Implementing Precision Medicine Approaches to Guide Anti-platelet Selection

NSTEMI - Non-ST Segment Elevation MI Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04090281
• Other study ID #: APP-19-00099
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: March 13, 2020
• Est. completion date: November 30, 2023

Study information

• Verified date: September 2021
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: November 30, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	LAC+USC Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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