Acute Coronary Syndromes, NSTEMI, STEMI, Unstable Angina
Conditions
Keywords
Intravascular Ultrasound, Percutaneous Coronary Intervention, Drug-Eluting Stent, Single Antiplatelet Therapy, Dual Antiplatelet Therapy
Brief summary
This is a prospective, open-label, multicenter, randomized, phase IV clinical trial designed to evaluate the safety and efficacy of early aspirin discontinuation followed by potent P2Y12 inhibitor monotherapy after intravascular ultrasound (IVUS)-guided drug-eluting stent implantation in patients with acute coronary syndrome. A total of 1,900 patients who achieve complete revascularization after IVUS-guided percutaneous coronary intervention (PCI) and meet the predefined successful IVUS-guided PCI criteria will be randomized in a 1:1 ratio to either the early single antiplatelet therapy group (Early SAPT: ticagrelor or prasugrel monotherapy) or the standard dual antiplatelet therapy group (Standard DAPT: aspirin plus ticagrelor or prasugrel). Randomization will be performed within 96 hours after completion of PCI, and clinical follow-up will be conducted at 1 month, 3 months, 6 months, and 12 months after randomization. The primary endpoints are major adverse cardiovascular events, defined as a composite of all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis occurring up to 12 months after randomization, and clinically relevant bleeding, defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding occurring up to 12 months after randomization. This study aims to determine whether early P2Y12 inhibitor monotherapy is non-inferior to standard dual antiplatelet therapy (DAPT) for ischemic events and is superior in reducing clinically relevant bleeding.
Detailed description
The study population will consist of patients diagnosed with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI), achieve complete revascularization (CR) of all clinically significant coronary lesions under intravascular ultrasound (IVUS) guidance, and meet the imaging criteria predefined in this study. Patients who meet all inclusion criteria and none of the exclusion criteria will be randomized within 96 hours after completion of PCI for CR, provided that no additional revascularization procedure is considered necessary. Before randomization, appropriate antiplatelet therapy including aspirin and a P2Y12 inhibitor may be administered according to the standard practice of each participating center. If staged PCI is planned, study enrollment and randomization will be allowed only after completion of all planned procedures. After the operator confirms successful procedural completeness based on final angiographic and IVUS images, eligible participants will be randomized in an open-label manner in a 1:1 ratio. After randomization, the treatment strategy will be as follows. In the early single antiplatelet therapy (Early SAPT) group, aspirin will be discontinued immediately after randomization once CR has been confirmed, and potent P2Y12 inhibitor monotherapy will be administered as prasugrel 10 mg once daily or ticagrelor 90 mg twice daily. In the standard dual antiplatelet therapy (Standard DAPT) group, aspirin 100 mg once daily will be administered in combination with prasugrel 10 mg once daily or ticagrelor 90 mg twice daily. All patients will continue standard cardiovascular preventive therapy, including high-intensity statin therapy, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), or angiotensin receptor blockers (ARBs), as appropriate. A proton pump inhibitor (PPI) may be used at the discretion of the treating physician in patients at risk of gastrointestinal bleeding. All randomized study participants will undergo clinical follow-up at 1 month, 3 months, 6 months, and 12 months after randomization.
Interventions
DRUGEarly P2Y12 Inhibitor Monotherapy
Participants randomized within 96 hours after successful IVUS-guided PCI will discontinue aspirin immediately after randomization and receive potent P2Y12 inhibitor monotherapy with ticagrelor 90 mg twice daily or prasugrel 10 mg once daily.
DRUGStandard Dual Antiplatelet Therapy
Participants randomized within 96 hours after successful IVUS-guided PCI will receive aspirin 100 mg once daily plus a potent P2Y12 inhibitor, consisting of ticagrelor 90 mg twice daily or prasugrel 10 mg once daily, for 12 months.
Sponsors
Gyeongsang National University Hospital
Genoss Co., Ltd.
CGBio Inc.
Biotronik SE & Co. KG
Dio Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, multicenter, randomized, parallel-group trial comparing early potent P2Y12 inhibitor monotherapy versus standard dual antiplatelet therapy after successful IVUS-guided PCI in patients with acute coronary syndrome.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>=18 years 2. Diagnosis of acute coronary syndrome, including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), or unstable angina (UA) 3. Successful IVUS-guided PCI with drug-eluting stent implantation 4. Randomization within 96 hours after PCI 5. Written informed consent
Exclusion criteria
1. Planned staged PCI or CABG 2. PCI failure, including no-reflow, major dissection, or thrombosis 3. Need for oral anticoagulation 4. Major bleeding within 30 days 5. History of hemorrhagic stroke or ischemic stroke within 6 months 6. Platelet count \<100,000/mm3 or WBC count \<3,000/mm3 7. Contraindication to aspirin, ticagrelor, or prasugrel 8. Life expectancy \<1 year 9. Current or potential pregnancy 10. Investigator deems participation inappropriate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiovascular Events | Up to 12 months after randomization | Major adverse cardiovascular events are defined as a composite of all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis occurring up to 12 months after randomization. |
| Clinically Relevant Bleeding | Up to 12 months after randomization | Clinically relevant bleeding is defined as the incidence of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events occurring up to 12 months after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Major and Minor Bleeding According to TIMI Criteria | Up to 12 months after randomization | TIMI bleeding definitions: • Major: Any intracranial bleeding (excluding microhemorrhages 10 mm evident only on gradient-echo MRI), clinically overt signs of hemorrhage associated with a drop in hemoglobin of 5 g/dL, Fatal bleeding (bleeding that directly results in death within 7 d) • Minor: Clinically overt (including imaging), resulting in hemoglobin drop of 3 to 5 g/dL, requiring medical attention, any overt sign of hemorrhage that meets one of the following criteria and does not meet criteria for a major or minor bleeding event, as defined above, requiring intervention (medical practitioner-guided medical or surgical treatment to stop or treat bleeding, including, temporarily or permanently discontinuing or changing the dose of a medication or study drug), leading to or prolonging hospitalization, prompting evaluation (leading to an unscheduled visit to a healthcare professional and diagnostic testing, either laboratory or imaging). |
| Incidence of Major and Minor Bleeding According to ISTH Criteria | Up to 12 months after randomization | * Major: 1. Fatal bleeding and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome. and/or 3. Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. * Minor: All non-major bleeds will be considered minor bleeds. Minor bleeds will be further divided into those that are clinically relevant and those that are not. |
| Incidence of All-Cause Death | Up to 12 months after randomization | All-cause mortality was used rather than cardiac mortality to eliminate the need for possibly difficult adjudication of causes of death, especially given the relatively low mortality expected. In addition, the cause of death will be adjudicated as being due to cardiovascular causes, non-cardiovascular causes, or undetermined causes. * Cardiovascular death includes sudden cardiac death, death due to acute MI, heart failure or cardiogenic shock, stroke, other cardiovascular causes, or bleeding * Non-cardiovascular death is defined as any death with known cause not of cardiac or vascular causes * Undetermined cause of death refers to a death not attributable to one of the above categories of cardiovascular death or to a noncardiovascular cause. For this trial all deaths of undetermined cause will be included in the cardiovascular category |
| Incidence of Myocardial Infarction | Up to 12 months after randomization | The definition of MI is based on the SCAI definition of clinically relevant MI. MI is defined as an abnormal cardiac biomarker level above the institutional upper limit of normal (either cardiac troponin or CK-MB), and either at least 1 of the following: a) Symptoms of myocardial ischemia, b) New or presumed new significant ST-segment-T wave (ST-T) changes or new LBBB on the ECG, c) Development of pathological Q waves on the ECG, d) Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, e) Identification of an intracoronary thrombus by angiography or autopsy. |
| Incidence of Ischemia-Driven Target Vessel Revascularization | Up to 12 months after randomization | A coronary revascularization procedure may be either a CABG or a PCI. • Target Vessel: The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion including upstream and downstream branches and the target lesion itself All revascularization events will be adjudicated as either ischemia-driven or non-ischemia-driven. Revascularization will be considered ischemia-driven if the diameter stenosis of the revascularized coronary segment is ≥50% by QCA and any of the following criteria for ischemia are met: a) History of angina pectoris, presumably related to the target vessel, b) Objective signs of ischemia at rest (electrocardiographic changes) or during exercise test (or equivalent), presumably related to the target vessel c) Abnormal results of any invasive functional diagnostic test (e.g., CFR or FFR). |
| Incidence of Definite or Probable Stent Thrombosis | Up to 12 months after randomization | * Definite stent thrombosis: defined as occurring when clinical presentation is consistent with acute coronary syndrome and angiography or autopsy examination confirm stent occlusion or thrombus. * Probable stent thrombosis: defined as death occurring within 30 days that cannot be attributed to another cause or when myocardial infarction occurs at any time point and is attributable to the target vessel in the absence of angiography confirming another culprit lesion. * Possible stent thrombosis: defined as occurring when the patient dies after \>30 days and death is not explained by another cause. |
| Incidence of Net Adverse Clinical Events | Up to 12 months after randomization | Net adverse clinical events are defined as a composite of major adverse cardiovascular events and clinically relevant bleeding. Major adverse cardiovascular events include all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis. Clinically relevant bleeding is defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. |
| All-Cause Rehospitalization Rate | Up to 12 months after randomization | All-cause rehospitalization is defined as any hospital admission occurring after randomization, regardless of cause. Rehospitalization events will be collected during follow-up and classified according to the reason for admission, including cardiovascular, bleeding-related, and non-cardiovascular causes. |
| Medication Adherence | Up to 12 months after randomization | Medication adherence is defined as adherence to the assigned antiplatelet treatment strategy during follow-up. At each follow-up visit, antiplatelet therapy status, discontinuation, switching, interruption, and compliance with aspirin, ticagrelor, or prasugrel will be assessed. |
| Survival Rate at 12 Months | At 12 months after randomization | Survival rate at 12 months is defined as the proportion of randomized participants who are alive at 12 months after randomization. Vital status will be assessed at follow-up, and deaths will be adjudicated according to cause when available. |
Countries
South Korea
Contacts
CONTACTJin-Sin Koh, MD, PhD
PRINCIPAL_INVESTIGATORJin-Sin Koh, MD, PhD
Gyeongsang National University Hospital
Outcome results
None listed