Ignite Creation Date:
2024-05-06 @ 7:48 PM
Last Modification Date:
2024-10-26 @ 3:14 PM
Study NCT ID:
NCT06143709
Status:
RECRUITING
Last Update Posted:
2023-11-22
First Post:
2023-11-16
Brief Title:
Precision PCI Registry
Sponsor:
University of Florida
Organization:
University of Florida
Study Overview
Official Title:
Precision Antiplatelet Therapy After Percutaneous Coronary Intervention Registry
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The feasibility and clinical benefit of using a patients 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 ie switching to less potent antiplatelet therapy after PCI in a real-world setting
3 Elucidate the effects of genotypes beyond CYP2C19 on platelet reactivity and clinical outcomes with clopidogrel after PCI
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 ie switching to less potent antiplatelet therapy after PCI in a real-world setting
3 Elucidate the effects of genotypes beyond CYP2C19 on platelet reactivity and clinical outcomes with clopidogrel after PCI
Detailed 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 CYP2C19 enzyme is essential for metabolism of clopidogrel a prodrug to its pharmacologically active form Approximately 30 of the US 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 eg 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 1500 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 effects 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 eg 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
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 eg 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 1500 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 effects 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 eg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL149752 | NIH | None | httpsreporternihgovquickSearchR01HL149752 |