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

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

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).

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Prasugrel 5mg; Drug: Ticagrelor 60mg

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 Type: Interventional
• Enrollment (Anticipated): 492
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 602-702
    • Not yet recruiting
    • Kosin University Gospel Hospital
    • Contact: Jung Ho Heo, MD, PhD; Email: duggymdc@hanmail.net
  • Busan, Korea, Republic of, 602-714
    • Not yet recruiting
    • Dong-A University Hospital
    • Contact: Moo Hyun Kim, MD, PhD; Email: kimmh@dau.ac.kr
  • Busan, Korea, Republic of, 602-739,
    • Not yet recruiting
    • Pusan National University Hospital,
    • Contact: Jin Sup Park, MD, PhD; Email: dr.jinsup@gmail.com
  • Busan, Korea, Republic of
    • Not yet recruiting
    • Inje University Busan Paik Hospital,
    • Contact: Tae-Hyun Yang, MD, PhD; Email: yangthmd@naver.com
  • Ulsan, Korea, Republic of
    • Not yet recruiting
    • Ulsan University Hospital
    • Contact: Gyung-Min Park, MD, PhD; Email: 0733719@uuh.ulsan.kr
  • Gyeongsangnam-do
    • Changwon, Gyeongsangnam-do, Korea, Republic of, 51472
      • Recruiting
      • Gyeongsang National University Changwon Hospital
      • Contact: Young-Hoon Jeong, MD, PhD; Phone Number: 82-55-214-3721; Email: goodoctor@naver.com
    • Jinju, Gyeongsangnam-do, Korea, Republic of
      • Recruiting
      • Gyeongsang National University Hospita
      • Contact: Jin-Sin Koh, MD, PhD; Email: kjs0175@gmail.com
    • Yangsan, Gyeongsangnam-do, Korea, Republic of, 626-770
      • Recruiting
      • Pusan National University Yangsan Hospital
      • Contact: Jeong-Su Kim, MD, PhD; Email: j25ngsukim@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: E5 group; Escalation in CHIP	Drug: Prasugrel 5mg; Prasugrel 20 mg loading, followed by prasugrel 5 mg/day for 12 months; Other Names: Effient
ACTIVE_COMPARATOR: T60 group; Escalation in CHIP	Drug: Ticagrelor 60mg; Ticagrelor 120 mg loading, followed by ticagrelor 60 mg bid for 12 months; Other Names: Brillinta

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet function test	VerifyNow PRU	1 month after PCI
Bleeding assessment	Assessment of BARC bleeding based on dedicated bleeding questionnaire	1 month after PCI
Dyspnea assessment	Assessment of dyspnea based on dedicated dyspnea questionnaire	1 month after PCI

Collaborators and Investigators

• Sponsor: Gyeongsang National University Hospital
• Collaborators: U&I Corporation
• Investigators: Principal Investigator: Young-Hoon Jeong, MD, PhD, Changwon Gyeongsang National University Hospital

Publications and helpful links

General Publications

• Schupke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I, Wohrle J, Richardt G, Liebetrau C, Witzenbichler B, Antoniucci D, Akin I, Bott-Flugel L, Fischer M, Landmesser U, Katus HA, Sibbing D, Seyfarth M, Janisch M, Boncompagni D, Hilz R, Rottbauer W, Okrojek R, Mollmann H, Hochholzer W, Migliorini A, Cassese S, Mollo P, Xhepa E, Kufner S, Strehle A, Leggewie S, Allali A, Ndrepepa G, Schuhlen H, Angiolillo DJ, Hamm CW, Hapfelmeier A, Tolg R, Trenk D, Schunkert H, Laugwitz KL, Kastrati A; ISAR-REACT 5 Trial Investigators. Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2019 Oct 17;381(16):1524-1534. doi: 10.1056/NEJMoa1908973. Epub 2019 Sep 1.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 15, 2020
• Primary Completion (ANTICIPATED): June 15, 2021
• Study Completion (ANTICIPATED): June 15, 2022

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (ACTUAL): February 2, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Ticagrelor; Prasugrel; High-risk coronary artery disease
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: E-5TION

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No