The Study of CYP2C19 Genotype-Guided Clopidogrel Treatment Models

Randomized Controlled Trial for Evaluating CYP2C19 Allele Genotype-guided Clopidogrel Treatment Outcomes in Real-world Practice After the ePCI

The study purposed to learn how clopidogrel-based antiplatelet treatment for preventing adverse cardiovascular events after ePCI works in chronic coronary artery disease when guided by personal genetic characteristics for drug metabolism.

The study aimed to answer two research questions:

• Does CYP2C19 genotype-guided clopidogrel treatment provide better clinical outcomes when compared with conventional treatment selection led without CYP2C19 genotyping?
• Can CYP2C19 genotype-guided antiplatelet treatment be beneficially applied in real-world clinical practice?

After obtaining the informed consent eligible study participants screened by inclusion and exclusion criteria were randomized and allocated into two groups:

• for whom the CYP2C19 genotype-guided clopidogrel treatment has been applied - the experimental group,
• for whom conventional clopidogrel has been applied without CYP2C19 genotyping - the control group.

The experimental group participants underwent CYP2C19 genotyping. Study participants with CYP2C19 normal function alleles (NFA) *2, *3 genotypes constituted the separate experimental arm and received clopidogrel-based preventive antiplatelet treatment.

Participants with CYP2C19 *2 and *3 loss of function (LoF) alleles were allocated to the separate experimental group and received preventive antiplatelet treatment alternative to clopidogrel.

Study participants who had not undergone CYP2C19 genotyping and received conventional preventive antiplatelet treatment with clopidogrel were assigned as active comparators.

All participants in the experimental and comparator groups underwent standard clinical investigations by current guideline recommendations for:

• the initial assessment,
• follow-up and detection of major adverse cardiovascular events. All patients received the conventional drug treatment by current guideline recommendations for chronic coronary artery disease and comorbid condition management and adverse cardiovascular events prevention.

The main research outcome measures include:

• evaluating clinical outcomes of CYP2C19 genotype-guided antiplatelet treatment application,
• describing models for application of CYP2C19 genotype-guided antiplatelet treatment,
• learning about potential access points to the real practice process pipeline for implementation of genotype-guided medication treatment.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Death; Bleeding; Coronary Thrombosis; Hospitalisations; Clopidogrel Resistance; Adverse Cardiac Events; Death From Cardiovascular Disease
• Intervention / Treatment: Other: CYP2C19 Genotype-Guided Clopidogrel Treatment; Other: CYP2C19 Genotype Guided Antiplatelet Treatment Alternative to Clopidogrel; Other: The Conventional Clopidogrel Treatment

Detailed Description

The concept of the study is based on current evidence from multiple genetic and clinical studies. At this stage of development preventive treatment of chronic coronary artery disease after ePCI is challenged by risks related to multi-morbidity, recurrent MACCEs and bleeding. Scientific evidence broadly supports pharmacogenetic approaches for routine use of P2Y12 inhibitors (clopidogrel or alternative). Clopidogrel remains the most commonly used P2Y12 inhibitor in the post-ePCI settings. Along with disease-related and co-morbid factors treatment effects are influenced by the variability of the CYP2C19 genotype in the population, which significantly increases the risk of MACCE in loss of function allele (LoF) carriers even with conventional clopidogrel treatment. To improve treatment, a pharmacogenetic expediency model for drug selection is introduced. CYP2C19 allele genotype-guided clopidogrel or an alternative P2Y12 inhibitor treatment is based on robust evidence.

The study aimed to learn the comparative benefits of CYP2C19 genotype-guided versus conventional clopidogrel treatment selection applied in real clinical practice for preventing adverse cardiovascular events after ePCI in chronic coronary artery disease.

For this purpose, the randomized parallel-group controlled study for CYP2C19 genotype-guided clopidogrel treatment outcomes evaluation for chronic coronary artery disease after the ePCI in real-world practice was conducted.

The study addressed research-specific objectives:

• forming and random allocating of participants into study arms for CYP2C19 allele genotype-guided versus conventional clopidogrel treatment,
• ensuring RT-PCR based assay for CYP2C19 *2, *3 LoF alleles detection in randomly selected study participants and forming the experimental study groups,
• characterizing clinical traits of study participants and observing adverse clinical events during the 12-month course of study intervention treatment;

• evaluating the clinical and non-clinical study outcomes. Following the completion of the informed consent, 283 patients eligible for inclusion and exclusion criteria have been enrolled in the study and randomly allocated into two groups.

  83 participants created the control group. They did not undergo CYP2C19 genotyping and received conventional antiplatelet treatment based on clopidogrel.

  200 participants were tested for CYP2C19 *2, *3 allele genotype. 157 of those who revealed normal CYP2C19 *2, *3 allele genotype received conventional preventive antiplatelet treatment based on clopidogrel and created a separate experimental arm.

  43 participants who revealed CYP2C19 *2, *3 LoF allele genotype required preventive antiplatelet treatment alternative to clopidogrel - based on ticagrelor or prasugrel were allocated into another separate experimental arm and assigned as the perspective arm for further study.

Before inclusion, informed consent was obtained from all study participants (or their legal representatives).

The randomization and study arm allocation processes were blinded for participants, healthcare teams providing medical care and study outcomes assessors. Nevertheless, after randomization and genetic testing, CYP2C19 allele genotyping results were disclosed to the medical care team and study participants to make ongoing clinical management safe and transparent but remained blinded for study outcomes assessors.

RT-PCR-based laboratory assay for CYP2C19 *2, *3 alleles genotyping was carried out only once after randomization for each study participant allocated into the experimental group. Tests were performed in the diagnostic laboratory of Vistamedi Ltd served as the central study laboratory.

The laboratory test report was provided to the authenticated investigator and as well as participant and entered in the study data report form.

Regular healthcare teams conducted clinical management of study participants in a real practice environment including medication treatment under conventional guideline recommendations were detected and initially reported major adverse cardiovascular outcomes, other adverse events, or additional clinical conditions diagnosed or study-related circumstances emerged through the study follow-up period up to the end of the study. Study participants (or their legal representatives) were also allowed to report adverse clinical outcomes, events or emerging circumstances.

For a study participant, the expected end of the study is defined as the end date of the 12-month follow-up from the date of the index ePCI. However, in the case of the clinical endpoint which corresponded to and defined the study outcome measure, the date of such endpoint event was determined as the end of the study, even if earlier than 12 months from the index ePCI.

The study participant could terminate participation by his or her independent decision, from any time of the research and for any reason, which could or could not be established.

Early withdrawal of a participant from the study was considered reasonable if there was repeated non-adherence to the treatment of study interest, rather than sporadic, or when there was preferred to terminate treatment based on the justified best interests of the participant.

Clinical outcomes conventionally defined by the Standardized Data Collection for Cardiovascular Trials Initiative (SCTI), the US Food and Drug Administration (FDA), the Academic Research Consortium for High Bleeding Risk (ARC-HBR) and WHO have been measured by clinical endpoints developed over the course of clinical cases.

Certain elements of the Coronary Revascularization Outcome Questionnaire (CROQ) and Patient-Reported Outcomes Measurement Information System®-Plus-Heart Failure profile were used for measuring of Patient-Reported Outcomes (PROs).

Study results were also analyzed using other non-clinical outcome measures that characterized the effectiveness of СYP2C19 genotype-guided P2Y12 inhibitor treatment utilization in real practice.

Data from each study participant were entered into a CRF, the form of which was the same for all participants and study centers.

Study data are collected, stored, and processed into a custom-designed electronic database. Identifiers, study variables and record data are validated with codes to ensure personal data protection.

Personal data, code keys and definitions, and research data are warehoused in separate databases. Only authenticated researchers have access to them. Research data collection centers do not have an internet connection or any other access to the database files.

Study data processing is only allowed by the study procedures given in the study protocol.

After the data collection, the database containing the personal data of the study participants will be deleted.

The de-identified electronic database will be stored after the end of the study for further research purposes for an indefinite period.

• Study Type: Interventional
• Enrollment (Actual): 283
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia
    • Tbilisi Institute of Medicine
  • Tbilisi, Georgia
    • 1st University Clinic of the Tbilisi State Medical University
  • Tbilisi, Georgia
    • Cardio Expert Ltd., Clinic Cardio
  • Tbilisi, Georgia
    • T. Oragvelidze Cardiology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with chronic coronary artery disease;
• Undergone elective PCI within the last 12 weeks without procedure-related complications;
• LVEF≥38% after index PCI;
• Completed informed consent form for participation in the study;

Exclusion Criteria:

• Concomitant using of potent CYP3A4 or CYP2C19 inhibitors;
• Morbid obesity, BMI 40 kg/sq.m or more;
• Type 1 diabetes mellitus;
• Poorly controlled type 2 diabetes mellitus, HbA1c - 9% or more;
• Acute Myocardium Infarction;
• Coronary artery bypass grafting performed within the last 12 weeks;
• Valvular heart disease due to dysplasia, connective tissue disorders or inflammatory disorders, or valvular disorders requiring cardiac surgery;
• History of severe hepatic impairment;
• Severe chronic kidney disease;
• Clinically important leucopenia, lymphopenia, thrombocytopenia or thrombocytosis;
• History of hemorrhagic diathesis or coagulopathy;
• An active or an obvious threat of bleeding (including GI bleeding):
• Bleeding within the past 6 months that required hospitalization;
• Blood transfusion during the past 6 months or its refusal;
• History of intracranial hemorrhage;
• Cardiac or non-cardiac degenerative disease, including: cardiomyopathy, restrictive lung disease, or Neurodegenerative diseases;
• Malignant tumor (cancer) that limits life expectancy to less than one year;
• Current chemotherapy or immunosuppressive therapy;
• Ongoing immunosuppression or immunosuppressive conditions;
• Pregnancy or lactation period;
• Any disease/condition control of which is not achieved;
• Personal (patient/physician dependent) or health care system-related circumstances that can restrict or limit any study procedures or operations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Metabolizers of Clopidogrel; 157 study participants diagnosed with chronic coronary artery disease who had undergone elective PCI, tested with CYP2C19 genotyping and identified as NFA *2, *3 carriers.	Other: CYP2C19 Genotype-Guided Clopidogrel Treatment; Clopidogrel as a component of preventive antiplatelet treatment such as double antiplatelet treatment (DAPT), or an antiplatelet drug (clopidogrel) combined with the non-vitamin K antagonist oral anticoagulants (NOAC), incl. triple antiplatelet treatment (Aspirin, Clopidogrel and a NOAC), or antiplatelet monotherapy (Clopidogrel).
Experimental: Passive Metabolizers of Clopidogrel; 43 study participants diagnosed with chronic coronary artery disease who had undergone elective PCI, tested with CYP2C19 genotyping, identified as LoF *2, *3 alleles carriers.	Other: CYP2C19 Genotype Guided Antiplatelet Treatment Alternative to Clopidogrel; An antiplatelet drug alternative to clopidogrel in conventional dosing regimen, as a component of preventive antiplatelet treatment, such as double antiplatelet treatment (DAPT) with ticagrelor or prasugrel, or prasugrel combined with the non-vitamin K antagonist oral anticoagulants (NOAC), or antiplatelet monotherapy (ticagrelor, or prasugrel).
Active Comparator: Unspecified Metabolizers of Clopidogrel; 83 participants diagnosed with chronic coronary artery disease who had undergone elective PCI were allocated to the arm through the randomization, without CYP2C19 genotyping and clopidogrel metabolism phenotype have not been specified.	Other: The Conventional Clopidogrel Treatment; Clopidogrel as a component of preventive antiplatelet treatment such as double antiplatelet treatment (DAPT), or clopidogrel combined with the non-vitamin K antagonist oral anticoagulants (NOAC), incl. triple antiplatelet treatment (Aspirin, Clopidogrel and a NOAC), or antiplatelet monotherapy (Clopidogrel).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants Who Died From Any Cause (Death From Any Cause)	The event of death from any cause reported by the physician according to the WHO Clinical criteria for the determination of death or the incident declared by the caregiver of the patient and checked for appropriateness in hospital registries or the national death registry within the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Died From Any Cardiovascular Cause (Death From Cardiovascular Cause)	The event of death from any cardiovascular cause reported by the physician according the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions or the incident declared by the caregiver of the patient and checked for appropriateness in hospital registries or the national death registry within the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Died From Non-cardiovascular Causes (Death From Non-cardiovascular Cause)	The event of death from a non-cardiovascular cause reported by the physician or the incident declared by the caregiver of the patient and checked for appropriateness in hospital registries or the national death registry within the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Participants Who Experienced Non-fatal Myocardial Infarction (Non-fatal Myocardial Infarction)	The clinical event of the non-fatal myocardial infarction detected during the study follow-up period and assessed by the 2012 Third Universal Definition of Myocardial Infarction as recommended by the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Experienced Unstable Angina or Angina Requiring Hospitalization (Unstable Angina)	The clinical event corresponding to the unstable angina, or angina that requires hospitalization detected during the study follow-up period and assessed by the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Experienced a Stroke or Transitory Cerebral Ischemic Event Within the Study Follow-up Period (Stroke or TIA)	The clinical event of the stroke or transitory ischemic attack detected during the study follow-up period and assessed by the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions for Stroke and Transient Ischemic Attack during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Experienced Major Bleeding (Major Bleeding)	The clinical event of major bleeding detected during the study follow-up period and assessed by the ARC-HBR (Academic Research Consortium for High Bleeding Risk) definitions as BARC type 3, 5 of bleeding during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Experienced Non-major Bleeding (Non-major Bleeding)	The clinical event of major bleeding detected during the study follow-up period and assessed by the ARC-HBR (Academic Research Consortium for High Bleeding Risk) definitions as BARC type 1 of bleeding during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Experienced Heart Failure Event (Heart Failure Event)	The clinical event of heart failure that requires hospitalization detected during the study follow-up period and assessed by the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Participants Who Experienced Percutaneous Coronary Intervention or Coronary Artery Bypass-grafting (Repeated Coronary Revascularization)	The clinical event of any repeated coronary revascularization: percutaneous coronary intervention or coronary artery bypass-grafting detected during the study follow-up period and assessed by the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Study Cases in Each Arm With a Composite of Death From Any Cause, Non-fatal Myocardial Infarction, Stroke/TIA, or Major Bleeding Within the Study Follow-up (Net Adverse Clinical Events - NACEs)	Net adverse clinical event (NACE) is assessed via measuring and putting together death from any cause, non-fatal myocardial infarction, stroke/TIA, or major bleeding (BARC type 3, 5) as potential outcomes for every studied case during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Cases in Each Study Arm With a Composite of Death From Any Cause, Myocardial Infarction, or Stroke/TIA Within the Study Follow-up (Major Adverse Cardiac or Cerebral Events - MACCEs)	Major adverse cardiac or cerebral event (MACCE) is assessed by measuring and putting together death from cardiovascular cause, non-fatal myocardial infarction, or stroke/TIA as potential outcomes for every studied case during the study follow-up period, from the date of study enrollment until the date of the event.	within a 12-month of the study follow-up
Number of Study Cases With Certain Antiplatelet Treatment Selection (Dual Antiplatelet Treatment, Triple Antiplatelet Treatment, Combined Antiplatelet and Anticoagulant, or Antiplatelet Monotherapy) in Each Study Arm	The number and percentage (%) of each arm of study participants treated with dual antiplatelet treatment, triple antiplatelet treatment, antiplatelet and non-vitamin K antagonist oral anticoagulant combination, or antiplatelet monotherapy	within a 12-month of the study follow-up
The Number of Study Cases With Certain Antiplatelet Medication (Aspirin, Clopidogrel, P2Y12 Inhibitor, Alternative to Clopidogrel, or A Non-vitamin K Antagonist Oral Anticoagulant (NOAC)) Prescription	The number and percentage (%) of study participants treated with a certain antiplatelet drug - aspirin, clopidogrel, P2Y12 inhibitor alternative to clopidogrel, or a non-vitamin K antagonist oral anticoagulant (NOAC) in each study arm	within a 12-month of the study follow-up
The Number of Study Cases With Lipid-lowering Medication (Statin, or Combination With Ezetimibe, or Ezetimibe and PCSK9i) Prescription	The number and percentage (%) of study participants treated with lipid-lowering medication - statin, or combined statin and ezetimibe, or statin, ezetimibe and PCSK9i in each study arm	within a 12-month of the study follow-up
The Number of Study Cases With Hypoglycemic Medication Prescription	The number and percentage (%) of study participants treated with certain hypoglycemic medication - insulin, sodium-glucose cotransporter-2 (SGLT2) inhibitor, metformin, glucagon-like peptide-1 (GLP-1) receptor agonist, or dipeptidyl peptidase IV (DPP IV) inhibitor in each study arm	within a 12-month of the study follow-up
The Number of Study Cases With Other Common Evidence-Based Medication Prescription for Cardiovascular Risk Reduction	The number and percentage (%) of study participants treated with other common evidence-based medication for cardiovascular risk reduction - angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), angiotensin receptor neprilysin inhibitor (ARNi), beta adrenergic blocker, loop diuretic, mineralocorticoid receptor antagonist (MCRA), thiazide diuretic, calcium channel blocker, anti-arrhythmic drug or ivabradine in each study arm	within a 12-month of the study follow-up
Number of Study Participants Who Reported Their Health Status as Good or Satisfactory; or With the Appearance of CVD Symptoms; or With a Significant Inability to Self-care (Patient-Reported Health Status)	The health status reported by the patient as: a) good or satisfactory; b) with the appearance of CVD symptoms; c) a significant inability to self-care ranked with severity degree of patient well-being, symptom burden, or ability for self-care, which is assessed according to the routine health related quality of life questionnaire definitions.	at 3, 6 and 12-month of the study follow-up
Number of Study Participants Self-reported Angina Not Required Hospitalization (Patient-Reported Angina Not Required Hospitalization)	The participant-reported last week episode of chest pain, or any discomfort, shortness of breath, or tightness in the chest due to angina not required hospitalization assessed by the CROQ (Coronary Revascularization Outcome Questionnaire) definitions.	at 3, 6 and 12-month of the study follow-up
Number of Study Participants Reported Last Week's Shortness of Breath Due to Heart Failure Not Requiring Hospitalization (Patient-Reported Heart Failure Severity)	The participant reported last week's shortness of breath due to mild physical activity or at rest not requiring hospitalization assessed by the PROMIS®-Plus-HF (Patient-Reported Outcomes Measurement Information System®-Plus-Heart Failure) profile definitions.	at 3, 6 and 12 months of the study follow-up

Collaborators and Investigators

• Sponsor: Vistamedi Ltd.
• Collaborators: Tbilisi State Medical University
• Investigators: Study Director: Levan Jijeishvili, MD, MPH, Vistamedi Ltd., Tbilisi Georgia; Principal Investigator: Konstantine Liluashvili, MD., PH.D., Tbilisi State Medical University; Study Chair: Tornike Batavani, MD, MPH, Vistamedi Ltd. Tbilisi, Georgia

Publications and helpful links

General Publications

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• 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.
• Pereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ, Mathew V, Goodman SG, Weinshilboum RM, Wang L, Baudhuin LM, Lerman A, Hasan A, Iturriaga E, Fu YP, Geller N, Bailey K, Farkouh ME. Clopidogrel Pharmacogenetics. Circ Cardiovasc Interv. 2019 Apr;12(4):e007811. doi: 10.1161/CIRCINTERVENTIONS.119.007811.
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• Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Postma MJ, de Boer A, Boersma C, Deneer VHM, Ten Berg JM. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N Engl J Med. 2019 Oct 24;381(17):1621-1631. doi: 10.1056/NEJMoa1907096. Epub 2019 Sep 3.
• Sibbing D, Aradi D, Alexopoulos D, Ten Berg J, Bhatt DL, Bonello L, Collet JP, Cuisset T, Franchi F, Gross L, Gurbel P, Jeong YH, Mehran R, Moliterno DJ, Neumann FJ, Pereira NL, Price MJ, Sabatine MS, So DYF, Stone GW, Storey RF, Tantry U, Trenk D, Valgimigli M, Waksman R, Angiolillo DJ. Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2019 Aug 26;12(16):1521-1537. doi: 10.1016/j.jcin.2019.03.034. Epub 2019 Jun 12.
• N. Mikaia, L. Jijeishvili, K. Liluashvili, M. Sebiskveradze, Z. Kavtaria, L. Bakashvili, M. Okujava, Implementation of molecular markers targeting thrombosis-related conditions in the real clinical practice, Clinica Chimica Acta, Volume 558, Supplement 1, 2024, 119263, ISSN 0009-8981, https://doi.org/10.1016/j.cca.2024.119263. (https://www.sciencedirect.com/science/article/pii/S0009898124015043)
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• Johnson SG, Gruntowicz D, Chua T, Morlock RJ. Financial Analysis of CYP2C19 Genotyping in Patients Receiving Dual Antiplatelet Therapy Following Acute Coronary Syndrome and Percutaneous Coronary Intervention. J Manag Care Spec Pharm. 2015 Jul;21(7):552-7. doi: 10.18553/jmcp.2015.21.7.552.
• 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.
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Helpful Links

• Clopidogrel, Drug Usage Statistics, United States, 2013 - 2022
• CPIC® Guideline for Clopidogrel and CYP2C19
• PharmGKB Clinical Annotations of Clopidogrel, information about variant-drug pairs based primarily on variant annotations and incorporating variant-specific prescribing guidance from clinical guidelines and FDA-approved drug labels, when available.
• Dean L, Kane M. Clopidogrel Therapy and CYP2C19 Genotype. 2012 Mar 8 [Updated 2022 Dec 1]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 20

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Actual): May 15, 2025
• Study Completion (Actual): July 5, 2025

Study Registration Dates

• First Submitted: September 29, 2024
• First Submitted That Met QC Criteria: October 28, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 6, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Clopidogrel Resistance; CYP2C19 Genotype-guided antiplatelet treatment; Double Antiplatelet Treatment; Chronic Coronary Artery Disease; Implementation of Genotype-guided Medication Treatment; Outcome Study
• Additional Relevant MeSH Terms: Vascular Diseases; Pathologic Processes; Heart Diseases; Embolism and Thrombosis; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Thrombosis; Pathological Conditions, Signs and Symptoms; Cardiovascular Diseases; Coronary Artery Disease; Death; Hemorrhage; Coronary Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: BREC-TSMU#2-2023/103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After deidentification of the data records, the deidentified IPD used for the results section intended for article publication will be shared.

The data set will contain certain demographics, risk factors, cardiovascular morbidity, co-morbidity, coronary angiography, doppler-echocardiography, medication selection records of intervention and control group patients as well as CYP2C19 gene *2, *3 allele profile of the intervention group patients.

Meta-data in the form of tables, figures, text or appendices will be available as well.

The study protocol, variable and recorded data coding, statistical analysis plan and informed consent form will be shared as well.

IPD Sharing Time Frame

The IPD will be available 1 month following the publication of the article containing study results. The anticipated date of final data collection for the primary outcome measures is March 2025. At this time two manuscripts for publication submission are expected to be completed and the study IPD will be available for sharing.

Before this time supporting information will be shared. After sharing IPD, supporting information will be available for researchers in the field related to this study.

The study IPD will remain available for sharing 36 months after the article publication.

IPD Sharing Access Criteria

IPD and supportive information will be accessible for researchers and investigators who will provide a methodologically sound proposal and whose proposed use of the data will be approved by the independent review and ethics boards. The proposal should display aims and types of IPD analysis, show intentions for IPD meta-analysis.

Possibility and appropriateness of the IPD for sharing should be confirmed by the National Personal Data Protection Service of Georgia.

The proposal can be submitted up to 36 months following the study article publication. After 36 months the IPD will be available in the VistaMedi Ltd data warehouse but without investigators support other than deposited meta-data.

Information regarding proposal submitting, IPD accessing procedures and more detailed plan for sharing IPD, Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF) and Variable Data codes will be released on the VistaMedi Ltd official website http://vistamedi.ge/en/.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No