Clinical trial NCT01742117: Tailored Antiplatelet Therapy Following PCI
Official title: Tailored Antiplatelet Initiation to Lesson Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Acute Coronary Syndrome
Stenosis
Keywords: percutaneous coronary intervention
angioplasty
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Spartan Bioscience Inc.
name: Applied Health Research Centre
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-12-05
Enrollment: 5276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.)

Primary outcomes:
measure: Occurrence of the a Major Adverse Cardiovascular Event in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.
timeFrame: 1 year after percutaneous coronary intervention (PCI)
measure: Occurrence of the a Major Adverse Cardiovascular Event
timeFrame: Approximately 3 years after percutaneous coronary intervention (PCI)
Secondary outcomes:
measure: Thrombolysis in Myocardial Infarction Major or Minor Bleeding in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.
timeFrame: 1 year after percutaneous coronary intervention (PCI)
measure: Thrombolysis in Myocardial Infarction Major or Minor Bleeding
timeFrame: Approximately 3 years after percutaneous coronary intervention (PCI)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: San Diego
country: United States
facility: Sharp HealthCare
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Naples
country: United States
facility: NCH Heart Institute
state: Florida
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Crestview Hills
country: United States
facility: St. Elizabeth Healthcare
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Duluth
country: United States
facility: Essentia Institute of Rural Health
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Jackson
country: United States
facility: The University of Mississippi Medical Center
state: Mississippi
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Manhasset
country: United States
facility: The Feinstein Institute for Medical Research
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Schenectady
country: United States
facility: Cardiology Associates of Schenectady
state: New York
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Eau Claire
country: United States
facility: MHS, Eau Claire
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic Health System
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Health Care
state: Wisconsin
city: Vancouver
country: Canada
facility: Vancouver General Hospital, UBC Division of Cardiology
state: British Columbia
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Humber River Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Services Center
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital - UHN
state: Ontario
city: Regina
country: Canada
facility: Regina General Hospital
state: Saskatchawan
city: Daejeon
country: Korea, Republic of
facility: Konyang University College of Medicine
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Seoul
country: Korea, Republic of
facility: Chung-Ang University Hospital
city: Mexico City
country: Mexico
facility: Hospital de Especialidades, Centro Medico Nacional 'La Raza'
city: Mexico City
country: Mexico
facility: Hospital REgional No. 1
city: Mexico City
country: Mexico
facility: Hospital de Cardiologia, Centro Medico Nacional Siglo XXI
Study officials:
affiliation: Mayo Clinic
name: Naveen Pereira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Toronto General Hospital
name: Michael E Farkouh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Kent R Bailey, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.