Tailored Antiplatelet Therapy Following PCI

NCT01742117 | Completed Phase 4 Results DMC FDA Drug

• 3 other identifiers: 11-0068375U01HL1286063U01HL128606-03S1
• Study Type: interventional
• Target: 5,276
• Locations: 4 countries
• Sites: 41

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.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Stenosis

Keywords

percutaneous coronary intervention; angioplasty

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Thrombolysis in Myocardial Infarction Major or Minor Bleeding in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.

  1 year after percutaneous coronary intervention (PCI)

• Thrombolysis in Myocardial Infarction Major or Minor Bleeding

  Approximately 3 years after percutaneous coronary intervention (PCI)

Study Arms (2)

Genotype-Guided Therapy

EXPERIMENTAL

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; Drug: Ticagrelor

Conventional Therapy

ACTIVE COMPARATOR

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

Interventions

Clopidogrel DRUG

One 75 mg tablet per day by mouth for one year

Also known as: Plavix

Conventional Therapy; Genotype-Guided Therapy

Ticagrelor DRUG

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

Also known as: Brilinta

Genotype-Guided Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• Spartan Bioscience Inc.: collaborator
• Applied Health Research Centre: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (41)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Sharp HealthCare

San Diego, California, 92123, United States

Location

Zuckerberg San Francisco General

San Francisco, California, 94110, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

NCH Heart Institute

Naples, Florida, 34102, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

St. Elizabeth Healthcare

Crestview Hills, Kentucky, 41017, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Essentia Institute of Rural Health

Duluth, Minnesota, 55805, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

The University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

The Feinstein Institute for Medical Research

Manhasset, New York, 11030, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cardiology Associates of Schenectady

Schenectady, New York, 12309, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

MHS, Eau Claire

Eau Claire, Wisconsin, 54702, United States

Location

Mayo Clinic Health System

La Crosse, Wisconsin, 54601, United States

Location

Aurora Health Care

Milwaukee, Wisconsin, 53215, United States

Location

Vancouver General Hospital, UBC Division of Cardiology

Vancouver, British Columbia, V5N 3W9, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Humber River Hospital

Toronto, Ontario, M3M 0B2, Canada

Location

Sunnybrook Health Services Center

Toronto, Ontario, M4N 3M5, Canada

Location

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Toronto General Hospital - UHN

Toronto, Ontario, M5B 2C4, Canada

Location

Regina General Hospital

Regina, Saskatchawan, S4P 0W5, Canada

Location

Hospital de Especialidades, Centro Medico Nacional 'La Raza'

Mexico City, 02990, Mexico

Location

Hospital REgional No. 1

Mexico City, 03100, Mexico

Location

Hospital de Cardiologia, Centro Medico Nacional Siglo XXI

Mexico City, 06720, Mexico

Location

Konyang University College of Medicine

Daejeon, 302-718, South Korea

Location

Chonnam National University Hospital

Gwangju, 501-757, South Korea

Location

Ajou University Hospital

Gyeonggi-do, South Korea

Location

Chung-Ang University Hospital

Seoul, 156-755, South Korea

Location

Related Publications (7)

• 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.

  PMID: 32840598 RESULT

• 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.

  PMID: 37045502 DERIVED

• 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.

  PMID: 36445624 DERIVED

• 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.

  PMID: 35699977 DERIVED

• 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.

  PMID: 35699175 DERIVED

• 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.

  PMID: 35449399 DERIVED

• 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.

  PMID: 35132875 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome; Constriction, Pathologic

Interventions

Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Naveen L. Pereira
• Organization: Mayo Clinic

Pereira.Naveen@mayo.edu

507-284-4441

Study Officials

• Naveen Pereira, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Michael E Farkouh, MD

  Toronto General Hospital

  PRINCIPAL INVESTIGATOR

• Kent R Bailey, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, College of Medicine

Study Record Dates

• First Submitted: December 3, 2012
• First Posted: December 5, 2012
• Study Start: May 1, 2013
• Primary Completion: October 31, 2020
• Study Completion: October 31, 2020
• Last Updated: November 9, 2021
• Results First Posted: November 9, 2021

Record last verified: 2021-10

Locations

ME (3); KR (4); US (26); CA (8)