Precision PCI Registry

Coronary Artery Disease Clinical Trial

Official title:

Precision Antiplatelet Therapy After Percutaneous Coronary Intervention Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06143709
• Other study ID #: IRB202000721
• Secondary ID: R01HL149752
• Status: Recruiting
• Start date: July 17, 2020
• Est. completion date: January 31, 2025

Study information

• Verified date: November 2023
• Source: University of Florida
• Contact: Larisa Cavallari, PharmD,BCPS,FCCP
• Phone: 352-273-8245
• Email: LCavallari[@]cop.ufl.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The feasibility and clinical benefit of using a patient's genotype to guide antiplatelet therapy prescribing has been demonstrated. However, a more precise understanding of who to genotype, what to include on a genetic testing panel, and how to change antiplatelet therapy based on genotype results and other patient-specific factors is needed to optimize the impact of genotype-guided antiplatelet therapy on patient outcomes.

The Precision PCI registry is a collaboration between the University of Florida, Gainesville and Jacksonville, USA, the University of North Carolina, Chapel Hill, USA, and University of Maryland, Baltimore, USA. This registry will include a diverse population of patients who undergo Percutaneous Coronary Intervention and clinical CYP2C19 genotyping, assess clinical outcomes over 12 months and collect DNA samples for additional genotyping, and conduct pharmacodynamic analysis of platelet function in a subset of patients.

Objectives of the study:

1. Define the influence of African ancestry and other patient-specific factors on clinical outcomes with genotype-guided antiplatelet therapy following PCI in a real-world setting

2. Evaluate the safety and effectiveness of genotype-guided de-escalation of antiplatelet therapy (i.e., switching to less potent antiplatelet therapy) after PCI in a real-world setting

3. Elucidate the effect(s) of genotypes beyond CYP2C19 on platelet reactivity and clinical outcomes with clopidogrel after PCI

Description:

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is the standard of care after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Prasugrel and ticagrelor are preferred over clopidogrel in patients with an acute coronary syndrome but are associated with greater bleeding risk. The cytochrome P450 (CYP)2C19 enzyme is essential for metabolism of clopidogrel (a prodrug) to its pharmacologically active form. Approximately 30% of the U.S. population carries a CYP2C19 loss-of-function (LOF) allele that reduces the bioactivation and effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI.

Previous studies have demonstrated the feasibility and effectiveness of incorporating CYP2C19 genotyping into clinical care to guide DAPT, with prasugrel or ticagrelor prescribed in patients with a CYP2C19 LOF allele. However, the influence of key patient-specific factors on outcomes with genotype-guided DAPT (notably African ancestry, comorbidities that impact clopidogrel effectiveness, and genotypes beyond CYP2C19) has not been defined but is critical to understand in order to optimize the clinical impact of genotype-guided DAPT. Moreover, the impact on clinical outcomes of using CYP2C19 genotype to guide de-escalation from more potent agents (e.g., prasugrel or ticagrelor) to clopidogrel in patients without a LOF allele, which has become highly clinically relevant due to more frequent initial use of prasugrel or ticagrelor after acute coronary syndrome and PCI, has not been investigated in a diverse, real-world clinical setting.

The long-term goal of this line of research is to optimize a precision medicine DAPT strategy that improves outcomes after PCI. The investigators hypothesize that multiple clinical and genetic factors jointly contribute to the effectiveness and safety of CYP2C19 LOF allele-guided selection of DAPT after PCI in a real-world clinical setting. This hypothesis will be tested by conducting a multi-center, observational study of 1,500 patients with PCI and clinical CYP2C19 genetic testing.

Aim 1: Define the influence of African ancestry and other patient-specific factors on clinical outcomes with CYP2C19 genotype-guided DAPT after PCI in a real-world setting

Aim 2: Evaluate the safety and effectiveness of CYP2C19 genotype-guided de-escalation of DAPT following PCI in a real-world setting

Aim 3: Elucidate the effect(s) of genetic variants beyond CYP2C19 LOF alleles on platelet reactivity and clinical outcomes with clopidogrel after PCI

A total of 1500 patients will be enrolled. Their data will be added to an existing cohort of approximately 4500 patients to address these aims.

Baseline data from the PCI admission will include:

• PCI indication

• Angiographic and procedural features (e.g. location of PCI, stent type)

• CYP2C19 genotype

• Discharge diagnoses

• Medications on admission, during hospitalization, and at discharge

• Self-reported race

• Socioeconomic status (including education, income and occupation)

• Health insurance type

Follow-up Data:

Patient follow-up will occur at 1, 6, and 12 months after PCI or until DAPT discontinuation via telephone call and EHR review to assess for hospitalizations and medication changes.

Data Management:

Data will be stored electronically in a secured database that is only accessible to study investigators. Quality assurance procedures will include use of a data dictionary, data checks ensure compliance with predefined rules for data ranges and checks for missing data. Hospitalization records will be reviewed by independent cardiologists to verify atherothrombotic and bleeding events. Deaths will be assessed by query of the National Death Index (NDI) and North Carolina state death index.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Age =18 years

• Underwent percutaneous coronary intervention for any indication

• Had clinical CYP2C19 genotyping

• Treated with dual antiplatelet therapy including clopidogrel, prasugrel, or ticagrelor plus aspirin or

• Treated with a combination of a P2Y12 inhibitor i.e. clopidogrel, prasugrel or ticagrelor plus an oral anticoagulant.

Exclusion Criteria:

• Managed surgically

• Treated with thrombolysis within 48 hours

Related Conditions & MeSH terms

• Coronary Artery Disease
• Percutaneous Coronary Intervention

Intervention

Other:
• DNA sample collection
Patients will be asked to provide a blood or mouth wash sample for DNA extraction

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida

Sponsors (4)

Lead Sponsor	Collaborator
University of Florida	National Heart, Lung, and Blood Institute (NHLBI), University of Maryland, Baltimore, University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major atherothrombotic events	Composite of death, myocardial infarction, ischemic stroke, stent thrombosis, and revascularization for unstable angina	12 months
Secondary	Net clinical benefit	Major atherothrombotic events or clinically significant bleeding	12 months
Secondary	Major adverse cardiovascular events	Composite of cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis	12 months
Secondary	Clinically significant bleeding	Moderate or severe/life-threatening bleeding according to GUSTO criteria	12 months
Secondary	All cause death	Death from any cause	12 months
Secondary	Cardiovascular death	Death resulting from myocardial infarction, arrhythmia, heart failure, stroke, or other cardiovascular cause	12 months
Secondary	Myocardial infarction	New ischemic symptoms and troponin elevation	12 months
Secondary	Ischemic stroke	Acute neurologic deficit that lasts over 24 hours and affects the ability to perform daily activities with or without confirmation of imaging	12 months
Secondary	Stent thrombosis	Definite or probable stent thrombosis defined according to the Academic Research Consortium	12 months
Secondary	Unstable angina	Acute ischemic event with no evidence of myocardial infarction and angiographic evidence of new or worsening obstructive coronary disease, or intracoronary thrombus, believed to be responsible for the ischemic symptoms and requiring coronary revascularization	12 months