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

NCT ID: NCT06283888

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2028-12-01

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.

Detailed Description

In the PRECISE-PCI (CYP2C19 Genotype-Guided P2Y12 RECeptor Inhibitor SElection After Complex PCI) trial, the investigators aim to evaluate the safety and efficacy of CYP2C19 genotype-guided P2Y12 receptor inhibitor selection, as compared with conventional therapy in Chinese with ACS undergoing complex PCI All eligible ACS patients will be received DAPT (ticagrelor 180 mg or clopidogrel 300/600 mg plus aspirin 300 mg loading) before PCI. Subsequently to be randomly assigned into the genotype-guided group (CPY2C19 *2 or *3 carrier: ticagrelor 60 mg bid, or 45mg bid if <50 kg, ≥75 years; CPY2C19 *2 or *3 non-carrier: clopidogrel 75 mg qd in combination with aspirin 100 mg qd) and conventional group (ticagrelor 90 mg bid or clopidogrel 75 mg qd in combination with aspirin 100 mg qd). At post-PCI 3 months, both groups will be treated with mono-ticagrelor/clopidogrel without aspirin therapy for a further 9 months.

The primary endpoint is focusing on the net adverse clinical events (NACEs, a composite of cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, stroke, or BARC-defined clinically significant bleeding type 2, 3, or 5) during 12-month follow-ups.

Conditions

ACS - Acute Coronary Syndrome; CYP2C19 Polymorphism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CYP2C19 Genotype Guided DAPT

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.

Group Type: EXPERIMENTAL

CYP2C19 Genotype Guided DAPT

Intervention Type: 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

Conventional DAPT

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.

Group Type: EXPERIMENTAL

Conventional DAPT

Intervention Type: DRUG

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

Interventions

CYP2C19 Genotype Guided DAPT

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

Intervention Type: DRUG

Conventional DAPT

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

Intervention Type: DRUG

Other Intervention Names

Guided DAPT; Unguided DAPT

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.
• PCI for chronic total occlusion.
• PCI for bypass graft.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zunyi Medical College

OTHER

Sponsor Role: lead

Responsible Party

Cai De Jin, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cai De Jin

Role: PRINCIPAL_INVESTIGATOR

Zunyi Medical College

Locations

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, China

Site Status: RECRUITING

Countries

China

Central Contacts

Cai De Jin, MD

Role: CONTACT

jincaide1118@163.com

86+173-8576-9997

Yan Yan Jin, MD

Role: CONTACT

jinyanyan850925@163.com

86+157-7229-0925

Facility Contacts

Cai De Jin, MD

Role: primary

jincaide@zmu.edu.cn

86+173-8576-9997

Yan Yan Jin, MD, PhD

Role: backup

jinyanyan850925@163.com

86+157-7229-0925

References

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Reference Type: BACKGROUND

PMID: 32543684 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 32029306 (View on PubMed)

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.

Reference Type: BACKGROUND

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Other Identifiers

PRECISE-PCI

Identifier Type: -

Identifier Source: org_study_id