Safety and Effectiveness of Agent Paclitaxel-Coated PTCA Balloon Catheter. (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.

A 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.

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.

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.

Inclusion Criteria:

1. Subject must be at least 20 years of age.

2. Subject understands the trial requirements and the treatment procedures and provides written informed consent before any study-specific tests or procedures are performed.

3. Subject is eligible for percutaneous coronary intervention (PCI).

4. 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.

5. Subject is an acceptable candidate for coronary artery bypass grafting (CABG).

6. Subject is willing to comply with all protocol-required follow-up evaluation.

7. Patients undergoing first or second treatment for ISR lesions for the non-randomized ISR substudy.

8. 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.

9. 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.).

Exclusion Criteria:

1. Subject has had an acute myocardial infarction within 72 hours prior to the index procedure.

2. Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, intractable ventricular arrhythmia, or ongoing intractable angina.

3. Subject has severe left ventricular dysfunction with ejection fraction <30%.

4. Subject has received an organ transplant or is on a waiting list for an organ transplant.

5. Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure.

6. Subject has renal failure with a serum creatinine of > 2.0mg/dL or who is receiving dialysis or chronic immunosuppressant therapy.

7. 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.
   • Current problems with substance abuse.
   • Planned procedure that may cause non-compliance with the protocol or confound data interpretation.

8. Planned PCI (including staged procedures) or CABG after the index procedure.

9. Subject previously treated at any time with intravascular brachytherapy.

10. Subject has a known allergy to contrast and/or the investigational device or protocol-required concomitant medications, iopromide, raw materials of Agent DCB and SeQuent Please DCB, P2Y12 inhibitor or aspirin).

11. Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3.

12. Subject has a white blood cell (WBC) count < 3,000 cells/mm3.

13. Subject has documented or suspected liver disease, including laboratory evidence of hepatitis.

14. Subject has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions.

15. Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months.

16. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding.

17. Target vessel has been treated with Paclitaxel Eluting Stent or Balloon prior to the index procedure.

18. Target vessel has been treated with any type of PCI within 6 months prior to the index procedure.

19. Target vessel requires the use of adjunctive primary treatment modalities immediately prior to investigational device's treatment.

20. Non-target vessel has been treated with any type of PCI within 24 hours prior to the index procedure.

21. Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint.

22. Subject intends to participate in another investigational drug or device clinical trial within 6 months after the index procedure.

23. Subject with known intention to procreate within 6 months after the index procedure.

24. Subject is a woman who is pregnant or nursing.

25. 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.).

26. 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.
    • 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.

27. Subject has unprotected left main coronary artery disease (>50% diameter stenosis).

28. Thrombus, or possible thrombus, present in the target vessel.

29. Subject with known coronary artery spasm.