Tailored Antiplatelet Therapy Following PCI

Coronary Artery Disease Clinical Trial

— TAILOR-PCI  

Official title:

Tailored Antiplatelet Initiation to Lesson Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01742117
• Other study ID #: 11-006837
• Secondary ID: 5U01HL1286063U01
• Status: Completed
• Phase: Phase 4
• Start date: May 2013
• Est. completion date: October 31, 2020

Study information

• Verified date: October 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 5276
• Est. completion date: October 31, 2020
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion

• Patient >18 years of age
• Patient presents with acute coronary syndrome (ACS) or stable coronary artery disease (CAD)
• Patient is eligible for PCI
• Patient is willing and able to provide informed written consent 5.3 Exclusion
• Patient not able to receive 12 months of dual anti-platelet therapy
• Failure of index PCI
• Patient or physician refusal to enroll in the study
• Patient with known CYP2C19 genotype prior to randomization
• Planned revascularization of any vessel within 30 days post-index procedure and/or of the target vessel(s) within 12 months post-procedure
• Anticipated discontinuation of clopidogrel or ticagrelor within the 12 month follow up period, example for elective surgery
• Serum creatinine >2.5 mg/dL within 7 days of index procedure
• Platelet count <80,000 or >700,000 cells/mm3, or white blood cell count <3,000 cells/mm3 if persistent (at least 2 abnormal values) within 7 days prior to index procedure.
• History of intracranial hemorrhage
• Known hypersensitivity to clopidogrel or ticagrelor or any of its components
• Patient is participating in an investigational drug or device clinical trial that has not reached its primary endpoint
• Patient previously enrolled in this study
• Patient is pregnant, lactating, or planning to become pregnant within 12 months
• Patient has received an organ transplant or is on a waiting list for an organ transplant
• Patient is receiving or scheduled to receive chemotherapy within 30 days before or after the procedure
• Patient is receiving immunosuppressive therapy or has known immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematous, etc.)
• Patient is receiving chronic oral anticoagulation therapy (i.e., vitamin K antagonist, direct thrombin inhibitor, Factor Xa inhibitor)
• Concomitant use of simvastatin/lovastatin > 40 mg qd
• Concomitant use of potent CYP3A4 inhibitors (atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole) or inducers (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, and rifapentine)
• Non-cardiac condition limiting life expectancy to less than one year, per physician judgment (e.g. cancer)
• Known history of severe hepatic impairment
• Patient has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions
• Patient has an active pathological bleeding, such as active gastrointestinal (GI) bleeding
• Inability to take aspirin at a dosage of 100 mg or less
• Current substance abuse (e.g., alcohol, cocaine, heroin, etc.)

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Coronary Artery Disease
• Stenosis

Intervention

Drug:
• Clopidogrel
One 75 mg tablet per day by mouth for one year
• Ticagrelor
One 90 mg tablet twice per day by mouth for one year

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Regina General Hospital	Regina	Saskatchawan
Canada	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	Humber River Hospital	Toronto	Ontario
Canada	St Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Services Center	Toronto	Ontario
Canada	Toronto General Hospital - UHN	Toronto	Ontario
Canada	Vancouver General Hospital, UBC Division of Cardiology	Vancouver	British Columbia
Korea, Republic of	Konyang University College of Medicine	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	Chung-Ang University Hospital	Seoul
Mexico	Hospital de Cardiologia, Centro Medico Nacional Siglo XXI	Mexico City
Mexico	Hospital de Especialidades, Centro Medico Nacional 'La Raza'	Mexico City
Mexico	Hospital REgional No. 1	Mexico City
United States	Albany Medical College	Albany	New York
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	MHS, Eau Claire	Eau Claire	Wisconsin
United States	NorthShore University Health System	Evanston	Illinois
United States	Greenville Health System	Greenville	South Carolina
United States	The University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mayo Clinic Health System	La Crosse	Wisconsin
United States	The Feinstein Institute for Medical Research	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	Aurora Health Care	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Minneapolis Heart Institute	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	NCH Heart Institute	Naples	Florida
United States	Columbia University Medical Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Rhode Island Hospital	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Sharp HealthCare	San Diego	California
United States	Zuckerberg San Francisco General	San Francisco	California
United States	Cardiology Associates of Schenectady	Schenectady	New York
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	Applied Health Research Centre, National Heart, Lung, and Blood Institute (NHLBI), Spartan Bioscience Inc.

Countries where clinical trial is conducted

United States,  Canada,  Korea, Republic of,  Mexico, 

References & Publications (1)

Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, Bell M, Bae JH, Jeong MH, Chavez I, Gordon P, Abbott JD, Cagin C, Baudhuin L, Fu YP, Goodman SG, Hasan A, Iturriaga E, Lerman A, Sidhu M, Tanguay JF, Wang L, Weinshilboum R, Welsh R, Rosenberg Y, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of the a Major Adverse Cardiovascular Event in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.	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.	1 year after percutaneous coronary intervention (PCI)
Primary	Occurrence of the a Major Adverse Cardiovascular Event	Number of subjects to experience a major adverse cardiovascular event as defined as cardiovascular death, myocardial infarction, stroke, severe recurrent ischemia, and stent thrombosis.	Approximately 3 years after percutaneous coronary intervention (PCI)
Secondary	Thrombolysis in Myocardial Infarction Major or Minor Bleeding in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.	Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding in subjects identified as CYP2C19 LOF carriers by TaqMan	1 year after percutaneous coronary intervention (PCI)
Secondary	Thrombolysis in Myocardial Infarction Major or Minor Bleeding	Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding	Approximately 3 years after percutaneous coronary intervention (PCI)

External Links

•   Mayo Clinic Clinical Trials