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Ticagrelor De-escalation Strategy in East Asian Patients With AMI

Primary Purpose

Acute Myocardial Infarction

Status

Recruiting

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Ticagrelor 90mg

Ticagrelor 60/45mg

About this trial

This is an interventional treatment trial for Acute Myocardial Infarction focused on measuring Ticagrelor, De-escalation strategy, East Asian

Eligibility Criteria

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

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.

Sites / Locations

DongA University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Ticagrelor 90mg

Ticagrelor 60/45mg

Arm Description

Standard strategy group receive ticagrelor 90mg twice daily

De-escalation strategy group receive ticagrelor 60 mg twice daily or 45mg twice daily if patients with body weight <60kg, or age >75 years old.

Outcomes

Primary Outcome Measures

Net adverse clinical and cerebral events (NACCE)

Composite of all-cause death, myocardial infarction, stroke or major bleeding according to PLATO criteria.

Primary safety endpoint

Clinically significant bleeding: a composite of major or minor bleeding according to PLATO criteria.

Secondary Outcome Measures

major adverse cardiac and cerebrovascular events (MACCE)

Defined as a composite of cardiac death, myocardial infarction, or stroke

Individual components of MACCE

Indicated cardiac death, myocardial infarction, or stroke

Secondary adverse events

Indicated non-cardiac death, target lesion/vessel revascularization, stent thrombosis.

Major or minor (PLATO) bleeding event

By PLAtelet inhibition and patient Outcomes (PLATO) criteria

Major or minor (TIMI) bleeding event

By the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria

BARC bleeding from type 1 to 5

By Bleeding Academic Research Consortium (BARC) definition.

Premature discontinuation of study drugs

The patients cannot tolerate to be continued study drugs, due to bleeding event, or side effect.

Full Information

NCT ID

NCT04755387

First Posted

February 11, 2021

Last Updated

February 11, 2021

Sponsor

Dong-A University

1. Study Identification

Unique Protocol Identification Number

NCT04755387

Brief Title

Ticagrelor De-escalation Strategy in East Asian Patients With AMI

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Recruiting

Study Start Date

February 15, 2021 (Anticipated)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Dong-A University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myocardial Infarction

Keywords

Ticagrelor, De-escalation strategy, East Asian

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

2000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor 90mg

Arm Type

Other

Arm Description

Standard strategy group receive ticagrelor 90mg twice daily

Arm Title

Ticagrelor 60/45mg

Arm Type

Experimental

Arm Description

De-escalation strategy group receive ticagrelor 60 mg twice daily or 45mg twice daily if patients with body weight <60kg, or age >75 years old.

Intervention Type

Drug

Intervention Name(s)

Ticagrelor 90mg

Other Intervention Name(s)

Brilinta 90mg

Intervention Description

Standard strategy initially receive ticagrelor 90mg twice daily for 12 months.

Intervention Type

Drug

Intervention Name(s)

Ticagrelor 60/45mg

Other Intervention Name(s)

Brilinta 60/45mg

Intervention Description

In-hospital treatment with standard strategy ticagrelor 90mg twice daily, following de-escalation strategy ticagrelor 60/45mg twice daily after discharge for 12 months.

Primary Outcome Measure Information:

Title

Net adverse clinical and cerebral events (NACCE)

Description

Composite of all-cause death, myocardial infarction, stroke or major bleeding according to PLATO criteria.

Time Frame

12 months

Title

Primary safety endpoint

Description

Clinically significant bleeding: a composite of major or minor bleeding according to PLATO criteria.

Time Frame

12 months

Secondary Outcome Measure Information:

Title

major adverse cardiac and cerebrovascular events (MACCE)

Description

Defined as a composite of cardiac death, myocardial infarction, or stroke

Time Frame

12 months

Title

Individual components of MACCE

Description

Indicated cardiac death, myocardial infarction, or stroke

Time Frame

12 months

Title

Secondary adverse events

Description

Indicated non-cardiac death, target lesion/vessel revascularization, stent thrombosis.

Time Frame

12 months

Title

Major or minor (PLATO) bleeding event

Description

By PLAtelet inhibition and patient Outcomes (PLATO) criteria

Time Frame

12 months

Title

Major or minor (TIMI) bleeding event

Description

By the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria

Time Frame

12 months

Title

BARC bleeding from type 1 to 5

Description

By Bleeding Academic Research Consortium (BARC) definition.

Time Frame

12 months

Title

Premature discontinuation of study drugs

Description

The patients cannot tolerate to be continued study drugs, due to bleeding event, or side effect.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Moo Hyun Kim, M.D.

Phone

+82-51-240-2976

kimmh@dau.ac.kr

First Name & Middle Initial & Last Name or Official Title & Degree

Cai De Jin, M.D.

Phone

+8619117712582

jincaide1118@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Moo Hyun Kim, M.D.

Organizational Affiliation

Dong-A University Hospital, Busan, Republic of Korea

Official's Role

Principal Investigator

Facility Information:

Facility Name

DongA University Hospital

City

Busan

ZIP/Postal Code

602-715

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Moo Hyun Kim, M.D.

Phone

+82-51-240-2976

kimmh@dau.ac.kr

First Name & Middle Initial & Last Name & Degree

Moo Hyun Kim, M.D.

12. IPD Sharing Statement

Citations:

PubMed Identifier

26376600

Citation

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.

Results Reference

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PubMed Identifier

28810251

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.

Results Reference

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Ticagrelor De-escalation Strategy in East Asian Patients With AMI

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