Clinical trial NCT04734353: Prasugrel 5 mg vs. Ticagrelor 60 mg in CHIP (E5TION)
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: High-risk coronary artery disease
Prasugrel
Ticagrelor
Lead sponsor: Gyeongsang National University Hospital
Sponsor class: OTHER
Collaborators: name: U&I Corporation
First posted: 2021-02-02
Enrollment: 492
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Major bleeding and adherence to DAPT regimen
timeFrame: 1 year after PCI
Secondary outcomes:
measure: MACE
timeFrame: 1 year after PCI
measure: Major bleeding
timeFrame: 1 year after PCI
measure: Major bleeding
timeFrame: 1 year post-PCI
measure: Adherence to DAPT regimen
timeFrame: 1 year after PCI
Other outcomes:
measure: Platelet function test
timeFrame: 1 month after PCI
measure: Bleeding assessment
timeFrame: 1 month after PCI
measure: Dyspnea assessment
timeFrame: 1 month after PCI
Locations:
city: Changwon
country: Korea, Republic of
facility: Gyeongsang National University Changwon Hospital
state: Gyeongsangnam-do
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospita
state: Gyeongsangnam-do
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital,
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital,
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Changwon Gyeongsang National University Hospital
name: Young-Hoon Jeong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.