Sequential MonotherApy of TicagrElor and Clopidogrel After Coronary Intervention

Study Overview
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Brief Summary
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The MATE study is a randomized, multicenter, open-label, investigator-initiated clinical trial aimed to evaluate efficacy and safety of sequential monotherapy of ticagrelor and clopidogrel in patients with acute coronary syndrome (ACS) after coronary intervention. Standard DAPT of aspirin plus ticagrelor will be given for the first 1 month after PCI. After 1 month, event-free subjects will be randomized at 1:1 ratio into receiving standard DAPT (DAPT) until 12months , or switch to ticagrelor monotherapy for another 5 months , and further de-escalated to monotherapy of clopidogrel for the last 6 months(SAPT).

Detailed Description
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Compared with clopidogrel, ticagrelor inhibit platelet aggregation faster and stronger, and significantly reduce the risk of cardiovascular and cerebrovascular adverse events. In recent years, it has been given the strongest recommendation for antiplatelet therapy in ACS patients. Nevertheless, it was shown that excessive bleeding events significantly affect its antithrombotic advantage and better safety by downgrading regimen can seek more net clinical benefit. However, there are still huge controversies regarding the degree or timing of the downgrading regimen. GLOBAL LEADERS study shortened the course of DAPT after PCI to 1 month in all-comer population of coronary heart disease , and then downgraded to ticagrelor monotherapy and continued 23 months. At 12 months, compared with standard DAPT, there was neither increased risk of thrombotic events, nor significant reduction in BARC3 or type 5 major bleeding events, which suggested satisfactory safety of 1-month DAPT, and relative insufficiency de-escalation. The most recent STOPDAPT-2 ACS study not only adapted 1-month DAPT (prasugrel or clopidogrel + aspirin) in ACS patients, but also directly downgraded to clopidogrel monotherapy. Compared with standard DAPT of clopidogrel + aspirin, clopidogrel monotherapy significantly reduces the risk of bleeding, however, it also increases the thrombotic risk. Overrall, the investigators believe that de-escalated antiplatelet therapy are most suitable in ACS patients undergoing PCI. Short-course DAPT based on potent P2Y12 inhibitors will not increase the thrombotic risk, but continuous application of one single P2Y12 receptor antagonists may be difficult to take into account both the antithrombotic efficacy and bleeding benefit, while the sequential monotherapy of ticagrelor and clopidogrel may be more conducive to balancing the two needs. In summary, the current project aimed atall-comerpopulation of ACS, for the first time proposed a de-escalated antiplatelet regimen of sequential monotherapy of ticagrelor and clopidogrel. In this project, ticagrelor monotherapy will be used 1 month after PCI, and the anti-platelet strength will be further downgraded 5 months later to clopidogrel (75 mg) monotherapy till 1 year, which is supposed to achieve a better safety benefit and a non-inferior efficacy.

Official Title
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Efficacy and Safety of Sequential Monotherapy of Ticagrelor and Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention With Acute Coronary Syndrome

Conditions
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Acute Coronary Syndrome, Percutaneous Coronary Intervention

Intervention / Treatment
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* Drug: Standard-DAPT of Ticagrelor plus aspirin
* Drug: Sequential monotherapy of Ticagrelor and clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years old; Acute coronary syndrome was diagnosed upon admission; Administered ticagrelor for at least 30 days after successful PCI with implantation of a current-generation drug-eluting stent(s) Agree to the study protocol and the schedule of clinical follow-up, and provides informed, written consent Exclusion Criteria: Implanted with first-generation DES or bioabsorbable stent(s) during hospitalization; Patients with active pathological bleeding (such as peptic ulcer or intracranial hemorrhage); History of intracranial hemorrhage, intracranial neoplasms, intracranial vascular malformations or hemangioma High potential risk of major bleeding, such as acute or chronic gastrointestinal ulcers or other gastrointestinal diseases, alignant tumors, etc.; Thrombolytic therapy within 24 hours of index PCI; Planned coronary revascularization (surgical or percutaneous) within 30 days; Allergic to ticagrelor, clopidogrel or aspirin and any excipients; Inability to tolerate 12-month DAPT (ticagrelor+aspirin) for any reason; Cardiogenic shock or hemodynamic instability; Diagnosed as active hepatitis or liver cirrhosis upon admission; Suffer from a known serious progressive disease (e.g. progressive cancer, chronic obstructive lung disease, etc.;) or estimated survival time<12 months ; Platelet count<100000 /mm3; Dialysis-dependent renal failure； Required use of oral anticoagulation (warfarin or other factor II or factor X inhibitors); Pregnant or plan to be pregnant within 1 year; Any condition that may interfere with any study procedures, such as dementia, immobility, alcohol use, etc; Participating in any other clinical trial of an investigational drug or device that has not met its primary endpoint.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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: Standard-DAPT of Ticagrelor plus aspirin (DAPT)<br>Patients will receive Standard-DAPT of Ticagrelor plus aspirin for 1month after PCI and continue to receive standard-DAPT till 1 year in this arm after as followed: Ticagrelor 90mg bid+Aspirin 100mg qd for 1month; Ticagrelor 90mg bid+Aspirin 100mg qd for another 11 months; | Drug: Standard-DAPT of Ticagrelor plus aspirin<br>* Ticagrelor 90mg bid+Aspirin 100mg qd for 1 month after PCI, Randomized subjects continue for another 11 months<br>* Other names: DAPT;|
| Experimental: Sequential monotherapy of Ticagrelor and Clopidogrel (SAPT)<br>Patients will receive Standard-DAPT of Ticagrelor plus aspirin for 1month after PCI and switch to ticagrelor monotherapy in the following 5 months, and then further de-escalated to clopidogrel monotherapy till 1 year in this arm as followed: Ticagrelor 90mg bid+Aspirin 100mg qd for 1 month; Ticagrelor 90mg bid, for 5 months; clopidogrel 75mg qd, for 6 months. | Drug: Sequential monotherapy of Ticagrelor and clopidogrel<br>* Ticagrelor 90mg bid+Aspirin 100mg qd for 1 month after PCI, Randomized subjects switch to ticagrelor 90mg bid for 5 months; then clopidogrel 75mg qd, for another 6 months.<br>* Other names: SAPT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NACCE | Cumulative incidence of cardiovascular death, myocardial infarction, stroke (ischaemic, haemorrhagic, or unknown aetiology), definite stent thrombosis and bleeding type 2, 3 or 5 according to the Bleeding Academic Research Consortium (BARC) criteria. | 1-12months after PCI (11 months after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACCE | The Key secondary endpoint for ischemic outcome is cumulative incidence of cardiovascular death, non-fatal myocardial infarction,definite stent thrombosis or stroke (ischaemic, haemorrhagic, or unknown aetiology) | 1-12months after PCI (11 months after randomization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ticagrelor, monotherapy