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Sequential MonotherApy of TicagrElor and Clopidogrel After Coronary Intervention (MATE)

Primary Purpose

Acute Coronary Syndrome, Percutaneous Coronary Intervention

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Standard-DAPT of Ticagrelor plus aspirin
Sequential monotherapy of Ticagrelor and clopidogrel
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome focused on measuring ticagrelor, monotherapy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. High potential risk of major bleeding, such as acute or chronic gastrointestinal ulcers or other gastrointestinal diseases, alignant tumors, history of intracranial bleeding, etc.;
  4. Thrombolytic therapy within 24 hours of index PCI;
  5. Planned major surgery within 1 year;
  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. Estimated survival time<12 months
  12. Suffer from a known serious progressive disease (e.g. progressive cancer, chronic obstructive lung disease, etc.;) or extremely exhausted;
  13. Platelet count<100000 /mm3;
  14. Dialysis-dependent renal failure;
  15. Required use of oral anticoagulation (warfarin or other factor II or factor X inhibitors);
  16. Pregnant or plan to be pregnant within 1 year;
  17. Any condition that may interfere with any study procedures, such as dementia, immobility, alcohol use, etc;
  18. Participating in any other clinical trial of an investigational drug or device that has not met its primary endpoint.

Sites / Locations

  • 2nd Affiliated Hospital, School of Medicine at Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard-DAPT of Ticagrelor plus aspirin (DAPT)

Sequential monotherapy of Ticagrelor and Clopidogrel (SAPT)

Arm Description

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;

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)

Full Information

First Posted
June 16, 2021
Last Updated
May 2, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT04937699
Brief Title
Sequential MonotherApy of TicagrElor and Clopidogrel After Coronary Intervention
Acronym
MATE
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 28, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome, Percutaneous Coronary Intervention
Keywords
ticagrelor, monotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2690 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard-DAPT of Ticagrelor plus aspirin (DAPT)
Arm Type
Active Comparator
Arm Description
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;
Arm Title
Sequential monotherapy of Ticagrelor and Clopidogrel (SAPT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Standard-DAPT of Ticagrelor plus aspirin
Other Intervention Name(s)
DAPT
Intervention Description
Ticagrelor 90mg bid+Aspirin 100mg qd for 1 month after PCI, Randomized subjects continue for another 11 months
Intervention Type
Drug
Intervention Name(s)
Sequential monotherapy of Ticagrelor and clopidogrel
Other Intervention Name(s)
SAPT
Intervention Description
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.
Primary Outcome Measure Information:
Title
NACCE
Description
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.
Time Frame
1-12months after PCI (11 months after randomization)
Secondary Outcome Measure Information:
Title
MACCE
Description
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)
Time Frame
1-12months after PCI (11 months after randomization)
Other Pre-specified Outcome Measures:
Title
BARC types 2,3 or 5 bleeding
Description
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.
Time Frame
1-12months after PCI (11 months after randomization)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heyang Wang, MD
Phone
86 0571-87783759
Email
whysmmu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Changling Li, MD
Phone
+86 0571 89713104
Email
HREC2013@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yong Sun, MD
Organizational Affiliation
Second Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd Affiliated Hospital, School of Medicine at Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heyang Wang, MD
Phone
0571-87783759
Email
whysmmu@126.com
First Name & Middle Initial & Last Name & Degree
Changling Li, MD
Phone
0571-87783759
Email
HREC2013@126.com
First Name & Middle Initial & Last Name & Degree
Changling Li, MD
First Name & Middle Initial & Last Name & Degree
Jun Jiang, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The deidentified data will be shared after publication of first manuscript
IPD Sharing Time Frame
Data will be available within 12 months of study completion.
IPD Sharing Access Criteria
Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement
Citations:
PubMed Identifier
35234821
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.
Results Reference
background
PubMed Identifier
19923168
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 effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.
Results Reference
result
PubMed Identifier
19717846
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 patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.
Results Reference
result
PubMed Identifier
25173339
Citation
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, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014 Oct 1;35(37):2541-619. doi: 10.1093/eurheartj/ehu278. Epub 2014 Aug 29. No abstract available.
Results Reference
result
PubMed Identifier
26498666
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 MK, de Lemos JA, Diercks DB, Fang JC, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. J Am Coll Cardiol. 2016 Mar 15;67(10):1235-1250. doi: 10.1016/j.jacc.2015.10.005. Epub 2015 Oct 21. No abstract available. Erratum In: J Am Coll Cardiol. 2016 Mar 29;67(12):1506.
Results Reference
result
PubMed Identifier
29094604
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.
Results Reference
result
PubMed Identifier
30127210
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(17):2017-2024. doi: 10.4103/0366-6999.239306.
Results Reference
result
PubMed Identifier
27554803
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 24;6:31838. doi: 10.1038/srep31838.
Results Reference
result
PubMed Identifier
29930021
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 Undergoing Percutaneous Coronary Intervention for Stable Coronary Artery Disease. Circulation. 2018 Sep 25;138(13):1290-1300. doi: 10.1161/CIRCULATIONAHA.118.034790. Epub 2018 Jul 24.
Results Reference
result
PubMed Identifier
29622168
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: 10.1016/j.jacc.2018.02.010. No abstract available.
Results Reference
result
PubMed Identifier
25154978
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 Oct;11(10):597-606. doi: 10.1038/nrcardio.2014.104. Epub 2014 Aug 26.
Results Reference
result
PubMed Identifier
30166073
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, Windecker S; GLOBAL LEADERS Investigators. Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial. Lancet. 2018 Sep 15;392(10151):940-949. doi: 10.1016/S0140-6736(18)31858-0. Epub 2018 Aug 27.
Results Reference
result

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Sequential MonotherApy of TicagrElor and Clopidogrel After Coronary Intervention

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