The Study of CYP2C19 Genotype-Guided Clopidogrel Treatment Models

NCT06665919 | Completed Results

• 1 other identifier: BREC-TSMU#2-2023/103
• Study Type: interventional
• Target: 283
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Coronary Artery Disease; Clopidogrel Resistance; Coronary Thrombosis; Adverse Cardiac Events; Bleeding; Hospitalisations; Death; Death From Cardiovascular Disease

Keywords

CYP2C19 Genotype-guided antiplatelet treatment; Clopidogrel Resistance; Double Antiplatelet Treatment; Chronic Coronary Artery Disease; Implementation of Genotype-guided Medication Treatment; Outcome Study

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• Number of Study Participants Who Experienced Non-fatal Myocardial Infarction (Non-fatal Myocardial Infarction)

  within a 12-month of the study follow-up

• Number of Study Participants Who Experienced Unstable Angina or Angina Requiring Hospitalization (Unstable Angina)

  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)

  within a 12-month of the study follow-up

• Number of Study Participants Who Experienced Major Bleeding (Major Bleeding)

  within a 12-month of the study follow-up

• Number of Study Participants Who Experienced Non-major Bleeding (Non-major Bleeding)

  within a 12-month of the study follow-up

Other Outcomes (10)

• 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)

  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)

  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

  within a 12-month of the study follow-up

Study Arms (3)

Normal Metabolizers of Clopidogrel

EXPERIMENTAL

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

Passive Metabolizers of Clopidogrel

EXPERIMENTAL

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

Unspecified Metabolizers of Clopidogrel

ACTIVE COMPARATOR

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

Interventions

CYP2C19 Genotype-Guided Clopidogrel Treatment OTHER

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).

Normal Metabolizers of Clopidogrel

CYP2C19 Genotype Guided Antiplatelet Treatment Alternative to Clopidogrel OTHER

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).

Passive Metabolizers of Clopidogrel

The Conventional Clopidogrel Treatment OTHER

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).

Unspecified Metabolizers of Clopidogrel

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Vistamedi Ltd.: lead
• Tbilisi State Medical University: collaborator

Study Sites (4)

1st University Clinic of the Tbilisi State Medical University

Tbilisi, Georgia

Location

Cardio Expert Ltd., Clinic Cardio

Tbilisi, Georgia

Location

T. Oragvelidze Cardiology Center

Tbilisi, Georgia

Location

Tbilisi Institute of Medicine

Tbilisi, Georgia

Location

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Related 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

MeSH Terms

Conditions

Coronary Artery Disease; Coronary Thrombosis; Cardiovascular Diseases; Hemorrhage; Death

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Thrombosis; Embolism and Thrombosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Konstantine Liluashvili , MD., PH.D.
• Organization: Tbilisi State Medical University

k.liluashvili@tsmu.edu

+995599908899

Study Officials

• Levan Jijeishvili, MD, MPH

  Vistamedi Ltd., Tbilisi Georgia

  STUDY DIRECTOR

• Konstantine Liluashvili, MD., PH.D.

  Tbilisi State Medical University

  PRINCIPAL INVESTIGATOR

• Tornike Batavani, MD, MPH

  Vistamedi Ltd. Tbilisi, Georgia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To evaluate CYP2C19 allele genotype-guided clopidogrel treatment outcomes after the ePCI study participants were randomly allocated into parallel study arms. Experimental arm participants have undergone CYP2C19 genotyping. Carriers of normal \*2, \*3 alleles - "normal metabolizers" phenotype separated as the experimental arm and participants randomly allocated in the comparators arm without CYP2C19 genotyping - the "unspecified metabolizers" phenotype, have been intervened with clopidogrel-based preventive antiplatelet treatment. Carriers of LoF \*2, \*3 alleles - the "poor metabolizers" phenotype, have been separated in the experimental arm, assigned as the additional comparators and intervened with preventive antiplatelet treatment alternative to clopidogrel. Clinical and non-clinical outcome measures are expected to be compared between parallel study groups.

Study Record Dates

• First Submitted: September 29, 2024
• First Posted: October 30, 2024
• Study Start: June 15, 2023
• Primary Completion: May 15, 2025
• Study Completion: July 5, 2025
• Last Updated: September 26, 2025
• Results First Posted: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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/.

Locations

GE (4)