardless 
of the reason for removal from use. At the end of the trial enrollment, all unused test product provided for 
the trial will be returned to Boston Scientific.  
5.8. 
Control Device 
SeQuent® Please Drug Eluting Balloon Catheter is the control device for the SV trial. The balloon size 
utilization is determined by the research investigator. And it should be used according to the localstandard 
care. 
SeQuent Please paclitaxel-coated balloon has a drug formulation consisting of paclitaxel (the active 
pharmaceutical ingredoent) and an iopromide (the inactive ingredient). The resulting drug dose density (total 
weight of drug per unit of balloon surface area) on the coated balloon is 3 μg/mm2. SeQuent Please paclitaxel-
coated balloon has been approved in Japan and indicated for percutaneous transluminal coronary angioplasty 
(PTCA) in the in-stent restenosis (ISR) and de novo small vessel disease (<3.00 mm in diameter).  
Note: A center may use the SeQuent® Please Neo Drug Eluting Balloon Catheter if it is approved and 
commercially available. 
5.8.1. 
Results of SeQuent Please Japan domestic trial 
The SeQuent Please Japan domestic trial was designed to evaluate the safety and effectiveness of the 
SeQuent Please paclitaxel-coated balloon for the treatment of subjects with a small vessel de novo lesion≤ 
22 mm in length in native coronary arteries ≥2.00 mm to <2.75 mm in diameter. The trial was a prospective, 
multicenter, 2:1 randomized (SeQuent Please paclitaxel-coated balloon versus percutaneous old balloon 
angioplasty), controlled trial. The trial enrolled 135 patients, of whom 93 were assigned to SeQuent Please 
DCB, 42 to POBA. The primary endpoint was TVF rate at 6 months post-procedure. The TVF rate for the 

 
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SeQuent Please DCB group was 3.1% and the TVF rate for the POBA group was 9.8%, respectively (P=0.20). 
The secondary endpoint was TLR rate and Late Loss at 6 months post-procedure. The TLR rate for the 
SeQuent Please DCB group was 2.0% and the TLR rate for the POBA group was 9.8%, respectively (P=0.06). 
The LL for the SeQuent Please DCB group was 0.01±0.31 mm and the LL for the POBA group was 0.32±
0.34 mm, respectively (P<0.001). MACE (death, myocardial infarction, or target lesion revascularization 
with repeat angioplasty or bypass graft surgery) in the SeQuent Please group and POBA group was 3.4% 
and 10.3%, respectively (P=0.20), at 6 months. Restenosis in the SeQuent Please DCB group and POBA 
group was 2.0% and 7.5%, respectively (P=0.15), at 6 months. Any death, MI, Thrombosis event and CABG 
was not occurred in both groups.16 
The SeQuent Please Japan domestic trial was designed to evaluate the safety and effectiveness of the 
SeQuent Please paclitaxel-coated balloon for the treatment of subjects with in-stent restenosis (ISR). The 
trial was a prospective, multicenter, 2:1 randomized (SeQuent Please paclitaxel-coated balloon versus 
percutaneous old balloon angioplasty), controlled trial. The trial enrolled 210 patients, of whom 138 were 
assigned to SeQuent Please DCB, 72 to POBA. The primary endpoint was TVF rate at 6 months post-
procedure. The TVF rate for the SeQuent Please DCB group was 6.4% and the TVF rate for the POBA group 
was 31.0%, respectively (P<0.01). The secondary endpoint was TLR rate and Late Loss at 6 months post-
procedure. The TLR rate for the SeQuent Please DCB group was 2.8% and the TLR rate for the POBA group 
was 31.0%, respectively (P<0.01). The LL for the SeQuent Please DCB group was 0.11±0.33 mm and the 
LL for the POBA group was 0.49±0.50 mm, respectively (P<0.01). MACE in the SeQuent Please DCB 
group and POBA group was 6.6% and 31.0%, respectively (P<0.01), at 6 months. Restenosis in the SeQuent 
Please group and POBA group was 2.9% and 18.8%, respectively (P<0.01), at 6 months. Any death, MI, 
Thrombosis event and CABG was not occurred in both groups.16  
 
6. Trial Objectives and Endpoints 
Primary objective is to evaluate the safety and effectiveness of the Agent™ Paclitaxel-Coated PTCA Balloon 
Catheter for the treatment of Japanese subjects with a small vessel de novo native atherosclerotic coronary 
artery lesion or in-stent restenosis (ISR) of a previously treated lesion.  
6.1. 
Primary Safety Endpoint 
The primary endpoint assesses Target Lesion Failure (TLF) rate at 6 months post index-procedure. TLF is 
defined as any ischemia driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-
wave and non–Q-wave) related to the target vessel, or cardiac death.  
6.2. 
Additional Endpoints 
Clinical endpoints measured at hospital discharge, 30 days, 6 months, 12 months, 24 months, 36 months, 48 
months and 60 months.  
 
TLR rate  
 
TLF rate  
 
TVR rate  
 
TVF rate  
 
MI (Q-wave and non–Q-wave) rate  
 
Cardiac death rate  
 
Non-cardiac death rate  
 
All death rate  
 
Cardiac death or MI rate  
 
All death or MI rate  
 
All death/MI/TVR rate  
 
Thrombosis related to target lesion rate  
 

 
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Change in Quality of Life: Functional status of general health-related quality of life measured by changes in 
EQ5D scores at hospital discharge, 6 months, 12 months, 24 months and 36 months. 
 
Angiographic endpoints at 6 months post-index procedure measured by angiography (In lesion/In stent and 
In segment):  
 
Percent diameter stenosis (%DS)  
 
Late lumen loss 
 
Binary restenosis rate  
 
Minimum lumen diamete  
 
Periprocedural endpoints:  
 
Technical success rate  
 
Clinical procedural success rate  
 
Criteria is defined as below.  
Technical success rate: Technical success is the ability to cross and dilate the lesion to achieve residual 
angiographic stenosis no greater than 30% as determined by the investigator. The result will be generally 
confirmed by an angiographic core lab.  
Clinical procedural success rate: Technical success with no death or MI noted within 24 hours of the index 
procedure.  
 
7. Study Design 
The clinical trial for SV trial is a prospective, multicenter, 2:1 randomized (Agent DCB to SeQuent Please 
DCB), controlled, single-blind, non-inferiority trial. Primary objective is to evaluate the safety and 
effectiveness of the Agent DCB for the treatment of Japanese subjects with a small vessel de novo native 
atherosclerotic coronary artery lesion.  
ISR substudy is a prospective, multicenter, single-arm, open trial. Primary objective is to evaluate the safety 
and effectiveness of the Agent DCB for the treatment of Japanese subjects with an In stent restenosis 
coronary artery lesion. 
7.1. 
Scale and Duration 
150 subjects will be randomized/enrolled to support a 2:1 randomization in this SV trial and 30 subjects will 
be enrolled in this ISR substudy. The trial is to be conducted in Japan at up to 15 investigational centers.  
Clinical follow-up will be required at the following time points: Hospital discharge, 30 days, 6 months, 12 
months, 24 months, 36 months, 48 months and 60 months after the index procedure. Follow-up office visits 
will be required at 6 months, 12 months, 24 months and 36 months after the index procedure. Subjects who 
are enrolled but who do not receive treatment with an investigational device will be followed through 30 
days only to assess their safety. 
It is estimated that it will take approximately 6 years to complete this trial. エラー! 参照元が見つかりませ
ん。 and Figure 7.1-2 show the schematic of the study design. 
 

 
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Figure 7.1-1: AGENT JapanSV Trial Design 
 

 
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1) If a non-target lesion is located in the target vessel, it should be apart more than 15 mm from the target 
lesion. 
2) Non-target lesion in target vessel is must be treated with commercially available DES or DCB coated 
with drug other than paclitaxcel, BMS, or balloon (POBA) and non-target lesion in non-target vessel is 
must be treated with commercially available PCI devices except for investigational devices or control 
devices. 
3) If non-target lesion is located distal to the target lesion in the same vessel and in the case that a target 
lesion needs pre-dilation prior to the treatment of non-target lesion to cross a device for the treatment 
of non-target lesion, protocol-defined pre-dilation for the target lesion could be done before the 
treatment of non-target lesion. After completing treatment of non-target lesion, remaining treatment 
for target lesion can be performed. After confirming completion of treatment of non-target lesion, 
subjects will be considered enrolled in the trial after they have been successfully randomized. 
 
 
 

 
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Figure 7.1-2： AGENT Japan ISR substudy Design 
 
1) Non-target lesion in non-target vessel must be treated with commercially available PCI devices except 
for investigational devices or control devices 
 
 

 
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7.2. 
Treatment Assignment 
SV trial:  
If after consenting, meeting clinical inclusion criteria and none of the clinical exclusion criteria and 
confirmed angiographically significant lesion in a small vessel de novo native coronary artery and successful 
protocol-defined pre-dilation, subjects are randomized 2:1 to either an Agent DCB (test) or a SeQuent Please 
DCB (control). Randomization will be stratified by site. After the guidewire successfully crosses the target 
lesion and successfully pre-dilates the target lesion, a randomization custom function within the Rave EDC 
database will be used to assign subjects to the test or control treatment group. Subjects will be considered 
enrolled in the trial after they have been successfully randomized (i.e. when a treatment assignment is 
received by the investigative site).  
 
ISR substudy: 
If after consenting, meeting clinical inclusion criteria and none of the clinical exclusion criteria and 
confirmed angiographically significant lesion in an ISR coronary artery and successful protocol-defined pre-
dilation, subjects will be considered enrolled in the ISR substudy. 
 
Note1: If the subject meets clinical inclusion criteria and none of the clinical exclusion criteria of both the 
SV trial and ISR substudy, either an SV lesion or an ISR lesion will be enrolled at the investigator’s discretion.  
Note2: If the subject is found to meet inclusion and exclusion criteria, the subject will be considered a screen 
failure and not be randomized/enrolled or receive an investigational device, nor should the subject be 
followed postprocedure per protocol.  
7.3. 
Blinding and Unblinding 
SV trial is conducted as single blind. Subjects will be blinded to treatment assigned and treatment received. 
All subjects must remain blinded until completion of 6-month follow-up visits (primary endpoint). Packaging 
of the test Agent DCB and control SeQuent Please DCB devices differ. Therefore, the investigator and staff 
performing the procedure will not be blinded to the assigned treatment arm or resulting treatment. The 
investigator and staff will be trained not to disclose the treatment assignment to the subject in order to 
minimize the potential unblinding of the subjects. Core Laboratory personnel and the Clinical Events 
Committee (CEC) will be blinded to a subject’s treatment assignment during the trial. The Biostatistician 
will remain blinded until the primary endpoint interim analysis.  
The ISR substudy is an open-label trial and not applicable. 
7.4. 
Target and Non-Target Lesions 
SV trial: 
Target Lesion 
A target lesion is one that meets the angiographic selection criteria and is to be treated with an investigational 
device during the index procedure. An investigational device may be used to treat one de novo lesion.  
If a subject has 2 or more lesions that meet the selection criteria, the target lesion is the more severe lesion 
based on visual estimate of percent diameter stenosis. The other lesion can be treated through planned staged 
PCI procedure before the index procedure or as a non-target lesion in the index procedure.  
 
Non-Target Lesion 
A non-target lesion is a lesion treated within a target vessel or non-target vessel during the index procedure 
for which treatment with an investigational device is not attempted. If a non-target lesion is located in the 
target vessel, it should be apart more than 15 mm from the target lesion. 
 
ISR substudy: 
Target Lesion 

 
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A target lesion is one that meets the angiographic selection criteria and is to be treated with an investigational 
device during the index procedure. An investigational device may be used to treat one ISR lesion.  
If a subject has 2 or more lesions that meet the selection criteria of ISR, the target lesion is the more severe 
lesion based on visual estimate of percent diameter stenosis. The other lesion can be treated through planned 
staged PCI procedure before the index procedure or as a non-target lesion in the index procedure. 
 
Non-Target Lesion 
A non-target lesion is a lesion treated within a non-target vessel during the index procedure for which 
treatment with an investigational device is not attempted. (The treatment of the non-target lesion in the target 
vessel is not allowed for the ISR substudy.) 
7.5. 
Justification for the Trial Design 
The AGENT Japan SV trial will evaluate the safety and effectiveness of the Agent DCB for the treatment of 
subjects with a small vessel de novo native coronary artery lesion compared with the SeQuent Please DCB. 
The SeQuent Please DCB was chosen as the control device because it is the commercially available DCB 
approved in Japan at the moment of planning this trial for treatment of small vessel de novo native coronary 
artery lesion. As reported in Section 5.8., the test and control DCB deliver the same drug, paclitaxel. 
Coronary artery disease patients with ISR will be considered as part of the ISR substudy. The ISR substudy 
will evaluate the safety and effectiveness of the Agent DCB for the treatment of subjects with an ISR 
coronary artery lesion. 
During the trial, ongoing dynamic data safety monitoring will be performed throughout the trial to minimize 
subject risk. All enrolled subjects receiving the investigational device will be followed for 60 months post 
index procedure.  
 
8. Subject Selection 
8.1. 
Trial Population and Eligibility 
Clinical and angiographic inclusion and exclusion criteria are included in Table 8.2-1 and Table 8.3-1. Prior 
to enrollment, a subject must meet all of the clinical and angiographic inclusion criteria and none of the 
clinical and angiographic exclusion criteria.  
8.2. 
Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion (see Section 8.3) is met.  
Table 8.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria  
CI1. Subject must be at least 20 years of age.  
CI2. Subject understands the trial requirements and the treatment procedures and 
provides written informed consent before any study-specific tests or procedures 
are performed. 
CI3. Subject is eligible for percutaneous coronary intervention (PCI).  
CI4. Subject has documented stable angina pectoris or unstable angina pectoris. If 
subject has documented stable angina pectoris, one of the following criteria meet. 
⁃ >90% diameter stenosis. 
⁃ Stenosis that is considered a cause of stable effort angina (Only when it's 
without confirmation of significant stenosis).  
⁃ Stenosis that is confirmed a cause of functional ischemia with any test. 

 
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CI5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG). 
CI6. Subject is willing to comply with all protocol-required follow-up evaluation. 
CI7. Patients undergoing first or second treatment for ISR lesions for the non-
randomized ISR substudy. 
Angiographic 
Inclusion 
Criteria (visual 
estimate)  
AI1. The target lesion meets all following criteria. 
⁃ Target lesion length must measure (by visual estimate) ≤28 mm. 
⁃ Target lesion must be a visually estimated reference vessel diameter (RVD) 
≥2.00mm and <3.00 mm (This applys for SV trial. For ISR substudy: RVD 
≥2.00mm and ≤4.00 mm.). 
⁃ Target lesion must be a de novo lesion located in a native coronary artery 
with visually estimated stenosis ≥75% and <100% (This applys for SV trial. 
For ISR substudy: Target lesion for ISR must be in-stent restenosis of a 
previously-treated lesion located in a native coronary artery with visually 
estimated stenosis ≥75% and <100%.). 
⁃ Coronary anatomy is likely to allow delivery of an investigational device to 
the lesions(s). 
⁃ Target lesion must be successfully pre-dilated. 
AI2. Planned treatment of 2 coronary artery lesions in 2 vessels may be treated (For 
SV trial, up to two lesions per vessel can be treated. For ISR substudy, single 
lesion per vessel can be treated.).  
 
8.3. 
Exclusion Criteria 
Subjects who meet any one of the following criteria (see Table 8.3-1) cannot be included in this study or will 
be excluded from this clinical study.  
Table 8.3-1: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
CE1. Subject has had an acute myocardial infarction within 72 hours prior to the index 
procedure.  
CE2. Subject has cardiogenic shock, hemodynamic instability requiring inotropic or 
mechanical circulatory support, intractable ventricular arrhythmia, or ongoing 
intractable angina. 
CE3. Subject has severe left ventricular dysfunction with ejection fraction <30%. 
CE4. Subject has received an organ transplant or is on a waiting list for an organ 
transplant.  
CE5. Subject is receiving or scheduled to receive chemotherapy within 30 days before 
or after the index procedure. 
CE6. Subject has renal failure with a serum creatinine of > 2.0mg/dL or who is 
receiving dialysis or chronic immunosuppressant therapy.  
CE7. Subjects has one of the following.  
⁃ Not expected to live for the duration of the study (1 year) by investigator’s 
discretion due to other serious medical illness (e.g. cancer, congestive heart 
failure).  
⁃ Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.). 
⁃ Planned procedure that may cause non-compliance with the protocol or 
confound data interpretation.  
CE8. Planned PCI (including staged procedures) or CABG after the index procedure.  
CE9. Subject previously treated at any time with intravascular brachytherapy.  
CE10. Subject has a known allergy to contrast (that cannot be adequately premedicated) 
and/or the investigational device or protocol-required concomitant medications 

 
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(e.g., paclitaxel, acetyl tributyl citrate (ATBC), iopromide, raw materials of 
Agent DCB and SeQuent Please DCB, P2Y12 inhibitor or aspirin).  
CE11. Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3.  
CE12. Subject has a white blood cell (WBC) count < 3,000 cells/mm3.  
CE13. Subject has documented or suspected liver disease, including laboratory 
evidence of hepatitis. 
CE14. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood 
transfusions.  
CE15. Subject has had a history of cerebrovascular accident (CVA) or transient 
ischemic attack (TIA) within the past 6 months. 
CE16. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding. 
CE17. Target vessel has been treated with Paclitaxel Eluting Stent or Balloon prior to 
the index procedure.  
CE18. Target vessel has been treated with any type of PCI (e.g. DES, BMS or PTCA) 
within 6 months prior to the index procedure. 
CE19. Target vessel requires the use of adjunctive primary treatment modalities (e.g. 
laser, atherectomy, other debulking devices, etc.) immediately prior to 
investigational device’s treatment. 
CE20. Non-target vessel has been treated with any type of PCI within 24 hours prior to 
the index procedure. 
CE21. Subject is participating in another investigational drug or device clinical trial that 
has not reached its primary endpoint.  
CE22. Subject intends to participate in another investigational drug or device clinical 
trial within 6 months after the index procedure.  
CE23. Subject with known intention to procreate within 6 months after the index 
procedure (women of child-bearing potential who are sexually active must agree 
to use a reliable method of contraception from the time of screening through 6 
months after the index procedure).  
CE24. Subject is a woman who is pregnant or nursing (a pregnancy test must be 
performed within 7 days prior to the index procedure in women of child-bearing 
potential).  
Angiographic 
Exclusion 
Criteria (visual 
estimate)  
AE1. Target lesion meets any of the following criteria:  
⁃ Left main location. 
⁃ Located within 5 mm of the origin of the left anterior descending (LAD) 
coronary artery or left circumflex (LCX) coronary artery by visual estimate.  
⁃ > 50% stenosis of an additional lesion proximal or distal to the target lesion 
(by visual estimate). 
⁃ Located within a saphenous vein graft or an arterial graft. 
⁃ Will be accessed via a saphenous vein graft or an arterial graft.  
⁃ Involves a complex bifurcation (e.g., bifurcations requiring treatment with 
more than 1 stent).  
⁃ TIMI flow 0 (total occlusion) prior to wire crossing.  
⁃ Excessive tortuosity proximal to or within the lesion.  
⁃ Extreme angulation proximal to or within the lesion.  
⁃ Target lesion and/or target vessel proximal to the lesion is severely calcified 
by visual estimate to expect sub-optimal balloon expansion.  
⁃ Target lesion and/or target vessel adjacent to the target lesion presents with 
dissection or aneurysm by visual estimate.  
⁃ Restenosis from previous intervention (This is applicable only to SV trial.).  
⁃ PCI within 10 mm proximal or distal to the target lesion (by visual estimate) 
at any time prior to the index procedure (This is applicable only to SV 
trial.). 

 
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⁃ Planned treatment of a single lesion with more than 1 investigational device. 
⁃ In-stent restenosis due to stent fracture or recoil (This is applicable only to 
ISR substudy.). 
AE2.  Non-target lesion to be treated during the index procedure meets any of the 
following criteria:  
⁃ Located in the target vessel (This is applicable only to ISR substudy.).  
⁃ Located within a bypass graft (venous or arterial).  
⁃ Left main location.  
⁃ Chronic total occlusion.  
⁃ Involves a complex bifurcation (e.g., bifurcations requiring treatment with 
more than 1 stent).  
⁃ Located within 15 mm of the proximal or distal shoulder of the target lesion 
by visual estimate in the case of the same vessel with a target lesion for 
SV trial. 
AE3. Subject has unprotected left main coronary artery disease (>50% diameter 
stenosis).  
AE4. Thrombus, or possible thrombus, present in the target vessel.  
AE5. Subject with known coronary artery spasm.  
 
9. Subject Accountability 
9.1. 
Point of Enrollment 
Subjects must sign and date the institutional review board (IRB)-approved trial-specific informed consent 
form (ICF) prior to the completion of any trial-related procedure(s). 
The subject must satisfy all clinical inclusion and none of the clinical exclusion prior to the intervention.  
If the subject is found to meet the inclusion criteria during the angiographic phase of the procedure, the 
subject will be considered eligible to be randomized/enrolled.  
SV trial:  
After the Investigator successfully crosses the target lesion with the guidewire and successfully pre-dilates 
the target lesion, a randomization custom function within the Rave EDC database will be used to the test or 
control group. Subjects will be considered enrolled in the trial after they have been successfully randomized 
(i.e. when a treatment assignment is received by the investigative site).  
When the non-target lesion is located distal to the target lesion in the same vessel and in the case that target 
lesion needs pre-dilation prior to the treatment of non-target lesion to cross the device for non-target lesion 
according to investigators decision, protocol-defined pre-dilation for the target lesion could be done before 
the treatment of non-target lesion. After completing treatment of non-target lesion, remaining treatment for 
target lesion can be performed. After confirming completion of successful treatment of non-target lesion, 
subjects will be considered enrolled in the trial after they have been successfully randomized.  
 
ISR substudy: 
After the Investigator successfully crosses the target lesion with the guidewire and successfully pre-dilates 
the target lesion, subjects will be considered enrolled in the ISR substudy. 
If the subject is found to meet inclusion and exclusion criteria, the subject will be considered a screen failure 
and not be randomized/enrolled or receive an investigational device, nor should the subject be followed 
postprocedure per protocol.  
9.2. 
Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) shall be 
accounted for and documented. If a subject withdraws from the clinical investigation, the reason(s) shall be 
reported. If such withdrawal is due to problems related to investigational device safety or performance, the 

 
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investigator shall ask for the subject’s permission to follow his/her status/condition outside of the clinical 
study. 
Subjects may withdraw from the trial at any time by notifying the trial investigator. The investigator may 
also terminate a subject’s participation in the trial (ie, if the subject routinely fails to complete required trial 
procedures or if the investigator believes it is in the subject’s best interest).  
Examples of reasons for trial withdrawal include, but are not limited to, those listed below:  
 
Failure to comply with the trial-required visit schedule 
 
Subject is lost to follow-up  
 
Subject voluntarily withdraws from the trial 
 
Adverse event such that continued trial participation would not be in the best interest of the subject  
 
Withdrawal of the subject by the investigator  
 
Subject death 
It is recommended that the reason for subject withdrawal is also documented in the subject’s medical record. 
If applicable, the investigator will attempt to complete an adverse event and/or device deficiency assessment 
prior to the subject’s withdrawal from the trial. All applicable electronic case report forms (eCRFs) are to be 
completed for all subjects who are enrolled in the trial and are then withdrawn from the trial for any reason. 
Withdrawn subjects will not undergo any further trial follow-up, nor will they be replaced because the 
justified sample size considers an estimated allowance for attrition. Data already collected will be retained 
and reported, however, no new data will be collected after the withdrawal. 
Withdrawn subjects will be followed according to the investigational center’s standard procedures. Serious 
adverse device-effects classified as related to the investigational device that are still ongoing at the end of 
the subject’s participation in the trial will be followed up for resolution status and this information will be 
provided to Boston Scientific for the purpose of regulatory agency reporting for the trial.  
9.3. 
Lost to Follow-Up 
Additional actions must be taken when a participant fails to attend a required study visit: 
The investigational center personnel will attempt to contact the study subject and reschedule the missed visit 
(within the visit window if possible) and counsel the subject on the importance of maintaining the assigned 
visit schedule.  
Prior to withdrawing a subject as lost to follow-up, the investigational center’s personnel must make at 
minimum 3 documented attempts (1 in writing and sent via a traceable method) to bring the subject in for a 
final trial visit. Other contacts (ie, telephone calls, emails) must be documented in the subject’s records at 
the investigational center. If all attempts to contact that subject have failed, the investigational center will 
withdraw the subject.  
9.4. 
End-of-Study Definition 
The trial will be considered complete (with regards to the primary endpoint) after all enrolled subjects have 
completed the 6 months follow-up visit, are withdrawn prior to 6 months follow-up visit, have died, or the 
last 6 months follow-up visit window is closed.  
The trial will be considered complete (with regards to all follow-up) after all enrolled subjects have 
completed the 60 months follow-up visit, are withdrawn prior to 60 months follow-up visit, have died, or the 
last 60 months follow-up visit window is closed.  
 
10. Trial Methods 
10.1. Data Collection 
The data collection schedule is shown in Table 10.1-1.  

 
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Table 10.1-1: Data Collection Requirements by Visit 
 
≤ 14 Days 
Before 
Procedure 
Procedure 
Postproced
ure/ 
Prehospital 
Discharge 
30 Day  
(±14 Day)a 
Telephone 
Interview 
or Office 
Visit 
6 Month  
(±30 Day)a 
Office Visit 
12 Month 
(±30 Day)a 
Office Visit 
24 Month  
(±30 Day)a 
Office Visit 
36 Month  
(±30 Day)a 
Office Visit 
48 Month 
(±30 Day)a 
Telephone 
Interview 
or Office 
Visit 
60 Month  
(±30 Day)a 
Telephone 
Interview 
or Office 
Visit 
Informed consent form, including informed 
consent signature date 
X 
 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 
Physical assessment, including weight and 
height 
X 
 
 
 
 
 
 
 
 
 
Medical history  
X 
 
 
 
 
 
 
 
 
 
Angina assessment  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D 
X 
 
X 
 
X 
X 
X 
X 
 
 
LVEFb 
X 
 
 
 
 
 
 
 
 
 
12-lead ECG  
X 
 
X 
 
X 
 
 
 
 
 
Laboratory tests  
 
 
 
 
 
 
 
 
 
 
Serum creatinine/ WBC and platelets  
X 
 
 
 
 
 
 
 
 
 
Pregnancy testc 
X 
 
 
 
 
 
 
 
 
 
Cardiac enzymes (CK or troponin)  
Xd 
 
Xe 
 
 
 
 
 
 
 
Cardiac medications  
X 
 
X 
 
 
 
 
 
 
 
Antithrombotic medications  
 
X 
 
 
 
 
 
 
 
 
Antiplatelet medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Most recent previous PCI procedure 
information  
X 
 
 
 
 
 
 
 
 
 
Procedural information  
 
X 
 
 
 
 
 
 
 
 
Randomization/Enrollment  
 
X 
 
 
 
 
 
 
 
 
Angiographic data, images, and technician’s 
worksheet for Angiographic Core Laboratoryf 
 
X 
 
 
X 
 
 
 
 
 
AE and device deficiency assessment  
 
X 
X 
X 
X 
X 
Xg 
Xg 
Xg 
Xg 
a. All follow-up dates will be calculated from the date of the index procedure. An office visit is required for the 6 months , 12 months, 24 months and 36 monts follow-up. 30 days, 48 months and 60 months 
follow-up may be performed via telephone interview with the subject if the subject is unable to return for an office visit within the applicable follow-up window. Subjects who are enrolled but who do not 
receive a treatment by investigational device will be followed through 30 days only to assess for the safety.  
b. LVEF may be evaluated by angiography, echocardiogram, or radionuclide ventriculography within 30 days prior to enrollment.  
c. A pregnancy test must be performed within 7 days prior to the index procedure in women of childbearing potential.  
d. Preprocedure cardiac enzymes can be drawn from the sheath at the time of sheath insertion.  
e. Two cardiac enzyme draws must be obtained at intervals per standard of care within 24 hours after the index procedure. The first draw should be performed 6-12 hours postprocedure and the second draw 
should be performed 18-24 hours postprocedure. If the subject is discharged prior to 18 hours postprocedure, the second draw should be obtained at the time of discharge (it is recommended that in these cases 
the second draw occur no earlier than 16 hours postprocedure).  

 
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≤ 14 Days 
Before 
Procedure 
Procedure 
Postproced
ure/ 
Prehospital 
Discharge 
30 Day  
(±14 Day)a 
Telephone 
Interview 
or Office 
Visit 
6 Month  
(±30 Day)a 
Office Visit 
12 Month 
(±30 Day)a 
Office Visit 
24 Month  
(±30 Day)a 
Office Visit 
36 Month  
(±30 Day)a 
Office Visit 
48 Month 
(±30 Day)a 
Telephone 
Interview 
or Office 
Visit 
60 Month  
(±30 Day)a 
Telephone 
Interview 
or Office 
Visit 
f. Angiographic data, images, and technician’s worksheets for the index procedure, the follow-up period (6 months) and for the trial during the index procedure and for subsequent target vessel revascularization 
procedures (up to 60 months post index procedure) must be forwarded to the Angiographic Core Laboratory for analysis. 
g. Reporting required through the end of trial for CECs, SADEs, SAEs, ADEs (including USADE/UAD) and ADEs/Device Deficiencies. AEs not related to the investigational device or procedure reported only 
through 12 months follow-up visit. 
Abbreviations: ADE=adverse device effect; AE=adverse event; CK=creatine kinase; PCI=percutaneous coronary intervention; SAE=serious adverse events; SADE=serious adverse device effect; TVR=target 
vessel revascularization; UADE = Unanticipated Adverse Device Effect; USADE = Unanticipated Serious Adverse Device Effect 

 
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10.2. Trial Candidate Screening 
A screening log will be maintained by each investigational center to document selected information about 
potential subjects who fail to meet the AGENT Japan SV trial eligibility criteria for enrollment including the 
reason for screen failure.  
10.2.1. 
Strategies for Recruitment and Retention 
Subjects may be recruited through the investigator’s practice, referring physicians and/or the use of recruitment 
tools. Potential subjects may be identified through an investigational center’s database query (chart reviews) or 
as new or existing patients attend clinic visits. Any information disseminated to potential subjects (eg, 
advertisements, pamphlets, posters) must be reviewed by the investigational center’s IRB prior to use.  
It is important that the investigational center personnel review the trial requirements with subjects to maximize 
compliance with the follow-up schedule and required medication regimen. A stipend may be provided to subjects 
to cover lodging or travel expenses incurred as a result of participation in the AGENT Japan SV trial with in 
accordance with pertinent laws and regulations and per the trial investigational center’s regulations.  
10.3. Informed Consent 
The subject must sign and date the ICF prior to any trial- required testing or procedures.  
Prior to signing the ICF the investigator, or qualified designee, will explain to each potential subject the purpose 
and nature of the trial, procedures, expected trial duration, available alternative therapies, the benefits and risks 
involved with trial participation. 
Trial personnel should explain to the subject that even if the subject agrees to participate in the trial and signs the 
ICF, the angiography assessment may demonstrate that the subject is not a suitable candidate for the trial. Refer 
to Section 9.1. Point of Enrollment.  
10.4. Quality of Life 
The QOL instruments used for the trial will be the EQ-5D for general health. 
The EQ-5D is a descriptive system of health-related quality of life states consisting of five dimensions (mobility, 
self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The 
responses record five levels of severity (no problems/slight problems/moderate problems/severe 
problems/extreme problems) within a particular EQ-5D dimension.  
10.5. Medications 
Antiplatelet medication use will be collected for the trial and reported on the electronic case report forms from 
the time of the pre-procedure visit through the 60 months follow up. Medication data collection at each visit will 
include: a complete listing of the antiplatelet medications the subject is taking, interruptions and cessation.  
Antiplatelet therapy with aspirin and P2Y12 inhibitor (e.g., clopidogrel, ticlopidine, prasugrel or ticagrelor) is 
required to decrease the risk of thrombotic or thromboembolic complications.  
Aspirin 
 
For subjects who have not been taking Aspirin at the time of the index procedure, the loading dose is 
required to be administered not more than 2 hours after the index procedure. 
 
After treatment by investigational device, it is recommened that Aspirin be given for at least 3 months in 
all subjects.  
P2Y12 inhibitor 
 
For subjects who have not been taking P2Y12 inhibitor at the time of the index procedure, the loading dose 
is required to be administered not more than 2 hours after the index procedure. 
 
After treatment by investigational device, it is recommened that P2Y12 inhibitor be given for at least 3 
months in all subjects.  
Note1: Anti-platelet therapy dosing should be according to the local standard care.  

 
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Note2: Additional concomitant medications may be prescribed at the discretion of the treating physician 
according to standard of care.  
10.6. Pre-Procedure Assessments – Within 14 Days Prior to Index Procedure 
The following pre-procedure data must be collected within 14 days prior to the index procedure (unless otherwise 
specified) for all subjects. Results may be available if test has been routinely performed within 14 days prior to 
the index procedure: 
When it is determined a subject does not satisfy the pre-procedure trial eligibility requirements, the trial-related 
procedures will stop, and the subject will be considered a screen failure and receive care according to the center’s 
standard procedures.  
 
Informed consent  
 
Demographics  
⁃ Age at time of consent and gender  
 
Physical assessment  
⁃ Weight and height  
 
Medical/surgical history  
 
Angina assessment  
 
EQ-5D 
 
LVEF  
Note1: LVEF may be evaluated by angiography, echocardiogram, or radionuclide ventriculography within 30 
days prior to enrollment. 
 
12-lead ECG  
 
Laboratory tests  
⁃ Serum creatinine 
⁃ WBC and platelets  
⁃ Cardiac enzymes (CK or troponin)  
Note2: While Troponin is the preferred cardiac enzyme, it is recommended that the same type of cardiac enzymes 
be analyzed prior to the index procedure and postprocedure for a given index hospitalization (i.e., not switching 
from CK MB to troponin or vice versa).  
Note3: Preprocedure cardiac enzymes can be drawn from the sheath at the time of sheath insertion.  
Note4: It is recommended that Preprocedure cardiac enzymes are obtained within 14 days prior to the procedure.  
 
Pregnancy test  
Note5: A pregnancy test must be performed within 7 days prior to the index procedure in women of childbearing  
 
Most recent previous PCI procedure information  
 
Medications  
⁃ Cardiac medications  
⁃ Antitplatelet medications  
10.7. Index Procedure 
Diagnostic angiography will be performed using the investigational center’s standard procedures. The 
investigator will confirm the subject satisfies all clinical inclusion and no clinical exclusion criteria prior to 
randomization/enrollment into the trial. 
Index procedure start time is defined as the time of sheath insertion. If a previously placed sheath is used (ie, 
from an earlier diagnostic procedure), index procedure start time is defined as the time of guide catheter insertion 
into sheath for the interventional procedure. 
An initial bolus of heparin must be administered after insertion of the arterial sheath. In addition, it is 
recommended that heparin administration be repeated as necessary to maintain an activated clotting time (ACT) 
≥250 seconds throughout the interventional portion of the procedure. 

 
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If the subject is found to meet the inclusion criteria during the angiographic phase of the procedure, the subject 
will be considered eligible to be randomized/enrolled. Refer to Section 9.1. Point of Enrollment. 
The Agent DCB will be used in compliance to the directions for use.  
Angiographic images must be sent to the Angiographic Core Laboratory for evaluation.  
10.7.1. 
Multiple Interventions During Index Procedure 
During the index procedure, a maximum of 1 target lesion and 1 non-target lesion (within target vessel or non-
target vessel) may be treated (Treatment of non-target lesion in target vessel is permitted in SV trial.).  
 
If a non-target lesion is treated, it must be treated before the target lesion is treated.  
 
At the time of the index procedure, there must be no revascularizations planned for the target or non-target 
vessels after the index procedure.  
 
In the case of the SV trial, if non-target lesion is located distal to the target lesion in the same vessel and in 
the case that a target lesion needs pre-dilation prior to the treatment of non-target lesion to cross a device 
for the treatment of non-target lesion according to investigators decision, protocol-defined pre-dilation for 
the target lesion could be done before the treatment of non-target lesion. After completing treatment of non-
target lesion, remaining treatment for target lesion can be performed. After confirming completion of 
treatment of non-target lesion, subjects will be considered enrolled in the trial after they have been 
successfully randomized. 
10.7.2. 
Treatment of Non-Target Lesions During the Index Procedure 
A maximum of 1 non-target lesion within the target vessel or the non-target vessel may be treated with a 
commercial device for non-DCB PCI treatment during the index procedure as described above under Multiple 
Interventions During Index Procedure. For the subject to be eligible for enrollment into the study, treatment of 
the non-target lesion must:  
 
Not require additional unplanned treatment.  
 
Must be successfully treated (<50% residual stenosis) prior to treatment of the target lesion. 
 
Have been completed prior to treatment of the target lesion.  
 
In the case of the SV trial, when non-target lesion is located distal to the target lesion in the same vessel 
and in the case that target lesion need pre-dilation prior to the treatment of non-target lesion to cross the 
device for non-target lesion according to investigators decision, protocol-defined pre-dilation for the target 
lesion could be done before the treatment of non-target lesion. 
Note1: Multiple focal stenosis will be considered as a single lesion if they can be completely covered with 1 
commercial device for PCI.  
Note2: Inclusion or exclusion criteria do not apply to treatment of non-target lesions during the index procedure. 
10.7.3. 
Criteria for Pre-index Procedures 
Planned staged PCI procedures are allowed prior to the index procedure. Subjects are excluded from this study 
based on prior procedures if they have had any of the following. 
 
Previous treatment at any time with coronary intravascular brachytherapy. 
 
Target vessel has been treated with Paclitaxel Eluting Stent or Balloon prior to the index procedure.  
 
Target vessel has been treated with any type of PCI (e.g. DES, BMS or PTCA) within 6 months prior to 
the index procedure.  
 
Non-target vessel has been treated with any type of PCI within 24 hours prior to the index procedure.  
 
PCI within 10 mm proximal or distal to the target lesion (by visual estimate) at any time prior to the index 
procedure (This is applicable only to SV trial.).  
10.7.4. 
Randomization/Enrollment 
Prior to enrollment, a subject must meet all of the clinical and angiographic inclusion criteria and none of the 
clinical and angiographic exclusion criteria. 

 
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If the subject is found to meet the eligibility criteria during the angiographic phase of the procedure, the subject 
will be considered eligible to be enrolled.  
SV trial: 
After the investigator successfully crosses the target lesion with the guidewire and successfully pre-dilates the 
target lesion, a randomization custom function within the Rave EDC database will be used to assign randomized 
subjects to the Agent DCB (test) or SeQuent Please DCB(control). The Agent DCB balloons are provided by 
the Sponsor. SeQuent Please DCB are commercially available balloons that the investigative sites utilize from 
their inventory. Subjects will be considered enrolled in the trial after they have been successfully randomized 
(i.e. when a treatment assignment is received by the investigative site). 
 
ISR substudy: 
After the Investigator successfully crosses the target lesion with the guidewire and successfully pre-dilates the 
target lesion, subjects will be considered enrolled in the ISR substudy. 
If the subject is found to meet inclusion and exclusion criteria, the subject will be considered a screen failure and 
not be randomized/enrolled or receive an investigational device, nor should the subject be followed 
postprocedure per protocol. 
Subjects who are enrolled but who do not receive treatment with an investigational device will be followed 
through 30 days only to assess their safety.  
10.7.5. 
Treatment of Target Lesion 
The Directions For Use (DFU) for the Agent DCB is located in the Manual of Operations. Prior to use of the 
device, the treating physician must carefully read and be familiar with the entire DFU. Refer to the DFU for 
detailed instructions about delivery system preparation and placement of the Agent DCB.  
Procedural information must be reported (specific data fields are noted in the electronic database).  
Agent DCB Procedure: 
Optimal target lesion/vessel preparation is required. Successful pre-dilation of the target lesion(s) with optimally 
sized balloon(s) is required before DCB deployment. Preparation will be performed using the investigational 
center’s standard procedures. Successful predilation occurs when the selected balloon opens vessel entry at 
nominal pressure without major (≥ NHLBI Type D) flow-limiting dissection or need for intervention (i.e. 
stenting), and residual angiographic stenosis no greater than 30% (visual estimate) as determined by the 
investigator. 
If the subject is not found to meet the protocol-defined pre-dilation of the target lesion, subject should not be 
enrolled into the trial. No follow up is required. 
Record the following information on pre-dilation balloon(s) used: 
 
Maximum balloon diameter (mm) inflated 
 
Maximum pressure (atmospheres) inflated 
 
Length of time (seconds) inflated 
The recommended Agent DCB inflation time is at least 30 seconds to ensure apposition to the arterial wall and 
to reduce the chance of vessel recoil. Post-dilation may be performed at the discretion of the Investigator. Record 
the following information on post-dilation balloon(s), if utilized:  
 
Maximum balloon diameter (mm) inflated 
 
Maximum pressure (atmospheres) inflated 
 
Length of time (seconds) inflated 
Bail out for peri-procedure dissections and post-procedure dissections (in cases where adequate results could not 
be obtained after using post-dilation balloons; such as in the case of remaining residual stenosis [≥ 50%] or major 
[≥ NHLBI Type D] flow-limiting dissection after post-dilation) will be followed according to the investigational 
center’s standard procedures.   
Haziness, lucency, or filling defects within or adjacent to the ballooned area, and angiographic complications 
such as distal thromboemboli or no reflow, should also be treated per standard practice. All angiographic 
complications that occur should be documented by angiography and submitted to the Angiographic Core 
Laboratory for analysis.  

 
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SeQuent Please DCB Procedure: 
For subjects randomized to the control arm in SV trial, treatment with commercially available SeQuent Please 
DCB (control) should be completed according to each individual device labelling. Bail out for peri-procedure 
dissections and pot procedure dissections will be also followed according to the investigational center’s standard 
procedures. 
10.7.6. 
Acceptable PCI Devices for Non-target Lesion 
If a non-target lesion is treated, it must be treated with following type of PCI devices. 
SV trial: 
Treatment of non-target lesion in target vessel or non-target vessel is acceptable. 
 
Non-target lesion in Target vessel: Commercially available DES or DCB coated with drug other than 
paclitaxcel, BMS, or balloon (POBA) 
 
Non-target lesion in Non-target vessel: Commercially available PCI devices except for investigational 
devices or control devices 
 
ISR substudy: 
Ttreatment of non-target lesion in non-target vessel is acceptable. 
 
Commercially available PCI devices except for investigational devices or control devices 
10.7.7. 
Post-procedure Angiogram 
Perform the post-procedure angiography according to Angiographic Core Laboratory protocol. Angiographic 
images must be sent to the angiographic core laboratory for analysis.  
10.8. End of the Index Procedure 
The index procedure end time is defined as the time the guide catheter is removed after the final angiography. 
The introducer(s) sheaths should be removed as per standard local practice. The following procedures must be 
completed:  
 
Document procedural, target lesion, non-target lesion (if applicable), pre-dilation, post-dilation (if 
applicable), investigational device, and non-investigational device (if applicable) on the appropriate eCRFs.  
 
Medications (Antithrombotic medications and Antitplatelet medications).  
 
AE and device deficiency assessment.  
 
Finalize angiographic procedure film and related required documentation to submit to the Angiographic 
Core Laboratory per instructions set in the Manual of Operations.  
10.9. Postprocedure/ Prehospital Discharge 
The subject may be discharged from the hospital when clinically stable at the Investigator’s discretion. The 
following assessments must be completed prior to hospital discharge.  
 
Angina assessment  
 
EQ-5D 
 
12-lead ECG  
 
Laboratory tests  
⁃ Cardiac enzymes (CK or troponin)  
Note1: Two cardiac enzyme draws must be obtained at intervals per standard of care within 24 hours after the 
index procedure. The first draw should be performed 6-12 hours postprocedure and the second draw should be 
performed 18-24 hours postprocedure.  

 
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Note2: If the subject is discharged prior to 18 hours postprocedure, the second draw should be obtained at the 
time of discharge (it is recommended that in these cases the second draw occur no earlier than 16 hours 
postprocedure).  
Note3: While Troponin is the preferred cardiac enzyme, it is recommended that the same type of cardiac enzymes 
be analyzed prior to the index procedure and postprocedure for a given index hospitalization (i.e., not switching 
from CK MB to troponin or vice versa).  
 
Medications  
⁃ Cardiac medications  
⁃ Antitplatelet medications  
 
AE and device deficiency assessment 
It is important that trial site personnel review the trial requirements with the subject to maximize compliance 
with the follow-up schedule and required medication regimen as per standard local practice. It is also important 
that trial site personnel instruct subjects to return for follow-up assessments according to the data collection 
schedule in Table 10.1-1. Study staff should establish a date for the follow-up visit with the subject and if possible, 
schedule the visit at the time of hospital discharge.  
10.10. Re-intervention in the target vessel 
Subjects who require re-intervention of the target vessel during the 60 months follow-up period will be treated 
according to the investigational center’s standard of care. The Agent DCB may not be used for re-intervention 
procedures.  
Angiographic images must be sent to the Angiographic Core Laboratory for analysis.  
10.11. Follow-up Visits 
AGENT Japan SV trial is a single blind trial. Subjects will be blinded to treatment assigned and treatment 
received. All subjects must remain blinded until completion of all 6 months follow-up visits (primary endpoint). 
Subjects will return for trial-required follow-up visits 30 days, 6 months, 12 months, 24 months, 36 months, 48 
months and 60 months post procedure. An office visit is required for the 6 months, 12 months, 24 months and 
36 months follow-up. The 30 days, 48 months and 60 months follow-up may be performed via telephone 
interview with the subject if the subject is unable to return for an office visit within the applicable follow-up 
window. 
Subjects who are enrolled but who do not receive a treatment by investigational device will be followed through 
30 days only to assess for the safety.  
Information on Device Deficiencies as well as all AEs, ADEs, SAEs, SADEs, UADEs and USADEs will be 
monitored and reported to Boston Scientific for from the time of enrollment thorough 1-year follow up.  
Data from the AGENT Japan SV trial collected through 6 months will be submitted as the primary data set for 
Japanese market approval. From 12 months follow-up will continue as planned in this protocol. 
Requirements of each follow-up evaluation are described below.  
10.11.1. 30 Day Follow-up Visit (30 ±14 Days) 
All enrolled subjects must be evaluated 30 days after the index procedure. The following assessments must be 
performed during the 30 days Office Visit/ Telephone Interview. 
Subjects who are enrolled but who do not receive treatment with an investigational device will be followed 
through 30 days only to assess their safety.  
 
Angina assessment  
 
Medications (Antitplatelet medications)  
 
AE and device deficiency assessment  

 
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10.11.2. 6 Month Follow-up Visit (180 ±30 Days) 
All enrolled subjects must be evaluated 6 months after the index procedure. The following assessments must be 
performed during the 6 months office visit. 
Perform the post-procedure angiography according to Angiographic Core Laboratory protocol. Angiographic 
images must be sent to the angiographic core laboratory for analysis.  
 
Angina assessment  
 
EQ-5D 
 
12-lead ECG  
 
Medications (Antitplatelet medications)  
 
Angiography  
 
AE and device deficiency assessment  
10.11.3. 12 Month Follow-up Visit (365 ±30 Days) 
All enrolled subjects must be evaluated 12 months after the index procedure. The following assessments must 
be performed during the 12 months Office Visit.  
 
Angina assessment  
 
EQ-5D 
 
Medications (Antitplatelet medications)  
 
AE and device deficiency assessment  
10.11.4. 24 Month Follow-up Visit (730 ±30 Days) 
All enrolled subjects must be evaluated 24 months after the index procedure. The following assessments must 
be performed during the 24 months Office Visit. 
 
Angina assessment 
 
EQ-5D 
 
Medications (Antitplatelet medications) 
 
AE and device deficiency assessment 
Note: Reporting required through the end of trial for CECs, SAEs, ADEs (including USADE/UAD) and 
ADEs/Device Deficiencies. 
10.11.5. 36 Month Follow-up Visit (1095 ±30 Days) 
All enrolled subjects must be evaluated 36 months after the index procedure. The following assessments must 
be performed during the 36 months Office Visit. 
 
Angina assessment 
 
EQ-5D 
 
Medications (Antitplatelet medications) 
 
AE and device deficiency assessment 
Note: Reporting required through the end of trial for CECs, SAEs, ADEs (including USADE/UAD) and 
ADEs/Device Deficiencies. 

 
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10.11.6. 48 Month Follow-up Visit (1460 ±30 Days) 
All enrolled subjects must be evaluated 48 months after the index procedure. The following assessments must 
be performed during the 48 months Office Visit/ Telephone Interview. 
 
Angina assessment 
 
Medications (Antitplatelet medications) 
 
AE and device deficiency assessment 
Note: Reporting required through the end of trial for CECs, SAEs, ADEs (including USADE/UAD) and 
ADEs/Device Deficiencies. 
10.11.7. 60 Month Follow-up Visit (1825 ±30 Days) 
All enrolled subjects must be evaluated 60 months after the index procedure. The following assessments must 
be performed during the 60 months Office Visit/ Telephone Interview. 
 
Angina assessment 
 
Medications (Antitplatelet medications) 
 
AE and device deficiency assessment 
Note: Reporting required through the end of trial for CECs, SAEs, ADEs (including USADE/UAD) and 
ADEs/Device Deficiencies. 
10.12. Trial Completion 
The trial will be considered complete (with regards to the primary endpoint) after all enrolled subjects have 
completed the 6 months follow-up visit, are withdrawn prior to 6 months follow-up visit, have died, or the last 6 
months follow-up visit window is closed.  
The trial will be considered complete (with regards to all follow-up) after all enrolled subjects have completed 
the 60 months follow-up visit, are withdrawn prior to 60 months follow-up visit, have died, or the last 60 months 
follow-up visit window is closed.  
10.13. Missed or Late Visits 
Every effort must be made by the site to retain study subjects for the duration of the study. Missed or late visits 
will be recorded as Protocol Deviations.  
10.14. Source Documents 
The investigator is responsible for the preparation, review and retention of records used for the trial. It is 
preferable that original source documents are maintained, when available. In lieu of original source documents, 
certified copies are required to be maintained. A certified copy is a copy (irrespective of the type of media used) 
of the original record that has been verified (ie, by a dated signature or by generation through a validated process) 
to have the same information, including data that describes the context, content, and structure, as the original.  
The investigator will, at minimum, maintain the following accurate, complete and current records relating to the 
investigator’s participation in the trial. 
 
Correspondence with another investigator, an IRB, the sponsor or a monitor including required reports  
 
Records of receipt, use or, disposition of test devices 
 
Records supporting each subject’s case history and exposure to the device. Case histories supporting data 
(source documentation)  
 
Signed and dated ICFs 
 
Medical records (ie, progress notes of the physicians, the subject hospital and clinic charts and the nurses 
notes 

 
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 
All reportable adverse event and adverse device effects information  
 
Clinical investigational plan and any amendments  
 
Kiki-Gaiyosho  
 
Signed clinical study agreement  
 
Center personnel trial training records  
 
11. Statistical Considerations 
This section describes statistical approaches of this study. More details will be described in a separate statistical 
analysis plan.  
11.1. Endpoints for SV study 
11.1.1. 
Primary Endpoint 
The primary endpoint in this trial is the TLF rate for SV study at 6 months post index-procedure. TLF is defined 
as any ischemia driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-wave and non–
Q-wave) related to the target vessel, or cardiac death. The missing values are excludeｄ from both of numerator 
and denominator.  
11.1.1.1. Hypotheses 
The primary endpoint in this trial is 6-month TLF of test group is non-inferior less than 13.2% to that of control 
group. If the resulting p-value become less than 0.025 (one-sided), it is regarded this endpoint is met. This is 
corresponding to the exact 97.5% lower confidence limit exceeding the Non-inferiority margin.  
11.1.1.2. Sample Size 
 
Agent DCB (test group) expected rate = 3.1% 
 
SeQuent Please DCB (control group) expected rate = 3.1% 
 
Non-inferiority margin (Δ) = 13.2% 
 
Test significant level (α) = 2.5% (one-sided) 
 
Statistical Power = 80% 
 
Total evaluable subjects = 144. (Agent DCB (2) : SeQuent Please DCB (1) = 96:48) 
 
Expected attrition rate = Approximately 3% 
 
Total subjects to be enroll = 150 subjects (100 Agent DCB, 50 SeQuent Please DCB) 
With this sample size (144 subjects), if the scientific significant difference falls into 4.1% (8.3% (8/96) Agent 
DCB, 4.2% (2/48) SeQuent Please DCB), it is still achievable.  
11.1.1.3. Statistical Methods 
The one-sided non-inferiority test of Agent DCB group against SeQuent Please group is to be done by The 
Farrington-Manning score test.  
H0： PAgent DCB_6MTLF– PSeQuent Please DCB_6MTLF ≥ Δ （inferior） 
H1： PAgent DCB_6MTLF– PSeQuent Please DCB_6MTLF < Δ （non-inferior） 
Where PAgent DCB 6MTLF and P SeQuentPlease DCB 6MTLF are then 6-months TLF rates for the Agent DCB group and 
SeQuent Please DCB group, respectively, and Δ is the non-inferiority margin. 

 
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11.2. Endpoints for ISR substudy 
11.2.1. 
Primary Endpoint 
The primary endpoint in this trial is the TLF rate for ISR substudy at 6 months post index-procedure. TLF is 
defined as any ischemia driven revascularization of the target lesion (TLR), myocardial infarction (MI, Q-wave 
and non–Q-wave) related to the target vessel, or cardiac death. The missing values are excludeｄ from both of 
numerator and denominator.  
11.2.1.1. Hypotheses 
The descriptive statistics only planned. 
11.2.1.2. Sample Size 
The sample size calculation for the primary endpoint of TLF at 6-month is based on the following assumptions: 
 
95% confidence interval with +/-10% accuracy 
 
Expected TLF event rate = 3-7% 
 
Number of evaluable subjects = 28 
 
Expected attrition rate = 4% 
 
Number of planned enrollments = 30 subjects 
11.2.1.3. Statistical Methods 
The descriptive statistics aer to be calculated. 
Taking into account the SeQuent Please DCB Japanese stusy, TLR event rate was 5.5% (3/55 leasion). The 
upper side of 95% both side confidence interval of 15.1% is set as the study success criteria.  
In this case, 4/28 (14.3%) is regard as study success. 
11.3. General Statistical Methods 
11.3.1. 
Analysis Sets 
The primary and pre-specified additional endpoints/measurements will be analyzed on an intention to treat (ITT) 
basis and on a per-protocol basis.  
For the ITT analysis, all subjects who sign the written ICF（see section 19） and are randomized/enrolled in 
the study will be included in the analysis sample as randomized, regardless of whether the study devices 
are used. PP analysis set is, in the ITT set, used a study device, but is based on the treatment actually used (as 
treated) no major violation was found which affect to the safety of each subjects, and/or no deviation which 
affect to the conclusion of study results. 
The primary analysis for primary variables are based on ITT set.  
11.3.2. 
Control of Systematic Error/Bias 
Selection of subjects will be made from the investigator’s usual patient load. All patients meeting the eligibility 
criteria and having signed the ICF will be eligible for enrollment in the study. In case of SV trial, after the 
investigator successfully crosses the target lesion with the guidewire and successfully pre-dilates the target lesion, 
a randomization custom function within the Rave EDC database will be used to assign randomized subjects to 
the Agent DCB (test) or SeQuent Please DCB(control). The Agent DCB balloons are provided by the Sponsor. 
SeQuent Please DCB are commercially available balloons that the investigative sites utilize from their inventory. 
Subjects will be considered enrolled in the trial after they have been successfully randomized (i.e. when a 
treatment assignment is received by the investigative site). In case of ISR substudy, after the Investigator 
successfully crosses the target lesion with the guidewire and successfully pre-dilates the target lesion, subjects 
will be considered enrolled in the ISR substudy. 

 
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To control for inter-observer variability among sites, a central Core Lab (see section 12.3) and an independent 
CEC (see section 20.3) will evaluate each data. By the standardized procedure, Core Lab Evaluate the 
angiography, and CEC evaluate the major adverse events.  
11.3.3. 
Number of Subjects per Investigative Site 
To avoid any center effect and bias, one center will not be authorized to implant or attempt more than 17% of 
the maximum number of subjects (i.e 25 subjects) and more than 50% of the maximum number of subjects (i.e 
15 subjects) into the SV study and ISR substudy separately.   
11.4. Data Analyses 
Descriptive statistics will be presented on the trial results by treatment group for randomized subjects. For 
continuous variables, summaries will include the sample size (N), mean, standard deviation, minimum, median 
and maximum. Frequency tables will be used to summarize discrete variables. The difference between 
comparison groups and its both sided 95% exact confidence intervals will be calculated. 
The data until 6 months will be summarized and submitted to the regulatory agency for approval of shonin 
application. 60 months FU data will be continued to collect as per protocol. Once the investigational device is 
granted regulatory approval in Japan, subjects will continue protocol required follow-up as part of a postmarket 
clinical trial (by interpreting the word “study” in this protocol as “post-market clinical trial”). 
11.4.1. 
Other Endpoints/Measurements 
The other parameters describe in section 6.2. those have no statistical hypothesis and then descriptive statistics 
are summarized mainly, but statistical tests as reference. 
For SV study, The TLR rate, TLF rate, TVR rate, TVF rate, MI(Q , non-Q) rate, cardiac death rate , All death 
rate, cardiac death or MI rate, All death or MI rates, All death and MI and TVR rate, thrombosis related to target 
lesion rate may include Kaplan-Meire cumulative events rate(until 1825 days post procedure) and it associated 
95% CI of difference at day 30,182 and 365, 730, 1095, 1460 and 1825 post procedure also be calculated.  
11.4.2. 
Interim Analyses 
No formal interim analyses are planned.  
11.4.3. 
Subgroup Analyses 
Analyses will be performed for each endpoint to determine whether significant differences exist in endpoint 
results between subgroups. The list of subgroups (with applicable definitions in parentheses) includes, but is 
not necessarily limited to:  
List of sub group for SV trial;  
 
Lesion (single treatment vs multi treatment) 
 
Sex (Female vs. Male) 
 
Age (< 65 years vs. ＞ 65 years and ≥ 75 years vs. 75 years≥) 
 
Lesion Characteristics (Reference vessel diameter, Target lesion length, quartiles based) 
 
Balloon size, Balloon diameter 
 
Additional stenting (Y/N) 
 
EQ-5D (quartiles based) 
 
Diabetes (medicine Y/N) 
 
Antitplatelet medications (pre proc.Y/N, post proc until 6months Y/N) 
 
Pre-dilation (Y/N) 
 
Smoking (current Y/N) 
 
Complications (each disease Y/N, cardiac history Y/N) 

 
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11.4.4. 
Justification of Pooling 
Not appreciable. 
11.4.5. 
Multivariable Analyses 
To explore predicted covariates for primary parameters, univariate and multivariate analyses to be performed 
(if applicable logistic model for binary variable, cox regression for time-to-event data). Details will be 
described in the Statistical Analysis Plan.  
11.4.6. 
Other Analyses 
Handling of dropouts and missing data will depend on their frequency and the nature of the outcome measure. 
Sensitivity analyses (e.g., tipping-point analysis) will be performed to assess the impact of subjects with 
inadequate follow-up (i.e., missing data) on the primary endpoint and to assess the robustness of the conclusion 
of the primary analysis.  Statistical models that account for censored data will be employed in appropriate 
circumstances (e.g., for time-to-event outcomes). Suspected invalid data will be queried and corrected in the 
database prior to statistical analysis. Additional information may be found in the Statistical Analysis Plan.  
11.4.7. 
Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the interim and full primary analyses 
(i.e. unblinding) will be documented in an amended Statistical Analysis Plan approved prior to performing the 
analyses. Changes from the planned statistical methods after performing the analyses will be documented in the 
clinical trial report along with a reason for the deviation.  
 
12. Data Management 
12.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) system. 
The clinical database will reside on a production server hosted by Medidata EDC System. All changes made to 
the clinical data will be captured in an electronic audit trail and available for review by sponsor or its 
representative. The associated Rave software and database have been designed to meet regulatory compliance 
for deployment as part of a validated system compliant with laws and regulations applicable to the conduct of 
clinical trials pertaining to the use of electronic records and signatures. Database backups are performed regularly.  
The investigator is responsible for the accuracy, completeness and timeliness of the data submitted and must 
review all data for accuracy and provides his/her electronic signature on the appropriate electronic case report 
forms (eCRFs) in compliance with local regulations. A written signature on printouts of the eCRFs must also be 
provided if required by local regulation. Changes to data previously submitted to the sponsor require a new 
electronic signature by the investigator acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data discrepancies. Manual and/or 
automatic queries will be created in the Medidata EDC system and will be issued to the site for appropriate 
response. Site staff will be responsible for resolving all queries in the database.  
12.2. Data and Record Retention 
The Principal Investigator or his/her desginee and Investigational site will maintain all essential trial documents 
and source documents, in original format, that support the data collected on study patients in compliance with 
GCP guidances. Documents must be retained for at least 3 years after the last approval of marketing application 
or the formal discontinuation of the clinical investigation of the device, whichever is longer. 
When these documents no longer need to be maintained, it is BSJ’s responsibility to inform the Investigator and 
Site. The Investigator and Site will take measures to ensure that these essential documents are not accidentally 
damaged or destroyed. If for any reason the Investigator and Site withdraw responsibility for maintaining these 

 
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essential documents, custody must be transferred to an individual who will assume responsibility. BSJ must 
receive written notification of this custodial change. 
If subjects will continue protocol required follow-up as post-market clinical trial, the investigator must maintain 
necessary essential documents for 3 years from the date of the marketing application approval or during the 
period of user-results evaluation, whichever is longer. BSJ must retain essential documents in accordance with 
GCP guidances and Good Post marketing Surveillance Practice and Test of Medical Devices (Ministrial 
Ordinance 38, 23 March, 2005). 
12.3. Core Laboratory 
The Angiographic core laboratory is planned for the AGENT Japan SV trial to assess angiograms taken during 
the index procedure and the follow-up period (6 months) and angiograms collected for the trial during the index 
procedure and for subsequent target vessel revascularization procedures (up to 60 months post index procedure). 
Detailed guidelines for the collection, analysis, and interpretation of the following data will be provided in the 
Manual of Operations.  
 
13. Deviations 
A trial deviation occurs when the investigator or the investigationali center personnel did not conduct the clinical 
trial according to the clinical protocol, clinical study agreement, or applicable laws and regulations.  
An Investigator must not make any changes or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency. An investigator shall notify the sponsor and the reviewing IRB of any 
deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency, 
and those deviations which affect the scientific integrity of the clinical investigation. Such notice shall be given 
as soon as possible, but no later than 5 working days after the emergency occurred. 
Deviations may include but are not limited to: 
 
Failure to obtain subject informed consent prior to beginning trial activities 
 
Violation of inclusion/exclusion criteria 
 
Failure to report serious or unanticipated adverse device effect or serious or unexpected AEs 
 
Failure to collect protocol-required assessments 
 
Subject missed visit or visit outside of window 
All deviations from the investigational plan, with the reason for the deviation and the date of occurrence, must 
be documented and reported to the sponsor using EDC system. Investigational centers will also be required to 
report deviations to the IRB, per local guidelines and government regulations. 
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate corrective and 
preventive actions (including IRB and regulatory authority notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor.  
 
14. Device Accountability 
The investigational devices shall be securely maintained, controlled, and used only in this clinical trial. The 
Medidata RAVE EDC will be used to track subjects and the device management vendor, Cenduit LLC, will 
track device allocations throughout the trial enrollment.  
The sponsor’s device management vendor shall keep records to document the physical location of all 
investigational devices from shipment of investigational devices from BSJ or designated facility/equipment to 
the investigation sites until return or disposal. Records shall be kept by the device management vendor, Fisher 
Clinical Services, to document the physical location and conditions of storage of all investigational devices. 
The principal investigator or an authorized designee shall keep records documenting the receipt, use, return and 
disposal of the Agent DCB (test) devices, which shall include the following: 
 
Date of receipt 

 
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 
Identification of each investigational device (lot number or unique code) 
 
Expiry date, as applicable 
 
Date or dates of use 
 
Subject identification 
 
Date on which the investigational device was returned, if applicable 
 
Date of return (and number) of unused, expired, or malfunctioning investigational devices, if applicable. 
 
Date on which the investigational device was discarded, if applicable 
 
15. Compliance 
15.1. Statement of Compliance 
The AGENT Japan SV clinical trial will be conducted in accordance with the ethical principles that have their 
origins in the Declaration of Helsinki and that are consistent with Good Clinical Practices (GCP), Order for 
Enforcement of the Pharmaceutical and Medical Device Law, regulatory requirements and this protocol. The 
study shall not begin until the required approval from the IRB and/or favorable opinion from regulatory authority 
has been obtained, if appropriate. Also, the study shall not begin prior to issuance of the site Authorization to 
Enroll, as provided by BSJ. Any additional requirements imposed by the IRB or regulatory authority shall be 
followed, if appropriate.  
15.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study is conducted in 
accordance with the Clinical Study Agreement, the clinical investigational plan, GCP, ethical principles that 
have their origins in the Declaration of Helsinki, any conditions of approval imposed by the reviewing IRB, and 
Pharmaceutical and Medical Device Law, Regulatory authority, whichever affords the greater protection to the 
subject.  
The Principal Investigator’s responsibilities include, but are not limited to, the following. 
 
Prior to beginning the study, sign the Clinical Study Agreement and comply with the Investigator 
responsibilities as described in such Agreement. 
 
Prior to beginning the study, sign the Protocol Signature page documenting his/her agreement to conduct 
the study in accordance with the protocol. 
 
Provide his/her qualifications and experience to assume responsibility for the proper conduct of the study 
and that of key members of the site team through up-to-date curriculum vitae or other relevant 
documentation. 
 
Make no changes in or deviate from this protocol, except to protect the life and physical well-being of a 
subject in an emergency; document and explain any deviation from the approved protocol that occurred 
during the course of the clinical investigation. 
 
Create and maintain source documents throughout the clinical study and ensure their availability with direct 
access during monitoring visits or audits; ensure that all clinical-investigation-related records are retained 
per requirements. 
 
Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the CRFs 
and in all required reports. 
 
Record, report, and assess (seriousness and relationship to the device/procedure) every adverse event as 
applicable per the protocol and observed device deficiency. 
 
Report to sponsor, per the protocol requirements, all serious adverse events (SAEs) and device deficiencies 
that could have led to a serious adverse device effect (SADE) and potential unanticipated serious adverse 
device effect (USADE) or unanticipated adverse device effect (UADE) 
 
Report to the IRB and regulatory authorities any SAEs and device deficiencies that could have led to a 
SADE and potential/USADE or UADE, if required by applicable laws or regulations or this protocol or by 
the IRB, and supply Boston Scientific (or delegate) with any additional requested information related to the 
safety reporting of a particular event 

 
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 
Maintain the control of the device, ensuring that the investigational device is used only by 
authorized/designated users and in accordance with this protocol and instructions/directions for use. 
 
Allow the sponsor to perform monitoring and auditing activities, and be accessible to the clinical research 
monitor or auditor and respond to questions during monitoring visits or audit(s). 
 
Allow and support regulatory authorities and the IRB when performing auditing activities. 
 
Ensure that informed consent is obtained in accordance with applicable laws, this protocol and local IRB 
requirements. 
 
Provide adequate medical care to a subject during and after a subject’s participation in a clinical study in 
the case of adverse events, as described in the Informed Consent Form (ICF). 
 
Inform the subject of the nature and possible cause of any adverse events experienced. 
 
Inform the subject of any new significant findings occurring during the clinical investigation, including the 
need for additional medical care that may be required. 
 
Provide the subject with well-defined procedures for possible emergency situations related to the clinical 
study, and make the necessary arrangements for emergency treatment, including decoding procedures for 
blinded/masked clinical investigations, as needed 
 
Ensure that clinical medical records are clearly marked to indicate that the subject is enrolled in this clinical 
study. 
 
Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided with some means of 
showing their participation in the clinical investigation, together with identification and compliance 
information for concomitant treatment measures (contact address and telephone numbers shall be provided). 
 
Inform, with the subject’s approval or when required by national regulations, the subject’s personal 
physician about the subject’s participation in the clinical investigation. 
 
Make all reasonable efforts to ascertain the reason(s) for a subject’s premature withdrawal from clinical 
investigation while fully respecting the subject’s rights. 
 
Ensure that an adequate investigation site team and facilities exist and are maintained and documented 
during the clinical investigation. 
15.2.1. 
Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting the informed 
consent process, the Principal Investigator is responsible for providing appropriate training, are competent to 
perform the tasks they have been delegated and adequate supervision of those to whom tasks are delegated. 
Where there is a sub investigator at a center, the sub investigator should not be delegated the primary supervisory 
responsibility for the investigational site. The investigator is accountable for regulatory violations resulting from 
failure to adequately supervise the conduct of the clinical study. 
15.3. Institutional Review Board 
The investigational site will obtain the written and dated approval/favorable opinion of the IRB for the clinical 
investigation before recruiting subjects and implementing all subsequent amendments, if required. 
A copy of the written IRB approval of the protocol (or permission to conduct the study) and ICF, must be 
received by the sponsor (or designee) before recruitment of subjects into the study and shipment of 
investigational product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB before the changes are implemented 
to the study. All changes to the ICF will be IRB approved; a determination will be made regarding whether a 
new ICF needs to be obtained from participants who provided consent, using a previously approved ICF. Annual 
IRB approval and renewals will be obtained throughout the duration of the study as required by IRB requirements. 
Copies of the study reports and the IRB continuance of approval must be provided to the sponsor (or designee).  
15.4. Sponsor Responsibilities 
The clinical trial organization in Japan, including investigational sites in Japan, is provided as an attachment to 
the protocol.  

 
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All information and data sent to Boston Scientific (or delegate) concerning subjects or their participation in this 
study will be considered confidential by Boston Scientific and will be kept confidential. Only authorized Boston 
Scientific personnel and/or a Boston Scientific representative including, but not limited to Contract Research 
Organization (CRO), will have access to this information. Authorized regulatory personnel have the right to 
inspect and copy all records pertinent to this study. Study data collected during this study may be used by Boston 
Scientific for the purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical research and proposals 
for developing new medical products and procedures. All data used in the analysis and reporting of this study or 
shared with a third-party researcher will be without identifiable reference to specific subjects.  
Boston Scientific will keep subjects’ identifiable health information confidential in accordance with all 
applicable laws and regulations. Boston Scientific may use subjects’ health information to conduct this research, 
as well as for additional purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products or procedures, and other business purposes. 
Information received during the study will not be used to market to subjects; subject names will not be placed 
on any mailing lists or sold to anyone for marketing purposes.  
Note: BSJ may utilize a contract research organization (CRO) or other contractors to act as its representative for 
carrying out designated tasks. Responsibilities for these entities are defined in the applicable contracts or 
agreements. Contact information for the CROs is provided as an attachment to the protocol or in the study 
Manual of Operations (MOP).  
15.4.1. 
Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health care personnel 
(collectively HCP) as needed during implant, testing required by the protocol, and follow-ups. Support may 
include HCP training, addressing HCP questions, or providing clarifications to HCPs concerning the operation 
of Boston Scientific devices.  
In addition, Boston Scientific personnel may perform certain activities to ensure study quality. These activities 
may include the following. 
 
Observing testing or medical procedures to provide information relevant to protocol compliance 
 
Reviewing collected data and study documentation for completeness and accuracy 
 
Boston Scientific personnel will not do the following. 
 
Practice medicine 
 
Provide medical diagnosis or treatment to subjects 
 
Discuss a subject’s condition or treatment with a subject 
 
Independently collect critical study data (defined as primary endpoint data) 
 
Enter data in electronic data capture systems or on paper case report forms 
15.5. Reimbursement and Compensation 
Subject Reimbursement: Travel and other expenses incurred by subjects as a result of participation in the study 
will be reimbursed in accordance with pertinent Regulations and per the investigational sites.  
Compensation for Subject’s Health Injury: BSJ will stipulate an insurance policy to cover potential health injury 
for study subjects. If any study related health injury occurs and a site is held responsible for its compensation, 
BSJ will assume the responsibility, except in the case those damages are incurred due to intentional misconduct 
or negligence at the site.  
 
16. Monitoring 
Monitoring will be performed to assess continued compliance with the protocol and applicable regulations. The 
monitoring plan contains the strategy for frequency of monitoring visits and source data verification to be 
completed for the trial. 

 
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The monitor verifies that trial records are adequately maintained, that data are reported in a satisfactory manner 
with respect to timeliness, adequacy, and accuracy, and that the investigator continues to have sufficient staff 
and facilities to conduct the trial safely and effectively. The investigator/institution guarantees direct access to 
original source documents (ie, paper and electronic hospital charts, appointment books, laboratory records) by 
Boston Scientific personnel, their designees, and applicable regulatory authorities. 
The trial may also be subject to a quality assurance audit by Boston Scientific or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the principal investigator and relevant trial 
personnel are available during on-site monitoring visits or audits and that sufficient time is devoted to the process. 
 
17. Potential Risks and Benefits 
17.1. Anticipated Adverse Events and Risks Associated with Use of the Agent DCB 
The following anticipated adverse events (AE) have been identified for this study, but not limited to, the 
following:  
 
Allergic reaction (device, contrast medium, medications) 
 
Arrhythmias 
 
Arteriovenous fistula 
 
Cardiac tamponade/pericardial effusion 
 
Coronary artery bypass graft surgery 
 
Death 
 
Embolization (air, device, plaque, etc.) 
 
Hematoma 
 
Hemodynamic instability 
 
Hemorrhage 
 
Myocardial ischemia 
 
Percutaneous re-intervention 
 
Pseudoaneurysm 
 
Respiratory insufficiency 
 
Sepsis/infection 
 
Slow flow/no reflow 
 
Thromboembolic episodes 
 
Vascular thrombosis 
 
Vasovagal reactions 
 
Vessel injury (e.g., dissection, perforation, rupture) 
 
Vessel occlusion 
 
Vessel spasm 
 
Volume overload 
17.2. Risks Associated with the Trial Device(s) Unique to Paclitaxel  
Certain side effects and discomforts have been reported in subjects that have received paclitaxel in intravenous 
forms as part of chemotherapy treatment. These subjects may have other comorbid conditions and/or have 
received concomitant medications that may also contribute to the reported side effects. In these circumstances 
the dose was delivered throughout the body by the blood and in doses hundreds of times higher than the total 
amount on the coated balloon for use in the proposed clinical trial. Potential adverse events that may be unique 
to the paclitaxel drug coating:  
 
Allergic/immunologic reaction to drug (paclitaxel or structurally-related compounds) or coating or its 
individual components 

 
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 
Alopecia 
 
Anemia 
 
Blood product transfusion 
 
Gastrointestinal symptoms 
 
Hematologic dyscrasia (including leukopenia, neutropenia, thrombocytopenia) 
 
Hepatic enzyme changes 
 
Histologic changes in vessel wall, including inflammation, cellular damage or necrosis 
 
Myalgia/Arthralgia 
 
Peripheral neuropathy 
17.3. Risks associated with Participation in the Clinical Trial 
There may be additional risks linked to the procedure, and follow-up testing which are unforeseen at this time. 
All testing planned for the follow-up period is standard of care.  
17.4. Possible Interactions with Concomitant Medical Treatments 
In addition to the aforementioned risks associated with the treatment of drug coated balloons and the use of 
paclitaxel, the use of prolonged dual antiplatelet therapy after the index procedure may increase the risk of 
bleeding. Refer to the local package insert for further information on drug interactions and side effects associated 
with paclitaxel or antithrombotic/antiplatelet medications. 
17.5. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, performing 
procedures in the appropriate hospital environment, adherence to subject selection criteria, close monitoring of 
the subject's physiologic status during research procedures and/or follow-ups and by promptly supplying Boston 
Scientific with all pertinent information required by this protocol.  
17.6. Anticipated Benefits 
Potential anticipated benefits include the effective treatment of a small vessel de novo coronary artery lesion or 
in-stent restenosis with improvement in the symptoms of disease. However, the Agent DCB is a test device and 
these potential benefits may or may not actually be present.  
17.7. Risk to Benefit Rationale 
The Agent DCB is expected to be suitable for its intended purpose. There are no unacceptable residual 
risks/intolerable risks and all applicable risks have been addressed through the provision of appropriate directions 
for use (DFU) and Kiki-Gaiyosho. The Agent DCB is expected to have an acceptable adverse event profile when 
used under the conditions intended; the benefits associated with the use of the Agent DCB are expected to 
outweigh the risks.  
 
18. Safety Reporting 
18.1. Reportable Events by investigational center to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSJ any event which occurs in any of following 
categories:  
 
All Serious Adverse Events (SAE) 
 
All Investigational Device Deficiencies 
 
Unanticipated Serious Adverse Device Effects (USADE)/ Unanticipated Adverse Device Effects (UADE) 
 
Adverse Device Effect (ADE)/ Serious Adverse Device Effect (SADE) 

 
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 
New findings/updates in relation to already reported events 
 
All other adverse events  
When possible, the medical diagnosis should be reported as the Event Term instead of individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot be isolated from 
the device or procedure, it should be submitted as an adverse event and/or device deficiency.  
Any AE event required by the protocol, experienced by the study subject after informed consent and once 
considered enrolled in the study, whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity or frequency during the course 
of the investigation. Death should not be recorded as an AE, but should only be reflected as an outcome of one 
(1) specific SAE (see Table 18.2-1 for AE definitions). 
Refer to Section 17 for the known risks associated with the study. 
18.2. Definitions and Classification 
Adverse event definitions are provided in Table 18.2-1. Administrative edits were made to combine definitions 
from GCP, Order for Enforcement of the Pharmaceutical and Medical Device Affairs Law, ISO 14155-2011.  
Table 18.2-1: Safety Definitions 
Term  
Definitiona 
Adverse Event (AE)  
 
Ref: GCP,Article 2 Part 20 
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3  
 
Any untoward or unintended disease or injury or untoward clinical signs 
(including an abnormal laboratory finding) occurrence in subjects, users or 
other persons on whom the investigational medical device has been used 
whether or not related to the investigational device.  
 
Note 1: This definition includes events related to the investigational 
medical device.  
Note 2: This definition includes events related to the procedures involved.  
Note 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE)  
 
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274  
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
Adverse event related to the use of an investigational medical device 
An event that is suspected of being caused by the use of an investigational 
medical device or a communicable disease suspected of being caused by 
its use.  
 
Note 1: This definition includes any adverse events resulting from 
insufficiencies or inadequacies in the instructions for use, the deployment, 
the implantation, the installation or operation, or any malfunction of the 
investigational medical device.  
Note 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device.  
Note 3: The definition of “an event that is suspected of being caused by 
the use of an investigational medical device” refers to an event other than 
that whose cause and effect relationship with the investigational medical 
device can be denied, and includes that whose cause and effect 
relationship is uncertain.  
Note 4: The definition of “a communicable disease that is suspected of 
being caused by its use” refers to the suspected contamination of the 
investigational medical device with biological ingredients by pathogen.  

 
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Term  
Definitiona 
Serious Adverse Event (SAE)  
 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
Note: This definition meets the reporting objectives and requirements of 
ISO 14155 and MEDDEV 2.7/3.  
Adverse event that: 
 
Led to death, 
 
Led to serious deteriorationin the health of the subject as defined by 
either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening 
illness or injury or permanent impairment to a body structure 
or a body function  
 
Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect.  
Note: Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event. 
 
Serious Adverse Device 
Effect (SADE) 
 
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Serious adverse effect that is suspected of being caused by the use of an 
investigational medical device or serious communicable disease suspected 
of being caused by its use.  
Unanticipated Adverse Device 
Effect (UADE)  
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the 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.  
Unanticipated Serious 
Adverse Device Effect 
(USADE)  
 
Ref: GCP, Article 28 Part 2 
and 3  
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274  
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of risk analysis 
report, including Chiken Kiki Gaiyo-sho.  
Note: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk analysis report, including Chiken Kiki Gaiyo-sho.  

 
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Term  
Definitiona 
Device Deficiency  
 
Ref: Order for Enforcement of 
the Pharmaceutical and 
Medical Device Law, Article 
274 
Ref: ISO 14155 
Ref: MEDDEV 2.7/3 
 
An inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer.  
Note 1: Device deficiencies include malfunctions, use errors, and 
inadequate labeling.  
Note 2: Regarding investigational medical device, device deficiency 
includes extensive, problematic effects for the quality, safety and 
performance of the investigational medical device such as damage and 
malfunction, and they may occur at any stage including design, deliverly, 
storage,or usage. 
 Note 3: All device deficiencies that could have led to a SAE if a) suitable 
action had not been taken or b) if intervention had not been made or c) if 
circumstances had been less fortunate.  These shall be reported as required 
by the local IRB, regulations in Japan, or the protocol.  
a: Other definitions may apply per local reporting requirements.  
 
A hospitalization for a purpose of tests or a hospitalization that is uncomplicated and elective/planned (i.e.If AEs 
occur during an elective/planned (i.e., planned prior to enrollment) hospitalization after enrollment, the 
complications and AEs must be reported as AEs or SAEs if they meet the protocol-specified definitions. 
Any AE experienced by study subjects beginning from time of enrollment must be reported 
Details on the CEC events and procedures are outlined in the CEC charter. 
18.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the reportable AE to the test device or procedure. See criteria in 
Table 18.3-1.  
Table 18.3-1: Criteria for Assessing Relationship of Trial Device or Procedure to Adverse Event 
Classification  
Descriptiona 
Not Related 
 
Ref: MEDDEV 2.7/3 
Relationship to the device or procedures can be excluded when: the event is not a 
known side effect of the product category the device belongs to or of similar devices 
and procedures; 
 
the event has no temporal relationship with the use of the investigational device 
or the procedures; 
 
the serious event does not follow a known response pattern to the medical 
device (if the response pattern is previously known) and is biologically 
implausible; 
 
the discontinuation of medical device application or the reduction of the level 
of activation/exposure - when clinically feasible – and reintroduction of its use 
(or increase of the level of activation/exposure), do not impact on the serious 
event; 
 
the event involves a body-site or an organ not expected to be affected by the 
device or procedure.  
 
the serious event can be attributed to another cause (e.g. an underlying or 
concurrent illness/ clinical condition, an effect of another device, drug, 
treatment or other risk factors); 
 
the event does not depend on a false result given by the investigational device 
used for diagnosis, when applicable; harms to the subject are not clearly due to 
use error; 

 
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Classification  
Descriptiona 
 
In order to establish the non-relatedness, not all the criteria listed above might 
be met at the same time, depending on the type of device/procedures and the 
serious event. 
Unlikely Related 
 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device or the procedure seems 
not relevant and/or the event can be reasonably explained by another cause, but 
additional information may be obtained.  
Possibly Related 
 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device or the procedure is weak 
but cannot be ruled out completely. Alternative causes are also possible (e.g. an 
underlying or concurrent illness/ clinical condition or/and an effect of another 
device, drug or treatment). Cases were relatedness cannot be assessed or no 
information has been obtained should also be classified as possible.  
Probably Related 
 
Ref: MEDDEV 2.7/3 
The relationship with the use of the investigational device or the procedure seems 
relevant and/or the event cannot be reasonably explained by another cause, but 
additional information may be obtained.  
Causal Relationship 
 
Ref: MEDDEV 2.7/3 
The serious event is associated with the investigational device or with procedures 
beyond reasonable doubt when: 
 
the event is a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
 
the event has a temporal relationship with investigational device 
use/application or procedures; 
 
the event involves a body-site or organ that 
⁃ the investigational device or procedures are applied to; 
⁃ the investigational device or procedures have an effect on; 
 
the serious event follows a known response pattern to the medical device (if 
the response pattern is previously known); 
 
the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
 
other possible causes (e.g. an underlying or concurrent illness/ clinical 
condition or/and an effect of another device, drug or treatment) have been 
adequately ruled out; 
 
harm to the subject is due to error in use; 
 
the event depends on a false result given by the investigational device used for 
diagnosis, when applicable; 
 
In order to establish the relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the 
serious event. 
a: Other definitions may apply per local reporting requirements.  
 
The investigator must assess the relationship of an AE to the antiplatelet medication as related or Not Related. 
See criteria in Table 18.3-2 
Table 18.3-2: Criteria for Assessing Relationship of Antiplatelet Medication to AE 
Classification  
Description  
Not Related 
The adverse event is determined to be due to a concurrent illness or effect of a device/drug 
and is not determined to be potentially related to the antiplatelet medication.  

 
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Classification  
Description  
Related 
The adverse event is determined to be potentially related to the antiplatelet medication, and 
an alternative etiology is equally or less likely compared to the potential relationship to 
antiplatelet medication.  
18.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSJ are as shown in Table 18.4-1.  
Note: The “become aware date” for an event that requires reporting per the protocol is the date that study 
personnel identify or are notified of the event.  
Table 18.4-1: Investigator Reporting Requirements 
Event Classification  
Communication Method  
Communication Timeline  
Unanticipated Serious 
Adverse Device Effect 
(USADE)/ Unanticipated 
Adverse Device Effect 
(UADE)  
Complete adverse event (AE) 
electronic case report form (eCRF) 
page with all available new and 
updated information 
 
Within 1 business day of first 
becoming aware of the event.  
 
Terminating at the end of the 
study. 
Provide copies of all relevant 
source documents (de-identified/ 
pseudonymized) for reported 
events 
 
At request of sponsor. 
Serious Adverse Event 
(SAE) 
Complete AE eCRF page with all 
available new and updated 
information 
 
Within 3 calendar days of first 
becoming aware of the even or 
as per local/regional regulations. 
 
Reporting required through the 
end of the study. 
Provide copies of all relevant 
source documentation (de-
identified/ pseudonymized) for 
reported event.  
 
At request of sponsor. 
Serious Adverse Device 
Effects (SADE) 
Complete AE eCRF page with all 
available new and updated 
information. 
 
Within 3 calendar days of first 
becoming aware of the event or 
as per local/regional regulations.  
 
Reporting required through the 
end of the study. 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported event.  
 
When documentation is available 
at sponsor request.  
Device Deficiencies 
(including but not limited to 
failures, malfunctions, and 
product nonconformities)  
Note: Any Investigational 
Device Deficiency that 
might have led to a serious 
adverse event if a) suitable 
action had not been taken or 
b) intervention had not been 
made or c) if circumstances 
had been less fortunate is 
Complete applicable eCRF 
fields/pages with all available new 
and updated information. 
 
Within 3 calendar days of first 
becoming aware of the event.  
 
Reporting required through the 
end of the study.  
Provide copies of all relevant 
source documentation (de-
identified/ pseudonymized) for 
reported event.  
 
At request of sponsor. 

 
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Event Classification  
Communication Method  
Communication Timeline  
considered a reportable 
event. 
Adverse Event (AE) 
including Adverse Devise 
Effects (ADE) 
Complete AE eCRF page which 
contains such information as date 
of AE, treatment of AE resolution, 
assessnent of seriousness and 
relationship to the device.  
 
In a timely manner (eg, 
Recommend within 10 business 
days) after becoming aware of 
the information. 
 
ADE Reporting required 
through the end of the study. 
 
AE reporting required through 
the 12 months follow-up.  
Provide all relevant source 
documentation (de-
identified/pseudonymized) for 
reported event.  
 
At request of sponsor.  
Note: The AE eCRF page contains information such as date of AE, treatment of AE resolution, assessment of seriousness, and 
relationship to the device.  
Abbreviations: eCRF=electronic case report form  
Source documentation for CEC events to be required by BSJ.  
 
18.5. Boston Scientific Device Deficiencies 
All Boston Scientific device deficiencies including Agent DCB deficiencies (including but not limited to failures, 
malfunctions, use errors, product nonconformities, and inadequacy in the information supplied by the 
manufacturer) will be documented and reported to BSC. If possible, the device(s) should be returned to BSC for 
analysis. Instructions for returning the investigational device(s) will be provided in the Manual of Operations. If 
it is not possible to return the device, the investigator should document why the device was not returned and the 
final disposition of the device. Device failures and malfunctions should also be documented in the subject’s 
medical record. 
Device deficiencies (including but not limited to failures, malfunctions, and product nonconformities) are not to 
be reported as adverse events. However, if there is an adverse event that results from a device failure or 
malfunction, would be recorded as an adverse event on the appropriate eCRF. 
Any Investigational Device Deficiency that might have led to a SAE if a) suitable action had not been taken or 
b) intervention had not been made or c) if circumstances had been less fortunate is considered a reportable 
event. 
18.6. Reporting to Regulatory Authorities / IRBs / Investigators 
BSJ will report to regulatory agency and notify all PIs and head of the investigational sites if any significant 
safety information was received. Additionally, information which implies possible influence to patient’s safety 
and the conduct of the study will also notified to all PIs and the head of the investigational sites. 
 
19. Informed Consent 
Subject participation in this clinical study is voluntary. Informed Consent is required from each subject. The 
Investigator is responsible for ensuring that Informed Consent is obtained prior to the use of any investigational 
devices, study-required procedures and/or testing, or data collection. 
The obtaining and documentation of Informed Consent must be in accordance with the ethical principles that 
have their origins in the Declaration of Helsinki and that are consistent with Good Clinical Practices (GCP), 
Pharmaceutical Affairs Law, regulatory authority and this protocol. The ICF must be accepted by BSJ or its 
delegate (e.g. CRO), and approved by the site’s IRB, or central IRB, if applicable. 

 
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BSJ will provide a study-specific template of the ICF to investigators participating in this study. The ICF 
template may be modified to meet the requirements of the investigative site’s IRB. Any modification requires 
acceptance from BSJ prior to use of the form. The ICF must be in a language understandable to the subject and 
if needed. Privacy language shall be included in the body of the form or as a separate form as applicable. 
The process of obtaining Informed Consent shall at a minimum include the following steps, as well as any other 
steps required by applicable laws, rules, regulations and guidelines: 
 
be conducted by the Principal Investigator or designee authorized to conduct the process, 
 
include a description of all aspects of the clinical study that are relevant to the subject’s decision to 
participate throughout the clinical study, 
 
avoid any coercion of or undue influence of subjects to participate, 
 
not waive or appear to waive subject’s legal rights, 
 
will use native language that is non-technical and understandable to the subject, 
 
provide ample time for the subject to consider participation and ask questions if necessary, 
 
ensure important new information is provided to new and existing subjects throughout the clinical study. 
The ICF shall always be signed and personally dated by the subject to sign the ICF under the applicable laws, 
rules, regulations and guidelines and by the investigator and/or an authorized designee responsible for conducting 
the informed consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original signed ICF will be 
retained by the site and a copy of the signed and dated document and any other written information must be 
given to the person signing the form. Informed Consent signature can be replaced by printed name and seals of 
appropriate individuals. 
If new information becomes available that can significantly affect a subject's future health and medical care, that 
information shall be provided to the affected subject(s) in written form via a revised ICF or, in some situations, 
enrolled subjects may be requested to sign and date an addendum to the ICF. In addition to new significant 
information during the course of a study, other situations may necessitate revision of the ICF, such as if there are 
amendments to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB. The new version of the ICF must be approved by the IRB. Acceptance by 
Boston Scientific Japan K.K. is required if changes to the revised ICF are requested by the site’s IRB. The IRB 
will determine the subject population to be re-consented. 
Study personnel should explain to the subject that even if the subject agrees to participate in the trial and signs 
the ICF, catheterization may demonstrate that the subject is not a suitable candidate for the trial. A Screening 
Log will be maintained by the investigational site to document select information about candidates who fail to 
meet the trial eligibility criteria, including, but not limited to, the reason for screen failure. 
 
20. Committees 
20.1. Executive Committee 
An Executive Committee composed of Boson Scientific Clinical Management and selected Coordinating 
Principal Investigator(s) will be convened. This committee will be responsible for the overall conduct of the 
study which will include protocol development, study progress, subject safety, overall data quality and integrity, 
and timely dissemination of study results through appropriate scientific sessions and publications. As appropriate 
the Executive Committee may request participation of AGENT Japan SV trial Investigators on the committee.  
20.2. Safety Monitoring Process 
To promote early detection of safety issues, the clinical events committee will provide evaluations of safety 
events. Success of this program requires dynamic collection of unmonitored data as soon as the event is reported. 
This is expedited through the Boston Scientific safety group (or designee), which is responsible for coordinating 
the collection of information for the subject dossier from Medidata Rave EDC database that is entered by the 
centers and core laboratories. During regularly scheduled monitoring activities, clinical research monitors will 
support the dynamic reporting process through their review of source document and other data information.  

 
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20.3. Clinical Events Committee 
The clinical events committee (CEC) is an independent group of individuals with no affiliation with Boston 
Scientific. Committee membership will include practitioners of cardiovascular intervention therapy, as well as 
other experts with the necessary therapeutic and subject matter expertise to review and adjudicate the following 
endpoints and major adverse events reported by the trial investigators:  
 
All deaths 
 
Target lesion revascularization 
 
Target vessel revascularization 
 
MI 
 
Thrombosis related to target lesion 
Responsibilities, qualifications, membership, and committee procedures are outlined in the CEC charter.  
 
21. Suspension or Termination 
21.1. Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise this right only for 
valid scientific or business reasons and reasons related to protection of subjects. Investigators, associated IRBs, 
and regulatory authorities, as applicable, will be notified in writing in the event of study termination.  
21.1.1. 
Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the following. 
 
The occurrence of unanticipated adverse device effects that present a significant or unreasonable risk to 
subjects enrolled in the study. 
 
An enrollment rate far below expectation that prejudices the conclusion of the study. 
 
A decision on the part of Boston Scientific to suspend or discontinue development of the device. 
21.2. Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval 
Any investigator, or associated IRB may discontinue participation in the study or withdraw approval of the study, 
respectively, with suitable written notice to Boston Scientific. Investigators, associated IRBs, and regulatory 
authorities, as applicable, will be notified in writing in the event of these occurrences.  
21.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature termination has occurred 
will be provided to all participating sites by Boston Scientific. The IRB and regulatory authorities, as applicable, 
will be notified. Detailed information on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB terminates participation in the study, participating investigators, associated IRBs, and 
regulatory authorities, as applicable, will be notified in writing. Detailed information on how enrolled subjects 
will be managed thereafter will be provided by Boston Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility will be transferred 
to another investigator, if possible. In the event there are no opportunities to transfer Principal Investigator 
responsibility; detailed information on how enrolled subjects will be managed thereafter will be provided by 
Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and investigational 
product to Boston Scientific, unless this action would jeopardize the rights, safety, or welfare of the subjects.  

 
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21.4. Criteria for Suspending/Terminating a Study Center 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time after the study 
initiation visit if no subjects have been enrolled for a period beyond 3 months after site initiation, or if the site 
has multiple or severe protocol violations/noncompliance without justification and/or fails to follow remedial 
actions.  
In the event of termination of site participation, all investigational and testing equipment, as applicable, will be 
returned to Boston Scientific unless this action would jeopardize the rights, safety or well-being of the subjects. 
The IRB and regulatory authorities, as applicable, will be notified. Study participants will be contacted, as 
applicable, and be informed of changes to study visit schedule.  
Criteria for Suspending/Terminating a Trial Center 
Boston Scientific reserves the right to stop the inclusion of subjects at an investigational center at any time under 
the following conditions: 
 
IRB approval lapse/expiration 
 
Noncompliance with the clinical protocol 
 
Failure to comply with the regulatory requirements 
 
Failure to implement required corrective and preventive actions 
 
Insufficient enrollment to complete the trial within the expected timeframe 
 
Loss of trained investigational center personnel 
 
Insufficient or lack of investigator oversight 
 
22. Publication Policy 
BSJ requires disclosure of its involvement as a sponsor or financial supporter in any publication or presentation 
relating to a BSJ study or its results. BSJ will submit study results for publication (regardless of study outcome) 
in a timely manner. Boston Scientific Corporation follows authorship principals as set forth in the Uniform 
Requirements of the International Committee of Medical Journal Editors (ICMJE; http://www.icmje.org). In 
order to ensure the public disclosure of study results in a timely manner, while maintaining an unbiased 
presentation of study outcomes, BSC personnel may assist authors and investigators in publication preparation 
provided the following guidelines are followed. 
 
All authorship and contributorship requirements as described above must be followed. 
 
BSJ involvement in the publication preparation and the BSC Publication Policy should be discussed with 
the Coordinating Principal Investigator(s) at the onset of the project. 
 
The First and Senior authors are the primary drivers of decisions regarding publication content, review, 
approval, and submission. 
 
 
 

 
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23. Bibliography 
1. 
De Labriolle A, Pakala R, Bonello L, Lemesle G, Scheinowitz M & Waksman R. Paclitaxel-Eluting 
Balloon: From Bench to Bed. Catheterization and Cardiovascular Interventions. (2009) 73: pp. 643-652. 
2. 
Cortese B & Bertoletti A. Paclitaxel coated balloons for coronary artery interventions: A comprehensive 
review of preclinical and clinical data. International Journal of Cardiology. (2012) 161: pp. 4 - 12. 
3. 
Gutiérrez-Chico JL, van Geuns RJ, Koch KT, Koolen JJ, Duckers H, Regar E & Serruys PW. Paclitaxel-
coated balloon in combination with bare metal stent for treatment of de novo coronary lesions: an optical 
coherence tomography firstin- human randomised trial, balloon first vs. stent first-in-human randomised 
trial. EuroIntervention. (2011) 7: pp. 711-722. 
4. 
Belkacemi A, Agostoni P, Voskuil M & Stella PR. Coronary bifurcation lesions treated with the drug-
eluting balloon: a preliminary insight from the DEBIUT study. EuroIntervention. (2011) 7 Suppl K: p. 
K66-9. 
5. 
Ahmed W, Shah MA, Thaver AM & Mirza J. Drug-eluting balloon (DEB) for de-novo coronary artery 
disease and in-stent restenosis: immediate and intermediate term results from a prospective registry. J Pak 
Med Assoc. (2011) 61: pp. 157-160. 
6. 
Ali RM, Degenhardt R, Zambahari R, Tresukosol D, Ahmad WAW, Kamar HBH, Kui-Hian S, Ong TK, 
bin Ismail O, bin Elis S, Udychalerm W, Ackermann H, Boxberger M & Unverdorben M. Paclitaxel-eluting 
balloon angioplasty and cobaltchromium stents versus conventional angioplasty and paclitaxel-eluting 
stents in the treatment of native coronary artery stenoses in patients with diabetes mellitus. EuroIntervention. 
(2011) 7 Suppl K: p. K83-92. 
7. 
Loh JP & Waksman R. Paclitaxel drug-coated balloons: a review of current status and emerging 
applications in native coronary artery de novo lesions. JACC Cardiovasc Interv. (2012) 5: pp. 1001-1012. 
8. 
Bonaventura K, Sonntag S & Kleber FX. Antiplatelet therapy in the era of percutaneous coronary 
intervention with drug-eluting balloons. EuroIntervention. (2011) 7 Suppl K: p. K106-11. 
9. 
Christian Hamm. Drug-coated Balloons for the Treatment of Coronary In-stent Restenosis: A Randomised, 
Multicentre, Controlled Clinical Study, In: Euro PCR. Paris, French; 2017. 
10. Holger Nef. One-year outcomes from a randomised multicentre study of two drug-coated balloons for the 
treatment of coronary in-stent restenosis. In: Euro PCR. Paris, French; 2018. 
11. Michael Joner. Trial of a novel paclitaxel-coated balloon with citrate excipient for restenosis in limus-
analogue drug-eluting coronary stents ISAR-DESIRE 3A. In: CRT. Washington DC, US; 2018. 
12. de Weger VA, Beijnen JH, Schellens JH. Cellular and clinical pharmacology of the taxanes docetaxel and 
paclitaxel--a review. Anticancer Drugs. 2014;25(5):488-494. 
13. Ng VG, Mena C, Pietras C, Lansky AJ. Local delivery of paclitaxel in the treatment of peripheral arterial 
disease. Eur. J. Clin. Invest. 2015;45(3):333-345.15 
14. Dake MD, Van Alstine WG, Zhou Q, Ragheb AO. Polymer-free paclitaxel-coated zilver PTX 
stentsevaluation of pharmacokinetics and comparative safety in porcine arteries. Journal of Vascular and 
Interventional Radiology. 2011;22(5):603-610. 
15. Banerjee S, Sarode K, Mohammad A, et al. Femoropopliteal artery stent thrombosis: Report from the 
excellence in peripheral artery disease registry. Circ. Cardiovasc. Interv. 2016;9:2 Article Number: 
e002730. 
16. DFU of SeQuent® Please DCB 
17. Cutlip DE, Windecker S, Mehran R et al. Clinical end points in coronary stent trials: a case for standardized 
definitions. Circulation 2007;115:2344-51. 
 
 

 
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24. Abbreviations and Definitions 
24.1. Abbreviations 
Abbreviations are shown in Table 24.1-1.  
Table 24.1-1: Abbreviations 
Abbreviation/Acronym  
Term  
ACC 
American College of Cardiology  
ACT 
Activated Clotting Time  
ADE 
Adverse Device Effect  
AE 
Adverse Event  
AHA 
American Heart Association  
BSC 
Boston Scientific Corporation 
BSJ 
Boston Scientific Japan  
BMS 
Bare Metal Stent 
CABG 
Coronary Artery Bypass Graft 
CEC 
Clinical Events Committee  
CK 
Creatine Kinase 
CRO 
Contract Research Organization  
eCRF 
electronic Case Report Form  
DAPT 
Dual Antiplatelet Therapy 
DCB 
Drug-Coated Balloon  
DES 
Drug-Eluting Stent 
ECG 
Electrocardiogram  
EDC 
Electronic Data Capture  
GCP 
Good Clinical Practices  
HCP 
Health Care Professional  
ICF 
Informed Consent Form  
IRB 
Institutional Review Board  
ISO 
International Standards Organization  
ISR 
In-Stent Restenosis 
IVUS 
Intravascular ultrasound  
LL 
Late Loss  
MACE 
Major Adverse Cardiac Event  
NHLBI 
National Heart, Lung, and Blood Institute  
MLD 
Minimum lumen diameter  
PCI 
Percutaneous Coronary Intervention 
POBA 
Plain Old Balloon Angioplasty  

 
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Abbreviation/Acronym  
Term  
PTCA 
Percutaneous Transluminal Coronary Angioplasty  
QCA 
Quantitative Coronary Angiography  
QOL 
Quolity of life  
RVD 
Reference Vessel Diameter  
SADE 
Serious Adverse Device effect  
SAE 
Serious Adverse Event  
SV 
Small Vessel  
TIMI 
Thrombolysis in Myocardial Infarction  
TLF 
Target Lesion Failure  
TLR 
Target Lesion Revascularization  
TVF 
Target Vessel Failure  
TVR 
Target Vessel Revascularization  
UADE 
Unanticipated Adverse Device Effect  
USADE 
Unanticipated Serious Adverse Device Effect  
 
 

 
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24.2. Definitions 
Terms are defined in Table 24.2-1.  
Table 24.2-1: Definitions 
Tearm  
Definition 
ABRUPT CLOSURE 
Abrupt closure is the occurrence of new severely reduced flow (TIMI grade 0 
or 1) within the target vessel that persists and requires bailout, including 
emergency surgery, or results in MI or death. Abrupt closure requires proven 
association with a mechanical dissection of the treatment site or instrumented 
vessel, coronary thrombus, or severe spasm. Abrupt closure does not connote 
“no reflow” due to microvascular flow limitation in which the epicardial 
artery is patent but has reduced flow. Abrupt closure also does not connote 
transient closure with reduced flow in which the assigned treatment reversed 
the closure. 
Sub-abrupt closure is an abrupt closure that occurs after the target procedure 
is completed and the subject has left the catheterization laboratory and before 
hospital discharge. 
Threatened abrupt closure is a grade B dissection and ≥50% diameter 
stenosis or any dissection of grade C or higher.  
 
ANTICIPATED EVENT 
Event that is previously identified in the Protocol, Kiki-gaiyosho, ICF, or DFU.  
ARRHYTHMIA 
An arrhythmia is any variation from the normal rhythm of the heart, including 
sinus arrhythmia, premature beats, heart block, atrial or ventricular fibrillation, 
atrial or ventricular flutter, and atrial or ventricular tachycardia.  
ARTERIOVENOUS 
FISTULA 
An arteriovenous fistula is an abnormal passage or communication between an 
artery and a vein. It may result from injury or it may occur as a congenital 
abnormality.  
BIFURCATION LESION 
A bifurcation lesion is a lesion associated with the area where a branch vessel 
>2.0 mm in diameter by visual estimate originates.  
BINARY RESTENOSIS 
Binary restenosis is a diameter stenosis >50% at the previously treated lesion 
site, including the original treated area and the adjacent proximal and distal 
QCA analysis segment.  
BLEEDING 
CLASSIFICATIONS 
（Ref： GUSTO） 
Severe or life-threatening: Either intracranial hemorrhage or bleeding that 
causes hemodynamic compromise and requires intervention 
Moderate: Bleeding that requires blood transfusion but does not result in 
hemodynamic compromise 
Mild: Bleeding that does not meet criteria for either severe or moderate 
bleeding 
 
CALCIFICATION 
Calcification is defined as readily apparent densities seen within the artery wall 
and site of lesion either as an x-ray absorbing mass or as an echogenic and 
shadow generating mass in intravascular ultrasound (IVUS) imaging. These 
can be classified as little/none, moderate, or severe.  
BRAUNWALD 
CLASSIFICATION OF 
UNSTABLE ANGINA  
Severity: 
Class I: New onset, severe or accelerated angina. Subjects with angina of less 
than 2 months duration, severe or occurring 3 or more times per day, or 
angina that is distinctly more frequent and precipitated by distinctly less 
exertion; no pain at rest in the last 2 months. 
Class II: Angina at rest, subacute. Subjects with 1 or more episodes of angina 
at rest during the preceding month, but not within the preceding 48 hours. 
Class III: Angina at rest, acute. 

 
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Definition 
Clinical Circumstances:  
Class A: Secondary unstable angina. A clearly identified condition extrinsic 
to the coronary vascular bed that has intensified myocardial ischemia (e.g., 
anemia, fever, infection, hypotension, tachyarrhythmia, thyrotoxicosis, and 
hypoxemia secondary to respiratory failure). 
Class B: Primary unstable angina. 
Class C: Postinfarction unstable angina (within 2 weeks of documented MI). 
CANADIAN 
CARDIOVASCULAR 
SOCIETY 
CLASSIFICATION 
Class 1: Ordinary physical activity does not cause angina, such as walking 
and climbing stairs. Angina with strenuous or rapid or prolonged exertion at 
work or recreation. 
Class 2: Slight limitation of ordinary activity. Walking or climbing stairs 
rapidly, walking uphill, walking or stair climbing after meals, or in cold, or in 
wind, or under emotional stress, or any only during the first hours after 
awakening. Walking more than 2 blocks on the level and climbing more than 
1 flight of ordinary stairs at a normal pace and in normal conditions. 
Class 3: Marked limitations of ordinary physical activity. Walking 1 to 2 
blocks on the level and climbing 1 flight of stairs in normal conditions and at 
a normal pace. 
Class 4: Inability to carry on any physical activity without discomfort; angina 
syndrome may be present at rest. 
CARDIAC 
TAMPONADE 
Cardiac tamponade is an acute compression of the heart due to effusion of the 
fluid into the pericardium, or the collection of blood in the pericardium, from 
rupture of the heart or penetrating trauma.  
CARDIOGENIC SHOCK 
Cardiogenic shock is a clinical state of hypoperfusion characterized by a 
systolic blood pressure <80 mmHg and/or a central filling pressure >20 
mmHg, or a cardiac index <1.8 liters/min/m2 where there is evidence of 
insufficient end organ profusion. Shock is also considered present if 
intravenous inotropes and/or intra-aortic balloon pump (IABP) are needed to 
maintain a systolic blood pressure >80 mmHg and a cardiac index >1.8 
liters/minute/m2.  
CLINICAL EVENTS 
COMMITTEE 
A CEC is an independent group of individuals with pertinent expertise that 
review and adjudicate important endpoints and relevant AEs reported by study 
investigators. 
CLINICAL EVENTS 
COMMITTEE EVENT 
The CEC will adjudicate all reported cases of TVR, TLR, MI (Q-wave and 
non–Q-wave), death (to ensure appropriate classification of death as cardiac or 
noncardiac) and thrombosis related to target lesion. A case adjudicated by the 
CEC is considered to be a CEC event.  
CLINICAL 
PROCEDURAL 
SUCCESS 
Clinical procedural success rate: Technical success with no death or MI noted 
within 24 hours of the index procedure.  
COMPLICATION 
（ANGIOGRAPHIC OR 
CLINICAL） 
A complication (angiographic or clinical) is an undesirable clinical event that 
results in death, injury, or invasive intervention. Complications may include, 
but are not limited to, perforation, occlusion, intimal flap, dissection, loss of 
side branch, distal embolization, nonfatal MI, elevated CK Total, prolonged 
angina, hypotension, hematoma, arrhythmias, etc. Complications may or may 
not be related to the investigational device. 
CONGESTIVE HEART 
FAILURE 
Congestive heart failure is an inadequacy of the heart such that it fails to 
maintain adequate circulation of blood, so that congestion and edema develop 
in the tissues. Clinical syndrome is characterized by shortness of breath, non-
pitting edema, enlargement of the liver, engorged neck veins, and pulmonary 
rales.  

 
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Definition 
CORONARY 
ANEURYSM 
A coronary aneurysm is a pathologic dilation of a segment of a blood vessel 
involving all three layers of the vessel wall ≥1.5× the RVD.  
CORONARY ARTERY 
SPASM 
Coronary artery spasm, or coronary vasospasm, is a spasm of a coronary artery, 
resulting in a decrease in lumen diameter. It may occur distal to the treatment 
site and is generally reversed with intracoronary administration of NTG or with 
adjunct balloon dilation.  
DEATH 
Death is categorized as cardiac or non-cardiac. 
Cardiac death is defined as death due to any of the following. 
 
Acute MI 
 
Cardiac perforation/pericardial tamponade 
 
Arrhythmia or conduction abnormality 
 
CVA through hospital discharge or CVA suspected of being related to 
the procedure 
 
Death due to complication of the procedure, including bleeding, vascular 
repair, transfusion reaction, or bypass surgery 
 
Any death in which a cardiac cause cannot be excluded 
Non-cardiac death is defined as a death not due to cardiac causes as defined 
above. 
DIAMETER STENOSIS 
The maximal narrowing of the target lesion relative to the reference vessel 
diameter.  
DISSECTION, NHLBI 
CLASSIFICATION 
Type A: Small radiolucent area within the lumen of the vessel disappearing 
with the passage of the contrast material 
Type B: Appearance of contrast medium parallel to the lumen of the vessel 
disappearing within a few cardiac cycles 
Type C: Dissection protruding outside the lumen of the vessel persisting after 
passage of the contrast material 
Type D: Spiral shaped filling defect with or without delayed run-off of the 
contrast material in the antegrade flow 
Type E: Persistent luminal filling defect with delayed run-off of the contrast 
material in the distal lumen 
Type F: Filling defect accompanied by total coronary occlusion 
DISTAL 
EMBOLIZATION 
Distal embolization is migration of a filling defect or thrombus to distally 
occlude the target vessel or one of its branches. 
EMERGENCY BYPASS 
SURGERY 
Emergency bypass surgery is CABG surgery performed on an urgent or 
emergent basis for severe vessel dissection or closure, or treatment failure 
resulting in new ischemia. 
EQ-5D™ 
A standardized instrument developed by the EuroQol Group as a measure of 
health-related quality of life. The descriptive system of health-related quality 
of life states consist of five dimensions (mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression) each of which can take one of five 
responses. The responses record five levels of severity (no problems/slight 
problems/moderate problems/severe problems/extreme problems) within a 
particular EQ-5D dimension.  
HEMATOMA 
A localized swelling filled with blood resulting from a break in a blood vessel.  
HYPERTENSION 
Hypertension is persistently high arterial blood pressure. Various criteria for 
its threshold have been suggested, ranging from 140 mmHg systolic and 90 
mmHg diastolic to as high as 220 mmHg systolic and 110 mmHg diastolic. 

 
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Definition 
Hypertension may have no known cause or be associated with other primary 
diseases.  
HYPOTENSION 
Sustained hypotension is a systolic blood pressure less than 80 mmHg lasting 
more than 30 minutes or requiring intervention (e.g., pacing, IABP, 
intravenous vasopressors, to sustain systolic blood pressure). This excludes 
transient hypotension or vagal reactions, which are self-limited or readily 
reversible. 
INDEX PROCEDURE 
START TIME 
Index procedure start time is defined as the time of sheath insertion. If a 
previously placed sheath is used (i.e., from an earlier diagnostic procedure), 
index procedure start time is defined as the time of guide catheter insertion into 
sheath for the interventional procedure.  
INDEX PROCEDURE 
END TIME 
Index procedure end time is defined as the time the guide catheter is removed 
after the final angiography. 
INTIMAL FLAP 
An intimal flap is an extension of the vessel wall into the arterial lumen.  
LEFT MAIN DISEASE 
Left main disease is a significant lesion in the left main coronary artery of at 
least 50% diameter stenosis. A protected left main artery means left main with 
a functioning graft, either venous or arterial, placed to any of the branches of 
the left main. This is usually the LAD or CX, but could also include one of the 
branches of those vessels. Having a stent in the left main coronary artery does 
not in itself constitute a protected left main.  
LEFT VENTRICULAR 
EJECTION FRACTION 
LVEF is an assessment of the amount of blood emptied from the left ventricle 
during systolic contraction, which is indicative of global ventricular function.  
LESION 
CHARACTERISTICS 
（ACC/AHA 
CLASSIFICATION） 
Type A lesions: Minimally complex, length <10 mm, concentric, readily 
accessible, non-angulated segment (<45°), smooth contour, little or no 
calcification, less than totally occlusive, not ostial in location, no major side 
branch involvement, and an absence of thrombus. 
Type B lesions: Moderately complex, tubular (length 10 to 20 mm), eccentric, 
moderate tortuosity of proximal segment, moderately angulated segment 
(>45°, <90°), irregular contour, moderate or heavy calcification, total 
occlusions <3 months old, ostial in location, bifurcation lesions requiring 
double guidewire, and some thrombus present. 
Type C lesions: Severely complex, diffuse (length ≥20 mm), excessive 
tortuosity of proximal segment, extremely angulated segments >90°, total 
occlusions >3 months old and/or bridging collaterals, inability 
LESION LENGTH 
Lesion length is measured as distance from the proximal to the distal shoulder 
in the view that demonstrates the stenosis in its most elongated projection. 
Lesion length is classified as discrete (<10 mm), tubular (10-20 mm), or diffuse 
(>20 mm).  
LESION LOCATION 
Lesion location is the location of the lesion according to the specific coronary 
artery (i.e., left main, LAD, LCX, or RCA) or bypass graft, and is specified as 
proximal, mid, or distal. A standard map will be provided to be used for 
location descriptions.  
Note: In the AGENT Japan SV trial, the ramus will be considered to be a 
branch of the LCX for purposes of determining eligibility and for determining 
TVR. 
LEUKOPENIA 
Leukopenia is a leukocyte count of <3.0 × 109/liter for more than 3 days. 
LATE LOSS 
Late loss is the postprocedure MLD minus the follow-up MLD as determined 
by angiography. 

 
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Definition 
MALFUNCTION 
A malfunction is a failure of the device to meet performance specifications or 
otherwise perform as intended.  
Minimal Lumen Diameter 
The vessel diameter as measured at the most narrow point of the lesion.  
MYOCARDIAL 
INFARCTION 
In the AGENT Japan SV clinical trial, MI will be defined according to the 3rd 
Universal Definition.  
Spontaneous MI: 
Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac 
troponin (cTn)] with at least one value above the 99th percentile upper 
reference limit (URL) and with at least one of the following: 
 
Symptoms of ischemia 
 
New or presumed new significant ST-segment-T wave (ST-T) changes 
or new left bundle branch block (LBBB) 
 
Development of pathological Q waves in the ECG 
 
Imaging evidence of new loss of viable myocardium or new regional wall 
motion abnormality 
 
Identification of an intracoronary thrombus by angiography or autopsy 
 
Percutaneous Coronary Intervention-Related Myocardial Infarction: 
Percutaneous coronary intervention (PCI) related MI is arbitrarily defined by 
elevation of cTn value (>5 x 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. 
            AND 
One of the following: 
(i) Symptoms suggestion of myocardial ischemia 
(ii) New ischemic ECG changes 
(iii) Angiographic findings consistent with a procedural complication 
(iv) Imaging demonstration of a new loss of viable myocardial or new 
regional wall motion abnormality are required 
 
Coronary Artery Bypass Grafting-Related Myocardial Infarction: 
Coronary artery bypass graft (CABG) related MI is arbitrarily defined by 
elevation of cardiac biomarker values (>10 x 99th percentile URL) in patients 
with normal baseline cTn values (<99th percentile URL). 
            AND 
One of the following: 
(i) New pathological Q waves or new LBBB 
(ii) Angiographic documented new graft or new native coronary artery 
occlusion 
(iii) Imaging evidence of new loss of viable myocardium or new regional 
wall motion abnormality 
 
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 occurred 

 
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Definition 
before cardiac biomarkers were obtained, or before cardiac marker values 
would be increased. 
 
Thrombosis- Related Myocardial Infarction: 
MI associated with thrombosis when detected by coronary angiography or 
autopsy in the setting of myocardial ischemia and with a rise and/or fall of 
cardiac biomarker values with at least one value above the 99th percentile 
URL. 
NEOINTIMAL 
HYPERPLASIA 
Neointimal hyperplasia is thickening of the neointima due to intimal cell 
accumulation.  
NEUTROPENIA  
Neutropenia is defined as <1,000 neutrophils/mm3. 
NON-TARGET LESION 
A non-target lesion is one for which treatment with a study stent is not 
attempted.  
NEW YORK HEART 
ASSOCIATION 
CLASSIFICATION 
Class I: Patients with no limitation of activities; they suffer no symptoms 
from ordinary activities 
Class II: Patients with slight, mild limitation of activity; they are comfortable 
with rest or with mild exertion 
Class III: Patients with marked limitation of activity; they are comfortable at 
rest  
Class IV: Patients who should be at complete rest, confined to bed or chair; 
any physical activity brings on discomfort and symptoms occur at rest 
OSTIAL LESION  
An ostial lesion is one involving the origin of the coronary artery within the 
first 5 mm.  
PERFORATION 
Perforations are classified as follows: 
 
Angiographic perforation: Perforation detected by clinical site or 
Angiographic Core Laboratory at any point during the procedure. 
 
Clinical perforation: Perforation requiring additional treatment, including 
efforts to seal the perforation or pericardial drainage, or resulting in 
significant pericardial effusion, abrupt closure, MI, or death. 
 
Pericardial hemorrhage/tamponade: Perforation causing tamponade. 
REFERENCE 
DIAMETER OF 
NORMAL ARTERY 
SEGMENT 
Reference diameter of the normal artery segment is an angiographic 
measurement of the artery proximal and/or distal to the lesion intended for 
angioplasty. This is also referred to as “reference vessel diameter” (RVD).  
REPEAT  
Repeat intervention is a PCI or CABG performed after the end of the index 
procedure. The repeat intervention should be performed to improve blood 
flow.  
RESTENOSED LESION 
A restenosed lesion is a previously treated lesion that again has a stenosis. 
RESTENOSIS 
See Binary Restenosis.  
THROMBOSIS (Ref: 
Academic Research 
Consortium Definition17) 
 
Thrombosis events should be reported as a cumulative value at the different 
time points and with the different separate time points. Time 0 is defined as 
the time point after the guide catheter has been removed and the subject left 
the catheterization lab. 
Timing: 
• 
Acute (stent) thrombosis: 0‑24 hours after index procedure 
• 
Subacute (stent) thrombosis: >24 hours to 30 days after index 
procedure 

 
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Definition 
• 
Late (stent) thrombosis: >30 days to 1 year after index procedure 
• 
Very late (stent) thrombosis: >1 year after index procedure 
 (Stent) thrombosis may be defined as: 
• 
Confirmed/definite 
• 
Probable 
• 
Possible 
Confirmed/Definite (is considered either angiographic confirmed or 
pathologic confirmed) 
Angiographic confirmed thrombosis is considered to have occurred if: 
• 
TIMI flow is: 
- 
TIMI flow grade 0 with occlusion originating in the target lesion/stent 
or in the segment 5mm proximal or distal to the target lesion/stent 
region in the presence of thrombus* 
- 
TIMI flow grade 1, 2 or 3 originating in the target lesion/stent or in the 
segment 5mm proximal or distal to the target lesion/stent region in the 
presence of a thrombus* 
AND at least one of the following criteria, up to 48 hours, has been 
fulfilled: 
• 
New onset of ischemic symptoms at rest (typical chest pain with 
duration >20 minutes) 
• 
New ischemic ECG changes suggestive of acute ischemia 
• 
Typical rise and fall in cardiac biomarkers (>2× ULN of CK) 
The incidental angiographic documentation of lesion occlusion in the absence 
of clinical syndromes is not considered a confirmed target lesion/stent 
thrombosis (silent thrombosis). 
* Intracoronary thrombus 
 
Non-occlusive thrombus: Spheric, ovoid or irregular non-calcified filling 
defect or lucency surrounded by contrast material (on 3 sides of within a 
coronary stenosis) seen in multiple projections, or persistence of contrast 
material within the lumen, or a visible embolization of intraluminal material 
downstream. 
 
1 intra-target lesion/stent or proximal to a target lesion up to the most 
adjacent proximal side branch or main branch (if originating from the side 
branch). 
Probable 
Clinical definition of probable thrombosis event is considered to have 
occurred in the following cases: 
• 
Any unexplained death within the first 30 days 
• 
Irrespective of the time after the index procedure and MI in the absence 
of any obvious cause which is related to documented acute ischemia in 
the territory of the target lesion/stent without angiographic 
confirmation of thrombosis 
Possible 
Clinical definition of possible thrombosis is considered to have occurred with 
any unexplained death beyond 30 days. 

 
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Definition 
STROKE/CEREBROVA
SCULAR ACCIDENT 
An acute symptomatic episode of neurological dysfunction attributed to a 
vascular cause lasting more than 24 hours or lasting 24 hours or less with a 
brain imaging study or autopsy showing infarction. 
Classification: 
 
Ischemic Stroke: An acute symptomatic episode of focal cerebral, spinal, 
or retinal dysfunction caused by an infarction of central nervous system 
tissue. 
 
Hemorrhagic Stroke: An acute symptomatic episode of focal or global 
cerebral 
or 
spinal 
dysfunction 
caused 
by 
a 
nontraumatic 
intraparenchymal, intraventricular, or subarachnoid hemorrhage. 
 
Undetermined Stroke: A stroke with insufficient information to allow 
categorization as ischemic or hemorrhagic. 
An event that lasts < 24 hours may be adjudicated as a stroke if the following 
treatments were used: 
 
Pharmacologic, i. e., thrombolytic drug administration, or 
 
Non-pharmacologic, i.e., neurointerventional procedure (e.g., intracranial 
angioplasty) 
SUCCESSFUL PRE-
DILATION/PRETREAT
MENT 
Successful predilation occurs when the selected balloon opens vessel entry at 
nominal pressure without major (≥ NHLBI Type D) flow-limiting dissection 
or need for intervention (i.e. stenting), and residual angiographic stenosis no 
greater than 30% （visual estimate) as determined by the investigator.  
TARGET LESION 
The target lesion is the lesion selected by the Investigator for treatment with 
an investigational device.  
TARGET LESION 
FAILURE 
Primary endpoint: Target Lesion Failure (TLF) rate at 6 months post index-
procedure. 
TLF is defined as any ischemia driven revascularization of the target lesion 
(TLR), myocardial infarction (MI, Q-wave and non–Q-wave) related to the 
target vessel, or cardiac death. 
TARGET LESION 
REVASCULARIZATION 
Target lesion revascularization is any ischemia-driven repeat percutaneous 
intervention, to improve blood flow, of the successfully treated target lesion or 
bypass surgery of the target vessel with a graft distally to the successfully 
treated target lesion. A TLR will be considered as ischemia-driven if the target 
lesion diameter stenosis is ≥50% by QCA and there is presence of clinical or 
functional ischemia which cannot be explained by other coronary or graft 
lesions. Clinical or functional ischemia is any of the following: 
 
The subject has a positive functional study corresponding to the area 
served by the target lesion. 
 
The subject has ischemic ECG changes at rest in a distribution consistent 
with the target vessel. 
 
The subject has ischemic symptoms referable to the target lesion. 
 
A TLR will be considered as ischemia-driven if the lesion diameter 
stenosis is ≥70% by QCA even in the absence of clinical or functional 
ischemia. 
TARGET VESSEL 
The target vessel is any coronary vessel (e.g., left main coronary artery, LAD, 
LCX, or RCA) containing a target lesion. Side branches of a target vessel such 
as the LAD are also considered part of the target vessel.  
Note: In the AGENT Japan SV trial, the ramus will be considered to be a 
branch of the LCX for purposes of determining eligibility and for determining 
TVR.  

 
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Definition 
TARGET VESSEL 
FAILURE 
Target vessel failure is any ischemia-driven revascularization of the target 
vessel, MI (Qwave and non–Q-wave) related to the target vessel or death 
related. For the purposes of this protocol, if it cannot be determined with 
certainty whether the MI related to the target vessel or death was, it will be 
considered a TVF.  
TARGET VESSEL 
REVASCULARIZATION 
Target vessel revascularization is defined as a TLR (see definition above) or a 
TVR remote (see definition below).  
TARGET VESSEL 
REVASCULARIZATION 
REMOTE 
Target vessel revascularization remote is any ischemia-driven repeat 
percutaneous intervention, to improve blood flow, or bypass surgery of not 
previously existing lesions diameter stenosis ≥50% by QCA in the target 
vessel, excluding the target lesion. A TVR will be considered ischemia-driven 
if the target vessel diameter stenosis is ≥50% by QCA and any of the following 
are present: 
 
The subject has a positive functional study corresponding to the area 
served by the target vessel. 
 
The subject has ischemic ECG changes at rest in a distribution consistent 
with the target vessel. 
 
The subject has ischemic symptoms referable to the target vessel.  
 
A TVR will also be considered as ischemia-driven if the lesion diameter 
stenosis is ≥70% even in the absence of clinical or functional ischemia. 
TECHNICAL SUCCESS 
Technical success rate: Technical success is the ability to cross and dilate the 
lesion to achieve residual angiographic stenosis no greater than 30% as 
determined by the investigator. The result will be generally confirmed by an 
angiographic core lab.  
TECHNICIAN 
WORKSHEET 
A Technician Worksheet is a record for listing the filming sequence and 
angulations of x-ray equipment, details of inflations, and description of 
lesion(s).  
THROMBUS 
（ANGIOGRAPHIC） 
Thrombus (angiographic) is discrete, mobile intraluminal filling with defined 
borders with/without associated contrast straining, classified as either absent 
or present. 
THROMBOLYSIS IN 
MYOCARDIAL 
INFARCTION 
CLASSIFICATION 
TIMI 0: No perfusion. 
TIMI 1: Penetration with minimal perfusion. Contrast fails to opacify the entire 
bed distal to the stenosis of the duration of the cine run. 
TIMI 2: Partial perfusion. Contrast opacifies the entire coronary bed distal to 
the stenosis. However, the rate of entry and/or clearance is slower in the 
coronary bed distal to the obstruction than in comparable areas not perfused by 
the dilated vessel. 
TIMI 3: Complete perfusion. Filling and clearance of contrast equally rapid in 
the coronary bed distal to stenosis as in other coronary beds.  
TOTAL OCCLUSION  
A total occlusion is a lesion with no flow (i.e., TIMI flow 0).  
TRANSIENT ISCHEMIC 
ATTACK 
A TIA is a focal ischemic neurological deficit of abrupt onset and of presumed 
vascular etiology that resolves completely within 24 hours of onset.