Half Dose of Prasugrel and Ticagrelor in Acute Coronary Syndrome (HOPE-TAILOR)

Study Overview
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Brief Summary
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East Asian patients will be required optimal dose of newer P2Y12 inhibitors (prasugrel or ticagrelor) to determine the safer treatment and better outcome. Whether lower dose of these regimens are more adequate for clinical practice in Korea is unclear. Therefore, the investigators aim to evaluate efficacy and safety of half dose of new oral P2Y12 inhibitors in Korean patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

Detailed Description
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In recent years, newer oral P2Y12 receptor blockers (prasugrel or ticagrelor) have been strong recommendations for management of patients with ACS undergoing (PCI). These drugs provided more profound inhibitory effects than clopidogrel, which could lead to marked reduction in ischemic events, with relatively increase in bleeding complication, specific to low body weight, especially in women and East Asian patients.

Official Title
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An Open-label, Randomized, Prospective Study Exploring Half Dose of Prasugrel and Ticagrelor in Platelet Response After Acute Coronary Syndromes

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Clopidogrel 75 mg
* Drug: Prasugrel 5 mg
* Drug: Ticagrelor 45 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients present with acute coronary syndrome undergoing primary PCI. Patients receive DAPT (conventional dose of P2Y12 inhibitors+aspirin) at least 1 month. Patients provide written informed consent prior to enrollment. Exclusion Criteria: Low body weight (<60kg). 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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Clopidogrel 75 mg<br>Clopidogrel 600 mg as loading dose and followed by 75 mg/day as maintenance dose. | Drug: Clopidogrel 75 mg<br>* Clopidogrel 600 mg as loading dose followed by 75 mg/day as maintenance dose.<br>* Other names: Plavix 75 mg;|
| Experimental: Prasugrel 5 mg<br>Loading / maintenance dose: prasugrel 60 mg / 10 mg/day; After 1-month treatment of conventional dose, followed half dose of 5 mg/day for chronic treatment. | Drug: Prasugrel 5 mg<br>* Loading / maintenance dose: prasugrel 60 mg / 10 mg/day; After 1-month treatment of conventional dose, followed half dose of 5 mg/day for chronic treatment.<br>* Other names: Effient 5 mg;|
| Experimental: Ticagrelor 45 mg<br>Loading / maintenance dose: ticagrelor 180 mg / 90 mg/bid; After 1-month treatment of conventional dose, followed half dose of 45 mg/bid for chronic treatment. | Drug: Ticagrelor 45 mg<br>* Loading / maintenance dose: ticagrelor 180 mg / 90 mg/bid; After 1-month treatment of conventional dose, followed half dose of 45 mg/bid for chronic treatment.<br>* Other names: Brilinta 45 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal platelet reactivity (OPR) rate | OPR, indicate 85 to 208 for P2Y12 reaction units (PRU) or 16% to 50% for vasodilator-stimulated phosphoprotein (VASP)-platelet reactivity index (PRI) | At post-PCI 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac and cerebrovascular events (MACCE) | MACCE: composite of cardiac death, non-fatal myocardial infarction, repeat revascularization and stroke | Post-PCI 6 months. | 
| Bleeding events | BARC: Bleeding Academic Research Consortium (BARC ≥2). | Post-PCI 6 months. | 
| Drug side effects | Dyspnea or ventricular pauses ≥3 sec | Post-PCI 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Half dose, Newer oral P2Y12 receptor inhibitors, Acute coronary syndrome