Prasugrel 5 mg vs. Ticagrelor 60 mg in CHIP (E5TION)

Study Overview
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Brief Summary
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E5TION will evaluate the efficacy, safety and tolerability of tailored two regimens (prasugrel 5mg/d vs. ticagrelor 60mg bid) in high-risk patients undergoing PCI (CHIP: COmplex and Higher-Risk Indicated PCI/PatieNts).

Detailed Description
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Because CHIP (COmplex and Higher-Risk Indicated PCI/PatieNts) has been related with the increased risk of ischemic events following PCI, there are unmet needs to develop the tailored strategies (e.g., intensified antiplatelet treatment) for this cohort. During antithrombotic treatment, East Asian patients have been prone to bleed compared with Western patients (East Asian Paradox). For example, standard-dose potent P2Y12 inhibitors (e.g., ticagrelor, prasugrel) vs. clopidogrel did not demonstrate the better net clinical benefit in patients with acute coronary syndrome. One of the tailored antiplatelet strategies for East Asian patients would be the de-escalated strategy of potent P2Y12 inhibitors (e.g., ticagrelor, prasugrel). The ISAR-REACT5 trial showed the lower ischemic event and better tolerability of ticagrelor vs. prasugrel in ACS patients. This E5TION trial will compare the efficacy, safety and tolerability of the de-escalated strategies (low-dose prasugrel and ticagrelor) in East Asian patients with CHIP character.

Official Title
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Efficacy, Safety and Tolerability of PrasugrEl 5mg or TIcagrelor 60mg in COmplex and Higher-Risk Indicated PCI/PatieNts: The Prospective, Randomized, Open-labeled, Blinded Endpoint (PROBE), Multi-center E5TION Trial

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Prasugrel 5mg
* Drug: Ticagrelor 60mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19 and more; and Subjects who scheduled for percutaneous coronary intervention(PCI) with Firehawk® drug-eluting stent At least one of the following high-risk factors; Clinical factors: diabetes, chronic kidney disease (GFR < 60ml/min/1.73m2), LV dysfunction (LV EF < 45%), or troponin (+). Lesion- or procedure-related factors: left main PCI, chronic total occlusion, bifurcation lesion requiring two-stent technique, severe calcification, in-stent restenosis, multi-vessel PCI (≥ 2 vessels requiring stent implantation), PCI for ≥ 3 lesions, ≥ 3 stents implanted, or total stent length > 60 mm. High platelet reactivity: VerifyNow PRU ≥ 266. Exclusion Criteria: Cardiogenic shock at the index admission Bleeding tendency, congenital or acquired Active bleeding or high-risk for major bleeding (e.g. active peptic ulcer disease, gastrointestinal pathology with a high-risk for bleeding, malignancies with a high-risk for bleeding) Need for chronic oral anticoagulation History of intracranial hemorrhage Intracranial neoplasm, AV fistula or aneurysm Platelet counts < 100,000/mm3 Liver cirrhosis with ascites or coagulopathy Dialysis-impending or -dependent renal failure Pregnant and/or lactating women Increased risk of bradycardia events (sick sinus, AV block grade II or III, bradycardia-induced syncope) Concomitant oral or i.v. therapy with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice >1L/day), CYP3A substrates with narrow therapeutic indices (e.g., cyclosporine, quinidine), or strong CYP3A inducers (e.g., rifampin/ rifampicin, phenytoin, carbamazepine, dexamethason, phenobarbital) that cannot be safely discontinued Concurrent medical condition with a life expectancy of less than 1 years

Ages Eligible for Study
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Minimum Age: 19 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E5 group<br>Escalation in CHIP | Drug: Prasugrel 5mg<br>* Prasugrel 20 mg loading, followed by prasugrel 5 mg/day for 12 months<br>* Other names: Effient;|
| Active Comparator: T60 group<br>Escalation in CHIP | Drug: Ticagrelor 60mg<br>* Ticagrelor 120 mg loading, followed by ticagrelor 60 mg bid for 12 months<br>* Other names: Brillinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major bleeding and adherence to DAPT regimen | Incidence of major bleeding (BARC type 2, 3 or 5) and prevalence of discontinuation/switch of antiplatelet regimen | 1 year after PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE | Incidence of MACE (CV death, myocardial infarction, stent thrombosis, stroke or urgent revascularization) | 1 year after PCI | 
| Major bleeding | Incidence of BARC type 2, 3 or 5 bleeding | 1 year after PCI | 
| Major bleeding | Incidence of ISTH major bleeding or clinically relevant non-major (CRNM) bleeding | 1 year post-PCI | 
| Adherence to DAPT regimen | Prevalence of discontinuation/switch of antiplatelet regimen d/t side effect | 1 year after PCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High-risk coronary artery disease, Prasugrel, Ticagrelor