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

March 18, 2024 updated by: Cai De Jin, MD, Zunyi Medical College

Safety and Efficacy of CYP2C19 Genotype-Guided P2Y12 Receptor Inhibitor Selection Versus Conventional Antiplatelet Therapy After Complex Percutaneous Coronary Intervention: The PRECISE-PCI Randomized Clinical Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1200

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guizhou
      • Zunyi, Guizhou, China, 563003
        • Recruiting
        • Affiliated Hospital of Zunyi Medical University
        • Principal Investigator:
          • Cai De Jin, MD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Ran Zun Zhao, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Conventional DAPT
Patients will be conventionally received ticagrelor 90mg bid or clopidogrel 75mg qd + aspirin 100 mg qd
Other Names:
  • Unguided DAPT
Experimental: 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.
Drug: 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
Other Names:
  • Guided DAPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NACE (net adverse clinical event)
Time Frame: At 12 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of clinically significant bleeding
Time Frame: At 12 months

The Bleeding Academic Research Consortium (BARC)-defined clinically significant bleeding (type 2, 3, or 5 bleeding) as follows:

Type 2: Any overt, actionable sign of hemorrhage, requiring nonsurgical, medical intervention by a healthcare professional; Leading to hospitalization or increased level of care; Prompting evaluation.

Type 3: Clinical, laboratory, and/or imaging evidence of bleeding with specific healthcare provider responses.

Type 3a: Overt bleeding plus hemoglobin drop of 3 to 5 g/dL; Any transfusion with overt bleeding.

Type 3b: Overt bleeding plus hemoglobin drop ≥5 g/dL; Cardiac tamponade; Bleeding requiring surgical intervention for control; Bleeding requiring intravenous vasoactive agents.

Type 3c: Intracranial hemorrhage; Subcategories confirmed by autopsy or imaging or lumbar puncture; Intraocular bleed compromising vision.

Type 5: Fatal bleeding is bleeding that directly causes death with no other explainable cause.
At 12 months
Incidence of MACCE
Time Frame: 12 months
The incidence of major adverse cardiac and cerebrovascular event (MACCE), is composite of cardiac death, non-fatal myocardial infarction, target vessel/lesion revascularization, or stroke.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zunyi Medical College

Investigators

  • Principal Investigator: Cai De Jin, Zunyi Medical College

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

February 21, 2024

First Submitted That Met QC Criteria

February 21, 2024

First Posted (Actual)

February 28, 2024

Study Record Updates

Last Update Posted (Actual)

March 20, 2024

Last Update Submitted That Met QC Criteria

March 18, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRECISE-PCI

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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