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Implementing Precision Medicine Approaches to Guide Anti-platelet Selection

Primary Purpose

Acute Coronary Syndrome (ACS), STEMI - ST Elevation Myocardial Infarction (MI), NSTEMI - Non-ST Segment Elevation MI

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
CYP2C19 genotyping
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome (ACS) focused on measuring precision medicine, antiplatelet, pharmacogenetics, de-escalation, dual antiplatelet therapy (DAPT), percutaneous coronary intervention (PCI)

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • LAC+USC Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Precision medicine implementation

Arm Description

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.

Outcomes

Primary Outcome Measures

Feasibility of implementing pharmacogenetics to guide antiplatelet therapy
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
The proportion of patients in whom a platelet reactivity phenotype-guided recommendation is accepted by the clinician

Secondary Outcome Measures

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
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
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 6, 2019
Last Updated
September 27, 2021
Sponsor
University of Southern California
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1. Study Identification

Unique Protocol Identification Number
NCT04090281
Brief Title
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

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 13, 2020 (Actual)
Primary Completion Date
May 31, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Southern California

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Prospective, single-center, single arm, pragmatic study to determine feasibility of intervention
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Precision medicine implementation
Arm Type
Other
Arm Description
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.
Intervention Type
Genetic
Intervention Name(s)
CYP2C19 genotyping
Other Intervention Name(s)
platelet reactivity phenotyping
Intervention Description
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
Primary Outcome Measure Information:
Title
Feasibility of implementing pharmacogenetics to guide antiplatelet therapy
Description
The proportion of patients in whom a genetic-guided recommendation is accepted by the clinician
Time Frame
12 months
Title
Feasibility of implementing platelet reactivity testing to guide de-escalation of antiplatelet therapy
Description
The proportion of patients in whom a platelet reactivity phenotype-guided recommendation is accepted by the clinician
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Net clinical utility
Description
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
Time Frame
30 days
Title
Net clinical utility
Description
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
Time Frame
12 months
Title
Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
Description
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.
Time Frame
30 days
Title
Change in score of anxiety using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
Description
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.
Time Frame
12 months
Title
Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
Description
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.
Time Frame
30 days
Title
Change in score of depression using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
Description
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.
Time Frame
12 months
Title
Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
Description
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.
Time Frame
30 days
Title
Change in score of social abilities using (Patient Reported Outcomes Measurement Information System (PROMIS) subscale)
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott A Mosley, PharmD
Organizational Affiliation
University of Southern California School of Pharmacy
Official's Role
Principal Investigator
Facility Information:
Facility Name
LAC+USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Plan to Share 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.

Learn more about this trial

Implementing Precision Medicine Approaches to Guide Anti-platelet Selection

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