Acetyl Salicylic Elimination Trial JAPAN: The ASET JAPAN Pilot Study

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University of Ireland, Galway, Ireland
• Collaborators: Boston Scientific Japan K.K.; Fujita Health University; Meditrix Corp
• Treatments: Prasugrel Hydrochloride

Criteria

Inclusion Criteria:

Inclusion Criteria phase 1 for CCS patients :

1. Successful PCI with optimal acute stent implantation results (based on local standard of care by angiography and/or findings from intracoronary imaging and on investigators' discretion) of one or more everolimus-eluting SYNERGY® stent(s). Typically, optimal acute coronary stenting result is a combination of successful stent implantation at the target lesion with absence of significant residual diameter stenosis (<20%), no edge dissection, no thrombus, no major side branch occlusion, "no-reflow", no major stent underexpansion or major stent incomplete apposition.

2. Everolimus-eluting SYNERGY® stent implantation was performed to treat:

1. patients with at least one stenosis (angiographic, visually determined de novo lesions with ≥50% Diameter Stenosis [DS]) in at least one major epicardial territory (Left Anterior Descending artery [LAD] and/or side branch, Circumflex artery [CX] and/or side branch, Right Coronary Artery [RCA] and/or side branch) with a vessel size between 2.25 mm and 5.0 mm in diameter supplying viable myocardium without left main stem involvement;

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 (e.g. treadmill exercise test, radionuclide scintigraphy, stress echocardiography, fractional flow reserve);

3. patients anatomical SYNTAX Score < 23 prior to everolimus-eluting SYNERGY® stent implantation;

3. Patient has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Ethical Committee of the respective clinical site;

Inclusion Criteria phase 2 NSTE-ACS patients :

1. Patients with diagnosed Non ST-elevation acute coronary syndrome;

2. Patients anatomical SYNTAX Score < 23 prior to everolimus-eluting SYNERGY® stent implantation;

3. Patient has been informed of the nature of the study and agrees to its requirements and has provided written informed consent as approved by the Ethical Committee of the respective clinical site;

Inclusion criteria post-PCI for NSTE-ACS patients:

4. Patient is free of angina symptoms at the end of PCI procedure.

5. Successful primary PCI with optimal acute stent implantation results (based on local standard of care by angiography and/or findings from intracoronary imaging and on investigators' discretion) of one or more everolimus-eluting SYNERGY® stent(s). Typically, optimal acute coronary stenting result is a combination of successful stent implantation at the target lesion with absence of significant residual diameter stenosis (<20%), edge dissection, thrombus, major side branch occlusion, "no-reflow" at the end of the procedure, major stent under expansion or major stent incomplete apposition and absence of persistent chest pain after the procedure.

6. Everolimus-eluting SYNERGY® stent implantation was performed to treat:

1. patients with at least one stenosis (angiographic, visually determined de novo lesions with ≥50% DS) in at least one major epicardial territory (LAD and/or side branch, CX and/or side branch, RCA and/or side branch) with a vessel size between 2.25 mm and 5.0 mm in diameter supplying viable myocardium without left main stem involvement;

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. Under the age of 20 years;

2. Unable to give Informed Consent;

3. Females of child-bearing potential unless negative pregnancy test at screening and willing to use effective contraception (i.e. established use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or barrier methods of contraception with spermicide or sole male partner with prior vasectomy and confirmed absence of sperm in ejaculate) for the duration of treatment with study medication.

4. Female who is breastfeeding at time of enrolment;

5. Patients treated with everolimus-eluting SYNERGY® stent(s) but who also concomitantly received any other non-study stent at the same procedure (all lesions must be treated with the everolimus-eluting SYNERGY® stent);

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 12 months;

8. Current (same hospitalization) or previous (within 12 months) acute coronary syndrome

9. Patient with following lesion characteristics prior to everolimus-eluting SYNERGY® stent implantation:

• Left-main disease

• Chronic Total Occlusion

• Bifurcation lesion requiring two stent treatment

• Saphenous or arterial graft

• Severe calcification necessitating the use of rotablator

• in-stent (re)stenosis

• thrombosis of the target lesion;

10. Patients with any previous history of definite stent thrombosis.

11. Concomitant cardiac valve disease requiring invasive therapy (reconstruction or replacement);

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. Patients treated with hemodialysis;

18. Treatment in the last 10 days or requirement for ongoing treatment with a strong CYP3A4 inhibitor or inducer;

19. Previous stroke or transient ischemic cerebrovascular accident (TIA);

20. Previous history of intracranial haemorrhage or other intracranial pathology associated with increased bleeding risk;

21. Haemoglobin <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 less than 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):

1. Under the age of 20 years;

2. Unable to give Informed Consent;

3. Females of child-bearing potential unless negative pregnancy test at screening and willing to use effective contraception (i.e. established use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or barrier methods of contraception with spermicide or sole male partner with prior vasectomy and confirmed absence of sperm in ejaculate) for the duration of treatment with study medication;

4. Female who is breastfeeding at time of enrolment;

5. Patients treated with everolimus-eluting SYNERGY® stent(s) but who also concomitantly received any other non-study stent at the same procedure (all lesions must be treated with everolimus-eluting SYNERGY® stent);

6. Patients with planned staged PCI or surgical intervention to treat any cardiac or non-cardiac condition;

7. Previous PCI with any non-SYNERGY® stents in the last 12 months;

8. Patient with following (target) lesion characteristics:

• Left-main disease

• Chronic Total Occlusion

• Bifurcation lesion requiring two stent treatment

• Saphenous or arterial graft

• Severe calcification necessitating the use of rotablator

• in-stent (re)stenosis

• thrombosis of the target lesion;

9. Patients with any previous history of definite stent thrombosis;

10. Concomitant cardiac valve disease requiring invasive therapy (reconstruction or replacement);

11. Known allergy to aspirin, prasugrel (or ticagrelor) or diagnosed lactose intolerance;

12. Previous stroke or transient ischemic cerebrovascular accident (TIA);

13. Previous history of intracranial haemorrhage or other intracranial pathology associated with increased bleeding risk;

14. Peptic ulceration documented by endoscopy within the last 3 months unless healing proven by repeat endoscopy;

15. Hemodynamic instability or cardiogenic shock;

16. Recurrent or ongoing chest pain refractory to medical treatment;

17. Life-threatening arrhythmias or cardiac arrest;

18. Mechanical complications of Myocardial Infarction;

19. Acute heart failure;

20. Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation;

21. Atrial fibrillation or other indication for oral anticoagulant therapy;

22. Myocarditis;

23. Cardiomyopathy;

24. Patients treated with hemodialysis;

25. Haemoglobin <10 g/dL or other evidence of active bleeding;

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. Assessment that the subject is not likely to comply with the study procedures or have complete follow-up;

29. Known drug or alcohol dependence within the past 12 months as judged by the investigator;

30. Co-morbidity associated with life expectancy less than 1 year.