Clinical trial NCT04937699: Sequential MonotherApy of TicagrElor and Clopidogrel After Coronary Intervention
Official title: Efficacy and Safety of Sequential Monotherapy of Ticagrelor and Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention With Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Percutaneous Coronary Intervention
Keywords: ticagrelor
monotherapy
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2021-06-24
Enrollment: 2690
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 at"all-comer"population 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-80 years old;
2. Acute coronary syndrome was diagnosed upon admission;
3. Administered ticagrelor for at least 30 days after successful PCI with implantation of a current-generation drug-eluting stent(s)
4. Agree to the study protocol and the schedule of clinical follow-up, and provides informed, written consent

Exclusion Criteria:

1. Implanted with first-generation DES or bioabsorbable stent(s) during hospitalization;
2. Patients with active pathological bleeding (such as peptic ulcer or intracranial hemorrhage);
3. History of intracranial hemorrhage, intracranial neoplasms, intracranial vascular malformations or hemangioma
4. High potential risk of major bleeding, such as acute or chronic gastrointestinal ulcers or other gastrointestinal diseases, alignant tumors, etc.;
5. Thrombolytic therapy within 24 hours of index PCI;
6. Planned coronary revascularization (surgical or percutaneous) within 30 days;
7. Allergic to ticagrelor, clopidogrel or aspirin and any excipients;
8. Inability to tolerate 12-month DAPT (ticagrelor+aspirin) for any reason;
9. Cardiogenic shock or hemodynamic instability;
10. Diagnosed as active hepatitis or liver cirrhosis upon admission;
11. Suffer from a known serious progressive disease (e.g. progressive cancer, chronic obstructive lung disease, etc.;) or estimated survival time\<12 months ;
12. Platelet count\<100000 /mm3;
13. Dialysis-dependent renal failure；
14. Required use of oral anticoagulation (warfarin or other factor II or factor X inhibitors);
15. Pregnant or plan to be pregnant within 1 year;
16. Any condition that may interfere with any study procedures, such as dementia, immobility, alcohol use, etc;
17. Participating in any other clinical trial of an investigational drug or device that has not met its primary endpoint.

Primary outcomes:
measure: NACCE
timeFrame: 1-12months after PCI (11 months after randomization)
Secondary outcomes:
measure: MACCE
timeFrame: 1-12months after PCI (11 months after randomization)
Other outcomes:
measure: BARC types 2,3 or 5 bleeding
timeFrame: 1-12months after PCI (11 months after randomization)
Locations:
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine at Zhejiang University
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Yong Sun, MD
role: PRINCIPAL_INVESTIGATOR
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