ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of reducing dual antiplatelet therapy (DAPT) duration to 1 month after implantation of the everolimus-eluting cobalt-chromium stent (CoCr-EES).

Detailed Description
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The drug-eluting stents (DESs) are currently used in the majority of percutaneous coronary intervention (PCI) procedures. On the other hand, the problems of the first-generation DES (late adverse events, such as very late stent thrombosis) have been pointed out. Dual antiplatelet therapy (DAPT) has become a standard regimen after DES implantation and for fear of very late stent thrombosis, DAPT is frequently performed for 1 year or longer in clinical practice. However, serious hemorrhagic complications associated with a prolonged DAPT duration can bring disadvantages to patients, and it is extremely important to clarify an optimal DAPT duration after DES procedure. Currently, 1-month DAPT regimen after bare metal stent (BMS) implantation is commonly used in clinical practice, producing no major problems. Based on a meta-analysis of recent clinical studies, it has also been reported that the use of Cobalt-Chromium Everolimus-Eluting Stent (CoCr-EES) reduces the risk of early stent thrombosis by half compared to the use of BMS. There is no necessity to extend antiplatelet therapy after CoCr-EES implantation longer than after BMS implantation, and it is considered possible to use the same 1-month DAPT duration as after BMS implantation. The investigators therefore planned a multicenter, randomized, open-label, controlled study, in which the subjects who have undergone CoCr-EES procedure will be divided into the 1-month DAPT and clopidogrel monotherapy group and the 12-month DAPT and aspirin monotherapy group. Primary endpoint is the incidence of composite events including cardiovascular death, myocardial infarction, stent thrombosis, stroke, and bleeding defined by TIMI major or minor bleeding. At first, the non-inferiority about primary endpoint of 1-month DAPT group will be evaluated at 12 months after index procedure and secondarily, the superiority about primary endpoint of 1-month DAPT group will be evaluated at 5 years after index procedure.

Official Title
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ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-2 Study

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: 1-month DAPT
* Drug: 12-month DAPT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients received percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent Patients who are capable of oral dual antiplatelet therapy consisting of asprin and P2Y12 receptor antagonist Exclusion Criteria: Patients requiring oral anticoagulants Patients with medical history of intracranial hemorrhage Patients who have experienced serious complications (myocardial infarction, stroke, and major bleeding) during hospital stay after percutaneous coronary intervention Patients with drug eluting stents other than Cobalt chromium everolimus eluting stents (Xience) implanted at the time of enrollment Patients comfirmed to have no tolerability to clopidgorel before enrollment Patients requiring continuous administration of antiplaelet drugs other than aspirin and P2Y12 receptor antagonists at the time of enrollment Patients with coronary bioabsorbable vascular scaffolds (BVS) implanted prior to or at the time of enrollment
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1-month DAPT<br>1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists , followed by 59-month clopidogrel monotherapy | Drug: 1-month DAPT<br>* 1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists<br>|
| Active Comparator: 12-month DAPT<br>1-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists with 11-month DAPT composed of aspirin and clopidogrel, followed by 48-month aspirin monotherapy | Drug: 12-month DAPT<br>* 12-month dual antiplatelet therapy (DAPT) composed of aspirin and P2Y12 receptor antagonists<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke/bleeding | Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke/bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group | 12-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke |  | 12-month | 
| Composite event of cardiovascular death/myocardial infarction/definite stent thrombosis/stroke |  | 60-month | 
| Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group |  | 12-month | 
| Bleeding defined as major or minor under the definition of Thrombolysis in Myocardial Infarction (TIMI) Study group |  | 60-month | 
| Upper gastrointestinal endoscopic examination or treatment |  | 60-month | 
| Composite event of all-cause death/myocardial infarction |  | 12-month | 
| Composite event of all-cause death/myocardial infarction |  | 60-month | 
| All-cause death |  | 12-month | 
| All-cause death |  | 60-month | 
| Composite event of cardiovascular death/myocardial infarction |  | 12-month | 
| Composite event of cardiovascular death/myocardial infarction |  | 60-month | 
| Cardiovascular death |  | 12-month | 
| Cardiovascular death |  | 60-month | 
| Myocardial infarction |  | 12-month | 
| Myocardial infarction |  | 60-month | 
| Stroke | a neurological deficit with acute onset that persists for at least 24 hours caused by a disturbance of the cerebral circulation due to ischemia or hemorrhage | 12-month | 
| Stroke | a neurological deficit with acute onset that persists for at least 24 hours caused by a disturbance of the cerebral circulation due to ischemia or hemorrhage | 60-month | 
| MACE (Major Adverse Cardiac Events) | Composite event of cardiac death, myocardial infarction and clinically-indicated target vesion revascularization | 12-month | 
| MACE (Major Adverse Cardiac Events) | Composite event of cardiac death, myocardial infarction and clinically-indicated target vesion revascularization | 60-month | 
| Definite stent thrombosis |  | 12-month | 
| Definite stent thrombosis |  | 60-month | 
| Target lesion failure | Composite event of cardiac death, myocardial infarction (MI) of target vessels, and Clinically-indicated TLR | 12-month | 
| Target lesion failure | Composite event of cardiac death, myocardial infarction (MI) of target vessels, and Clinically-indicated TLR | 60-month | 
| Target vessel failure |  | 12-month | 
| Target vessel failure |  | 60-month | 
| Target lesion revasucularization | PCI performed in the target lesion (within 5 mm of the stent edges), or CABG performed for restenosis of the target lesion or for treatment of other complications | 12-month | 
| Target lesion revasucularization | PCI performed in the target lesion (within 5 mm of the stent edges), or CABG performed for restenosis of the target lesion or for treatment of other complications | 60-month | 
| Clinically-driven target lesion revascularization | the revascularization that meets the following criteria; (1) recurrence of angina pectoris, presumably related to the target vessel, (2) objective signs of ischemia at rest or during exercise test (or equivalent), presumably related to the target vessel, (3) Signs of functional ischemia revealed by any invasive diagnostic test (e.g., Doppler flow velocity reserve [FVR], fractional flow reserve [FFR]), and (4) revascularization for ≥ 70% diameter stenosis even in the absence of the above-mentioned ischemic signs or symptoms. Presence/absence of clinical findings is judged by the operator of the procedure before the revascularization. | 12-month | 
| Clinically-driven target lesion revascularization | the revascularization that meets the following criteria; (1) recurrence of angina pectoris, presumably related to the target vessel, (2) objective signs of ischemia at rest or during exercise test (or equivalent), presumably related to the target vessel, (3) Signs of functional ischemia revealed by any invasive diagnostic test (e.g., Doppler flow velocity reserve [FVR], fractional flow reserve [FFR]), and (4) revascularization for ≥ 70% diameter stenosis even in the absence of the above-mentioned ischemic signs or symptoms. Presence/absence of clinical findings is judged by the operator of the procedure before the revascularization. | 60-month | 
| Non target lesion revascularization |  | 12-month | 
| Non target lesion revascularization |  | 60-month | 
| Coronary artery bypass graft |  | 12-month | 
| Coronary artery bypass graft |  | 60-month | 
| Target vessel revascularization |  | 12-month | 
| Target vessel revascularization |  | 60-month | 
| Any coronary reascluarization |  | 12-month | 
| Any coronary reascluarization |  | 60-month | 
| Bleeding complications | Evaluated with TIMI (major/minor/minimal), GUSTO (severe/moderate) and BARC (Type 1, 2, 3a, 3b, 3c, 4, 5a, 5b) | 12-month | 
| Bleeding complications | Evaluated with TIMI (major/minor/minimal), GUSTO (severe/moderate) and BARC (Type 1, 2, 3a, 3b, 3c, 4, 5a, 5b) | 60-month | 
| Gastrointestinal bleeding | Bleeding events requiring upper gastrointestinal endoscopic study or treatment. | 12-month | 
| Gastrointestinal bleeding | Bleeding events requiring upper gastrointestinal endoscopic study or treatment. | 60-month | 
| Gastrointestinal complaints | Symptoms requiring upper gastrointestinal endoscopic study or treatment | 12-month | 
| Gastrointestinal complaints | Symptoms requiring upper gastrointestinal endoscopic study or treatment | 60-month | 
| Newly diagnosed cancer | The endpoint is a newly diagnosed malignancy during the follow-up period that has not been previously diagnosed before enrollment. This does not include recurrent tumor after remission, includes early-stage cancer eligible for endoscopic treatment, and includes the tumors which are not diagnosed by tissue biopsy but are judged to be clinically malignant on imaging. | 60-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors