Clinical trial NCT04014803: Aspirin and a PoTent P2Y12 Inhibitor Versus Aspirin and Clopidogrel in Patients Undergoing PCI for Complex Lesion
Official title: Aspirin and a Potent P2Y12 Inhibitor Versus Aspirin and Clopidogrel Therapy in Patients Undergoing Elective Percutaneous Coronary Intervention for Complex Lesion Treatment (SMART-ATTEMPT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Percutaneous Coronary Intervention
Dual Antiplatelet Therapy
Complex Coronary Lesion
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Inje University Ilsan Paik Hospital
name: Seoul St. Mary's Hospital
name: Mediplex Sejong Hospital
name: Chonnam National University Hospital
name: Sejong General Hospital
name: Wonkwang University Hospital
name: Gachon University Gil Medical Center
name: Keimyung University Dongsan Medical Center
name: Chungbuk National University Hospital
name: Yeungnam University Hospital
name: Chungnam National University Hospital
name: Wonju Severance Christian Hospital
name: Konkuk University Chungju Hospital
name: Chung-Ang University Hosptial, Chung-Ang University College of Medicine
name: Dankook University
name: Incheon St.Mary's Hospital
name: Gyeongsang National University Hospital
name: Soonchunhyang University Hospital
name: Ewha Womans University Seoul Hospital
First posted: 2019-07-10
Enrollment: 3500
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, open label, two-arm, randomized multicenter trial to evaluate the efficacy and safety of aspirin plus prasugrel as compared with aspirin plus clopidogrel in patients undergoing elective percutaneous coronary intervention with drug eluting stents for complex coronary lesions.

Detailed description: Over the past several decades, dual antiplatelet therapy (DAPT) with the combination of aspirin and a P2Y12 inhibitor has become an essential treatment in patients undergoing percutaneous coronary intervention (PCI) to reduce ischemic events. Although the optimal duration of DAPT still remains controversial in patients with coronary artery disease, the recommended duration of maintenance of DAPT for patients undergoing PCI with drug-eluting stent is ≥12 months for those with acute coronary syndrome (ACS), and ≥6 months for those with stable coronary artery disease according to the current guidelines. However, individualized approach based on ischemic versus bleeding risks assessment is needed to determine the optimal duration of DAPT in various population.

Several studies reported that patients undergoing PCI for complex lesions had significantly higher rates of ischemic events than those with non-complex lesions. Moreover, prolonged DAPT of aspirin and clopidogrel more than 1 year significantly reduced the risk of cardiac ischemic events up to 44% in patients undergoing PCI for complex coronary lesions, and the current guideline recommends prolonged DAPT duration may be considered in patients undergoing complex PCI. Apart from prolonged use of DAPT, use of more potent P2Y12 inhibitor than clopidogrel may be another strategy to reduce ischemic events in patients undergoing PCI for complex coronary lesions. Prasugrel, a new thienopyridine, inhibits platelet aggregation more rapidly and potently than clopidogrel. In the TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel) study, prasugrel reduced ischemic events compared with clopidogrel in patients with acute coronary syndrome. Moreover, low dose prasugrel also reduced ischemic events without an excessive bleeding risk in Japanese population. Therefore, DAPT of aspirin and prasugrel would reduce recurrent ischemic events than DAPT of aspirin and clopidogrel in patients undergoing PCI for complex lesions, a high risk group of ischemic events, even when they do not present with myocardial infarction. So far, there have been no data on this issue.

The aim of the SMART-ATTEMPT (Aspirin and a PoTent P2Y12 inhibitor versus aspirin and clopidogrel Therapy in patients undergoing Elective percutaneous coronary intervention for coMPlex lesion Treatment) trial is to evaluate the efficacy and safety of aspirin plus prasugrel as compared with aspirin plus clopidogrel in patients undergoing elective PCI for complex lesions.

Eligibility criteria: Inclusion Criteria:

* ① Subject must be at least 19 years of age
* ② Subject who can verbally confirm understandings of risks, benefits and treatment alternatives and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure
* ③ Patients undergoing elective PCI as follows:

  1. True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5 mm size
  2. Chronic total occlusion (≥3 months) as target lesion
  3. PCI for unprotected left main disease (left main ostium, body, or distal bifurcation including non-true bifurcation lesions)
  4. Long coronary lesions (expected stent length ≥38 mm)
  5. Multi-vessel PCI (≥2 vessels treated at one PCI session)
  6. Multiple stent needed (≥3 stents per patient)
  7. In-stent restenosis lesion as target lesion
  8. Severely calcified lesion (encircling calcium in angiography)
  9. Ostial lesions of left anterior descending artery, left circumflex artery, or right coronary artery

Exclusion Criteria:

* ① Hemodynamic instability or cardiogenic shock
* ② Subjects with serious bleeding (Intracerebral hemorrhage, gastrointestinal bleeding, hematuria, hemoptysis, and etc.)
* ③ Previous history of intracerebral hemorrhage, transient ischemic attack, or stroke
* ④ Known hypersensitivity or contraindications to study medications (aspirin, clopidogrel, and prasugrel)
* ⑤ Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study
* ⑥ Non-cardiac co-morbid conditions are present with life expectancy \<1 year or that may result in protocol non-compliance (per site investigator's medical judgment)
* ⑦ Patients presenting with biomarker positive acute coronary syndrome
* ⑧ Patients chronically taking prasugrel or ticagrelor (≥1 week)
* ⑨ Subjects ≥75 years of age or \<60 kg of body weight
* ⑩ Patients taking warfarin or novel oral anticoagulants (dabigatran, rivaroxaban, edoxaban, or apixaban)

  * Eligible patients will be randomly assigned to treatment arms, stratified by participating centers, presence of diabetes mellitus, and stent types.

Primary outcomes:
measure: Major adverse cardiac events (MACE)
timeFrame: 1-year after randomization
Secondary outcomes:
measure: All-cause death
timeFrame: 1-year after randomization
measure: Cardiac death
timeFrame: 1-year after randomization
measure: Myocardial infarction
timeFrame: 1-year after randomization
measure: Stent thrombosis
timeFrame: 1-year after randomization
measure: Target lesion revascularization
timeFrame: 1-year after randomization
measure: Target vessel revascularization
timeFrame: 1-year after randomization
measure: Any revascularization
timeFrame: 1-year after randomization
measure: A composite of all-cause death/myocardial infarction/stent thrombosis/any revascularization
timeFrame: 1-year after randomization
measure: A composite of all-cause death/myocardial infarction
timeFrame: 1-year after randomization
measure: A composite of cardiac death/myocardial infarction
timeFrame: 1-year after randomization
measure: Cerebrovascular accident
timeFrame: 1-year after randomization
measure: A composite of all-cause death/myocardial infarction/cerebrovascular accident
timeFrame: 1-year after randomization
measure: A composite of cardiac death/myocardial infarction/cerebrovascular accident
timeFrame: 1-year after randomization
measure: A composite of cardiac death/myocardial infarction/stent thrombosis
timeFrame: 1-year after randomization
measure: Bleeding by BARC types 3 or 5
timeFrame: 1-year after randomization
measure: Bleeding by BARC types 2, 3, or 5
timeFrame: 1-year after randomization
measure: Net adverse clinical events
timeFrame: 1-year after randomization
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Joo-Yong Hahn, MD, PhD
role: STUDY_CHAIR
References: