Clinical trial NCT04090281: Implementing Precision Medicine Approaches to Guide Anti-platelet Selection
Official title: Implementing Precision Medicine Approaches to Guide Anti-platelet Selection Following Percutaneous Coronary Intervention (PCI)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Coronary Syndrome (ACS)
STEMI - ST Elevation Myocardial Infarction (MI)
NSTEMI - Non-ST Segment Elevation MI
Unstable Angina (UA)
Keywords: precision medicine
antiplatelet
pharmacogenetics
de-escalation
dual antiplatelet therapy (DAPT)
percutaneous coronary intervention (PCI)
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2019-09-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, single-center, single arm, pragmatic study to determine feasibility of intervention
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility of implementing pharmacogenetics to guide antiplatelet therapy
timeFrame: 12 months
measure: Feasibility of implementing platelet reactivity testing to guide de-escalation of antiplatelet therapy
timeFrame: 12 months
Secondary outcomes:
measure: Net clinical utility
timeFrame: 30 days
measure: Net clinical utility
timeFrame: 12 months
measure: Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
timeFrame: 30 days
measure: Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
timeFrame: 12 months
measure: Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
timeFrame: 30 days
measure: Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
timeFrame: 12 months
measure: Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
timeFrame: 30 days
measure: Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
timeFrame: 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
Study officials:
affiliation: University of Southern California School of Pharmacy
name: Scott A Mosley, PharmD
role: PRINCIPAL_INVESTIGATOR
References: