Tailored Antiplatelet Therapy Following PCI (TAILOR-PCI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Mayo Clinic
Sponsor:
Collaborator:
Applied Health Research Centre (AHRC)
Information provided by (Responsible Party):
Naveen L. Pereira, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01742117
First received: December 3, 2012
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Acute Coronary Syndrome
Stenosis
Drug: Clopidogrel
Drug: Ticagrelor
Genetic: Retrospective Genotype testing
Genetic: Prospective Genotype testing
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tailored Antiplatelet Initiation to Lesson Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Occurrence of the a major adverse cardiovascular event (MACE) [ Time Frame: Randomization, one year after percutaneous coronary intervention (PCI) ] [ Designated as safety issue: Yes ]
    MACE will include non-fatal myocardial infarction, non-fatal stroke, cardiovascular mortality, severe recurrent ischemia, and stent thrombosis


Secondary Outcome Measures:
  • Number of subjects with reduced function CYP2C19 allele(s) who have major or minor bleeding [ Time Frame: One year after PCI ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 5270
Study Start Date: May 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Clopidogrel then Retrospective Genotyping
Standard clinical practice of clopidogrel 75 mg daily for one year following PCI. DNA samples taken at baseline will be frozen, then at 12 months will be genotype tested to determine the *2 & *3 reduced function or wild type allele status.
Drug: Clopidogrel
Subjects will receive Clopidogrel, one 75 mg tablet per day by mouth for one year.
Other Name: Plavix
Genetic: Retrospective Genotype testing
Mayo Clinic will use ABI TaqMan assay of three variants in the CYP2C10 gene: *2, *3 and *17
Active Comparator: Prospective Genotyping - Clopidogrel
Patients with the wild type CYP2C19 allele (based on prospective genotype testing) will be assigned to receive a clopidogrel 75mg tablet daily for one year following PCI.
Drug: Clopidogrel
Subjects will receive Clopidogrel, one 75 mg tablet per day by mouth for one year.
Other Name: Plavix
Genetic: Prospective Genotype testing
Rapid turnaround Spartan^TM Bioscience in vitro diagnostic assay for analysis of three variants in the CYP2C19 gene: *2, *3 and *17
Active Comparator: Prospective Genotyping - Ticagrelor
Patients with the CYP2C19 heterozygous and homozygous *2 and *3 reduced function allele (based on prospective genotype testing) will be assigned to receive a ticagrelor 90 mg tablet twice per day for one year following PCI.
Drug: Ticagrelor
Subjects will receive Ticagrelor, one 90 mg tablet twice per day by mouth.
Other Name: Brilinta
Genetic: Prospective Genotype testing
Rapid turnaround Spartan^TM Bioscience in vitro diagnostic assay for analysis of three variants in the CYP2C19 gene: *2, *3 and *17

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01742117

Contacts
Contact: Kelly Paulson 507-266-3415 paulson.kelly@mayo.edu
Contact: Sarah Boilson 507-255-2648 boilson.sarah@mayo.edu

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Sheena Lamon, RN       Lamon.Sheena@mayo.edu   
Principal Investigator: John Sweeney, MD         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224
Contact: Grace Staggs, RN       staggs.estela@mayo.edu   
Principal Investigator: Gary E Lane, MD         
NCH Heart Institute Recruiting
Naples, Florida, United States, 34102
Contact: Suzanne Kirkland, RN    239-624-4242    Suzanne.Kirkland@nchmd.org   
Principal Investigator: Adam Frank, M.D.         
United States, Illinois
NorthShore University Health System Recruiting
Evanston, Illinois, United States, 60201
Contact: Ann Joseph    847-570-3861    AJoseph@northshore.org   
Principal Investigator: Jorge Saucedo, M.D.         
United States, Minnesota
Minneapolis Heart Institute Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Amy McMeans, RN    612-863-3895    Amy.McMeans@allina.com   
Principal Investigator: Ivan J Chavez, MD         
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Diane Batzel       batzel.diane@mayo.edu   
Contact: Jill Boyum       boyum.jill@mayo.edu   
Principal Investigator: Verghese Mathew, MD         
United States, New York
The Feinstein Institute for Medical Research Recruiting
Manhasset, New York, United States, 11030
Contact: Miriam Lucca-Susana    212-434-3734    Mluccasusa@NSHS.edu   
Principal Investigator: Kirk N Garratt, MSc, M.D.         
United States, Wisconsin
MHS, Eau Claire Recruiting
Eau Claire, Wisconsin, United States, 54702
Contact: Vy T Nguyen    715-464-8131    Nguyen.Vy1@mayo.edu   
Contact: Dawn Mrozonski, RN    715-838-6356    Mrozinski.Dawn@mayo.edu   
Principal Investigator: Fearghas O'Cochlain, MD         
Mayo Clinic Health System Recruiting
LaCrosse, Wisconsin, United States, 54601
Contact: Diane Johnson, RN       Johnson.Diane5@mayo.edu   
Principal Investigator: Charles R Cagin, DO         
Canada, British Columbia
Vancouver General Hospital, UBC Division of Cardiology Recruiting
Vancouver, British Columbia, Canada, V5N 3W9
Contact: Robyn Tkatch    604-875-5106    Robyn.Tkatch@vch.ca   
Contact: Jennifer Timer    604-875-5106    Jennifer.Timer@vch.ca   
Principal Investigator: Jacqueline Saw, MD         
Canada, Ontario
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Lyne Stuwe, RN       LStuewe@ottawaheart.ca   
Contact: Cheryl Charlebois, RN       ccharlesbois@ottawaheart.ca   
Principal Investigator: Derek So, MD         
St Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Sandra Felix, RN       felixS@smh.ca   
Principal Investigator: John Graham, MD         
Toronto General Hospital - UHN Recruiting
Toronto, Ontario, Canada, M5B 2C4
Contact: Christina Drake, RN    416 340 4800    Christina.Drake@uhn.ca   
Principal Investigator: Chris Overgaard, MD         
Sunnybrook Health Services Center Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Patricia Reilly    416-480-6060 ext 5253    patricia.reilly@sunnybrook.ca   
Principal Investigator: Mina Madan, MD         
Korea, Republic of
Konyang University College of Medicine Recruiting
Daejeon, Korea, Republic of, 302-718
Contact: YoungHee Bae    82-42-600-9409    prettyyh0028@naver.com   
Principal Investigator: Jang-Ho Bae, M.D.         
Chonnam National University Hospital Recruiting
Gwangju, Korea, Republic of, 501-757
Contact: Eun Jung Kim    82.62.220.5783    kej-shep@hanmail.net   
Contact: Hyun Yee Gook    82-62-220-5783    kiznetic@hanmail.net   
Principal Investigator: Myung Ho Jeong, M.D., Ph.D.         
Chung-Ang University Hospital Recruiting
Seoul, Korea, Republic of, 156-755
Contact: Eun-mi Kim       eunmi986.ek@gmail.com   
Principal Investigator: Joonhwa Hong, M.D.         
Sponsors and Collaborators
Mayo Clinic
Applied Health Research Centre (AHRC)
Investigators
Principal Investigator: Naveen Pereira, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Naveen L. Pereira, Assistant Professor of Medicine, College of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01742117     History of Changes
Other Study ID Numbers: 11-006837
Study First Received: December 3, 2012
Last Updated: July 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
percutaneous coronary intervention
angioplasty

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Acute Coronary Syndrome
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Ticlopidine
Ticagrelor
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 22, 2014