SMART-CHOICE3: SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3

Sponsor

Joo-Yong Hahn (Other)

Overall Status

Recruiting

CT.gov ID

NCT04418479

Collaborator

(none)

5,000

Enrollment

Location

Arms

52.7

Anticipated Duration (Months)

94.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is prospective, open-label, two-arm, randomized multicenter trial to evaluate the efficacy and safety of clopidogrel monotherapy as compared with aspirin monotherapy beyond 12 months after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Aspirin Drug: Clopidogrel	Phase 4

Detailed Description

After the introduction of the second-generation drug-eluting stents (DES), the rates of device-related failure or target lesion failure such as restenosis and stent thrombosis has been markedly decreased, compared with the era of bare-metal stents or first-generation DES. Nevertheless, the risk of ischemic events including very late stent thrombosis after percutaneous coronary intervention (PCI) has still remained even though the use of second-generation DES. In this regard, the ACC (American College of Cardiology)/AHA (American Heart Association) and ESC (European Society of Cardiology) guidelines recommended that dual antiplatelet therapy (DAPT) should be considered for 12 months or longer in patients presented with acute coronary syndrome (ACS) and for 6 months or longer in patients presented with stable ischemic heart disease (SIHD) after PCI with DES. In particular, patients presented with a high risk of ischemic events such as diabetes mellitus, myocardial infarction, or complex coronary lesions were associated with significantly increased future recurrent ischemic events after PCI with DES. In addition, maintenance of DAPT for 12 months or longer has been shown to reduce the recurrence of ischemic events up to 44% in patients treated with PCI for complex coronary artery lesion; therefore the current guideline recommended that prolonged DAPT might be considered when performing complex PCI. However, prolonged DAPT increases bleeding risk and cost. Endoscopic, dental, and surgical procedures are often delayed due to prolonged DAPT, which may affect the patient's quality of life. Therefore, to determine the optimal or minimal necessary duration of DAPT is very important.

The other important issue is that which antiplatelet agent is more appropriate after DAPT. Aspirin monotherapy has been recommended traditionally. However, there is no randomized comparison study between aspirin monotherapy versus clopidogrel monotherapy after DAPT in patients undergoing PCI with DES. Furthermore, clopidogrel is also actively used as a monotherapy after DAPT in real-world practice. In CAPRIE (clopidogrel versus aspirin in patients at risk of ischemic events) trial, clopidogrel showed a superior efficacy in preventing ischemic events compared with aspirin. Moreover, the incidence of gastrointestinal bleeding was significantly lower with clopidogrel than with aspirin. Clopidogrel monotherapy can reduce ischemic events and bleeding risk compared with aspirin monotherapy.

Therefore, the purpose of the SMART-CHOICE 3 (SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3) trial is to determine the efficacy and safety of clopidogrel monotherapy as compared with aspirin monotherapy beyond 12 months after PCI with current-generation DES in patients being treated with DAPT at high risk for recurrent ischemic events.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

5000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, open-label, two-arm, randomized controlled trialProspective, open-label, two-arm, randomized controlled trial

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clopidogrel Versus Aspirin Monotherapy Beyond Twelve Months After Percutaneous Coronary Intervention in Patients at High Risk for Recurrent Ischemic Events

Actual Study Start Date :

Aug 10, 2020

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aspirin monotherapy arm Patients will receive 100 mg of aspirin once daily.	Drug: Aspirin Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events who have been over 12 months after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken aspirin 100 mg once daily during the study period.
Experimental: Clopidogrel monotherapy arm Patients will receive 75 mg of clopidogrel once daily.	Drug: Clopidogrel Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events who have been over 12 months after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken clopidogrel 75 mg once daily during the study period.

Arm

Intervention/Treatment

Active Comparator: Aspirin monotherapy arm

Patients will receive 100 mg of aspirin once daily.

Drug: Aspirin

Randomization will be performed 1:1 between clopidogrel and aspirin monotherapy in patients being treated with dual antiplatelet therapy (DAPT) at high risk for recurrent ischemic events who have been over 12 months after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). This group will be taken aspirin 100 mg once daily during the study period.

Experimental: Clopidogrel monotherapy arm

Patients will receive 75 mg of clopidogrel once daily.

Drug: Clopidogrel

Outcome Measures

Primary Outcome Measures

Rates of major adverse cardiac and cerebrovascular event (MACCE) [1-year after last patient enrollment]
a composite of all-cause death, myocardial infarction, or stroke

Secondary Outcome Measures

Rates of all-cause death [1-year after last patient enrollment]
Death by any cause
Rates of cardiac death [1-year after last patient enrollment]
Death by cardiac cause
Rates of myocardial infarction [1-year after last patient enrollment]
Myocardial infarction
Rates of stroke [1-year after last patient enrollment]
Stroke
Rates of stent thrombosis [1-year after last patient enrollment]
definite or probable by Academic Research Consortium [ARC] definition
Rates of all-cause death or MI [1-year after last patient enrollment]
A composite of all-cause death or MI
Rates of cardiac death or MI [1-year after last patient enrollment]
A composite of cardiac death or MI
Rates of cardiac death, MI, or stroke [1-year after last patient enrollment]
A composite of cardiac death, MI, or stroke
Rates of cardiac death, MI, or stent thrombosis [1-year after last patient enrollment]
A composite of cardiac death, MI, or stent thrombosis
Rates of major Bleeding [1-year after last patient enrollment]
BARC [Bleeding Academic Research Consortium] types 3 or 5
Rates of bleeding [1-year after last patient enrollment]
BARC [Bleeding Academic Research Consortium] types 2, 3, or 5
Rates of upper gastrointestinal clinical event [1-year after last patient enrollment]
A composite of upper gastrointestinal clinical event
Rates of gastrointestinal ulcer or bleeding [1-year after last patient enrollment]
A composite of gastrointestinal ulcer or bleeding
New diagnosed rates of gastroesophageal reflux disease (GERD) [1-year after last patient enrollment]
Gastroesophageal reflux disease (GERD)
Rates of NACE (Net adverse clinical events) [1-year after last patient enrollment]
MACCE + BARC type 3 or 5 bleeding
Rates of Target-lesion revascularization (TLR) [1-year after last patient enrollment]
Target-lesion revascularization (TLR)
Rates of Target-vessel revascularization (TVR) [1-year after last patient enrollment]
Target-vessel revascularization (TVR)
Rates of any revascularization [1-year after last patient enrollment]
any revascularization including TLR, TVR, and non-TVR re-percutaneous coronary intervention
Medical cost [1-year after last patient enrollment]
Medical cost

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject must be at least 19 years of age
Subject who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.
Patients being treated with DAPT at high risk for recurrent ischemic events* who underwent PCI at least 12 months ago.

*High risk for recurrent ischemic events was defined as one or more of the following clinical or lesion characteristics.

Clinical characteristics

Patients presented with acute myocardial infarction.
Patients with diabetes mellitus who receiving oral hypoglycemic agent or insulin.

Complex lesion characteristics**

**Complex lesion was defined as one or more of the following.

True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) and is able to assess the side branch ostium
Chronic total occlusion (≥3 months) as target lesion
PCI for unprotected left main disease (left main ostium, body, or distal bifurcation including non-true bifurcation lesions)
Long coronary lesions (implanted stent length ≥38 mm)
Multi-vessel PCI (≥ 2 vessels treated at one PCI session)
Multiple stent needed (≥ 3 stents per patient)
In-stent restenosis lesion as target lesion
Severely calcified lesion (encircling calcium in angiography)
Ostial lesions of left anterior descending artery, left circumflex artery, or right coronary artery

Exclusion Criteria:

Known hypersensitivity or contraindications to study medications (aspirin or clopidogrel)
Patients taking warfarin or non-vitamin K antagonist (dabigatran, rivaroxaban, edoxaban, or apixaban)
Patients who require DAPT due to atherosclerotic disease other than coronary artery disease
Patients who are scheduled for revascularization treatment of coronary artery
Pregnant or lactating women
Non-cardiac co-morbid conditions are present with life expectancy <2 year or that may result in protocol non-compliance (per site investigator's medical judgment)