MonotherApy of Low-does TicagrElor After Percutaneous Coronary Intervention

Efficacy and Safety of Sequential Single Antiplatelet Therapy of Low-dose Ticagrelor and Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention With Acute Coronary Syndrome and High Bleeding Risk

Sponsors

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

Source Second Affiliated Hospital, School of Medicine, Zhejiang University
Brief Summary

The MATE study is a randomized, multicenter, open-label, investigator-initiated clinical trial aimed to evaluate efficacy and safety of sequential single antiplatelet therapy of low-dose Ticagrelor and clopidogrel in patients with acute coronary syndrome (ACS) and high bleeding risk after coronary intervention. Eligible patients will be randomized at 1:1 ratio after PCI, into receiving low-dose ticagrelor monotherapy (LD.T), or standard-dose ticagrelor with aspirin (SD.T+A). 6 months after PCI, LD.T will be further de-escalated to clopidogrel monotherapy, with SD.T+A remained,for another 6 months. The current study is a pre-trial to preliminary observe whether the low-does potent P2Y12 inhibitor can largely reduce clinical-relevant bleeding versus dual antiplatelet therapy, while keep non-inferior on thrombotic risk in ACS patients with high bleeding risk, which will provide supporting data for the later large-scale clinical trial.

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 only by downgrading regimen to improve safety can we seek the maximum net clinical benefit, especially in people at high risk of bleeding. However, there are still huge controversies regarding the degree or timing of the downgrading regimen. The current study analyzes in detail the advantages and limitations of the existing research, and makes a groundbreaking reform from the following three aspects: First, the Degree. A series of studies have shown that compared with standard-does ticagrelor, low-does ticagrelor(60mg) has nearly the same pharmacodynamic level on platelet function inhibition in patients of either healthy volunteers, or stable angina and ACS. Therefore, low-does ticagrelor with aspirin should be the starting point but not the end point of down-degrading. On this basis, this study for the first time suggest the monotherapy of low-dose ticagrelor in patients with high bleeding risk. Second, the Timing. It has been shown that ticagrelor-related bleeding events mainly happened in the first 3-4 months after PCI. This stage should not be a "forbidden zone" for all patients. In the current study, monotherapy of low-dose ticagrelor will be used right after PCI in patients excluding STEMI and left main, to observe whether it is not inferior to the standard DAPT on antithrombotic efficacy. Finally, the Combination. The 2nd generation drug-eluding stents and drug-coated balloons significantly shortened the course of dual antiplatelet therapy after PCI. Most of relative studies have set ti to 6 months. Therefore, this study continue to downgrade to clopidogrel monotherapy 6 months after PCI, maximizing the benefits of bleeding reduction on the basis of meeting safety requirements. In summary, the current project aimed at high-bleeding-risk people with ACS, taking full advantage of powerful antiplatelet drug of ticagrelor, for the first time proposed a de-escalated antiplatelet regimen of sequential monotherapy of low-dose ticagrelor and clopidogrel. In this project, low-does ticagrelor was used in the first 6 months after PCI, and the strength of anti-platelet will be further downgraded to clopidogrel (75 mg) in the following 6 months, which is supposed to achieve a better safety benefit and a non-inferior efficacy.

Overall Status Not yet recruiting
Start Date 2021-12-01
Completion Date 2023-12-01
Primary Completion Date 2023-12-01
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
BARC 2, 3 or 5 bleeding 12 months after randomization.
Secondary Outcome
Measure Time Frame
MACCE 12 months after randomization.
Enrollment 510
Condition
Intervention

Intervention Type: Drug

Intervention Name: Standard-Does Ticagrelor plus aspirin

Description: ticagrelor 90mg bid plus aspirin 100mg qd, for 12months after randomization

Arm Group Label: Standard-Does Ticagrelor plus aspirin (SD.T+A)

Other Name: SD.T+A

Intervention Type: Drug

Intervention Name: Low-Does Ticagrelor monotherapy

Description: ticagrelor 60mg bid for 6months after randomization, then clopidogrel 75mg qd for another 6 months

Arm Group Label: Low-Does Ticagrelor monotherapy (LD.T)

Other Name: LD.T

Eligibility

Criteria:

Inclusion Criteria: 1. Age 18-80 years old; 2. Acute coronary syndrome was diagnosed upon admission; 3. Must meet at least one of the following high-risk clinical criteria for bleeding: 1. Female 2. Age ≥65 years old 3. Hemoglobin≤110g/L 4. Diabetes treated with medications (oral drugs or subcutaneous insulin injections) 5. eGFR<60 ml/min/1.73m2 (MRDR formula) 4. Implant a second-generation drug-eluting stent or apply a drug-coated balloon during hospitalization 5. Intended treatment with dual antiplatelet therapy (aspirin + ticagrelor) after the procedure for at least 12 months 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. Previous drug-related bleeding requiring medications within 12 months; 4. High potential risk of major bleeding, such as acute or chronic gastrointestinal ulcers or other gastrointestinal diseases, malignant tumors, etc.; 5. Previous stroke; 6. Thrombolytic therapy within 24 hours of coronary intervention; 7. STEMI within 1 month; 8. current coronary intervention in the left main; 9. Allergic to ticagrelor, clopidogrel or aspirin and any excipients; 10. Inability to tolerate 12-month DAPT (ticagrelor+aspirin) for any reason; 11. Cardiogenic shock or hemodynamic instability; 12. Diagnosed as active hepatitis or liver cirrhosis upon admission; 13. Estimated survival time<12 months or extremely exhausted (e.g. progressive cancer, chronic obstructive lung disease, etc.;); 14. Planned surgery within 1 year; 15. Hemoglobin <90g/L; 16. Platelet count<100×109 pcs/L; 17. Dialysis-dependent renal failure; 18. Required use of oral anticoagulation (warfarin or other factor II or factor X inhibitors); 19. Pregnant or plan to be pregnant within 1 year; 20. Any condition that may interfere with any study procedures, such as dementia, immobility, alcohol use, etc; 21. Participating in any other clinical trial of an investigational drug or device that has not met its primary endpoint.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Changling Li Principal Investigator Second Affiliated Hospital, School of Medicine, Zhejiang University
Overall Contact

Last Name: Changling Li

Phone: 86 0571-87783759

Email: [email protected]

Location
Facility: Contact: Contact Backup: Investigator: 2nd Affiliated Hospital, School of Medicine at Zhejiang University Changling Li 0571-87783759 [email protected] Changling Li Principal Investigator Heyang Wang, MD Sub-Investigator
Location Countries

China

Verification Date

2021-06-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Standard-Does Ticagrelor plus aspirin (SD.T+A)

Type: Active Comparator

Description: Patients will be randomized after PCI, and receive standard-does ticagrelor plus aspirin in this arm as followed: Ticagrelor 90mg bid+Aspirin 100mg qd

Label: Low-Does Ticagrelor monotherapy (LD.T)

Type: Experimental

Description: Patients will be randomized after PCI, and receive low-does ticagrelor monotherapy during the first 6 months after PCI, and then clopidogrel monotherapy for another 6 months in this arm as followed: Ticagrelor 60mg bid, for 6 months + clopidogrel 75mg qd, for 6 months

Acronym MATE
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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