Impact of CYP2C19 Genotype-guided Approach in Antiplatelet Therapy on Platelet Reactivity Index Among Coronary Artery Disease (CAD) Patients

NCT06759272 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: 311224
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if the pilot intervention of CYP2C19 genotype-guided antiplatelet therapy works to reduce the occurrence of cardiovascular events after Percutaneous Coronary Intervention (PCI) done in coronary artery disease patients. It will also learn about the comparison between clopidogrel and ticagrelor. The main questions it aims to answer are: To compare the impact of CYP2C19 genotype-guided antiplatelet therapy, universal use of clopidogrel and ticagrelor treatment on platelet reactivity. To compare the impact of CYP2C19 genotype-guided antiplatelet therapy, universal use of clopidogrel and ticagrelor treatment on the risk of major adverse cardiovascular events (MACE) among newly recruited stable CAD patients. Participants will: Take drug clopidogrel or ticagrelor, based on the random group allocation every day for 1 month. One group of patients will undergone CYP2C19 genetic test for genotype-guided antiplatelet therapy, whether clopidogrel or ticagrelor. Visit the clinic post 30 days of PCI for follow-ups and platelet function tests.

Conditions

Coronary Arterial Disease (CAD); ACS (Acute Coronary Syndrome); SCAD

Keywords

CYP2C19 genotype-guided antiplatelet therapy

Outcome Measures

Primary Outcomes (1)

• Major adverse cardiovascular events (MACE)

  Major adverse cardiovascular events (MACE) is defined as the composite of all-cause mortality, recurrent myocardial infarction (MI), repeat revascularization and stroke. The fourth universal definition of MI was used to retrospectively analyse recurrent MI. Any revascularization of the target coronary artery following the index incident, whether percutaneous or surgical, was referred to as repeat revascularization.

  From enrollment to 30 days post PCI

Secondary Outcomes (1)

• Platelet Reactivity Index (PRI)

  From enrollment to at least 2 weeks of maintenance dose

Study Arms (3)

Intervention group

EXPERIMENTAL

Pre-emptive genetic testing will be done on the patients allocated randomly to the intervention group after obtaining their consent. The clinical decision making on the antiplatelet (either clopidogrel or ticagrelor) will be done based on the presence of genetic markers CYP2C19\*2 and CYP2C19\*3, according to the latest Clinical Pharmacogenetics Implementation Consortium (CPIC) 2022 guideline. Patients who are identified to have reduced function CYP2C19 allele will receive 90 mg ticagrelor and patients with wild-type CYP2C19 allele will receive clopidogrel 75 mg in the next scheduled dose.

Genetic: CYP2C19 genotype-guided antiplatelet therapy

Universal Clopidogrel

NO INTERVENTION

All patients in the control group 1 will receive clopidogrel (300 mg loading dose to 75 mg daily maintenance dose) without any genetic screening done for 30 days.

Universal Ticagrelor

NO INTERVENTION

All patients in the control group 2 will ticagrelor (180 mg loading dose to 90 mg twice daily as maintenance dose) without any genetic screening done for 30 days.

Interventions

CYP2C19 genotype-guided antiplatelet therapy GENETIC

A panel of genes including CYP2C19\*2 (rs4244285) and CYP2C19\*3 (rs4986893) will be genotyped using the real-time PCR and the expected turnover time will be 48 hours. Patients who are identified to have reduced function CYP2C19 allele will receive 90 mg ticagrelor and patients with wild-type CYP2C19 allele will receive clopidogrel 75 mg in the next scheduled dose. The switching done from clopidogrel to ticagrelor is supported by Antiplatelet Therapy Switching Clinician Guideline, whereby in the maintenance or low risk phase, there is generally no need to administer a loading dose of ticagrelor; one can switch directly to ticagrelor maintenance dose 24 hours after the last dose of clopidogrel

Also known as: CYP2C19 screening test, Precision medicine

Intervention group

Eligibility Criteria

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

You may qualify if:

• Males or females
• Aged between 18 to 80 years old
• Patients presents with stable CAD or acute coronary syndrome (ACS)
• Eligible for percutaneous coronary intervention (PCI)
• Willing to provide DNA sample via blood drawn for genotyping and platelet reactivity assessment
• Willing and able to provide informed written consent

You may not qualify if:

• Primary PCI or rescue PCI
• Any urgent/emergent coronary angiography procedure that would not allow for genetic testing to be performed before PCI
• Failure of index PCI
• Patient or physician refusal to enroll in the study
• Patient with known CYP2C19 genotype prior to randomization
• Planned revascularization of any vessel within 30 days post-index procedure and/or of the target vessel(s) within 12 months post-procedure
• Anticipated discontinuation of clopidogrel or ticagrelor within the 12 months follow up period (e.g. for elective surgery)
• History of ischaemic or haemorrhagic stroke
• History of allergies to aspirin, ticagrelor, or clopidogrel
• Suffering from HIV or any blood transmitted disease.
• Considered at high risk of bleeding\*
• Stage 5 chronic kidney disease (CKD) based on the National Kidney Foundation, Kidney disease quality outcome initiative (KDQOI) definition (Levey et al., 2005), or those who were on haemodialysis
• Pre-existing liver cirrhosis
• Pregnant women at any stage of gestation
• Patient is receiving immunosuppressive therapy or has known immunosuppressive or autoimmune disease (e.g. human immunodeficiency virus, systemic lupus erythematous, etc.)

Sponsors & Collaborators

• Nur Hafizah Annezah binti Utuh: lead

Study Sites (1)

Hospital Pakar Universiti Sains Malaysia

Kota Bharu, Kelantan, 16150, Malaysia

Location

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Precision Medicine

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD)

  School of Pharmaceutical Sciences, Universiti Sains Malaysia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD)

CONTACT

601133178262; hafizah.anis67@student.usm.my

Nur Aizati Athirah Daud, Doctor of Philosophy (PhD)

CONTACT

aizati@usm.my

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 29, 2024
• First Posted: January 6, 2025
• Study Start: February 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: January 7, 2025

Record last verified: 2025-01

Locations

MY (1)