Tailored Antiplatelet Therapy Following PCI

Phase 4

Completed

Brief Summary: Clopidogrel is an anti-platelet medication approved by the U.S. Federal Drug Administration (FDA) for use in patients who undergo Percutaneous Coronary Intervention (PCI) with coronary stent implantation. Anti-platelet medications work to prevent blood clots from forming. Some studies have suggested that patients who have a certain genetic liver enzyme abnormality (known as cytochrome P450 2C19 \[CYP2C19\] \*2 or \*3 allele) may have a reduced ability to activate clopidogrel, and therefore may have a lowered response to clopidogrel. It is thought that perhaps people who have a coronary stent procedure may have this genetic liver enzyme abnormality. There is a research genetic test available to determine whether or not someone has this genetic liver enzyme abnormality. Ticagrelor, is a newer anti-platelet drug that is not dependent on the CYP2C19 liver enzyme for its activation and hence in poor clopidogrel metabolizers, alternative drugs like Ticagrelor have been recommended for use as an anti-platelet agent after PCI. The purpose of this study is to determine if genetic testing can identify the best anti-platelet therapy, for patients who undergo a coronary stent placement and do not activate clopidogrel very well.

Detailed Description: TAILOR-PCI is a multi-site, open label, prospective, randomized trial testing the hypothesis that after percutaneous coronary intervention (PCI), using a genotyping strategy ticagrelor 90 mg twice per day is superior to clopidogrel 75 mg per day in reducing a composite endpoint of major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, severe recurrent ischemia, cardiovascular (CV) death, and stent thrombosis (primary endpoints) in CYP2C19 reduced function allele patients. Patients who undergo PCI will be randomized to a conventional therapy arm (i.e., to receive clopidogrel 75 mg once daily without prospective genotyping guidance) versus a prospective CYP2C19 genotype-based anti-platelet therapy approach (ticagrelor 90 mg bid in CYP2C19 \*2 or \*3 reduced function allele patients, clopidogrel 75 mg once daily in non-\*2 or -\*3 CYP2C19 patients). Buccal swabs will be obtained for those subjects randomized to the prospective genotyping arm. All subjects will have a blood sample drawn for DNA analysis but genotyping using these DNA samples will be performed only after completion of the duration of anti-platelet therapy (i.e., after one year). The primary endpoints will be assessed prospectively and will be compared between the conventional arm and the prospective genotyping arm among those identified as reduced function CYP2C19 allele carriers according to the 1-year genotype results.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Conventional Therapy	Clopidogrel	Subjects will receive clopidogrel once daily after the index PCI and will be retrospectively genotyped for CYP2C19\2, \3 and \*17 alleles after completion of one year of treatment with clopidogrel.
Genotype-Guided Therapy	Ticagrelor	Subjects will be genotyped prospectively for CYP2C19\2, \3 and \17 alleles and will receive treatment based on their genotype. In this group, patients who have the CYP2C19 reduced function allele \[i.e., \2 allele (heterozygous or homozygous) or \*3 allele (heterozygous or homozygous)\] patients will receive ticagrelor 90 mg bid. The WT YP2C19 patients will receive clopidogrel 75 mg once daily.
Genotype-Guided Therapy	Clopidogrel	Subjects will be genotyped prospectively for CYP2C19\2, \3 and \17 alleles and will receive treatment based on their genotype. In this group, patients who have the CYP2C19 reduced function allele \[i.e., \2 allele (heterozygous or homozygous) or \*3 allele (heterozygous or homozygous)\] patients will receive ticagrelor 90 mg bid. The WT YP2C19 patients will receive clopidogrel 75 mg once daily.

Primary Outcome Measures

Name	Time	Method
Occurrence of the a Major Adverse Cardiovascular Event	Approximately 3 years after percutaneous coronary intervention (PCI)	Number of subjects to experience a major adverse cardiovascular event as defined as cardiovascular death, myocardial infarction, stroke, severe recurrent ischemia, and stent thrombosis.
Occurrence of the a Major Adverse Cardiovascular Event in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.	1 year after percutaneous coronary intervention (PCI)	Number of subjects who experienced major adverse cardiovascular event as defined as cardiovascular death, myocardial infarction, stroke, severe recurrent ischemia, and stent thrombosis in subjects identified as CPY2C19 LOF carriers by TaqMan.

Secondary Outcome Measures

Name	Time	Method
Thrombolysis in Myocardial Infarction Major or Minor Bleeding in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.	1 year after percutaneous coronary intervention (PCI)	Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding in subjects identified as CYP2C19 LOF carriers by TaqMan
Thrombolysis in Myocardial Infarction Major or Minor Bleeding	Approximately 3 years after percutaneous coronary intervention (PCI)	Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding

Locations (41): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Sharp HealthCare
🇺🇸
San Diego, California, United States
Zuckerberg San Francisco General
🇺🇸
San Francisco, California, United States
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
NCH Heart Institute
🇺🇸
Naples, Florida, United States
NorthShore University Health System
🇺🇸
Evanston, Illinois, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
St. Elizabeth Healthcare
🇺🇸
Crestview Hills, Kentucky, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Essentia Institute of Rural Health
🇺🇸
Duluth, Minnesota, United States
Scroll for more (31 remaining)
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States