Implementing Precision Medicine Approaches to Guide Anti-platelet Selection

Sponsor

University of Southern California (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04090281

Collaborator

(none)

200

Enrollment

Location

Arm

44.6

Anticipated Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study aims to determine the feasibility and clinical utility of incorporating precision medicine approaches, incorporating both cytochrome P450 2C19 (CYP2C19) genotyping and platelet reactivity phenotyping, with standard of care for patients with acute coronary syndromes (ACS), post PCI.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome (ACS) STEMI - ST Elevation Myocardial Infarction (MI) NSTEMI - Non-ST Segment Elevation MI Unstable Angina (UA)	Genetic: CYP2C19 genotyping	Phase 4

Detailed Description

Study Population:

Adult patients will be eligible for inclusion if they provide informed consent and have no contraindications for 12-months of dual antiplatelet therapy (DAPT).

Baseline Evaluation:

Overview of clinical protocol: Patients with successful PCI will receive a genotype guided recommendation, upon discharge, based on CYP2C19 genotype. Patients who are determined to have CYP2C19 poor metabolizer (PM) or intermediate metabolizer (IM) status will be recommended to receive 12-months of prasugrel. Patients who are determined to have CYP2C19 normal metabolizer (NM), rapid metabolizer (RM), or ultra-rapid metabolizer (UM) phenotype will be recommended to receive a de-escalation treatment, guided by on-treatment platelet reactivity phenotype at 14 days, post discharge.

30-day, 6-month, and 12-month Follow-up: Patients will be contacted by phone or visited during one of their regularly scheduled appointments, at 14 days, 30 days, 6 months , and 12 months, to complete "Follow-up Case Report Forms" to collect outcomes data. The 12-month follow up communication with enrolled patients will end their participation in the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Prospective, single-center, single arm, pragmatic study to determine feasibility of interventionProspective, single-center, single arm, pragmatic study to determine feasibility of intervention

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Implementing Precision Medicine Approaches to Guide Anti-platelet Selection Following Percutaneous Coronary Intervention (PCI)

Actual Study Start Date :

Mar 13, 2020

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Precision medicine implementation Patients will receive a precision medicine approach, incorporating both CYP2C19 genotyping and platelet reactivity phenotyping, to guide dual antiplatelet therapy selection for patients with ACS, post PCI and followed over a 12 month period.	Genetic: CYP2C19 genotyping Upon hospital discharge, patients will undergo CYP2C19 genotyping to guide initial P2Y12 inhibitor selection. At 14 days, post discharge, patients will undergo on treatment platelet reactivity phenotyping to further guide deescalation of P2Y12 inhibitor therapy Other Names: platelet reactivity phenotyping

Arm

Intervention/Treatment

Other: Precision medicine implementation

Patients will receive a precision medicine approach, incorporating both CYP2C19 genotyping and platelet reactivity phenotyping, to guide dual antiplatelet therapy selection for patients with ACS, post PCI and followed over a 12 month period.

Genetic: CYP2C19 genotyping

Upon hospital discharge, patients will undergo CYP2C19 genotyping to guide initial P2Y12 inhibitor selection. At 14 days, post discharge, patients will undergo on treatment platelet reactivity phenotyping to further guide deescalation of P2Y12 inhibitor therapy

Other Names:

platelet reactivity phenotyping

Outcome Measures

Primary Outcome Measures

Feasibility of implementing pharmacogenetics to guide antiplatelet therapy [12 months]
The proportion of patients in whom a genetic-guided recommendation is accepted by the clinician
Feasibility of implementing platelet reactivity testing to guide de-escalation of antiplatelet therapy [12 months]
The proportion of patients in whom a platelet reactivity phenotype-guided recommendation is accepted by the clinician

Secondary Outcome Measures

Net clinical utility [30 days]
The incidence of combined endpoints of major adverse cardiovascular events (MACE), stent thrombosis, unstable angina, major and minor bleeding, all-cause mortality, and hospital readmission rate within 30 days, post discharge
Net clinical utility [12 months]
The incidence of combined endpoints of MACE, stent thrombosis, unstable angina, major and minor bleeding, all-cause mortality, and hospital readmission rate within 12 months, post discharge
Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale) [30 days]
Patient Reported Outcomes Measurement Information System (PROMIS) subscale for anxiety include fear, anxiety, worry, and uneasiness. A score of 0 to 20 based on survey responses will be resulted for this subscale, with higher values representing a worse outcome.
Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale) [12 months]
Patient Reported Outcomes Measurement Information System (PROMIS) subscale for anxiety include fear, anxiety, worry, and uneasiness. A score of 0 to 20 based on survey responses will be resulted for this subscale, with higher values representing a worse outcome.
Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale) [30 days]
Patient Reported Outcomes Measurement Information System (PROMIS) subscale for depression include worthless, helpless, depressed, and hopelessness. A score of 0 to 20 based on survey responses will be resulted for this subscale, with higher values representing a worse outcome.
Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale) [12 months]
Patient Reported Outcomes Measurement Information System (PROMIS) subscale for depression include worthless, helpless, depressed, and hopelessness. A score of 0 to 20 based on survey responses will be resulted for this subscale, with higher values representing a worse outcome.
Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale) [30 days]
Patient Reported Outcomes Measurement Information System (PROMIS) subscale for social abilities include leisure, family, usual work, and friends. A score of 0 to 20 based on survey responses will be resulted for this subscale, with higher values representing a worse outcome.
Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale) [12 months]
Patient Reported Outcomes Measurement Information System (PROMIS) subscale for social abilities include leisure, family, usual work, and friends. A score of 0 to 20 based on survey responses will be resulted for this subscale, with higher values representing a worse outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with troponin positive ACS
Patients scheduled for left heart catheterization and undergoing PCI
Age 18-80 years at time of enrollment
Currently receiving or anticipated to receive DAPT, with P2Y12 inhibitor
Ability to follow-up for a clinic visit with LAC+USC outpatient cardiology
Written informed consent

Exclusion Criteria:

Subjects with known contraindications to clopidogrel treatment, which are hypersensitivity to the drug substance or any component of the product and active pathological bleeding such as peptic ulcer or intracranial hemorrhage
Subjects with known contraindications to prasugrel treatment, which are hypersensitivity to the drug substance or any component of the product, active pathological bleeding such as peptic ulcer or intracranial hemorrhage, and a history of prior transient ischemic attack (TIA) or stroke
Subjects with a history of a complicated or prolonged cardiogenic shock in the last two weeks prior to enrolling in this study. A complicated or prolonged cardiogenic shock is defined by a cardiogenic shock that required mechanical ventilation or the cardiovascular support with positive inotropic drugs (i. v. catecholamines) for ≥7 days.
Subjects requiring concomitant treatment with an anticoagulant agent (Vitamin-K antagonists or novel oral anticoagulants such as rivaroxaban, dabigatran or apixaban)
Indication for major surgery (per decision of the treating physician) for the planned duration of the study
Subject with history of liver transplant or plan to undergo liver transplant during the next 12 months
Evidence of significant active neuropsychiatric disease, in the investigator's opinion.