Tailored Antiplatelet Therapy Following PCI

NCT ID: NCT01742117

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 5276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2020-10-31

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.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Stenosis

Keywords

percutaneous coronary intervention; angioplasty

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Clopidogrel

Intervention Type: DRUG

One 75 mg tablet per day by mouth for one year

Ticagrelor

Intervention Type: DRUG

One 90 mg tablet twice per day by mouth for one year

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.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

One 75 mg tablet per day by mouth for one year

Interventions

Clopidogrel

One 75 mg tablet per day by mouth for one year

Intervention Type: DRUG

Ticagrelor

One 90 mg tablet twice per day by mouth for one year

Intervention Type: DRUG

Other Intervention Names

Plavix; Brilinta

Eligibility Criteria

Inclusion Criteria

• 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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spartan Bioscience Inc.

INDUSTRY

Sponsor Role: collaborator

Applied Health Research Centre

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Naveen L. Pereira

Professor of Medicine, College of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Naveen Pereira, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Michael E Farkouh, MD

Role: PRINCIPAL_INVESTIGATOR

Toronto General Hospital

Kent R Bailey, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Sharp HealthCare

San Diego, California, United States

Zuckerberg San Francisco General

San Francisco, California, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

NCH Heart Institute

Naples, Florida, United States

NorthShore University Health System

Evanston, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, 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

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

The University of Mississippi Medical Center

Jackson, Mississippi, United States

Albany Medical College

Albany, New York, United States

The Feinstein Institute for Medical Research

Manhasset, New York, United States

Winthrop University Hospital

Mineola, New York, United States

New York University Langone Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Cardiology Associates of Schenectady

Schenectady, New York, United States

Rhode Island Hospital

Providence, Rhode Island, United States

The Miriam Hospital

Providence, Rhode Island, United States

Greenville Health System

Greenville, South Carolina, United States

MHS, Eau Claire

Eau Claire, Wisconsin, United States

Mayo Clinic Health System

La Crosse, Wisconsin, United States

Aurora Health Care

Milwaukee, Wisconsin, United States

Vancouver General Hospital, UBC Division of Cardiology

Vancouver, British Columbia, Canada

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, Canada

Humber River Hospital

Toronto, Ontario, Canada

Sunnybrook Health Services Center

Toronto, Ontario, Canada

St Michael's Hospital

Toronto, Ontario, Canada

Toronto General Hospital - UHN

Toronto, Ontario, Canada

Regina General Hospital

Regina, Saskatchawan, Canada

Hospital de Especialidades, Centro Medico Nacional 'La Raza'

Mexico City, , Mexico

Hospital REgional No. 1

Mexico City, , Mexico

Hospital de Cardiologia, Centro Medico Nacional Siglo XXI

Mexico City, , Mexico

Konyang University College of Medicine

Daejeon, , South Korea

Chonnam National University Hospital

Gwangju, , South Korea

Ajou University Hospital

Gyeonggi-do, , South Korea

Chung-Ang University Hospital

Seoul, , South Korea

Countries

United States; Canada; Mexico; South Korea

References

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.

Reference Type: RESULT

PMID: 32840598 (View on PubMed)

Ingraham BS, Farkouh ME, Lennon RJ, So D, Goodman SG, Geller N, Bae JH, Jeong MH, Baudhuin LM, Mathew V, Bell MR, Lerman A, Fu YP, Hasan A, Iturriaga E, Tanguay JF, Welsh RC, Rosenberg Y, Bailey K, Rihal C, Pereira NL. Genetic-Guided Oral P2Y12 Inhibitor Selection and Cumulative Ischemic Events After Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2023 Apr 10;16(7):816-825. doi: 10.1016/j.jcin.2023.01.356.

Reference Type: DERIVED

PMID: 37045502 (View on PubMed)

Mathew RO, Sidhu MS, Rihal CS, Lennon R, El-Hajjar M, Yager N, Lyubarova R, Abdul-Nour K, Weitz S, O'Cochlain DF, Murthy V, Levisay J, Marzo K, Graham J, Dzavik V, So D, Goodman S, Rosenberg YD, Pereira N, Farkouh ME. Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study. Cardiovasc Drugs Ther. 2024 Jun;38(3):447-457. doi: 10.1007/s10557-022-07392-2. Epub 2022 Nov 29.

Reference Type: DERIVED

PMID: 36445624 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35699977 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35699175 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35449399 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35132875 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

5U01HL128606

Identifier Type: NIH

Identifier Source: secondary_id

View Link

3U01HL128606-03S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

11-006837

Identifier Type: -

Identifier Source: org_study_id