Tailored Antiplatelet Therapy Following PCI (TAILOR-PCI)

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Acute Coronary Syndrome; Stenosis
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor

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.

• Study Type: Interventional
• Enrollment (Actual): 5276
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5N 3W9
      • Vancouver General Hospital, UBC Division of Cardiology
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada, M3M 0B2
      • Humber River Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St Michael's Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Services Center
    • Toronto, Ontario, Canada, M5B 2C4
      • Toronto General Hospital - UHN
  • Saskatchawan
    • Regina, Saskatchawan, Canada, S4P 0W5
      • Regina General Hospital
• Korea, Republic of
  • Daejeon, Korea, Republic of, 302-718
    • Konyang University College of Medicine
  • Gwangju, Korea, Republic of, 501-757
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of
    • Ajou University Hospital
  • Seoul, Korea, Republic of, 156-755
    • Chung-Ang University Hospital
• Mexico
  • Mexico City, Mexico, 02990
    • Hospital de Especialidades, Centro Medico Nacional 'La Raza'
  • Mexico City, Mexico, 03100
    • Hospital REgional No. 1
  • Mexico City, Mexico, 06720
    • Hospital de Cardiología, Centro Médico Nacional Siglo XXI
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • San Diego, California, United States, 92123
      • Sharp HealthCare
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
    • Naples, Florida, United States, 34102
      • NCH Heart Institute
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Health System
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • St. Elizabeth Healthcare
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Institute of Rural Health
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • The University of Mississippi Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Manhasset, New York, United States, 11030
      • The Feinstein Institute for Medical Research
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • Schenectady, New York, United States, 12309
      • Cardiology Associates of Schenectady
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54702
      • MHS, Eau Claire
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genotype-Guided Therapy; 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.	Drug: Clopidogrel; One 75 mg tablet per day by mouth for one year; Other Names: Plavix; Drug: Ticagrelor; One 90 mg tablet twice per day by mouth for one year; Other Names: Brilinta
Active Comparator: Conventional Therapy; 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.	Drug: Clopidogrel; One 75 mg tablet per day by mouth for one year; Other Names: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Spartan Bioscience Inc.; Applied Health Research Centre
• Investigators: Principal Investigator: Naveen Pereira, MD, Mayo Clinic; Principal Investigator: Michael E Farkouh, MD, Toronto General Hospital; Principal Investigator: Kent R Bailey, PhD, Mayo Clinic

Publications and helpful links

General Publications

• 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, Bailey K, Rihal C. Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial. JAMA. 2020 Aug 25;324(8):761-771. doi: 10.1001/jama.2020.12443.
• Avram R, So D, Iturriaga E, Byrne J, Lennon R, Murthy V, Geller N, Goodman S, Rihal C, Rosenberg Y, Bailey K, Farkouh M, Bell M, Cagin C, Chavez I, El-Hajjar M, Ginete W, Lerman A, Levisay J, Marzo K, Nazif T, Olgin J, Pereira N. Patient Onboarding and Engagement to Build a Digital Study After Enrollment in a Clinical Trial (TAILOR-PCI Digital Study): Intervention Study. JMIR Form Res. 2022 Jun 13;6(6):e34080. doi: 10.2196/34080.
• Madan M, Abbott JD, Lennon R, So DYF, MacDougall AM, McLaughlin MA, Murthy V, Saw J, Rihal C, Farkouh ME, Pereira NL, Goodman SG; TAILOR-PCI Investigators *. Sex-Specific Differences in Clinical Outcomes After Percutaneous Coronary Intervention: Insights from the TAILOR-PCI Trial. J Am Heart Assoc. 2022 Jun 21;11(12):e024709. doi: 10.1161/JAHA.121.024709. Epub 2022 Jun 14.
• Baudhuin LM, Train LJ, Goodman SG, Lane GE, Lennon RJ, Mathew V, Murthy V, Nazif TM, So DYF, Sweeney JP, Wu AHB, Rihal CS, Farkouh ME, Pereira NL. Point of care CYP2C19 genotyping after percutaneous coronary intervention. Pharmacogenomics J. 2022 Dec;22(5-6):303-307. doi: 10.1038/s41397-022-00278-4. Epub 2022 Apr 21.
• Capodanno D, Angiolillo DJ, Lennon RJ, Goodman SG, Kim SW, O'Cochlain F, So DY, Sweeney J, Rihal CS, Farkouh M, Pereira NL. ABCD-GENE Score and Clinical Outcomes Following Percutaneous Coronary Intervention: Insights from the TAILOR-PCI Trial. J Am Heart Assoc. 2022 Feb 15;11(4):e024156. doi: 10.1161/JAHA.121.024156. Epub 2022 Feb 8.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): October 31, 2020

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: December 3, 2012
• First Posted (Estimate): December 5, 2012

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; angioplasty
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: 11-006837; 5U01HL128606 (U.S. NIH Grant/Contract); 3U01HL128606-03S1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No