Implementing Precision Medicine Approaches to Guide Anti-platelet Selection

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: NSTEMI - Non-ST Segment Elevation MI; Acute Coronary Syndrome (ACS); STEMI - ST Elevation Myocardial Infarction (MI); Unstable Angina (UA)
• Intervention / Treatment: Genetic: CYP2C19 genotyping

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 Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • LAC+USC Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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
2. 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
3. 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.
4. Subjects requiring concomitant treatment with an anticoagulant agent (Vitamin-K antagonists or novel oral anticoagulants such as rivaroxaban, dabigatran or apixaban)
5. Indication for major surgery (per decision of the treating physician) for the planned duration of the study
6. Subject with history of liver transplant or plan to undergo liver transplant during the next 12 months
7. Evidence of significant active neuropsychiatric disease, in the investigator's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net clinical utility	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	30 days
Net clinical utility	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	12 months
Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	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.	30 days
Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	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.	12 months
Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	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.	30 days
Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	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.	12 months
Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	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.	30 days
Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)	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.	12 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: Scott A Mosley, PharmD, University of Southern California School of Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2020
• Primary Completion (Anticipated): May 31, 2023
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (Actual): September 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: pharmacogenetics; antiplatelet; precision medicine; de-escalation; percutaneous coronary intervention (PCI); dual antiplatelet therapy (DAPT)
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Acute Coronary Syndrome; Angina, Unstable
• Other Study ID Numbers: APP-19-00099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: Study protocol is anticipated to be published within 12 months of completing the study, and not anticipated to have a time limit.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No