CYP2C19 Genotype-Guided P2Y12 Receptor Inhibitor Selection After Complex Percutaneous Coronary Intervention

NCT06283888 | Recruiting Phase 4

• 1 other identifier: PRECISE-PCI
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

In Ease Asia clinical trials, P2Y12 inhibitor (ticagrelor or clopidogrel) monotherapy after 3-month dual antiplatelet therapy (DAPT) resulted in a lower incidence of clinically significant bleeding, without increasing risk of major adverse cardiac and cerebrovascular events, even if acute coronary syndrome (ACS) following complex percutaneous coronary intervention (PCI) when compared with standard DAPT. Although better understood "East Asian Paradox", finding the right CYP2C19 genotype-guided P2Y12 inhibitor selection to balance maintaining ischaemic prevention and less bleeding remains a topic in real-world clinical practice.

Conditions

ACS - Acute Coronary Syndrome; CYP2C19 Polymorphism

Keywords

CYP2C19 Genotype; P2Y12 Receptor Inhibitor; Complex PCI

Outcome Measures

Primary Outcomes (1)

• NACE (net adverse clinical event)

  The incidence of NACE (composite of cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, stroke, or clinically significant bleeding according to BARC criteria).

  At 12 months

Secondary Outcomes (2)

• Incidence of clinically significant bleeding

  At 12 months

• Incidence of MACCE

  12 months

Study Arms (2)

CYP2C19 Genotype Guided DAPT

EXPERIMENTAL

Patients with CYP2C19 \*2 or \*3 carrier will be received ticagrelor 60mg or 45mg bid (if \<50 kg, ≥75 years) + aspirin 100 mg Patients with CYP2C19 \*2 or \*3 non-carrier will be received clopidogrel 75mg qd + aspirin 100 mg qd At post-PCI 3 months, monotherapy P2Y12 inhibitor (ticagrelor or clopidogrel) will be treated for a further 9 months.

Drug: CYP2C19 Genotype Guided DAPT

Conventional DAPT

EXPERIMENTAL

Patients will be conventionally received ticagrelor 90mg bid or clopidogrel 75mg qd + aspirin 100 mg qd At post-PCI 3 months, monotherapy P2Y12 inhibitor (ticagrelor or clopidogrel) will be treated for a further 9 months.

Drug: Conventional DAPT

Interventions

CYP2C19 Genotype Guided DAPT DRUG

Patients with \*2 or \*3 carrier will be received ticagrelor 60mg or 45mg bid (if \<50 kg, ≥75 years) + aspirin 100 mg qd; Patients with \*2 or \*3 non-carrier will be received clopidogrel 75mg qd + aspirin 100 mg qd

Also known as: Guided DAPT

CYP2C19 Genotype Guided DAPT

Conventional DAPT DRUG

Patients will be conventionally received ticagrelor 90mg bid or clopidogrel 75mg qd + aspirin 100 mg qd

Also known as: Unguided DAPT

Conventional DAPT

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical Criteria:
• Patients aged between 18-80 years old.
• Patients with ACS (UA/NSTEMI/STEMI) undergoing PCI.
• Patients will be treated with DAPT (P2Y12 inhibitors+aspirin) for at least 3 months.
• Patients are willing to provide a DNA sample (via blood draw) for CYP2C19 genotyping.
• Patients provide written informed consent before enrollment.
• Angiographic Criteria (meet at least 1 of the following characteristics):
• Thrombotic target lesion.
• Calcified target lesion requiring rotational atherectomy or intravascular lithotripsy
• Multivessel (≥2 vessels) disease will be treated.
• Multi-target lesions (≥3 lesions) will be treated.
• Multi-stent (≥3 stents) will be implanted.
• Total stent length≥60 mm.
• Bifurcation lesion requiring at least 2 stents.
• PCI for left main.

You may not qualify if:

• Patient with known CYP2C19 genotype before randomization.
• Anticipated discontinuation of clopidogrel or ticagrelor within the 12-month follow-up period.
• Planned surgery within 90 days.
• Requiring oral anticoagulation therapy (eg, atrial fibrillation, deep vein thrombosis, pulmonary thromboembolism)
• Intracranial/gastrointestinal/urogenital bleeding within 6 months.
• Active bleeding or bleeding diathesis, thrombocytopenia (platelet \<100,000/mL) or hemoglobin \<10 g/dL
• Hepatic dysfunction (serum liver enzyme\>3 times the normal limit)
• Renal failure (eGFR \<15 ml/min/1.73m2 or requiring dialysis)
• Concomitant therapy with a strong CYP3A4 inhibitor or inducer
• Life expectancy \< 1 year

Sponsors & Collaborators

• Zunyi Medical College: lead

Study Sites (1)

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, 563003, China

RECRUITING

Related Publications (5)

• Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, Bell M, Bae JH, Jeong MH, Chavez I, Gordon P, Abbott JD, Cagin C, Baudhuin L, Fu YP, Goodman SG, Hasan A, Iturriaga E, Lerman A, Sidhu M, Tanguay JF, Wang L, Weinshilboum R, Welsh R, Rosenberg Y, Bailey K, Rihal C. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA. 2020 Aug 25;324(8):761-771. doi: 10.1001/jama.2020.12443.

  PMID: 32840598 BACKGROUND

• Kim BK, Hong SJ, Cho YH, Yun KH, Kim YH, Suh Y, Cho JY, Her AY, Cho S, Jeon DW, Yoo SY, Cho DK, Hong BK, Kwon H, Ahn CM, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Hong MK, Jang Y; TICO Investigators. Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial. JAMA. 2020 Jun 16;323(23):2407-2416. doi: 10.1001/jama.2020.7580.

  PMID: 32543684 BACKGROUND

• Hahn JY, Song YB, Oh JH, Chun WJ, Park YH, Jang WJ, Im ES, Jeong JO, Cho BR, Oh SK, Yun KH, Cho DK, Lee JY, Koh YY, Bae JW, Choi JW, Lee WS, Yoon HJ, Lee SU, Cho JH, Choi WG, Rha SW, Lee JM, Park TK, Yang JH, Choi JH, Choi SH, Lee SH, Gwon HC; SMART-CHOICE Investigators. Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial. JAMA. 2019 Jun 25;321(24):2428-2437. doi: 10.1001/jama.2019.8146.

  PMID: 31237645 BACKGROUND

• Jin C, Kim MH, Guo LZ, Jin E, Shin ES, Ann SH, Cho YR, Park JS, Kim SJ, Lee MS. Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial). Int J Cardiol. 2020 Apr 15;305:11-17. doi: 10.1016/j.ijcard.2020.01.058. Epub 2020 Jan 25.

  PMID: 32029306 BACKGROUND

• Jin CD, Kim MH, Song K, Jin X, Lee KM, Park JS, Cho YR, Yun SC, Lee MS. Pharmacodynamics and Outcomes of a De-Escalation Strategy with Half-Dose Prasugrel or Ticagrelor in East Asians Patients with Acute Coronary Syndrome: Results from HOPE-TAILOR Trial. J Clin Med. 2021 Jun 18;10(12):2699. doi: 10.3390/jcm10122699.

  PMID: 34207339 BACKGROUND

MeSH Terms

Conditions

Acute Coronary Syndrome

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Cai De Jin

  Zunyi Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cai De Jin, MD

CONTACT

86+173-8576-9997; jincaide1118@163.com

Yan Yan Jin, MD

CONTACT

86+157-7229-0925; jinyanyan850925@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: February 28, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 20, 2024

Record last verified: 2024-03

Locations

CN (1)