Acetyl Salicylic Elimination Trial JAPAN: The ASET JAPAN Pilot Study

A Multicenter, Single Arm, Open-label Trial of Prasugrel Monotherapy After PCI With the SYNERGY® Stent in Patients With Chronic Coronary Syndrome or Non-ST-elevation Acute Coronary Syndromes

The ASET Japan Pilot study is a multicenter, single arm, open-label trial of single antiplatelet therapy with prasugrel for patients undergoing successful and optimal Percutaneous Coronary Intervention (PCI) for Chronic Coronary Syndrome (CCS) and Non-ST elevation Acute coronary syndrome (NSTE-ACS). The enrollment consists of two phases: i) 200 patients presenting with CCS; ii) 200 patients presenting with NSTE-ACS. The patients will be loaded with standard dual antiplatelet therapy according to local practice (usually aspirin 81 to 330 mg and clopidogrel 300 mg or prasugrel 20 mg or ticagrelor 180 mg, unless patient is on long-term therapy) prior to the PCI procedure. After PCI, if the results are considered to be satisfactory by the operator based on clinical (e.g. clinical status, ECG, etc.), angiographic and/or findings from intracoronary imaging, only then patients will be enrolled in the study and loaded with prasugrel 20 mg if the patients have not loaded prasugrel prior to PCI or have not taken a maintenance dose of prasugrel before the index PCI. Patients continued with prasugrel only (3.75 mg once a day) for three months in CCS patients and for 12 months in NSTE-ACS patients. Aspirin, clopidogrel, and ticagrelor will be discontinued just after the index procedure.

i. CCS patients (phase 1): At the 3-months follow-up visit, prasugrel monotherapy will be replaced by aspirin monotherapy or dual-antiplatelet therapy according to local standard of care. Clinical follow-up with office visit will be performed at 3 months and telephone contacts at 1, and 4 months (final follow-up).

ii. NSTE-ACS patients (phase 2): At the 12-months follow-up visit, prasugrel monotherapy will be replaced by aspirin monotherapy for an observational period of 1 month, followed by antiplatelet treatment according to local practice. Clinical follow-up with office visit will be performed at 1 and 12 months and telephone contacts at 3, 6, 9 and 13 months (final follow-up).

All events will be adjudicated by an independent clinical events committee (CEC).

An independent Data Safety and Monitoring Board (DSMB) will monitor the individual and collective safety of the patients in the study during enrolment of CCS patients and up to 3 months follow-up of CCS patients, and during enrollment of NSTE-ACS patients and up to 12 months follow-up of NSTE-ACS patients (timepoint for primary endpoint).

Inclusion Criteria:

Inclusion Criteria for CCS patients (phase 1) :

1. Successful PCI with optimal acute stent implantation of one or more SYNERGY stent(s).

2. SYNERGY stent implantation was performed to treat:

   1. at least one de novo lesion with ≥50% diameter stenosis determined by visual assessment in at least one native coronary artery with a vessel size between 2.25 mm and 5.0 mm in diameter.
   2. Non-acute coronary disease, with normal cardiac biomarker values prior to the PCI procedure, and evidences of myocardial ischemia by symptoms or non-invasive/invasive testing.
   3. patients with anatomical SYNTAX Score < 23 prior to PCI

3. Patient has provided written informed consent as approved by the Ethical Committee of the respective clinical site.

Inclusion Criteria for NSTE-ACS patients (phase 2) :

1. Patients with diagnosed Non ST-elevation acute coronary syndrome
2. Patients with anatomical SYNTAX Score < 23 prior to PCI
3. Patient provided written informed consent as approved by the Ethical Committee of the respective clinical site

Post PCI criteria for NSTE-ACS patients

1. Patient is free of angina symptoms at the end of PCI procedure.
2. Successful PCI with optimal acute stent implantation of one or more SYNERGY stent(s).
3. SYNERGY stent implantation was performed to treat at least one de novo lesion with ≥50% diameter stenosis determined by visual assessment in at least one native coronary artery with a vessel size between 2.25 mm and 5.0 mm in diameter.

Exclusion Criteria:

Exclusion Criteria for CCS patients (phase 1):

Candidates will be ineligible for enrolment in the study if any of the following conditions apply:

1. ≤ 20 years of age
2. Unable to give Informed Consent
3. Females of child-bearing potential unless negative pregnancy test at screening and willing to use effective contraception for the duration of treatment with study medication
4. Female who is breastfeeding at time of enrolment
5. Patients concomitantly received any other non-study stent at the same procedure
6. Patients with planned PCI or surgical intervention to treat any cardiac or non-cardiac condition;
7. Previous PCI with any non-SYNERGY stents in the last 6 months
8. Current (same hospitalization) or previous (within 12 months) acute coronary syndrome
9. Patient with following lesion characteristics prior to PCI; Saphenous or arterial graft, in-stent (re)stenosis
10. History of definite stent thrombosis
11. Concomitant cardiac valve disease requiring invasive therapy
12. Atrial fibrillation or other indication for oral anticoagulant therapy
13. Known allergy to aspirin, prasugrel or diagnosed lactose intolerance
14. Acute heart failure
15. Active myocarditis
16. Cardiomyopathy
17. Patient in hemodialysis
18. Treatment in the last 10 days or requirement for ongoing treatment with a strong CYP3A4 inhibitor or inducer;
19. History of stroke or transient ischemic cerebrovascular accident
20. History of intracranial hemorrhage or other intracranial pathology associated with increased bleeding risk
21. Hemoglobin <10 g/dL or other evidence of active bleeding
22. Peptic ulceration documented by endoscopy within the last 3 months unless healing proven by repeat endoscopy
23. Any other condition deemed by the investigator to place the patient at excessive risk of bleeding with prasugrel
24. Participation in another trial with an investigational drug or device
25. Co-morbidity associated with life expectancy <1 year
26. Assessment that the subject is not likely to comply with the study procedures or have complete follow-up
27. Known drug or alcohol dependence within the past 12 months as judged by the investigator

Exclusion Criteria for NSTE-ACS patients (Phase 2):

Candidates will be ineligible for enrolment if any of the following conditions apply:

1. ≤ 20 years of age
2. Unable to give Informed Consent
3. Females of child-bearing potential unless negative pregnancy test at screening and willing to use effective contraception for the duration of treatment with study medication
4. Female who is breastfeeding at time of enrolment
5. Patients concomitantly received any other non-study stent at the same procedure
6. Patients with planned PCI or surgical intervention to treat any cardiac or non-cardiac condition;
7. Previous PCI with any non-SYNERGY stents in the last 6 months
8. Patient with following lesion characteristics prior to PCI; Saphenous or arterial graft, in-stent (re)stenosis
9. History of definite stent thrombosis
10. Concomitant cardiac valve disease requiring invasive therapy
11. Known allergy to aspirin, prasugrel or diagnosed lactose intolerance
12. Atrial fibrillation or other indication for oral anticoagulant therapy;
13. History of stroke or transient ischemic cerebrovascular accident
14. History of intracranial haemorrhage or other intracranial pathology associated with increased bleeding risk
15. Acute heart failure
16. Active myocarditis
17. Cardiomyopathy
18. Patient in hemodialysis
19. Haemoglobin <10 g/dL or other evidence of active bleeding
20. Hemodynamic instability or cardiogenic shock
21. Recurrent or ongoing chest pain refractory to medical treatment
22. Life-threatening arrhythmias or cardiac arrest;
23. Mechanical complications of myocardial infarction
24. Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation
25. Peptic ulceration documented by endoscopy within the last 3 months unless healing proven by repeat endoscopy
26. Any other condition deemed by the investigator to place the patient at excessive risk of bleeding with prasugrel
27. Participation in another trial with an investigational drug or device
28. Co-morbidity associated with life expectancy < 1 year
29. Assessment that the subject is not likely to comply with the study procedures or have complete follow-up;
30. Known drug or alcohol dependence within the past 12 months as judged by the investigator