Coronary Arterial Disease (CAD)Phase 4NCT06759272
Impact of CYP2C19 Genotype-guided Approach in Antiplatelet Therapy on Platelet Reactivity Index Among Coronary Artery Disease (CAD) Patients
A Phase 4 study testing CYP2C19 genotype-guided antiplatelet therapy in people with Coronary Arterial Disease (CAD) and ACS (Acute Coronary Syndrome), run by Nur Hafizah Annezah binti Utuh at 1 site in Malaysia.
Trial summary
The goal of this clinical trial is to learn if the pilot intervention of CYP2C19 genotype-guided antiplatelet therapy works to reduce the occurrence of cardiovascular events after Percutaneous Coronary Intervention (PCI) done in coronary artery disease patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Coronary Arterial Disease (CAD), ACS (Acute Coronary Syndrome), SCAD
- What is being tested?
- CYP2C19 genotype-guided antiplatelet therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteMalaysia
- Study dates
- Feb 2025to Feb 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females
- Aged between 18 to 80 years old
- Patients presents with stable CAD or acute coronary syndrome (ACS)
- Eligible for percutaneous coronary intervention (PCI)
- Willing to provide DNA sample via blood drawn for genotyping and platelet reactivity assessment
- Willing and able to provide informed written consent
Who cannot join
- Primary PCI or rescue PCI
- Any urgent/emergent coronary angiography procedure that would not allow for genetic testing to be performed before PCI
- 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
Show all 19Show fewer
- Anticipated discontinuation of clopidogrel or ticagrelor within the 12 months follow up period (e.g. for elective surgery)
- History of ischaemic or haemorrhagic stroke
- History of allergies to aspirin, ticagrelor, or clopidogrel
- Suffering from HIV or any blood transmitted disease.
- Considered at high risk of bleeding*
- Stage 5 chronic kidney disease (CKD) based on the National Kidney Foundation, Kidney disease quality outcome initiative (KDQOI) definition (Levey et al., 2005), or those who were on haemodialysis
- Pre-existing liver cirrhosis
- Pregnant women at any stage of gestation
- 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 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 a year, per judgement of physician
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD) contact
Nur Aizati Athirah Daud, Doctor of Philosophy (PhD) contact
Malaysia1 site
Hospital Pakar Universiti Sains Malaysia
Kota Bharu, Kelantan, 16150
Nur Aizati Athirah Daud, Doctor of Philosophy, 60139310969, aizati@usm.my
Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD)
About this study
Official title: Pharmacogenomic Markers of Clopidogrel Resistance in Malaysian CAD Patients: Clinical Efficacy and Economic Evaluation of CYP2C19 Genotype-Guided Therapy
The goal of this clinical trial is to learn if the pilot intervention of CYP2C19 genotype-guided antiplatelet therapy works to reduce the occurrence of cardiovascular events after Percutaneous Coronary Intervention (PCI) done in coronary artery disease patients. It will also learn about the comparison between clopidogrel and ticagrelor.
The main questions it aims to answer are:
Read more
To compare the impact of CYP2C19 genotype-guided antiplatelet therapy, universal use of clopidogrel and ticagrelor treatment on platelet reactivity.
To compare the impact of CYP2C19 genotype-guided antiplatelet therapy, universal use of clopidogrel and ticagrelor treatment on the risk of major adverse cardiovascular events (MACE) among newly recruited stable CAD patients.
Participants will:
Take drug clopidogrel or ticagrelor, based on the random group allocation every day for 1 month. One group of patients will undergone CYP2C19 genetic test for genotype-guided antiplatelet therapy, whether clopidogrel or ticagrelor.
Visit the clinic post 30 days of PCI for follow-ups and platelet function tests.
Read the detailed description
Clopidogrel, a prodrug that inhibits platelet aggregation, is widely used in patients undergoing percutaneous coronary interventions to prevent recurrent cardiovascular events. However, clopidogrel resistance has emerged as a great concern, whereby it causes inadequate platelet inhibition and leads to antiplatelet treatment failure with prevalence as high as 44% in Asian population. Due to various established evidence from pharmacogenomics studies, US FDA has issued a black-box warning notifying that CYP2C19 polymorphisms may impaired the ability of a patient to convert clopidogrel into its active metabolite. Currently, the availability of newer P2Y12 receptor inhibitors has prompted medical professionals to consider genotype-guided treatment, which may include escalation or de-escalation of the antiplatelet based on CYP2C19 genetic result. We hypothesize that CYP2C19 genotype guided therapy will reduce the occurrence of MACE and improve platelet reactivity to prevent clopidogrel resistance. The estimated sample size required for pilot intervention study is 120 patients. Knowledge of potential pharmacogenetic markers for clopidogrel resistance, clinical efficacy and cost evaluation of genotype-guided antiplatelet therapy will provide a comprehensive insight into adopting such approach in a real routine clinical setting.
- Being tested
- CYP2C19 genotype-guided antiplatelet therapy
- Keywords
- CYP2C19 genotype-guided antiplatelet therapy
- Medical subject headings
- Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYP2C19 genotype-guided antiplatelet therapyGenetic
Also called CYP2C19 screening test, Precision medicine
A panel of genes including CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) will be genotyped using the real-time PCR and the expected turnover time will be 48 hours. Patients who are identified to have reduced function CYP2C19 allele will receive 90 mg ticagrelor and patients with wild-type CYP2C19 allele will receive clopidogrel 75 mg in the next scheduled dose. The switching done from clopidogrel to ticagrelor is supported by Antiplatelet Therapy Switching Clinician Guideline, whereby in the maintenance or low risk phase, there is generally no need to administer a loading dose of ticagrelor; one can switch directly to ticagrelor maintenance dose 24 hours after the last dose of clopidogrel
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Pre-emptive genetic testing will be done on the patients allocated randomly to the intervention group after obtaining their consent. The clinical decision making on the antiplatelet (either clopidogrel or ticagrelor) will be done based on the presence of genetic markers CYP2C19*2 and CYP2C19*3, according to the latest Clinical Pharmacogenetics Implementation Consortium (CPIC) 2022 guideline. Patients who are identified to have reduced function CYP2C19 allele will receive 90 mg ticagrelor and patients with wild-type CYP2C19 allele will receive clopidogrel 75 mg in the next scheduled dose. Receives: Genetic: CYP2C19 genotype-guided antiplatelet therapy |
| Universal Clopidogrel | No intervention | All patients in the control group 1 will receive clopidogrel (300 mg loading dose to 75 mg daily maintenance dose) without any genetic screening done for 30 days. |
| Universal Ticagrelor | No intervention | All patients in the control group 2 will ticagrelor (180 mg loading dose to 90 mg twice daily as maintenance dose) without any genetic screening done for 30 days. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major adverse cardiovascular events (MACE)
Major adverse cardiovascular events (MACE) is defined as the composite of all-cause mortality, recurrent myocardial infarction (MI), repeat revascularization and stroke. The fourth universal definition of MI was used to retrospectively analyse recurrent MI. Any revascularization of the target coronary artery following the index incident, whether percutaneous or surgical, was referred to as repeat revascularization.
Measured: From enrollment to 30 days post PCI
Secondary outcomes (1)
Platelet Reactivity Index (PRI)
Based on the PRI assessment, the participants can be categorised into treatment responders and non-responders. Clopidogrel and ticagrelor non-responses will be reported based on the cut-off point of PRI≥50%. For VASP method, a platelet reactivity index (PRI) of > 50% was defined as high on-treatment platelet reactivity (HTPR) which could lead to higher risk of ischaemic events post PCI, and a PRI of < 16% was defined as low on-treatment platelet reactivity (LTPR) which could lead to higher risk of bleeding. Hence, the optimal therapeutic window for antiplatelet therapy according to this VASP method is 17-49%
Measured: From enrollment to at least 2 weeks of maintenance dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2025
- Study startFeb 2025 (estimated)
- Primary completionFeb 2026 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Arterial Disease (CAD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nur Hafizah Annezah binti Utuh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nur Hafizah Annezah binti Utuh, Universiti Sains Malaysia
- Investigators
- Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD), Principal investigator, School of Pharmaceutical Sciences, Universiti Sains Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06759272
- Sponsor's protocol ID
- 311224
- Status last verified
- Jan 2025
- First submitted
- 29 Dec 2024
- Last updated
- 7 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomic Markers of Clopidogrel Resistance in Malaysian CAD Patients: Clinical Efficacy and Economic Evaluation of CYP2C19 Genotype-Guided Therapy
- ClinicalTrials.gov ID
- NCT06759272
- Acronym / sponsor ID
- 311224
- Keywords
- CYP2C19 genotype-guided antiplatelet therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Nur Hafizah Annezah binti UtuhUniversity, hospital or other
- Study start
- Feb 2025 (estimated)
- Primary completion
- Feb 2026 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 6 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if the pilot intervention of CYP2C19 genotype-guided antiplatelet therapy works to reduce the occurrence of cardiovascular events after Percutaneous Coronary Intervention (PCI) done in coronary artery disease patients. It will also learn about the comparison between clopidogrel and ticagrelor.
The main questions it aims to answer are:
To compare the impact of CYP2C19 genotype-guided antiplatelet therapy, universal use of clopidogrel and ticagrelor treatment on platelet reactivity.
To compare the impact of CYP2C19 genotype-guided antiplatelet therapy, universal use of clopidogrel and ticagrelor treatment on the risk of major adverse cardiovascular events (MACE) among newly recruited stable CAD patients.
Participants will:
Take drug clopidogrel or ticagrelor, based on the random group allocation every day for 1 month. One group of patients will undergone CYP2C19 genetic test for genotype-guided antiplatelet therapy, whether clopidogrel or ticagrelor.
Visit the clinic post 30 days of PCI for follow-ups and platelet function tests.
Detailed description
Clopidogrel, a prodrug that inhibits platelet aggregation, is widely used in patients undergoing percutaneous coronary interventions to prevent recurrent cardiovascular events. However, clopidogrel resistance has emerged as a great concern, whereby it causes inadequate platelet inhibition and leads to antiplatelet treatment failure with prevalence as high as 44% in Asian population. Due to various established evidence from pharmacogenomics studies, US FDA has issued a black-box warning notifying that CYP2C19 polymorphisms may impaired the ability of a patient to convert clopidogrel into its active metabolite. Currently, the availability of newer P2Y12 receptor inhibitors has prompted medical professionals to consider genotype-guided treatment, which may include escalation or de-escalation of the antiplatelet based on CYP2C19 genetic result. We hypothesize that CYP2C19 genotype guided therapy will reduce the occurrence of MACE and improve platelet reactivity to prevent clopidogrel resistance. The estimated sample size required for pilot intervention study is 120 patients. Knowledge of potential pharmacogenetic markers for clopidogrel resistance, clinical efficacy and cost evaluation of genotype-guided antiplatelet therapy will provide a comprehensive insight into adopting such approach in a real routine clinical setting.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Genetic: CYP2C19 genotype-guided antiplatelet therapyPre-emptive genetic testing will be done on the patients allocated randomly to the intervention group after obtaining their consent. The clinical decision making on the antiplatelet (either clopidogrel or ticagrelor) will be done based on the presence of genetic markers CYP2C19*2 and CYP2C19*3, according to the latest Clinical Pharmacogenetics Implementation Consortium (CPIC) 2022 guideline. Patients who are identified to have reduced function CYP2C19 allele will receive 90 mg ticagrelor and patients with wild-type CYP2C19 allele will receive clopidogrel 75 mg in the next scheduled dose. |
| Universal Clopidogrel | No intervention | –All patients in the control group 1 will receive clopidogrel (300 mg loading dose to 75 mg daily maintenance dose) without any genetic screening done for 30 days. |
| Universal Ticagrelor | No intervention | –All patients in the control group 2 will ticagrelor (180 mg loading dose to 90 mg twice daily as maintenance dose) without any genetic screening done for 30 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Males or females
- Aged between 18 to 80 years old
- Patients presents with stable CAD or acute coronary syndrome (ACS)
- Eligible for percutaneous coronary intervention (PCI)
- Willing to provide DNA sample via blood drawn for genotyping and platelet reactivity assessment
Key exclusion criteria (19 listed)
- Primary PCI or rescue PCI
- Any urgent/emergent coronary angiography procedure that would not allow for genetic testing to be performed before PCI
- Failure of index PCI
- Patient or physician refusal to enroll in the study
- Patient with known CYP2C19 genotype prior to randomization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYP2C19 genotype-guided antiplatelet therapyAlso: CYP2C19 screening test, Precision medicineA panel of genes including CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) will be genotyped using the real-time PCR and the expected turnover time will be 48 hours. Patients who are identified to have reduced function CYP2C19 allele will receive 90 mg ticagrelor and patients with wild-type CYP2C19 allele will receive clopidogrel 75 mg in the next scheduled dose. The switching done from clopidogrel to ticagrelor is supported by Antiplatelet Therapy Switching Clinician Guideline, whereby in the maintenance or low risk phase, there is generally no need to administer a loading dose of ticagrelor; one can switch directly to ticagrelor maintenance dose 24 hours after the last dose of clopidogrel | Genetic | Intervention group |
Primary outcome
Major adverse cardiovascular events (MACE)
Time frame: From enrollment to 30 days post PCI
Major adverse cardiovascular events (MACE) is defined as the composite of all-cause mortality, recurrent myocardial infarction (MI), repeat revascularization and stroke. The fourth universal definition of MI was used to retrospectively analyse recurrent MI. Any revascularization of the target coronary artery following the index incident, whether percutaneous or surgical, was referred to as repeat revascularization.
1 secondary outcome
Platelet Reactivity Index (PRI)
Time frame: From enrollment to at least 2 weeks of maintenance dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD) contact
Nur Aizati Athirah Daud, Doctor of Philosophy (PhD) contact
Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD) principal investigator
School of Pharmaceutical Sciences, Universiti Sains Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing CYP2C19 genotype-guided antiplatelet therapy in people with Coronary Arterial Disease (CAD) and ACS (Acute Coronary Syndrome), run by Nur Hafizah Annezah binti Utuh at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nur Hafizah Annezah Utuh, Doctor of Philosophy (PhD) (601133178262, hafizah.anis67@student.usm.my), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major adverse cardiovascular events (MACE) (time frame: From enrollment to 30 days post PCI). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2025.