Tailored Antiplatelet Therapy Following PCI - Full Text View

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:

Drug Information available for: Clopidogrel bisulfate Ticagrelor

U.S. FDA Resources

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:	March 2020
Estimated Primary Completion Date:	September 2019 (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 (Adult, Senior)
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: Monica Olson	507-255-2649	rstTAILORPCI@mayo.edu

Show 29 Study Locations

Sponsors and Collaborators

Mayo Clinic

Spartan Bioscience Inc.

Applied Health Research Centre

National Heart, Lung, and Blood Institute (NHLBI)

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

More Information


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:	June 17, 2016
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 Ticagrelor Clopidogrel Ticlopidine Purinergic P2Y Receptor Antagonists	Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Platelet Aggregation Inhibitors Fibrinolytic Agents Fibrin Modulating Agents Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016

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

Tailored Antiplatelet Therapy Following PCI (TAILOR-PCI)