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

Phase 4

• Conditions: Coronary Artery Disease
• Interventions: Drug: Prasugrel 5mg; Drug: Ticagrelor 60mg

• Registration Number: NCT04734353
• Lead Sponsor: Gyeongsang National University Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2020-01-15
• Study First Submitted: 2020-08-18
• Status Verified: 2021-01
• Study First Submitted QC: 2021-01-28
• Last Update Submitted: 2021-01-28
• Study First Posted: 2021-02-02
• Last Update Posted: 2021-02-02
• Primary Completion: 2021-06-15
• Study Completion: 2022-06-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 492

Inclusion Criteria

1. Age 19 and more; and

2. Subjects who scheduled for percutaneous coronary intervention(PCI) with Firehawk® drug-eluting stent

3. 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

1. Cardiogenic shock at the index admission
2. Bleeding tendency, congenital or acquired
3. 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)
4. Need for chronic oral anticoagulation
5. History of intracranial hemorrhage
6. Intracranial neoplasm, AV fistula or aneurysm
7. Platelet counts < 100,000/mm3
8. Liver cirrhosis with ascites or coagulopathy
9. Dialysis-impending or -dependent renal failure
10. Pregnant and/or lactating women
11. Increased risk of bradycardia events (sick sinus, AV block grade II or III, bradycardia-induced syncope)
12. 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
13. Concurrent medical condition with a life expectancy of less than 1 years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
E5 group	Prasugrel 5mg	Escalation in CHIP
T60 group	Ticagrelor 60mg	Escalation in CHIP

Primary Outcome Measures

Name	Time	Method
Major bleeding and adherence to DAPT regimen	1 year after PCI	Incidence of major bleeding (BARC type 2, 3 or 5) and prevalence of discontinuation/switch of antiplatelet regimen

Secondary Outcome Measures

Name	Time	Method
MACE	1 year after PCI	Incidence of MACE (CV death, myocardial infarction, stent thrombosis, stroke or urgent revascularization)
Major bleeding	1 year post-PCI	Incidence of ISTH major bleeding or clinically relevant non-major (CRNM) bleeding
Adherence to DAPT regimen	1 year after PCI	Prevalence of discontinuation/switch of antiplatelet regimen d/t side effect

Trial Locations

Locations (8)

Pusan National University Yangsan Hospital; 🇰🇷 Yangsan, Gyeongsangnam-do, Korea, Republic of

Kosin University Gospel Hospital; 🇰🇷 Busan, Korea, Republic of

Gyeongsang National University Hospita; 🇰🇷 Jinju, Gyeongsangnam-do, Korea, Republic of

Pusan National University Hospital,; 🇰🇷 Busan, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of

Gyeongsang National University Changwon Hospital; 🇰🇷 Changwon, Gyeongsangnam-do, Korea, Republic of

Dong-A University Hospital; 🇰🇷 Busan, Korea, Republic of

Inje University Busan Paik Hospital,; 🇰🇷 Busan, Korea, Republic of