Clinical trial NCT04755387: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Myocardial Infarction
Keywords: Ticagrelor
De-escalation strategy
East Asian
Lead sponsor: Dong-A University
Sponsor class: OTHER
First posted: 2021-02-16
Enrollment: 2000
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Net adverse clinical and cerebral events (NACCE)
timeFrame: 12 months
measure: Primary safety endpoint
timeFrame: 12 months
Secondary outcomes:
measure: major adverse cardiac and cerebrovascular events (MACCE)
timeFrame: 12 months
measure: Individual components of MACCE
timeFrame: 12 months
measure: Secondary adverse events
timeFrame: 12 months
measure: Major or minor (PLATO) bleeding event
timeFrame: 12 months
measure: Major or minor (TIMI) bleeding event
timeFrame: 12 months
measure: BARC bleeding from type 1 to 5
timeFrame: 12 months
measure: Premature discontinuation of study drugs
timeFrame: 12 months
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: DongA University Hospital
Study officials:
affiliation: Dong-A University Hospital, Busan, Republic of Korea
name: Moo Hyun Kim, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.