NCT06759272

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

Pharmacogenomic Markers of Clopidogrel Resistance in Malaysian CAD Patients: Clinical Efficacy and Economic Evaluation of CYP2C19 Genotype-Guided Therapy

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Nur Hafizah Annezah binti Utuh · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Clopidogrel, a prodrug that inhibits platelet aggregation, is widely used in patients undergoing percutaneous coronary interventions to prevent recurrent cardiovascular events. However, clopidogrel resistance has emerged as a great concern, whereby it causes inadequate platelet inhibition and leads to antiplatelet treatment failure with prevalence as high as 44% in Asian population. Due to various established evidence from pharmacogenomics studies, US FDA has issued a black-box warning notifying that CYP2C19 polymorphisms may impaired the ability of a patient to convert clopidogrel into its active metabolite. Currently, the availability of newer P2Y12 receptor inhibitors has prompted medical professionals to consider genotype-guided treatment, which may include escalation or de-escalation of the antiplatelet based on CYP2C19 genetic result. We hypothesize that CYP2C19 genotype guided therapy will reduce the occurrence of MACE and improve platelet reactivity to prevent clopidogrel resistance. The estimated sample size required for pilot intervention study is 120 patients. Knowledge of potential pharmacogenetic markers for clopidogrel resistance, clinical efficacy and cost evaluation of genotype-guided antiplatelet therapy will provide a comprehensive insight into adopting such approach in a real routine clinical setting.

Conditions

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

Interventions

Type	Name	Description
GENETIC	CYP2C19 genotype-guided antiplatelet therapy	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

Timeline

• Start date: 2025-02-01
• Primary completion: 2026-02-01
• Completion: 2026-02-01
• First posted: 2025-01-06
• Last updated: 2025-01-07

Locations

1 site across 1 country: Malaysia

Regulatory

• FDA-regulated drug study