Sequential MonotherApy of TicagrElor and Clopidogrel After Coronary Intervention

Acute Coronary Syndrome Clinical Trial

— MATE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04937699
• Other study ID #: 2021-MATE-01
• Status: Recruiting
• Phase: Phase 4
• Start date: March 28, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Heyang Wang, MD
• Phone: 86 0571-87783759
• Email: whysmmu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2690
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Percutaneous Coronary Intervention
• Syndrome

Intervention

Drug:
• Standard-DAPT of Ticagrelor plus aspirin
Ticagrelor 90mg bid+Aspirin 100mg qd for 1 month after PCI, Randomized subjects continue for another 11 months
• Sequential monotherapy of Ticagrelor and clopidogrel
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.

Locations

Country	Name	City	State
China	2nd Affiliated Hospital, School of Medicine at Zhejiang University	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

References & Publications (12)

Authors/Task Force members; Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Tag — View Citation

Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effe — View Citation

Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Ting HH, O'Gara PT, Kushner FG, Ascheim DD, Brindis RG, Casey DE Jr, Chung M — View Citation

Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, Taubert K, Smith SC Jr. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol. 2014 — View Citation

Li P, Gu Y, Yang Y, Chen L, Liu J, Gao L, Qin Y, Cai Q, Zhao X, Wang Z, Ma L. Low-dose ticagrelor yields an antiplatelet efficacy similar to that of standard-dose ticagrelor in healthy subjects: an open-label randomized controlled trial. Sci Rep. 2016 Aug — View Citation

Orme RC, Parker WAE, Thomas MR, Judge HM, Baster K, Sumaya W, Morgan KP, McMellon HC, Richardson JD, Grech ED, Wheeldon NM, Hall IR, Iqbal J, Barmby D, Gunn JP, Storey RF. Study of Two Dose Regimens of Ticagrelor Compared with Clopidogrel in Patients Unde — View Citation

Park DW, Lee PH, Jang S, Lim HS, Kang DY, Lee CH, Ahn JM, Yun SC, Park SW, Park SJ. Effect of Low-Dose Versus Standard-Dose Ticagrelor and Clopidogrel on Platelet Inhibition in Acute Coronary Syndromes. J Am Coll Cardiol. 2018 Apr 10;71(14):1594-1595. doi — View Citation

Vranckx P, Valgimigli M, Juni P, Hamm C, Steg PG, Heg D, van Es GA, McFadden EP, Onuma Y, van Meijeren C, Chichareon P, Benit E, Mollmann H, Janssens L, Ferrario M, Moschovitis A, Zurakowski A, Dominici M, Van Geuns RJ, Huber K, Slagboom T, Serruys PW, Wi — View Citation

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patient — View Citation

Wang HY, Li Y, Xu XM, Li J, Han YL. Impact of Baseline Bleeding Risk on Efficacy and Safety of Ticagrelor versus Clopidogrel in Chinese Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. Chin Med J (Engl). 2018 Sep 5;131( — View Citation

Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, Obayashi Y, Ogita M, Suwa S, Isawa T, Domei T, Yamaji K, Tatsushima S, Watanabe H, Ohya M, Tokuyama H, Tada T, Sakamoto H, Mori H, Suzuki H, Nishikura T, Wakabayashi K, Hibi K, Abe M, Kawai K, Nakao K, Ando K, Tanabe K, Ikari Y, Morino Y, Kadota K, Furukawa Y, Nakagawa Y, Kimura T; STOPDAPT-2 ACS Investigators. Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial. JAMA Cardiol. 2022 Apr 1;7(4):407-417. doi: 10.1001/jamacardio.2021.5244. — View Citation

Wu B, Lin H, Tobe RG, Zhang L, He B. Ticagrelor versus clopidogrel in East-Asian patients with acute coronary syndromes: a meta-analysis of randomized trials. J Comp Eff Res. 2018 Mar;7(3):281-291. doi: 10.2217/cer-2017-0074. Epub 2017 Nov 2. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	BARC types 2,3 or 5 bleeding	The Key secondary endpoint for bleeding outcome is cumulative incidence of BARC types 2,3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) criteria.	1-12months after PCI (11 months after randomization)
Primary	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	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)