Tailored Antiplatelet Therapy Following PCI (TAILOR-PCI)

Tracking Information
First Submitted Date ICMJE	December 3, 2012
First Posted Date ICMJE	December 5, 2012
Last Update Posted Date	November 21, 2017
Study Start Date ICMJE	May 2013
Estimated Primary Completion Date	September 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 13, 2013)	Occurrence of the a major adverse cardiovascular event (MACE) [ Time Frame: Randomization, one year after percutaneous coronary intervention (PCI) ]; MACE will include non-fatal myocardial infarction, non-fatal stroke, cardiovascular mortality, severe recurrent ischemia, and stent thrombosis
Original Primary Outcome Measures ICMJE; (submitted: December 3, 2012)	Time to occurrence of the composite endpoint of a major adverse cardiovascular event (MACE) [ Time Frame: Randomization, one year after percutaneous coronary intervention (PCI) ]; MACE will include non-fatal myocardial infarction, non-fatal stroke, cardiovascular mortality, severe recurrent ischemia, and stent thrombosis
Change History	Complete list of historical versions of study NCT01742117 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 12, 2017)	Number of subjects with reduced function CYP2C19 allele(s) who have major or minor bleeding [ Time Frame: One year after PCI ]; Includes subjects who have bleeding events
Original Secondary Outcome Measures ICMJE; (submitted: December 3, 2012)	Number of subjects with reduced function CYP2C19 allele(s) who have major or minor bleeding [ Time Frame: One year after PCI ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Tailored Antiplatelet Therapy Following PCI
Official Title ICMJE	Tailored Antiplatelet Initiation to Lesson Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI)
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.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Coronary Artery Disease; Acute Coronary Syndrome; Stenosis
Intervention ICMJE	Drug: Clopidogrel Subjects will receive Clopidogrel, one 75 mg tablet per day by mouth for one year. Other Name: Plavix; Drug: Ticagrelor Subjects will receive Ticagrelor, one 90 mg tablet twice per day by mouth. Other Name: Brilinta; Genetic: Retrospective Genotype testing Mayo Clinic will use ABI TaqMan assay of three variants in the CYP2C10 gene: *2, *3 and *17; 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
Study Arms	Active Comparator: Clopidogrel then Retrospective Genotyping Clopidogrel 75 mg daily for 1 year after PCI. DNA samples at baseline to be frozen. At 12 months DNA will be genotyped to determine the *2 & *3 reduced function/wild type allele status. Interventions: Drug: Clopidogrel Genetic: Retrospective Genotype testing; 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 1 year following PCI. Interventions: Drug: Clopidogrel Genetic: Prospective Genotype testing; 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. Interventions: Drug: Ticagrelor Genetic: Prospective Genotype testing
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: April 11, 2014)	5270
Original Estimated Enrollment ICMJE; (submitted: December 3, 2012)	5945
Estimated Study Completion Date	March 2020
Estimated Primary Completion Date	September 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Monica Olson 507-255-2649 rstTAILORPCI@mayo.edu
Listed Location Countries ICMJE	Canada, Korea, Republic of, Mexico, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01742117
Other Study ID Numbers ICMJE	11-006837; 5U01HL128606 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Naveen L. Pereira, Mayo Clinic
Study Sponsor ICMJE	Mayo Clinic
Collaborators ICMJE	Spartan Bioscience Inc.; Applied Health Research Centre; National Heart, Lung, and Blood Institute (NHLBI)
Investigators ICMJE	Principal Investigator: Naveen Pereira, MD Mayo Clinic Principal Investigator: Michael E Farkouh, MD Toronto General Hospital Principal Investigator: Kent R Bailey, PhD Mayo Clinic
PRS Account	Mayo Clinic
Verification Date	November 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP