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

Coronary Artery Disease Clinical Trial

— E-5TION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04734353
• Other study ID #: E-5TION
• Status: Recruiting
• Phase: Phase 4
• Start date: January 15, 2020
• Est. completion date: June 15, 2022

Study information

• Verified date: January 2021
• Source: Gyeongsang National University Hospital
• Contact: Young-Hoon Jeong, MD, PhD
• Phone: 82-55-214-3721
• Email: goodoctor[@]naver.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 492
• Est. completion date: June 15, 2022
• Est. primary completion date: June 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Prasugrel 5mg
Prasugrel 20 mg loading, followed by prasugrel 5 mg/day for 12 months
• Ticagrelor 60mg
Ticagrelor 120 mg loading, followed by ticagrelor 60 mg bid for 12 months

Locations

Country	Name	City	State
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Inje University Busan Paik Hospital,	Busan
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Pusan National University Hospital,	Busan
Korea, Republic of	Gyeongsang National University Changwon Hospital	Changwon	Gyeongsangnam-do
Korea, Republic of	Gyeongsang National University Hospita	Jinju	Gyeongsangnam-do
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan	Gyeongsangnam-do

Sponsors (2)

Lead Sponsor	Collaborator
Gyeongsang National University Hospital	U&I Corporation

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, Richardt G, Liebetrau C, Witzenbichler B, Antoniucci D, Akin I, Bott-Flügel L, Fischer M, Landmesser U, Katus HA, Sibbing D, Seyfarth M, Janisch M, Boncompagni D, Hilz R, Rottbauer W, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Platelet function test	VerifyNow PRU	1 month after PCI
Other	Bleeding assessment	Assessment of BARC bleeding based on dedicated bleeding questionnaire	1 month after PCI
Other	Dyspnea assessment	Assessment of dyspnea based on dedicated dyspnea questionnaire	1 month after PCI
Primary	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	MACE	Incidence of MACE (CV death, myocardial infarction, stent thrombosis, stroke or urgent revascularization)	1 year after PCI
Secondary	Major bleeding	Incidence of BARC type 2, 3 or 5 bleeding	1 year after PCI
Secondary	Major bleeding	Incidence of ISTH major bleeding or clinically relevant non-major (CRNM) bleeding	1 year post-PCI
Secondary	Adherence to DAPT regimen	Prevalence of discontinuation/switch of antiplatelet regimen d/t side effect	1 year after PCI

External Links

•   ISAR-REACT 5