TAILOR-PCI: Tailored Antiplatelet Therapy Following PCI

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01742117
• Collaborator: Spartan Bioscience Inc. (Industry), Applied Health Research Centre (Other), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 5,276
• Locations: 41
• Arms: 2
• Duration (Months): 90
• Patients Per Site: 128.7
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease; Acute Coronary Syndrome; Stenosis	Drug: Clopidogrel; Drug: Ticagrelor	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 5276 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tailored Antiplatelet Initiation to Lesson Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention (TAILOR-PCI)
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Oct 31, 2020
• Actual Study Completion Date: Oct 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Clopidogrel; One 75 mg tablet per day by mouth for one year; Other Names: Plavix ; Drug: Ticagrelor; One 90 mg tablet twice per day by mouth for one year; Other Names: Brilinta
Active Comparator: 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.	Drug: Clopidogrel; One 75 mg tablet per day by mouth for one year; Other Names: Plavix

Outcome Measures

Primary Outcome Measures

1. Occurrence of the a Major Adverse Cardiovascular Event in Subjects Identified as CPY2C19 LOF Carriers by TaqMan. [1 year after percutaneous coronary intervention (PCI)]

   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.

2. Occurrence of the a Major Adverse Cardiovascular Event [Approximately 3 years after percutaneous coronary intervention (PCI)]

   Number of subjects to experience a major adverse cardiovascular event as defined as cardiovascular death, myocardial infarction, stroke, severe recurrent ischemia, and stent thrombosis.

Secondary Outcome Measures

1. Thrombolysis in Myocardial Infarction Major or Minor Bleeding in Subjects Identified as CPY2C19 LOF Carriers by TaqMan. [1 year after percutaneous coronary intervention (PCI)]

   Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding in subjects identified as CYP2C19 LOF carriers by TaqMan

2. Thrombolysis in Myocardial Infarction Major or Minor Bleeding [Approximately 3 years after percutaneous coronary intervention (PCI)]

   Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Sharp HealthCare	San Diego	California	United States	92123
3	Zuckerberg San Francisco General	San Francisco	California	United States	94110
4	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224
5	NCH Heart Institute	Naples	Florida	United States	34102
6	NorthShore University Health System	Evanston	Illinois	United States	60201
7	Loyola University Medical Center	Maywood	Illinois	United States	60153
8	St. Elizabeth Healthcare	Crestview Hills	Kentucky	United States	41017
9	Henry Ford Hospital	Detroit	Michigan	United States	48202
10	Essentia Institute of Rural Health	Duluth	Minnesota	United States	55805
11	Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407
12	University of Minnesota	Minneapolis	Minnesota	United States	55455
13	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
14	The University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
15	Albany Medical College	Albany	New York	United States	12208
16	The Feinstein Institute for Medical Research	Manhasset	New York	United States	11030
17	Winthrop University Hospital	Mineola	New York	United States	11501
18	New York University Langone Medical Center	New York	New York	United States	10016
19	Columbia University Medical Center	New York	New York	United States	10032
20	Cardiology Associates of Schenectady	Schenectady	New York	United States	12309
21	Rhode Island Hospital	Providence	Rhode Island	United States	02903
22	The Miriam Hospital	Providence	Rhode Island	United States	02906
23	Greenville Health System	Greenville	South Carolina	United States	29605
24	MHS, Eau Claire	Eau Claire	Wisconsin	United States	54702
25	Mayo Clinic Health System	La Crosse	Wisconsin	United States	54601
26	Aurora Health Care	Milwaukee	Wisconsin	United States	53215
27	Vancouver General Hospital, UBC Division of Cardiology	Vancouver	British Columbia	Canada	V5N 3W9
28	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7
29	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario	Canada	P7B 6V4
30	Humber River Hospital	Toronto	Ontario	Canada	M3M 0B2
31	Sunnybrook Health Services Center	Toronto	Ontario	Canada	M4N 3M5
32	St Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
33	Toronto General Hospital - UHN	Toronto	Ontario	Canada	M5B 2C4
34	Regina General Hospital	Regina	Saskatchawan	Canada	S4P 0W5
35	Konyang University College of Medicine	Daejeon		Korea, Republic of	302-718
36	Chonnam National University Hospital	Gwangju		Korea, Republic of	501-757
37	Ajou University Hospital	Gyeonggi-do		Korea, Republic of
38	Chung-Ang University Hospital	Seoul		Korea, Republic of	156-755
39	Hospital de Especialidades, Centro Medico Nacional 'La Raza'	Mexico City		Mexico	02990
40	Hospital REgional No. 1	Mexico City		Mexico	03100
41	Hospital de Cardiologia, Centro Medico Nacional Siglo XXI	Mexico City		Mexico	06720

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 13, 2019

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Naveen L. Pereira, Professor of Medicine, College of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01742117
• Other Study ID Numbers: 11-006837; 5U01HL128606; 3U01HL128606-03S1
• First Posted: Dec 5, 2012
• Last Update Posted: Nov 9, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Naveen L. Pereira, Professor of Medicine, College of Medicine, Mayo Clinic: percutaneous coronary intervention; angioplasty
• Additional relevant MeSH terms: Coronary Artery Disease; Acute Coronary Syndrome; Clopidogrel; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Genotype-Guided Therapy	Conventional Therapy
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year	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. Clopidogrel: One 75 mg tablet per day by mouth for one year
Period Title: Overall Study
STARTED	2641	2635
COMPLETED	2641	2635
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Genotype-Guided Therapy	Conventional Therapy	Total
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year	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. Clopidogrel: One 75 mg tablet per day by mouth for one year	Total of all reporting groups
Overall Participants	2641	2635	5276
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	62	62
Sex: Female, Male (Count of Participants)
Female	648 24.5%	645 24.5%	1293 24.5%
Male	1993 75.5%	1990 75.5%	3983 75.5%
Race/Ethnicity, Customized (Count of Participants)
White	1750 66.3%	1754 66.6%	3504 66.4%
East Asian	595 22.5%	592 22.5%	1187 22.5%
South Asian	116 4.4%	120 4.6%	236 4.5%
African America	57 2.2%	67 2.5%	124 2.4%
Other, Unknown or Not Reported	123 4.7%	102 3.9%	225 4.3%
Hispanic or Latinx ethnicity	78 3%	70 2.7%	148 2.8%
Region of Enrollment (participants) [Number]
Canada	577 21.8%	580 22%	1157 21.9%
South Korea	654 24.8%	650 24.7%	1304 24.7%
United States	1359 51.5%	1358 51.5%	2717 51.5%
Mexico	51 1.9%	47 1.8%	98 1.9%

Outcome Measures

1. Primary Outcome

Title	Occurrence of the a Major Adverse Cardiovascular Event in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.
Description	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.
Time Frame	1 year after percutaneous coronary intervention (PCI)

Outcome Measure Data

Analysis Population Description

For 1 year endpoint in Genotype-Guided Therapy arm 1738 were excluded from data analysis due Identified as CYP2C19 LOF noncarriers by TaqMan or no TaqMan results available. For 1 year endpoint in Conventional Therapy arm 1689 were excluded from data analysis due Identified as CYP2C19 LOF noncarriers by TaqMan or no TaqMan results available.

Arm/Group Title	Genotype-Guided Therapy	Conventional Therapy
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year	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. Clopidogrel: One 75 mg tablet per day by mouth for one year
Measure Participants	903	946
Count of Participants [Participants]	35 1.3%	54 2%

2. Secondary Outcome

Title	Thrombolysis in Myocardial Infarction Major or Minor Bleeding in Subjects Identified as CPY2C19 LOF Carriers by TaqMan.
Description	Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding in subjects identified as CYP2C19 LOF carriers by TaqMan
Time Frame	1 year after percutaneous coronary intervention (PCI)

Outcome Measure Data

Analysis Population Description

For 1 year endpoint in Genotype-Guided Therapy arm 1738 were excluded from data analysis due Identified as CYP2C19 LOF noncarriers by TaqMan or no TaqMan results available. For 1 year endpoint in Conventional Therapy arm 1689 were excluded from data analysis due Identified as CYP2C19 LOF noncarriers by TaqMan or no TaqMan results available.

Arm/Group Title	Genotype-Guided Therapy	Conventional Therapy
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year	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. Clopidogrel: One 75 mg tablet per day by mouth for one year
Measure Participants	903	946
Count of Participants [Participants]	16 0.6%	14 0.5%

3. Secondary Outcome

Title	Thrombolysis in Myocardial Infarction Major or Minor Bleeding
Description	Number of subjects that experienced thrombolysis in myocardial infarction major or minor bleeding
Time Frame	Approximately 3 years after percutaneous coronary intervention (PCI)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genotype-Guided Therapy	Conventional Therapy
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year	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. Clopidogrel: One 75 mg tablet per day by mouth for one year
Measure Participants	2641	2635
Count of Participants [Participants]	54 2%	53 2%

4. Primary Outcome

Title	Occurrence of the a Major Adverse Cardiovascular Event
Description	Number of subjects to experience a major adverse cardiovascular event as defined as cardiovascular death, myocardial infarction, stroke, severe recurrent ischemia, and stent thrombosis.
Time Frame	Approximately 3 years after percutaneous coronary intervention (PCI)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genotype-Guided Therapy	Conventional Therapy
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year	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. Clopidogrel: One 75 mg tablet per day by mouth for one year
Measure Participants	2641	2635
Count of Participants [Participants]	262 9.9%	269 10.2%

Adverse Events

Time Frame	Adverse events were collected from baseline to end of study participation for a total of approximately one year on all participants.
Arm/Group Title	Genotype-Guided Therapy		Conventional Therapy
Arm/Group Description	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. Clopidogrel: One 75 mg tablet per day by mouth for one year Ticagrelor: One 90 mg tablet twice per day by mouth for one year		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. Clopidogrel: One 75 mg tablet per day by mouth for one year
All Cause Mortality
	Genotype-Guided Therapy		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/2641 (3.6%)		98/2635 (3.7%)
Serious Adverse Events
	Genotype-Guided Therapy		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2641 (0%)		0/2635 (0%)
Other (Not Including Serious) Adverse Events
	Genotype-Guided Therapy		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2641 (0%)		0/2635 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.