Ticagrelor De-escalation Strategy in East Asian Patients With AMI

Acute Myocardial Infarction Clinical Trial

Official title:

A Prospective, Randomized, Open-Label, Multicenter Study Assessing Efficacy and Safety of Ticagrelor De-escalation Strategy in East Asian Acute Myocardial Infarction With Coronary Intervention: EASTYLE Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04755387
• Other study ID #: EASTYLE
• Status: Recruiting
• Phase: Phase 4
• Start date: February 15, 2021
• Est. completion date: January 31, 2024

Study information

• Verified date: February 2021
• Source: Dong-A University
• Contact: Moo Hyun Kim, M.D.
• Phone: +82-51-240-2976
• Email: kimmh[@]dau.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ticagrelor as nonthienopyridine, direct-acting P2Y12 receptor antagonist, had significantly greater platelet inhibition, which could reduce ischemic events at acute phase, however, resulting in more incidence of bleedings than pro-drug P2Y12 receptor inhibitor during chronic phase for management of acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). Also, East Asians have higher response to potent agent, like ticagrelor, when compared with Caucasians. With this in mind, East Asian patients will be required optimal, potentially reduced dose of ticagrelor to improve the safety profile, maintaining better vascular outcomes. Similarly, there are insufficient East Asian data on the efficacy and safety of low-dose ticagrelor in real-word practice. Whether the de-escalation strategy (ticagrelor 60/45 mg twice daily) are more adequate for clinical practice in East Asian is unclear. Therefore, the investigators design the EASTYLE study, hypothesis that low-dose ticagrelor would be more likely adequate for optimal antiplatelet treatment without increasing ischemic and bleeding events in East Asian with AMI compared with standard-dose ticagrelor. In the EASTYLE trial, further clinical data of de-escalation strategy guided AMI management in East Asian will be provided.

Description:

In EASTYLE trial, the investigators aim to evaluate the efficacy and safety of de-escalation strategy ticagrelor (60/45 mg twice daily), as compared with standard strategy ticagrelor (90 mg twice daily) in East Asian patients with AMI undergoing PCI. All eligible AMI patients receive loading dose of ticagrelor 180 mg plus aspirin 300 mg, following ticagrelor 90 mg twice daily plus aspirin 100 mg daily during the index hospitalization. Subsequently, to be randomly assigned into ticagrelor 90 mg and ticagrelor 60/45 mg twice daily in combination with aspirin 100 mg daily at discharge for at least 12-month period treatment. The investigators focusing on the efficacy and safety endpoint, is net adverse clinical and cerebrovascular events (NACCE), composite of all-cause mortality, myocardial infarction, stroke, and major bleeding.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: January 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients present with acute myocardial infarction undergoing PCI.
• Patients receive potent DAPT (Ticagrelor 180 mg loading dose followed by 90 mg twice daily plus Aspirin 300 mg loading dose followed by 100 mg daily).
• Patients provide written informed consent prior to enrollment.

Exclusion Criteria:

• History of transient ischemic attack or stroke.
• History of upper gastrointestinal bleeding in recent 6 months.
• Renal dysfunction defined as serum creatinine > 2.5 mg/dl.
• Severe hepatic dysfunction defined as serum transaminase > 3 times normal limit.
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
• Bleeding tendency.
• Thrombocytopenia defined by platelet < 100,000/ml.
• Anemia defined by hemoglobin < 10 g/dl.
• Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin.
• Known severe chronic obstructive pulmonary disease or bradycardia (sick sinus syndrome (SSS) or high degree AV block without pacemaker protection).
• Contraindication for study drugs.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Ticagrelor 90mg
Standard strategy initially receive ticagrelor 90mg twice daily for 12 months.
• Ticagrelor 60/45mg
In-hospital treatment with standard strategy ticagrelor 90mg twice daily, following de-escalation strategy ticagrelor 60/45mg twice daily after discharge for 12 months.

Locations

Country	Name	City	State
Korea, Republic of	DongA University Hospital	Busan

Sponsors (1)

Lead Sponsor	Collaborator
Dong-A University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Goto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome -- randomized, double-blind, phase III PHILO study. Circ J. 2015;79(11):2452-60. doi: 10.1253/circj.CJ-15-0112. Epub 2015 Sep 16. — View Citation

Jin C, Kim MH, Bang J, Serebruany V. A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study. Cardiology. 2017;138(4):201-206. doi: 10.1159/000478000. Epub 2017 Aug 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Net adverse clinical and cerebral events (NACCE)	Composite of all-cause death, myocardial infarction, stroke or major bleeding according to PLATO criteria.	12 months
Primary	Primary safety endpoint	Clinically significant bleeding: a composite of major or minor bleeding according to PLATO criteria.	12 months
Secondary	major adverse cardiac and cerebrovascular events (MACCE)	Defined as a composite of cardiac death, myocardial infarction, or stroke	12 months
Secondary	Individual components of MACCE	Indicated cardiac death, myocardial infarction, or stroke	12 months
Secondary	Secondary adverse events	Indicated non-cardiac death, target lesion/vessel revascularization, stent thrombosis.	12 months
Secondary	Major or minor (PLATO) bleeding event	By PLAtelet inhibition and patient Outcomes (PLATO) criteria	12 months
Secondary	Major or minor (TIMI) bleeding event	By the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria	12 months
Secondary	BARC bleeding from type 1 to 5	By Bleeding Academic Research Consortium (BARC) definition.	12 months
Secondary	Premature discontinuation of study drugs	The patients cannot tolerate to be continued study drugs, due to bleeding event, or side effect.	12 months